Lignocellulosic biomass has garnered attention as an abundant and sustainable alternative energy source that can facilitate reliable and environmentally friendly energy generation. Energy security improves, and environmental impacts diminish when bioethanol, a biofuel produced via lignocellulose-based processes, is utilized. The lignocellulosic biomass of Thysanolaena latifolia has considerable potential as a bioethanol feedstock due to its high carbohydrate content (62.4 ± 0.7%). In this study, feedstock derived from T. latifolia was pretreated with various concentrations of H3PO4 to determine the ideal conditions for enzymatic hydrolysis to convert the feedstock to fermentable sugar. The findings revealed that hydrolysis efficiency and glucose recovery yields were substantially improved compared to those of the untreated sample. Pretreated samples were enzymatically digested to produce a liquid hydrolysate. This hydrolysate was fermented without detoxification using Saccharomyces cerevisiae TISTR 5339 to produce ethanol. The results indicated that T. latifolia biomass hydrolysate is a promising long-term carbon source for ethanol production from cellulosic biomass. Furthermore, the morphological and crystallographic characteristics of the treated T. latifolia biomass were influenced by H3PO4 concentration, as indicated by the SEM images, X-ray diffractogram patterns, and crystallinity index values. Therefore, utilizing T. latifolia feedstock to produce bioethanol can enhance bioenergy sustainability.

Early and accurate mapping of winter canola planting areas provides critical support for sustainable cropland management. Although some methods have been proposed to map the winter canola at the flowering or later stage, mapping winter canola planting areas at the early stage is still challenging, due to the insufficient understanding of the multi-source remote sensing features sensitive for winter canola mapping. This study proposed an early-stage winter canola area mapping method by using the combination of optical and synthetic aperture radar (SAR) data. We analyzed the spectral features, backscatter coefficients, and textural features of winter canola based on Sentinel-2 and Sentinel-1 images. Random forest (RF) and Support Vector Machine (SVM) classification models were built to map winter canola based on early-stage images and field samples in 2017 and then apply the best model to corresponding satellite data in 2018-2022. Results showed that: (1) The red edge and near-infrared-related spectral features were most important for the mapping of early-stage winter canola, followed by VV, DVI and GOSAVI, which also showed greater differences than the other features; (2) Based on Sentinel-1 and Sentinel-2 data, winter canola could be earliest mapped around 130 days prior to ripening (i.e., early overwinter stage) with the F-score over 0.85 and the OA over 81%; (3) Adding Sentinel-1 could improve the OA by about 2%-4% and the F-score by about 1% -2% in winter canola mapping. (4) The F-score of winter canola mapping based on the classifier transfer approach in 2018-2022 varied between 0.75 and 0.97, and the OA ranged from 79% to 86%. This study demonstrates the potential of early-stage winter canola mapping using the combination of Sentinel-2 and Sentinel-1 images, which could provide valuable and timely information for stakeholders and decision makers.

Zwitterionic polymers emerge as very useful materials for applications in antifouling surfaces. The properties of these polymers can be tuned by variation of the chemical structure of the corresponding monomer. In this study, two zwitterionic ammonium sulfonate monomers bearing an hydroxyl function and a styrenic polymerizable groups were prepared in two steps. The two monomers were obtained using 4-vinylbenzyl chloride as the key precursor. The zwitterionic monomers were characterized by 1H NMR, 13C NMR, IR spectroscopy and high-resolution mass spectrometry (HRMS). These two monomers enable the preparation of novel zwitterionic polymers with enhanced hydrophilicity due to the presence of a hydroxyl group.

Background/Objectives Gastroparesis, a chronic digestive disorder characterized by delayed gastric emptying, often results from diabetes, post-surgical complications, autoimmune diseases, and neurological disorders. In approximately 50% of cases, the cause is idiopathic gastroparesis (IGD). Recent studies suggest a link between chronic enteroviral infections and persistent gas-trointestinal symptoms, including delayed gastric emptying. This study investigates the effects of a silydianin-rich extract from Silybum marianum seeds on enteroviral infections in vitro and the mitigation of delayed gastric emptying in mice. Silydianin, a key bioactive compound known for its liver-protective and antioxidant properties, has not been extensively studied for its impact on enteroviral infections and gastroparesis; Methods NMR spectroscopy (¹H, ¹³C, and DEPT) identi-fied silydianin as the primary compound, with minor flavonolignans and trace amounts of an oxidation product. The study assessed the cytotoxicity and antiviral activity of the extract at various stages of the viral life cycle, including virucidal activity, cell protection, and post-infection effects, using neutral red assays in RD cells, with results confirmed by real-time PCR. The viruses studied included Coxsackievirus B2, Coxsackievirus A10, Poliovirus SL-1, and Enterovirus EV71. The impact on delayed gastric emptying was evaluated in a mouse model of gastroparesis using doses of 100 and 200 mg/kg compared to a control; Results: The silydianin-rich extract exhibited con-sistent antiviral activity, with the highest selectivity index (SI) for EV71 (4.08) during virucidal activity. It provided moderate cell protection, with EC50 values ranging from 120.88 to 186.10 µg/mL and SI values from 2.20 to 3.39. Post-infection treatment showed varying efficacy, with Coxsackie A10 demonstrating the highest SI (3.90). In vivo, the extract at 200 mg/kg significantly improved gastric emptying to 96.47% and slightly increased gastrointestinal transit from 50.33% to 61.46%; Conclusions These results suggest that silydianin may be effective in treating enteroviral infections and enhancing intestinal function, making it a promising candidate for gastroparesis treatment and warranting further research.

The influence of polysialic acid (PSA) and sialic acid (SA) on the gut microbial community composition and metabolites in healthy human was investigated using a bionic gastrointestinal reactor. The results indicated that PSA and SA significantly changed the gut microbiota and metabolites in different degrees. PSA can increase the relative abundances of Faecalibacterium and Allisonella, whereas SA can increase those of Bifidobacterium and Megamonas. Both can significantly increase the content of short-chain fatty acids. The results of metabolome analysis showed that PSA can upregulate ergosterol peroxide and gallic acid and downregulate the harmful metabolite N-acetylputrescine. SA can upregulate 4-pyridoxic acid and lipoic acid. PSA and SA affect gut microbiota and metabolites in different ways and have positive effects on human health. These results will provide reference for the further development of PSA- and SA-related functional foods and health products.

Ingestion of corrosive agents is a well-known cause of extensive and severe gastrointestinal tract injury. Acids can result in significant acute complications throughout the gastrointestinal system. Herein, we present a case of total gastrointestinal necrosis after a patient ingested a large amount of concentrated hydrochloric acid. Of note, the patient developed an intestinal fistula six days following ingestion, requiring surgical intervention. This case underscores the potential for delayed gastrointestinal necrosis with high-volume and concentrated hydrochloric acid ingestion. Early CT evaluationto and multi-organ protectionis are crucial for such patients. For patients with no signs of perforation, multidisciplinary physicians should comprehensively evaluate the necessity of surgical exploration. In such cases, comprehensive treatment strategies can significantly improve outcomes. The purpose of this case report is to highlight the complexities and challenges in managing severe hydrochloric acid ingestion, to discuss the multidisciplinary approach required for such cases, and to contribute to the existing literature by providing detailed insights into the clinical presentation, treatment, and outcomes of a rare and severe instance of concentrated HCl ingestion.

A phase 1-2, prospective, multicenter, randomized, open-label clinical trial (Code RPCEC00000382, https://rpcec.sld.cu/trials/RPCEC00000382-En/), with parallel groups, involving 1161 participants was designed to assess safety and immunogenicity of two Cuban COVID-19 vaccines (Mambisa and Abdala) in boosting COVID-19 immunity of convalescent adults after receiving one dose of either vaccine. The main safety outcome was severe vaccination adverse events occurring in <5% of vaccinees. Main immunogenicity success endpoints were ≥4-fold anti-RBD IgG seroconversion or ≥20% increase in ACE2-RBD inhibitory antibodies in >55% of vaccinees in Phase 1 and >70% in Phase 2. Neutralizing antibody titers against SARS-CoV-2 variants were evaluated. Both vaccines were safe; no deaths or severe adverse events occurred. Mild intensity adverse events were the most frequent (>73%); headache predominated for both vaccines. Phase 1 responders were 83.3% (p = 0.0018) for Abdala. Mambisa showed similar results. Phase 2 responders were 88.6% for Abdala (p <0.0001) and 74.2% for Mambisa (p = 0.0412). In both phases, anti-RBD IgG titers, inhibition percentages and neutralizing antibody titers increased significantly after the booster dose. Both vaccines were safe and their immunogenicity surpassed the study endpoints.

All over the world birds’ eggs are an important and valuable component of the human diet. The study aimed to compare the content of lipid components and their nutritional value as well as iron and zinc levels in chicken and quail eggs commonly available on the market. In egg lipids, unsaturated acids were dominated, especially oleic acid, the content of which was about 40% of total fatty acids (TFA). Linoleic acid was the major polyunsaturated fatty acid. Compared to other products of animal origin, eggs were characterized by favourable values of lipid quality indices, especially index of atherogenicity, thrombogenicity and hypocholesterolemic to hypercholesterolemic ratio. In the present study, no differences in the content of tested nutrients between eggs from different production methods (organic, free-range, barn, cages), as well as inter-breed differences were noticed. Cluster analysis showed that eggs enriched in n3 PUFA (according to producers’ declaration) differ from other groups of chicken eggs. However, only in eggs from one producer, the amount of EPA and DHA exceed 80 mg per 100 g, entitling to use the nutrition claim on the package. Quail eggs differed from chicken eggs in FA profile; they also had much higher iron and cholesterol levels.

This research focussed on utilisation of salmon protein and lipid to manipulate pasta glycaemic index and protein digestibility. Salmon fish (Oncorhynchus tschawytscha) powder (SFP) supplemented pasta flour at the from 5% to 20% (w/w). Inclusion of SFP lead to a significant reduction in starch digestibility and hence the potential glycaemic values of pasta (experimental pasta being up to 143% lower than control values). SFP addition to pasta increased the release of phenolic compounds from pasta during both a gastric digestion (179%) and pancreatic digestion ( 133%) in comparison to the control sample. At the same time, the antioxidant activity of the digested pasta was increased by up to 263% (gastric) and 190% (pancreatic) in comparison to durum wheat pasta alone. Interestingly, although protein levels increased with incorporation of SFP, the digestibility values of the protein decreased from 86.41% for the control pasta to 81.95% for 20% SFP pasta. This may indicate that there are interactions between phenolic and protein in the pasta samples which affect overall protein digestibility levels.

Omicron SARS-CoV-2 variants have dominated the strains of COVID-19 circulating worldwide for the last two years. Although the mortality rate of the COVID-19 Omicron variants is only approximately half that of previous variants, vaccines effective against Omicron are needed. Demonstrating that a SARS-CoV-2 vaccine can protect against Omicron in an in vivo infection model, particularly in that of Syrian hamsters, is important for the preclinical characterization of SARS-CoV-2 vaccines. Here, we report on the evaluation of W-PreS-O for its ability to protect Syrian hamsters against infection by Omicron. W-PreS-O is a chimeric vaccine based on a single fusion protein (W-PreS-O), combining RBDs from Wuhan hu-1 wild-type and Omicron adsorbed to aluminum hydroxide. The Syrian hamsters were immunized three times at three-week intervals with W-PreS-O or with aluminum hydroxide (placebo), and then they were infected with Omicron BA.1. Non-infected and non-vaccinated animals served as controls. Neutralizing antibody (nAB) titers, weight, lung symptoms (i.e., edema and pneumonia index), and viral loads, as measured using RT-PCR in the upper and lower respiratory tracts, were determined. In addition, infectious virus titers from the lungs were measured using a plaque-forming assay. W-PreS-O-vaccinated hamsters developed robust nABs against Omicron, showed almost no development of pneumonia, and had significantly reduced infectious virus titers in the lungs. Importantly, the viral loads in the nasal cavities of W-PreS-O-vaccinated hamsters were close to or above the PCR cycle threshold considered to be non-infectious. Our data provide compelling evidence demonstrating that the W-PreS-O vaccine has protective effect against Omicron in a Syrian hamster in vivo infection model. W-PreS-O is therefore a highly promising candidate vaccine for Omicron infections, and it should be further evaluated in clinical studies.

Background and Objectives: In recent years, electric scooters have gained widespread popularity as an easy and affordable mode of transport in urban areas worldwide. Simultaneously, trauma centres have observed an increasing number of associated injuries to users. While injury patterns associated with other vehicles are now well-researched, electric scooter-related injuries are a new topic in the literature. Our study aims to investigate the disparities in injury patterns and other critical accident characteristics among bicycle, electric scooter, and scooter riders. Materials and Methods: In this one-year prospective observational study, we examined patients who sustained injuries while riding bicycles, electric scooters, or scooters between April 2021 and March 2022 at Hungary's largest trauma centre in Budapest. During this one-year period, we identified 1938 patients, 1378 cyclists, 370 electric scooters and 190 scooter users. We collected basic demographic information, recorded injury type and severity, time of day the injury occurred, and alcohol intoxication. Results: While 4.6% of cyclists and 5.8% of scooter riders had consumed alcohol, 26.8% of electric scooter riders were intoxicated at the time of their accident. 45.8% of electric scooter-related injuries occurred at night, compared to only 9.2% and 14.1% of bike and scooter-related injuries, respectively. Sober patients were more likely to suffer mild and severe limb injuries (Odds Ratio (OR): 3.85, P = .0001 and OR: 3.26, P = .0001), but less likely to experience mild and severe head injuries (OR: 0.1, P = .0001 and OR: 0.25, P = .0001) than intoxicated patients. Cyclists had significantly fewer cases of severe head trauma than those injured while using electric scooters (OR: 0.34, P = .0166). Conclusions: Severe craniofacial injuries are more common in intoxicated patients and in patients injured using electric scooters.

Postharvest 1-MCP treatment can inhibit lignification of fruit and vegetables. It has been suggested that the mode of action of 1-MCP is through inhibiting ethylene production, but the effect of 1-MCP and ethylene on lignification of common bean remain unknown. This work compared the effect of 0.5 μL L-1 1-MCP and 100 μL L-1 ethylene on lignification of common bean during storage. Postharvest 1-MCP significantly inhibited the increase of lignified cell group, sclerenchyma became thicker, vascular bundles thickened and lignified cells grew during storage, while ethylene is the opposite. 1-MCP inhibited the increase in respiration rate, sucrose phosphate synthase (SPS), sucrose synthase (SuSy), phenylalanine ammonialyase (PAL), cinnamyl-alcohol dehydrogenase (CAD), and peroxidase (POD) activities, whereas ethylene hastened all. Ethylene treatment can be stimulated and 1-MCP inhibited the decline of reducing sugar and cellulose content. Expression of genes, including PvACO1, PvAOG1, PvSuSy, PvPAL3, and Pv4CL1, PvCOMT1 together with lignin content were significantly increased in common bean during storage. 1-MCP treatment markedly inhibited expression of PvACO1, PvSuSy2, PvPAL3, Pv4CL1 and PvCOMT1 genes, while strengthened expression of PvETR1 and PvAOG1, while ethylene was opposite. This work provides evidence that ethylene plays a key role in regulating the lignin biosynthesis of common bean, and also provides strategies for the maintenance of fruit quality during storage.

Polyelectrolyte-drug complexes are interesting alternatives to improve unfavourable drugs properties. Vancomycin (VAN) is an antimicrobial used in the treatment of methicillin-resistant Staphylococcus aureus pulmonary infections in patients with cystic fibrosis. It is generally administered intravenously with high incidence of adverse side effects, which could be reduced by intrapulmonary administration. Currently, there are no commercially available inhalable formulations containing VAN. Thus, the present work focuses on the preparation and characterization of an ionic complex between hyaluronic acid (HA) and VAN with potential use as inhalable formulations. Particulate-solid HA-VAN25 complex by spray drying from an aqueous dispersion was obtained. FTIR spectroscopy and thermal analysis confirmed the ionic interaction between HA and VAN, while an amorphous diffraction pattern by X-ray was observed. The powder density, geometric size and morphology showed a suitable aerosolization and aerodynamic performance of the powder, indicating the capability of reaching the deep lung. An in vitro extended-release profile of VAN from the complex was obtained, exceeding 24 hours. Microbiological assays against methicillin-resistant and -sensitive reference strains of Staphylococcus aureus, showed that VAN preserves its antibacterial efficacy. In conclusion, HA-VAN25 exhibited interesting properties for the development of inhalable formulations with potential efficacy and safety advantages over conventional treatment.

The current globally dominant SARS-CoV-2 variants are showing immune escape and reduced susceptibility to antiviral drugs. Therefore, agencies responsible for drug evaluation and regulation such as the FDA and EMA are revising their emergency authorization use of several COVID-19 neutralizing antibodies. These MAbs proved to be unlikely effective against new variants especially Omicron descendants and several pharmaceutical companies are pursuing the development of more potent neutralizing antibodies. To address this issue, we used In Silico method we previously developed to assess 10 anti-SARS-CoV-2 antibodies propensity to neutralize the new Omicron’s subvariants EG.5, BA.2.86 and JN.1, based on comparative binding affinity of 3D generated models and previous experimental and clinical observations. Nine of these MAbs were once granted emergency use authorization, and one is currently under clinical investigation. The results showed that one antibody showed a marked increase of the binding energy for EG.5 compared to two antibodies that showed a significant increase with Pirola (BA.2.86) and JN.1. This data indicates that the new SARS-CoV-2 variant escapes neutralization of most of the available therapeutic NAbs. Furthermore, the data showed new potential therapeutic MAbs combination that could be effective for the treatment countermeasure of the new Omicron’s descendants or potential novel variants.

Background: Primary deficit schizophrenia (DS) is characterized by enduring negative symptoms and represents a qualitatively different disease entity with respect to non-deficit schizophrenia (NDS). No studies investigated the association between the enzyme paraoxonase 1 (PON1) and DS and its phenomenology. Methods: In this case-control study, Thai women and men, aged 18-65 years, were divided in DS (n=40) and NDS (n=40) and were compared to controls (n=40). PON1 activities against 4-(chloromethyl)phenyl acetate (CMPA) and phenylacetate were determined. Moreover, subjects were genotyped for their PON1 Q192R polymorphism and IgA levels responses directed to Gram-negative bacteria were measured. Results: DS is significantly associated with the QQ genotype and the Q allele as compared with NDS and controls. PON1 activities are significantly and inversely associated with negative symptoms, formal thought disorders, psychomotor retardation, excitation and DS. The presence of the Q allele is associated with increased IgA responses to Pseudomonas aeruginosa, Morganella morganii, and Pseudomonas putida as compared with RR carriers. Conclusions: The PON1 Q allele and lower PON1 activities especially against CMPA are associated with DS, indicating lowered quorum quenching abilities as well as lowered defenses against lipoperoxidation and immune activation. It is suggested that lowered PON1 activity in DS constitutes an impairment in the innate immune system which together with lowered natural IgM may cause lower immune regulation thereby predisposing towards greater neurotoxic effects of immune-inflammatory, oxidative and nitrosative pathways and Gram-negative microbiota.

Nanostructured lipid carriers (NLC) are typically composed of liquid lipids, solid lipids, and surfactants, enabling the encapsulation of lipophilic drugs. Butamben is a Class II anesthetic drug according to the Biopharmaceutical Classification System (BCS), it has a log P 2.87 and is considered a 'brick dust' (poorly water-soluble and poorly lipid-soluble) drug. This characteristic poses a challenge for the development of NLCs, as they are not soluble in the liquid lipid present in the NLC core. In a previous study [1] we have developed a NLC core consisting of solid lipid (CrodamolTM CP), liquid lipid of medium polarity (SRTM Lauryl lactate), and a hydrophilic excipient (SRTM DMI) that allowed the solubilization of 'brick dust' type of drugs including butamben. In this study, starting from the NLC core formulation previously developed we carried out the optimization of the surfactant system and evaluated their performance in aqueous medium. Three different surfactants (CrodasolTM HS HP, SynperonicTM PE/F68, and CroduretTM 40) were studied and, for each of them, a 2³ factorial design was stablished, with total lipids, % surfactant, and sonication time (min) as the input variables and particle size (nm), polydispersity index (PDI) and zeta potential (mV) as the response variables. Stable NLCs were obtained using CrodasolTM HS HP and SynperonicTM PE/F68 as surfactants. Through a comparison between NLCs developed with and without SRTM DMI, it was observed that besides helping the solubilization of butamben in the NLC core, this excipient helped stabilizing the system and decreasing particle size NLCs containing CrodasolTM HS HP and SynperonicTM PE/F68 presented particle size values in the nanometric scale, PDI lower than 0.3 and zeta potential above |10|mV. Concerning NLCs stability, SBTB-NLC with SynperonicTM PE/F68 and butamben demonstrated stability over a 3-month period in aqueous medium. The remaining NLCs showed phase separation or precipitation during the 3-month analysis. Nevertheless, these formulations could be freeze-dried after preparation, which would avoid precipitation in aqueous medium.

Headache is considered to be one of the most common causes of medical treatment and evaluation worldwide in both acute and outpatient settings. It is the most common neurological symptom seen worldwide affecting all genders, ages, ethnicities, and socioeconomic levels. It’s impact is noted in educational decline in school-aged children and decreased productivity through sick leave in adults. Its overall burden is well documented in well-resourced countries but limited data is seen low resourced countries. While many underlying causes bring about secondary headaches, primary headaches and more specifically migraines have been more widely explored. Migraines have a distinct criterion that is inclusive of one day duration (4 hours to 7 days, unilateral distribution, nausea and vomiting and disability as a few examples. However, migraines can vary and proper documentation through a migraine diary can help to guide treatment. Management of migraines can vary. Lifestyle modification is a key factor in the overall prevention and reduction of triggers in migraines. In addition to this, pharmacotherapy can be given in a tier-based approach based on overall severity and frequency of the migraine. Interventions have progressed from botox injection and have seen the advent of new medications such as nasal sprays to novel formulations of pre-existing drug formulations. Nonetheless, there is great room for further studies of headaches and migraines. Research specifically in low-resource countries can prove to beneficial.

According to cancer death rates for women worldwide, this form of cancer ranks fourth after breast, bronchopulmonary, and colorectal cancer, affecting around 570,000 women annually. About 270,000 women each year pass away from this illness, 85% of them are from underdeveloped nations where cervical cancer claims more lives than any other kind of cancer. In Romania, cervical cancer ranks fourth in terms of death, behind breast, bronchopulmonary, and colorectal cancers, and second in terms of incidence, behind breast cancer. Endometriosis in the cervical region is quite uncommon. Only a tiny fraction of women had the condition upon diagnosis. It might be challenging to detect cervical endometriosis since it rarely manifests any symptoms or markers. Women who are asymptomatic can manage the condition expectantly; however, if the symptoms return often, surgery may be required. As many patients have concurrent diseases such fibroids, adenomyosis, ovarian cysts, and pelvic endometriosis, cervical endometriosis therapy appears to be straightforward. There ought to be surgical intervention. Symptomatic cervical endometriosis, such as irregular or post-coital bleeding, may be treated surgically using the LLETZ surgery or another cervical ablation approach. Background and Objectives: (1) To assess one's degree of knowledge on the signs, causes, and methods of preventing cervical cancer or cervical endometriosis, as well as screening for these conditions. (2) To ascertain how the responder behaves about cervical cancer screening and prevention, as well as endometriosis in the cervical region. Materials and Methods: A case report about cervical cancer or cervical endometriosis was conducted among a patient from Romania, Timisoara. Results: In this study, we report the patient with cervical endometriosis, although he was initially diagnosed with cervical cancer. Conclusions: Cervical cancer, a condition that can have serious repercussions on the patient's health, even if there is no clear picture of paraclinical investigations, to raise the suspicion of cervical endometriosis and not cervical cancer.

Reducing overall food intake or lowering the proportion of protein relative to other macronutrients, can extend lifespan in diverse organisms. A number of mechanistic theories have been developed to explain this phenomenon, mostly assuming that the molecules connecting diet to lifespan are evolutionarily conserved. A recent study using Drosophila melanogaster females has pinpointed a single essential micronutrient that can explain how lifespan is changed by dietary restriction. Here, we propose a likely mechanism for this observation, which involves a trade-off between lifespan and reproduction, but in a manner that is conditional on the dietary supply of an essential micronutrient – a sterol. Importantly, these observations argue against previous evolutionary theories that rely on constitutive resource reallocation or damage directly inflicted by reproduction. Instead, they are compatible with a model in which the inverse relationship between lifespan and food level is caused by the consumer suffering from varying degrees of malnutrition when maintained on lab food. The data also indicate that animals on different lab foods may suffer from different nutritional imbalances and that the mechanisms by which dietary restriction benefits the lifespan of different species may vary. This means that translating the mechanistic findings from lab animals to humans will not be simple and should be interpreted in light of the range of challenges that have shaped each organism’s lifespan in the wild and the composition of the natural diets they would feed on.

Background. Sarcopenia, defined as the loss of skeletal muscle mass and function, is a major clinical problem in many chronic illnesses, in cancer and in the elderly. Exercise and adequate nutrition, peculiarly dependents on availability of essential amino acids, considered the primary strategies for prevention and treatment of protein synthetic deficits, affect both the efficient scavenging of aged and overused protein molecules and the renewal, by maintaining muscular protein synthesis. Many questions still remain about the regulation of protein syntheses and degradation. Degradation of inefficient proteins or organelles is performed by the sum of micro and macro-autophagy plus ubiquitin-proteasome system, activities known as proteostasis, necessary to preserve and promote protein masses and consequently, the body’s reserves. However, how protein synthesis is regulated, and how activation of the mTOR complex may modulate and transduce the flow of information provided by exercise and nutrition to balance proteostasis and syntheses, is far from being fully understood. We suggest that energy production and availability, thus also mitochondria, may have a pivotal role in synchronizing activity and functional outcomes of protein syntheses, and that those syntheses, since higly energy demanding, are main effectors of AMPK dependent autophagy activation by consuming ATP and producing AMP. Conclusion. While in normal conditions protein syntheses drive autophagy activation by decreasing ATP to AMP ratio, conversely autophagy may be inefficiently activated when chronic both low production and consumption of ATP would result in lowest concentrations of AMP, and therefore both blunted rates of protein syntheses and autophagy would be observed. We suggest that this functional hypothesis may explain sarcopenia in many pathological conditions , as in cancer or in aging muscles.

As neck and/or shoulder pain (NSP) frequently occur together with tension-type headache (TTH) and migraine, we explored how concomitant NSP affects perceived treatment responses to an analgesic. An anonymous survey was performed among 895 TTH and migraine sufferers who used the analgesic 400 mg ibuprofen/100 mg caffeine. NSP was relatively abundant among patients (42.4% for TTH; 39.2% for migraine), and associated with >1 additional day with headache per month. Reported pain reduction was independent from NSP for TTH and migraine. More patients became pain-free at 2 h in migraine with NSP (42.9%) compared to migraine without NSP (32.2%), which is different from TTH with NSP (60.6%) and TTH without NSP (71.4%). For both, migraine and TTH, a recurrence of headache on the same day was more prevalent in those with concomitant NSP leading to a greater likelihood of taking a second dose of the analgesic. NSP frequently occurs together with TTH and migraine patients. In migraine, NSP seems to be associated with a better treatment response at 2 h. The more frequent recurrence of pain in those with concomitant NSP indicates that NSP makes both headache types worse. Further studies are needed to substantiate these effects.

This is a review on social laser theory completed with its new developments and applications. An important methodological step towards similarity with quantum physics is the invention and consistent operation with infons. These are excitations of the quantum social-information field carrying social energy and coarse grained content of communications (their color and quasi-color). We study in more detail interactions of infons with social atoms, the processes of absorption and emission (spontaneous and stimulated). We also analyze the dynamics of iterations of the cascades of infons in the social resonators. The latter are based on social networks coupled to laser's gain medium composed of social atoms. Consideration of the pro-war and pro-peace beams leads to the general discussion on the competing beams of social radiation and the conditions for their creation and coexistence. The role of social networks in lasing is illustrated by the protests during the COVID-19 pandemic. It is highlighted that a human gain medium can approach the state of population inversion with supply of infons of one sort (quasi-color), but the stimulated emission can be induced by injection into the gain medium of infons of a different quasi-color. We call this behavior of social atoms memorylessness. This theoretical property is illustrated with the examples from the modern social-political life.

In tumour cells of more than 20 different cancer types, the CXCR4-CXCL12-axis is involved in multiple key processes including proliferation, survival, migration, invasion, and metastasis. Since data on this axis in diffuse large B cell lymphoma (DLBCL) are inconsistent and limited, we comprehensively studied the CXCR4-CXCL12-axis in our DLBCL cohort as well as the effects of CXCR4 antagonists on lymphoma cell lines in vitro. In DLBCL, we observed a 140-fold higher CXCR4 expression compared to non-neoplastic controls. Interestingly, high expression of CXCR4 was associated with poor clinical outcome. Furthermore, in corresponding bone marrow biopsies, we observed a correlation of CXCL12 expression and lymphoma infiltration rate as well as a reduction of CXCR4 expression in remission of bone marrow involvement after treatment. Furthermore, the niacin derivate of the CXCR4 antagonist AMD070, which was synthesized by us, demonstrated stronger pro-apoptotic effects than AMD070 in vitro and induced expression of certain pro-apoptotic genes in CXCR4 positive lymphoma cell lines. Finally, WK1 treatment resulted in reduced expression of JNK-, ERK1/2- and NFκB/BCR-target genes. These data indicate that the CXCR4-CXCL12-axis impacts the pathogenesis of DLBCL and represents a potential therapeutic target in aggressive lymphomas.

Objective: A 1964 study challenged the consensus that saturated fat consumption increased the risk for myocardial infarction (MI). Roseto Pennsylvania, an Italian-American enclave of 1600 people, had similar rates of cigarette smoking, obesity and higher saturated fat consumption as neighboring towns, but far lower MI death rates. More than 50 years later, it remains uncertain if Roseto’s residents had better heart health than the average American and if so, what factors were responsible. Methods: We compared MI deaths in Roseto and neighboring towns to the Framingham Heart Study cohort matched for age and sex. Results: We found no evidence that MI deaths were lower in Roseto, PA than in Framingham, MA when controlling for age and sex. While the role of social support in health is uncontested, methodological issues, confounding factors and biases challenge the validity of the Roseto study. Conclusions: The dramatically lower MI and MI mortality rates among males in Roseto reflects biases in sampling and comparison populations, which also impacted the contrasting Diet-Heart hypothesis that saturated fats cause heart disease. Although social support enhances health outcomes, the Roseto study neither supported nor refuted this connection.

Research on green-certified buildings has often been focused on the benefits of green standards, such as energy efficiency, smart growth, resource conservation, and health protection. Recent studies suggest the adoption of a reductionist sustainability planning language can turn green-certified houses into luxury goods, attracting White, prime-age, college-educated households with some pro-environmental attitudes who replace existing long-term, lower-income residents in core urban areas. While many factors may work together in driving neighborhood change and gentrification in cities, the question this study aims to address is to what extent the supply of green-certified units can affect neighborhood change and gentrification? We use Central Virginia’s Multiple Listing Service (MLS) housing market transactions data and the U.S. Census Bureau’s socioeconomic data to present the differential effect of new construction of market-rate, green-certified units in a natural experiment using difference-in-differences estimates. We find that neighborhoods that include new, green-certified units have experienced a statistically significant increase in population, supporting new construction and positively affecting house prices. We also detect some negative effects on minorities and minority owners, but these effects have not yet reached statistical significance. This study finds strong evidence of green housing providing the conditions that make areas ripe for gentrification, but more studies should follow up to better measure and generalize this finding.

Understanding the factors which control endothelial cell (EC) function and angiogenesis is crucial for developing the horse as a disease model, but equine ECs remain poorly studied. In this study we have optimised methods for the isolation and culture of equine aortic endothelial cells (EA-oECs) and characterised their angiogenic functions in vitro. Mechanical dissociation, followed by magnetic purification using an anti-VE-cadherin antibody, resulted in EC-enriched cultures suitable for further study. Fibroblast growth factor 2 (FGF2) increased EAoEC proliferation rate and stimulated scratch wound closure and tube formation by EAoECs on extracellular matrix. Pharmacological inhibitors of FGFR1 (SU5402) or MEK (PD184352) blocked FGF2-induced ERK1/2 phosphorylation and functional responses, suggesting that these are dependent on FGFR1/MEK-ERK signalling. In marked contrast, VEGF-A had no effect on EAoEC proliferation, migration or tubulogenesis and did not promote ERK1/2 phosphorylation, indicating a lack of sensitivity to this classical pro-angiogenic growth factor. Gene expression analysis showed that, unlike human ECs, FGFR1 is expressed by EAoECs at a much higher level than both VEGFR1 and VEGFR2. These results suggest a predominant role for FGF2 versus VEGF-A in controlling the angiogenic functions of equine ECs. Collectively, our novel data provide a sound basis for stud-ying angiogenic processes in the horse and lay the foundations for comparative studies of EC biology in horses versus humans.

Biofilms are complex communities of microorganisms that adhere to surfaces and develop a protective matrix. The colonization of devices in the food and health care industries by microbial biofilms poses numerous risks. Existing antimicrobial agents often fail to penetrate the biofilm matrix, allowing the pathogen to grow and persist. The objective of this study was to evaluate the impact of MADIO PRO+ multipurpose disinfectant on Salmonella Typhimurium biofilm using crystal violet assay and FTIR spectroscopy. Results demonstrated that MADIO PRO+ multipurpose disinfectant significantly (p<0.05) inhibited biomass of S. Typhimurium biofilm and altered the structure of S. Typhimurium biofilm. In conclusion, MADIO PRO+ multipurpose disinfectant offers an advantage in biofilm control strategy. This discovery could help the food and health care industries to plan better microbial intervention strategies.

Ovine footrot is a complex multifactorial infectious disease, causing lameness in sheep with major welfare and economic consequences. Dichelobacter nodosus is the main causative bacterium, however, footrot is a polymicrobial disease with Fusobacterium necrophorum, Mycoplasma fermentans and Porphyromonas asaccharolytica also associated. There is limited understanding of the host response involved. Proinflammatory mediators interleukin (IL)-1β and C-X-C Motif Chemokine Ligand 8 (CXCL8) have been shown to play a role in the early response to D. nodosus in dermal fibroblasts and interdigital skin explant models. To further understand the response of ovine skin to bacterial stimulation, and to build the understanding of the role of the cytokines and chemokines identified in transcriptomic data, primary ovine interdigital fibroblasts and keratinocytes were isolated, cultured and stimulated with lipopolysaccharide (LPS), D. nodosus or F. necrophorum in the presence and absence of M. fermentans, whilst measuring mRNA expression and protein release of CXCL8 and, IL-1β. Stimulation with LPS, D. nodosus or F. necrophorum resulted in increased transcript levels of IL-1β and CXCL8 in M. fermentans free cells, however, only an increase in CXCL8 protein release was observed. No IL-1β protein release was detected despite increases in IL-1β mRNA, suggesting the signal for intracellular pre-IL-1β processing may be lacking when culturing primary cells in isolation. Keratinocytes and fibroblasts naturally infected with M. fermentans showed little response to LPS, a range of D. nodosus preparations or heat-inactivated F. necrophorum. Primary single cell culture models complement ex vivo organ culture models to study different aspects of the host response to D. nodosus. Ovine keratinocytes and fibroblasts infected with M. fermentans had a reduced response to experimental bacterial stimulation. However, in the case of footrot where Mycoplasma spp. are associated with diseased feet, this natural infection gives important insights into the impact of multiple pathogens on the host response.

Cement manufacturing is one of the most energy-intensive industries in the world. Most of the cost of producing cement is accounted by fuel consumption and power expenditures. Thermal power plants are the major source of electricity in Pakistan. But they are not efficient and environmentally friendly. This study simulates four different models for five cement plants of Pakistan on Homer Pro software and compares the optimal solutions based on the net present cost (NPC), levelized cost of electricity (LCOE) and greenhouse gas (GHG) emissions. Model-1 consists of solar panels, electrolyzer, hydrogen tank, hydrogen generator and converter. Model-2 has only a diesel generator and acts as a base case in this study. Model-3 has solar panels and a battery-converter system. In Model-4, diesel generators, solar panels and converters are considered. Based on NPC, the most optimal model is Model-4, having a 0.249 $/KWh LCOE in islanded systems. The NPC and operating costs are US$540 million and US$ 32.5 million per year, respectively, with a 29.80% reduction in CO2 emissions when compared to the base case. Based on GHG emissions, Model-1 and Model-3 are the best models with 0% GHG emissions. Sensitivity analyses is also performed using the parameters of load, inflation rate and discounted rate. The results prove that the proposed hybrid micropower systems (HMS) can sustainably provide electricity for 24 hours a day to the sites under consideration with minimum objectives.

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus considered as a threat to human health due to large epidemics and serious clinical outcomes such as microcephaly in newborns. Like all flaviviruses, ZIKV relies on the cellular machinery to complete its viral cycle, with the endoplasmic reticulum (ER) being the critical site of viral replication factories. The sudden high protein load in the ER induces an ER stress to which the cell responds with an appropriate unfolded protein response (UPR) in an attempt to restore its disturbed homeostasis. When the restoration fails, the cell signaling leads to a programmed cell death by apoptosis with the upregulation of the UPR-induced C/EBP homologous protein (CHOP) which acts as the main trigger for this fatal outcome. Our previous studies have shown the ability of ZIKV to manipulate various cellular responses in order to optimize virus production. ZIKV is able to delay apoptosis to its benefit and although ER stress is induced, the UPR is not complete. Here we discovered that ZIKV impairs the expression of CHOP/DDIT3, the main factor responsible of ER-stress driven apoptosis. Surprisingly, the mechanism does not take place at the transcriptional level but at the translational level.

Discovery of inhibitors for endothelial-related transcription factors can contribute to the development of angiogenic therapies that treat diseases ranging from cardiovascular to cancer. The role of transcription factor Vezf1 in vascular development and regulation of angiogenesis has been defined by several earlier studies. Through construction of a computational model for Vezf1, work here has identified a novel small molecule drug capable of inhibiting Vezf1 from binding to its cognate DNA binding site. Using structure-based design and virtual screening of the NCI Diversity Compound Library, 12 shortlisted compounds were tested for their ability to interfere with the binding of Vezf1 to DNA using electrophoretic gel mobility shift assays. We identified one compound, T4, which has an IC50 of 20uM. Using murine endothelial cells, MSS31, we tested the effect of T4 on endothelial cell viability and angiogenesis by using tube formation assay. Our data show that addition of T4 in cell culture medium does not affect cell viability at concentrations lower or equal to its IC 50 but strongly inhibits the network formation by MSS31 in the tube formation assays. Given its potential efficacy, this inhibitor has significant therapeutic potential in several human diseases raging from wound healing to cancer.

The RV144 trial represents the only vaccine trial to demonstrate any protective effect against HIV-1 infection. While the reason(s) for this protection are still being evaluated, it serves as justification for widespread efforts aimed at developing new, more effective HIV-1 vaccines. Advances in our knowledge of HIV-1 immunogens and host antibody responses to these immunogens are crucial to informing vaccine design. While the envelope (Env) protein is the only viral protein present on the surface of virions, it exists in a complex trimeric conformation and is decorated with an array of variable N-linked glycans, making it an important but difficult target for vaccine design. Thus far, efforts to elicit a protective humoral immune response using structural mimics of native Env trimers have been unsuccessful. Notably, the aforementioned N-linked glycans serve as a component of many of the epitopes crucial for the induction of potentially protective broadly neutralizing antibodies (bnAbs). Thus, a greater understanding of Env structural determinants, most critically Env glycosylation, will no doubt be of importance in generating effective immunogens. Recent studies have identified the HIV-1 Env signal peptide (SP) as an important contributor to Env glycosylation. Further investigation into the mechanisms by which the SP directs glycosylation will be important, both in the context of understanding HIV-1 biology and in order to inform HIV-1 vaccine design.

In recent decades, a number of high-profile cases involving fraud as research misconduct have been in the media and resulted in severe consequences for those convicted. According to the increased cases of allegations and coverage in the media, this reflects a heightened awareness that fraudulent actions exist. Nonetheless, the Office of Research Integrity data suggests that despite the growth in the number of the cases of allegation there has not been a commensurate increase in findings of misconduct. The purpose of this paper is to explore misconduct to better understand what it entails. An analysis of misconduct from the perspective of the definitions of allegations and fraud of is conducted and potential frameworks for understanding both are considered. The paper considers serial-positioning effects of primacy and recency on allegation phenomena, as well as supervenience theory and contextualism as a lens for understanding fraud. Discussion of the relational semantics of the core aspects of fraud and de facto grouping of forms of misconduct. It is concluded that the interrogative pronouns of “what” and “when” could be used to categorize forms of misconduct laying the foundation for the next paper that deconstructs the definition of falsification according to the Public Health Service.

Rapid emergence of evasive SARS-CoV-2 variants is an on-going challenge for COVID-19 vaccinology. Traditional virus neutralization tests provide detailed datasets of neutralization titers against the viral variants. Such datasets are difficult to interpret and do not immediately inform on the sufficiency of the breadth of antibody response. Some of these issues could be tackled using the antigenic cartography approach. In this study, we created antigenic maps using neutralization titers of sera from donors who received Sputnik V booster vaccine after primary Sputnik V vaccination and compared them with the antigenic maps based on serum neutralization titers of Comirnaty-boosted donors. Traditional analysis of neutralization titers against WT, Alpha, Beta, Delta, Omicron BA.1 and BA.4/BA.5 showed a significant booster humoral response after both homologous (Sputnik V) and heterologous (Comirnaty) revaccinations against all the studied viral variants. However, despite this, a more in-depth analysis using antigenic cartography revealed that Omicron variants remain antigenically distant from WT, which is indicative of the formation of insufficient levels of cross-neutralizing antibodies. The implications of these findings may be significant when developing a new vaccine regimen.

Identifying a panel of markers detecting kidney injury before the glomerular filtration rate (GFR) reduction is the challenge to improve the diagnosis and the management of acute kidney injury (AKI) in septic patients. This study evaluated the roles of tissue inhibitor metal proteinase, insulin growth factor binding protein (TIMP2*IGFBP7), and mid-regional pro-adrenomedullin (MR-proADM) in AKI patients. Patients and Methods: This study was prospectively conducted in the Intensive Care Unit (ICU) enrolling 230 patients who underwent cardiac surgery. Biomarkers were evaluated before and after 4 hours of the cardiac surgery. Results: Whereas urine and creatinine alterations appeared at 23.2 (12.7 – 36.5) hours, after cardiac surgery, urinary TIMP2*IGBP7 levels were higher at 4 hours in AKI patients (1.1±0.4 mg/l vs 0.08±0.02 mg/l; p < 0.001). Its concentration >2 mg/l increases the AKI risk within the following 24 hours, clearly identifying the population at high risk of renal replacement therapy (RRT). In patients with sepsis, MR-proADM levels were 2.3 nmol/l (0.7–7.8 nmol/l), with the highest values observed in septic shock [5.6 nmol/l (3.2–18 nmol/l)] and a better diagnostic profile than procalcitonin and C-reactive protein to identify septic patients. MR-proADM values >5.1 nmol/l and urine TIMP2*IGBP7 levels > 2 mg/l showed a significantly faster progression to RRT, with a mean follow-up time of 1.1 days. Conclusions: TIMP2*IGBP7 and MR-proADM precociously diagnose AKI in septic patients after cardiac surgery, giving prognostic information for RRT requirement.

Pregnancy is associated with significant physiological changes, including alterations in lipid metabolism, which can have implications for both maternal and fetal health. This study aimed to evaluate serum lipid profile variations among healthy Sudanese women during the second and third trimesters of pregnancy. A total of 60 pregnant women, divided equally between the second and third trimesters, were compared with 30 non-pregnant, age-matched controls. Serum levels of total cholesterol, triglycerides, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were measured using a BTS-Biosystem analyzer. The results revealed a statistically significant increase in total cholesterol, triglycerides, LDL, and HDL levels among pregnant women compared to the control group (p < 0.01). Additionally, lipid levels were significantly higher in the third trimester than in the second trimester. A weak positive correlation was found between parity and serum levels of total cholesterol, triglycerides, and LDL, while no significant correlation was observed for HDL. These findings suggest that pregnancy, particularly in the third trimester, is associated with substantial increases in serum lipid levels, highlighting the need for monitoring lipid profiles during pregnancy to manage potential risks of hyperlipidemia and its associated complications.

Edible oils have commercial and nutritional value due to the presence of essential fatty acids. They can be consumed fresh in the form of capsules known as nutraceuticals. The quality of such products is of interest to the consumer. In this context, this study describes a method based on high resolution nuclear magnetic resonance (NMR) and Fourier transform mid-infrared spectroscopic analysis (FTIR), combined with statistical analyzes to differentiate different edible oils used as nutraceuticals in Brazil by fatty acid content. Through the analysis of 1H NMR spectra, the levels of saturated and unsaturated fatty acids in edible oils were characterized and quantified. Statistical analysis of the data confirmed the real distinction between nutraceutical raw materials, with emphasis on ω-9, ω-6 and ω-3 fatty acids. The analytical approach presented also demonstrated potential to identify the origin (animal or vegetable) of edible oils used as nutraceuticals.

Cryopreservation is a stressful process for sperm as it is associated with an increased production of reactive oxygen species (ROS). Elevated ROS levels, which create an imbalance with antioxidant capacity, may result in membrane lipid peroxidation (LPO), protein damage and DNA fragmentation. This study aimed to determine whether membrane LPO and DNA fragmentation of frozen-thawed horse sperm relies upon the antioxidant activity, including enzymes (superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT), and paraoxonase type 1 (PON1)); non-enzymatic antioxidant capacity (Trolox equivalent antioxidant capacity (TEAC), plasma ferric reducing antioxidant capacity (FRAP), and cupric reducing antioxidant capacity (CUPRAC)); and the oxidative stress index (OSI), of their seminal plasma (SP). Based on total motility and plasma membrane integrity (SYBR14+/PI−) after thawing, ejaculates were hierarchically (p &lt; 0.001) clustered into two groups of good (GFE) and poor (PFE) freezability. LPO and DNA fragmentation (global DNA breaks) were higher (p &lt; 0.05) in PFE than in GFE, with LPO and DNA fragmentation (global DNA breaks) after thawing showing a positive relationship (p &lt; 0.05) with SP-OSI levels and ROS production. In addition, sperm motility and membrane integrity after thawing were negatively (p &lt; 0.05) correlated with the activity levels of SP antioxidants (PON1 and TEAC). The present results indicate that LPO and DNA fragmentation in frozen-thawed horse sperm vary between ejaculates. These differences could result from variations in the activity of antioxidants (PON1 and TEAC) and the balance between the oxidant and antioxidant components present in the SP.

USP21, a member of the ubiquitin protease family, plays a vital role in various biological functions. However, the effects of USP21 dysfunction have yet to be fully understood. Here, we generated Usp21 knockout (KO) mice and conducted microarray to identify genes that Usp21 regulates. Its results raised several genes based on their biological characteristics, and RT-qPCR confirmed their expression. KO mice exhibited significant elevations in the expression of the genes Fabp7 and Nlrc5, which play a role in lipid metabolisms, compared to wild-type mice. Blood tests showed no impairment of liver function but did reveal elevated levels of total cholesterol and free fatty acids in KO mice compared to wild-type mice. These data suggest that Usp21 may play roles in lipid metabolism associated with Fabp7 and Nlrc5. To clarify the involvement of USP21 in human hypercholesterolemia, we examined single nucleotide polymorphisms (SNPs) around USP21 in non-hypercholesterolemic and hypercholesterolemic outpatients. We found that the rs11421 SNP downstream of USP21 was associated with hypercholesterolemia. These data suggest that USP21 plays a role in mice and human lipid metabolism and that its polymorphism may be a diagnostic marker for human hypercholesterolemia.

Background: The mechanisms underlying the effect of estradiol (E2) on low-density lipoprotein cholesterol (LDL-C) levels are not completely understood, although a role for proprotein con-vertase subtilisin/kexin type 9 (PCSK9) has been proposed. We aimed to investigate the association between levels of E2, PCSK9 and lipid parameters in premenopausal women undergoing in vitro fertilization (IVF). Methods: Healthy women undergoing IVF in the Department of Obstetrics and Gynecology of the University General Hospital of Ioannina were recruited. Levels of E2, pro-protein convertase subtilisin/kexin type 9 (PCSK9), total cholesterol (TCHOL), high-density lip-oprotein cholesterol (HDL-C), LDL-C, and triglycerides (TGs) were measured 10 days after ovarian depression (E2min) and 7 days after ovarian stimulation (E2max). Results: A total of 34 consecutive healthy women aged 38 (26-46) years old who underwent a full IVF cycle were included. E2 levels increased by 329.6% from E2min to E2max (108 [47-346] to 464 [241-2471] pg/mL, p<0.05). At the same time, serum PCSK9 levels significantly decreased by 30.8% (245 ± 80 to 170 ± 64 ng/mL, p<0.05). No significant changes in TCHOL, LDL-C, TGs and HDL-C were found (-0.4%, -3.8%, -2.2%, and +5.3%, p >0.05). Conclusions: The increase in endogenous E2 production during an IVF cycle was associated with a significant decrease in serum PCSK9 levels during a 7-day period.

A comprehensive lipid profile was analyzed in patients with non-small cell lung cancer (NSCLC) using nanoflow ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. The study investigated 297, 202, and 166 lipids in saliva, plasma, and fecal samples, respectively, comparing NSCLC patients to healthy controls. Lipids with significant changes (&gt;2-fold, p&lt;0.05) were further analyzed in each sample type. Both saliva and plasma exhibited similar lipid alteration patterns in NSCLC, but saliva showed more pronounced changes and fecal lipids had weak correlation with those of saliva and plasma. Total triglycerides (TGs) increased (&gt;2–3 folds) in plasma and saliva but decreased in fecal samples. Three specific TGs (50:2, 52:5, and 54:6) were significantly increased in NSCLC across all sample types. A common ceramide species (d18:1/24:0) decreased in both plasma and saliva but increased in fecal samples. Additionally, phosphatidylinositol 38:4 decreased by approximately 2-fold in plasma and saliva. Phosphatidylserine 36:1 was selectively detected in saliva and showed a subsequent decrease, making it a potential biomarker for predicting lung cancer. The study identifies 27 salivary, 10 plasma, and 16 fecal lipids as candidate markers for NSCLC by statistical evaluations. Moreover, it highlights the potential of saliva in understanding changes in lipid metabolism associated with NSCLC.

Olfactory Receptors (ORs) are a large family of G protein coupled receptors predominantly expressed by the main olfactory epithelium at nasal level and are responsible for the generation of smelling sense. Microarray and deep sequencing analyses, however, have demonstrated that ORs are ectopically expressed in various human tissues including testis, kidneys, adipose tissue and liver and their biological functions become to be unrevealed. Molecular and pharmacological approaches have shown that some of these ORs modulate glucose and lipid metabolism at multiple interfaces, suggesting that ORs might be part of the large family of nutrient sensors. i.e. molecular/ cellular machines that respond to a specific nutrient component. By using nutrients- derived agonists it has been shown that ORs effectively modulates glucose and lipid metabolism raising interest on their possible therapeutic application in the treatment of metabolic disorders including dyslipidemia, obesity and metabolic syndrome.

Peach is the third most important temperate fruit crop considering fruit production and harvested area in the world. Exporting peaches represents a challenge due to the long-distance export markets. This requires fruit to be placed in cold storage for a long time, which can induce a physiological disorder known as chilling injury (CI). The main symptom of CI is mealiness which is perceived as non-juicy fruit by consumers. The purpose of this work was to identify and compare the metabolic and lipid profile between two siblings from a contrasting population for juice content, at harvest and after 30 days at 0°C. A total of 119 metabolites and 189 lipids were identified, which showed significant differences of abundance including mainly in amino acids, sugars and lipids. Our results indicate that some of the top metabolites and lipids could be used as biomarkers associated with mealiness at harvest and after cold storage.

The periodontal ligament (PDL) is a complex connective tissue that connects the tooth root to the dental alveolar bone and plays crucial mechanical roles. PDL also exhibits regenerative roles and regulatory functions to maintain per-iodontium integrity and homeostasis. While PDL exposure to oral microbial pathogens is common, virtually nothing is known regarding viral infections of PDL. In particular, human herpes simplex virus type 1 (HSV-1) persistently infects the oral cavity through infections of the oral epithelium, connective tis-sue and neurons. While the oral spread of HSV-1 is generally asymptomatic, this virus has also been implicated in various oral pathologies. In this study, using a primary cell model derived from PDL (PDL-cells), and whole surgical fragments of PDL, we provide evidence supporting the efficient infection of PDL by HSV-1 and the promotions of cytopathic effects. Infection of PDL by HSV-1 was also associated with an acute innate inflammatory response, as il-lustrated by the production of the antiviral interferons and pro-inflammatory cytokines. Furthermore, this inflammatory response to HSV-1 was exacerbated in the presence of bacterial-derived products, such as peptidoglycans. This work therefore highlights the ability of HSV-1 to infect mesenchymal cells from PDL, suggesting that PDL may serve as a viral reservoir for the perio-dontal spread of HSV-1. Moreover, this raises questions about HSV-1 oral pathogenesis, as HSV-1-associated cytopathic and inflammatory effects may contribute to profound alterations of PDL integrity and functioning.

Epilepsy is a non-communicable neurological disease characterized by abnormal brain activity with conceivable peripheral implications. Few studies examine the role of peripheral and brain inflammation in the relationship between seizure predisposition and nonalcoholic fatty liver disease. Severe early-life infections leading to sepsis results in increased inflammation that can aggravate epilepsy and hepatic damage progression both associated with increased odds for hospital admissions in epileptic patients. Here, we examined the effect of early LPS challenge (1 mg/kg, i.p. at post-natal day3, PND3) in inducing hepatic damage in a genetic model of young epileptic WAG/Rij rats (PND45), evaluating the intra- and inter-gender differences on systemic and liver inflammation, hepatic lipid dysmetabolism and oxidative damage associated to mitochondrial functional impairment. First, epileptic rats exposed to LPS, regardless of gender, displayed increased serum hepatic enzymes and altered lipid profile. Early LPS challenge induced a major inflammatory and immune response in male epileptic rats than females in both serum and liver, increasing pro-inflammatory cytokines and hepatic immune cell recruitment. Conversely, LPS-insulted females showed a marked alteration in hepatic metabolic and lipid profile and the reduction in mitochondrial fatty acid oxidation. The two different gender-related mechanisms of LPS-induced liver injury converge in mitochondrial oxidative damage with intensified ROS production in both sexes, that notably induced a compensatory increase in antioxidant defense only in females. Our study with a translational potential points out that early postnatal infections predispose epileptic rats to develop or worsen hepatic disorders in a sex-dependent manner, amplifying inflammation, lipid dysmetabolism, and mitochondrial impairment.

Nanoparticles offer available tools for MDD research. In this assay, we applied CBR1 (cannabinoid receptor 1) knockout (CB1-/-) mice to study whether functionalized solid lipid nanoparticles loading with curcumin and dexanabinol (Cur/SLNs-HU-211) exhibited anti-depressant outcomes through CBR1. Wild-type (CB1+/+) animals together with CBR1 knockout (CB1-/-) animals received daily injections of Corticosterone (CORT) for 3 weeks to obtain MDD mice model, and then the therapeutic action of Cur/SLNs-HU-211 were evaluated, respectively. Our work show that Cur/SLNs-HU-211 nanoparticles in the existence of CBR1 facilitate an efficient motor function improvement in CORT-induced MDD mice model. Cur/SLNs-HU-211 nanoparticles alleviated symptoms on CB1+/+ MDD mice and resulted in dopamine and norepinephrine recovery following CORT-induced neurotoxicity. In conclusion, the possible mechanisms underlying the antidepressant effect of Cur/SLNs-HU-211 might be the induction of CB1 expression and downstream RASGEF1C and Egr1 expression, together with a significantly upregulation of neuron-specific genes in CB1+/+ mice only. In conclusion, CBR1 is necessary during the process of antidepressant activities of Cur/SLNs-HU-211 nanoparticles. This study confirms that Cur/SLNs-HU-211 nanoparticles based CBR1 in vivo targeting would be a potentially feasible and safe way to motivate future therapeutic strategies of Major Depressive Disorder.

Wooden breast is a muscle disorder affecting modern commercial broiler chickens that causes a palpably firm pectoralis major muscle and severe reduction in meat quality. Most studies have focused on advanced stages of wooden breast apparent at market age, resulting in limited insights into the etiology and early pathogenesis of the myopathy. Therefore, the objective of this study was to identify early molecular signals in the wooden breast transcriptional cascade by performing gene expression analysis on the pectoralis major muscle of two-week-old birds that may later exhibit the wooden breast phenotype by market age at 7 weeks. Biopsy samples of the left pectoralis major muscle were collected from 101 birds at 14 days of age. Birds were subsequently raised to 7 weeks of age to allow sample selection based on the wooden breast phenotype at market age. RNA sequencing was performed on 5 unaffected and 8 affected female chicken samples, selected based on wooden breast scores (0 to 4) assigned at necropsy where affected birds had scores of 2 or 3 (mildly or moderately affected) while unaffected birds had scores of 0 (no apparent gross lesions). Differential expression analysis identified 60 genes found to be significant at an FDR-adjusted p value of 0.05. Of these, 26 were previously demonstrated to exhibit altered expression or genetic polymorphisms related to glucose tolerance or diabetes mellitus in mammals. Additionally, 9 genes have functions directly related to lipid metabolism and 11 genes are associated with adiposity traits such as intramuscular fat and body mass index. This study suggests that wooden breast disease is first and foremost a metabolic disorder characterized primarily by ectopic lipid accumulation in the pectoralis major.

The energy sensor AMP-activated protein kinase (AMPK) is a key player in the control of energy metabolism. AMPK regulates hepatic lipid metabolism through the phosphorylation of its well-recognized downstream target acetyl CoA carboxylase (ACC). Although AMPK activation is proposed to lower hepatic triglyceride (TG) content via the inhibition of ACC to cause inhibition of de novo lipogenesis and stimulation of fatty acid oxidation (FAO), its contribution to the inhibition of FAO in vivo has been recently questioned. We generated a mouse model of AMPK activation specifically in the liver achieved by expression of a constitutively active AMPK using adenoviral delivery. Indirect calorimetry studies revealed that liver-specific AMPK activation is sufficient to induce a reduction in the respiratory exchange ratio and an increase in FAO rates in vivo. This led to a more rapid metabolic switch from carbohydrate to lipid oxidation during the transition from fed to fasting. Finally, mice with chronic AMPK activation in the liver display high fat oxidation capacity evidenced by increased [C14]-palmitate oxidation and ketone body production leading to reduced hepatic TG content and body adiposity. Our findings suggest a role for hepatic AMPK in the remodeling of lipid metabolism between the liver and adipose tissue.

In the majority of children with growth hormone (GH) deficiency (GHD), normal GH secretion may occur before the attainment of final height. The aim of the study was to assess the incidence of persistent and transient GHD and the effectiveness of recombined human GH (rhGH) therapy in children with isolated idiopathic GHD, with respect to the moment of therapy withdrawal and according to different diagnostic criteria of GHD. Analysis included 260 patients (173 boys, 87 girls) with isolated idiopathic GHD who completed rhGH therapy and have reassessed GH and IGF-1 secretion. The incidence of transient GHD with respect to different pre- and post-treatment criteria was compared together with assessment of GH therapy effectiveness. Incidence of transient GHD, even with respect to pediatric criteria was very high. Normal GH secretion occurred before the attainment of near-final height. Application of more restricted criteria decreased the number of children diagnosed with GHD but not the incidence of transient GHD among them. Poor response to GH therapy was observed mainly in patients with normal IGF-1 before treatment, suggesting that diagnosis of GHD may be false positive. Further efforts should be made to avoid overdiagnosis GHD and overtreatment of the patients.

Inverse gas chromatography at infinite dilution was used to determine the surface thermodynamic properties of silica particles and PMMA adsorbed on silica, and more particularly, to quantify the London dispersive energy γsd, the Lewis acid γs+ and base γs- polar surface energies of PMMA/silica composites as a function of the temperature and the recovery fraction θ of PMMA. The polar acid–base surface energy γsAB and the total surface energy of the different composites were then deduced as a function of the temperature. In this paper, the Hamieh thermal model was used to quantify the surface thermodynamic energy of poly methyl methacrylate (PMMA) adsorbed on silica particles at different recovery fractions. A comparison of the new results was carried out with those obtained by applying other molecular models of the surface areas of organic molecules adsorbed on the different solid substrates. An important deviation of these molecular models from the thermal model was proved. The determination of γsd, γs+, γs-, and γsAB of PMMA in both bulk and adsorbed phases showed an important non-linearity variation of these surface parameters as a function of the temperature. The presence of maxima in the curves of γsd(T) highlighted the second order transition temperatures in PMMA showing beta-relaxation, glass transition and liquid-liquid temperatures. These three transition temperatures depended on the adsorption rate of PMMA on silica. The proposed method gave a new relation between the recovery fraction of PMMA and its London dispersive energy showing an important effect of the temperature on the surface energy parameters of adsorption of PMMA on silica. A universal equation relating γsd(T,θ) of the systems PMMA/silica to the recovery fraction and the temperature was proposed.

This research was devoted to study the effect of the tacticity of PMMA on the surface physicochemical properties such as the London dispersive component of the surface energy of the polymer, the polar and dispersive free energies, the Lewis’s acid-base surface parameters, and the Lewis acid and base surface energies of atactic, isotactic and syndiotactic PMMAs as a function of the temperature. Inverse gas chromatography (IGC) at infinite dilution was used to determine the surface thermodynamic properties of PMMA at different tacticities. The experimental values of the net retention time and volume of model organic molecules adsorbed on the atactic, isotactic and syndiotactic PMMAs, were obtained by IGC technique at infinite dilution. The London dispersion interaction energy was used for the separation of the polar and dispersive energy of the different n-alkanes and polar solvents adsorbed on the different PMMA surfaces. The London dispersive surface energy γ_s^d (T) of PMMAs was determined by applying the Hamieh thermal model that took into account the effect of the temperature on the surface area of adsorbed molecules. The obtained results showed non-linear variations of γ_s^d (T) of atactic, isotactic, and syndiotactic PMMAs with three maxima characterizing the three transition temperatures of PMMAs, T_g, T_g and T_(liq-liq) with a shift of these temperatures with the isotactic and syndiotactic PMMAs. It was showed that the polar interaction free energy ∆G_a^p (T) also showed the presence of the three above transition temperatures of the polymers. The study showed an important non-linearity variation of the different acid-base parameters in the various polymer surfaces proving the highest effect of the temperature and the tacticity on these parameters. The determination of the enthalpic and entropic Lewis’s acid-base parameters showed an amphoteric character for the different PMMAs. The basicity of the atactic PMMA was about four times larger than its acidity outside the neighborhood of the transition temperatures of the polymer. Whereas, the isotactic PMMA was about 2 to 2.5 times more basic than acid, while the syndiotactic PMMA exhibited the highest basicity by showing a surface 5 to 8 times more basic than acid. However, the Lewis acid-base parameters strongly depended on the temperature and sudden variations of these surface parameters were observed around the transition temperatures largely depending on the PMMA tacticity. The determination of the polar acid and base surface energies of the three PMMAs led to the same previous transition temperatures with an important effect of the tacticity of PMMA on the values of these acid-base surface energies.

The ribonuclease H (RNase H) active site of HIV-1 reverse transcriptase (RT) is the only viral enzyme not targeted by approved antiretroviral drugs. Using a fluorescence-based in vitro assay, we screened 65,239 compounds at a final concentration of 10 µM to identify inhibitors of RT RNase H activity. We identified 41 compounds that exhibited 50% inhibitory concentration (i.e., IC50) values &lt; 1.0 µM. Two of these compounds, 2-(4-methyl-3-(piperidin-1-ylsulfonyl)phenyl)benzo[d]isothiazol-3(2H)-one (1) and ethyl 2-(2-(3-oxobenzo[d]isothiazol-2(3H)-yl)thiazol-4-yl)acetate (2), which both share the same benzisothiazolone pharmacophore, demonstrate robust antiviral activity (50% effective concentrations of 1.68 ± 0.94 µM and 2.68 ± 0.54, respectively) in the absence of cellular toxicity. A limited structure-activity relationship analysis identified two additional benzisothiazolone analogs, 2-methylbenzo[d]isothiazol-3(2H)-one (3) and N,N-diethyl-3-(3-oxobenzo[d]isothiazol-2(3H)-yl)benzenesulfonamide (4), which also resulted in inhibition of RT RNase H activity and virus replication. Compounds 1, 2 and 4, but not 3, inhibited the DNA polymerase activity of RT (IC50 values ~ 1 to 6 µM). In conclusion, benzisothiazolone derivatives represent a new class of multifunctional RT inhibitors that warrants further assessment for the treatment of HIV-1 infection.

Daily vitamin D supplementation using higher than normal dosing (up to the upper limit, UL) and intermittent (once or twice per week) dosing were studied in patients with increased risk of vitamin D deficiency. Using a PubMed database an adequate search for published randomized control trials and other studies was done and results were analyzed. This review provides overview of use of 7000 IU daily, 30,000 IU per week or twice weekly and 50,000 IU weekly of vitamin D on rapid restore of 25(OH)D concentrations to at least 30 ng/mL in different groups of patients at high risk of vitamin D deficiency. The above mention dosing should be considered in adults with obesity or multi-diseased patients on requiring multi-treatment with the use of several drugs, including drugs affecting vitamin D metabolism. The simple schedule for 7000 IU/day, 30,000 IU/week or twice weekly or 50,000 IU/week, all for 6-8 weeks of use by patients representing the increased risk of vitamin D deficiency were provided for consideration. It appeared that higher daily doses or intermittent doses suggested above are effective, safe and responsive for patient’s preferences.

We describe the behavior of mixtures of stearic acid (SA) and its hydroxylated counterpart 12-hydroxystearic acid (12-HSA) in aqueous mixtures at room temperature, as function of the 12-HSA/(fatty acid) mole ratio R. The morphologies of the self-assembled aggregates are obtained by a multi-structural approach that combines confocal and cryo-TEM microscopies with Small-Angle Neutron Scattering (SANS) and Wide-Angle X-Rays Scattering (WAXS) measurements, coupled with rheology measurements. Fatty acids are solubilized by an excess of ethanolamine counterions, so that their heads are negatively charged. The behavior is driven by the competition between mixing entropy and enthalpic effects. A clear trend towards partitioning between the two types of fatty acids is observed, presumably driven by the favorable formation of a H-bond network between hydroxyl OH function on the 12th carbon. For all R, the self-assembled structures are locally lamellar, with bilayers composed of crystallized and strongly interdigitated fatty acids. At high R, multi-lamellar tubes are formed, similarly as for pure aqueous solutions of 12-HSA. The doping by a low amount of SA molecules only slightly modify the dimensions of the tubes (radius and length), and slightly decreases the bilayers rigidity. The solutions have a gel-like behavior originating from entanglements between tubes and show a yield stress. At intermediate R, a partial local partitioning occurs between the two types of fatty acids. The tubes coexist in solution with helical ribbons. The two structures possibly merge to form very long snaky objects with straight and curved parts. The rigidity of the bilayers and the rheological behavior of the solutions are very similar to those of the high R case. At low R, local partitioning also occurs, and the architecture of the self-assemblies associates the two morphologies of the pure fatty acids systems, respectively 2-D planar bilayers for SA and the tubes describe above for the 12-HSA molecules: they are facetted objects with planar domains enriched in SA molecules, capped with curved domains enriched in 12-HSA molecules. The rigidity of the bilayers is strongly increased, as well their storage modulus, compared to systems with larger R. The solutions remain however viscous fluids in this regime of low R.

The endogenous pool of phytoregulators in plant tissues supplied with microbial secondary metabolites may be crucial for the development of winter wheat seedlings during cool springs. Phytohormones may be synthesized by psychrotrophic microorganisms in lower temperatures occurring in temperate climate. Two fungal isolates from the Spitzbergen soils after the microscopic observations and ITS region molecular characterization were identified as Mortierella antarctica (MA DEM 7) and Mortierella verticillata (MV DEM32). To study the synthesis of indoleacetic acid (IAA) and gibberellic acid (GA) Mortierella strains were grown on media supplemented with precursors of phytohormones (tryptophan or methionine) at 9, 15 and 20 °C for 9 days. The highest amount of IAA synthesis was observed in MV DEM 32 9-day culture at 15 °C with 1.5 mM of tryptophan. At the same temperature the significant promoting effect (about 40% root and shoot fresh weight) of this strain on seedlings was observed. However, only MA DEM 7 had the ACC-deaminase activity with the highest efficiency in 9 °C and at this temperature synthesized IAA without tryptophan also at the same conditions the strain confirmed the strong promoting effect (about 40% root and 24% shoot fresh weight) on seedlings. Both strains synthesized GA in all tested terms and temperatures. Tested Mortierella strains had some important traits to consider them as microbial biofertilizers component improving plant growth in difficult temperate climate.

Acquired immunodeficiency syndrome (AIDS) is an enormous global health threat stemming from human immunodeficiency virus (HIV-1) infection. Up to now, the tremendous advances in combination antiretroviral therapy (cART) have shifted HIV-1 infection from a fatal illness into a manageable chronic disorder. However, the presence of latent reservoirs, multifaceted nature of HIV-1, drug resistance, severe off-target effects, poor adherence, and high cost restrict the efficacy of current cART targeting the distinct stages of the virus life cycle. Therefore, there is an unmet need for discovery of new therapeutics that not only bypass the limitations of the current therapy but also protect the body health at the same time. The main goal for complete HIV-1 eradication is purging latently infected cells from the patients’ bodies. A potential strategy called “lock-in apoptosis” targeting the budding phase of life cycle of virus leading to susceptibility to apoptosis of HIV-1 infected cells for elimination of HIV-1 reservoirs and ultimately for a complete eradication. The current work intends to present the main advantages and disadvantages of United States Food and Drug Administration (FDA) approved anti-HIV-1 drugs as well as plausible strategies for the design and development of more anti-HIV-1 compounds with better potency, favorable pharmacokinetic profiles, and improved safety issues.

2-(Adamantan-1-yl)-2H-isoindole-1-carbonitrile (1) has been identified as a neurobiological fluorescent ligand that may be used to develop receptor and enzyme binding affinity assays. Compound 1 was synthesised using an optimised microwave irradiation reaction and crystallised from ethanol. Crystallization occurred in the orthorhombic space group P212121 with unit cell parameters: a = 6.4487(12) Å, b = 13.648(3) Å, c = 16.571(3) Å, V = 1458(5) Å3, Z = 4. Density functional theory (DFT) (B3LYP/6-311++G (d,p)) calculations of 1 were carried out. Results showed that the optimised geometry is similar to the crystal structure parameters with a root-mean-squared deviation of 0.143 Å. Frontier molecular orbital energies and net atomic charges are discussed with a focus on potential biological interactions. Docking experiments within the active site of the neuronal nitric oxide synthase (nNOS) protein crystal structure were carried out and analysed. Important binding interactions between the DFT optimised structure and amino acids within the nNOS active site were identified that explain the strong NOS binding affinity reported. Fluorescent properties of 1 were studied using aprotic solvents of different polarities. Compound 1 showed the highest fluorescence intensity in polar solvents with excitation and emission values of 336 nm and 380 nm, respectively.

In chemotherapy practice the dexamethasone is used as concomitant agent to mitigate the side effects of antitumor drug cisplatin. However, it is known, that both cisplatin and dexamethasone are capable to stimulate the production of reactive oxygen spacies, which targets various biomolecules, including lipids. This work is devoted to the study of quantitative changes in products of lipid peroxidation in the nuclei of cells of some tissues of rats after separate and combined use of cisplatin and dexamethasone. The amount of lipid peroxidation products was determined by spectrophotometric method after its extraction by heptan-isopropanol mixture. When used separately, cisplatin and dexamethasone enhance the formation of lipid peroxidation products in the studied tissues of rats to various degrees. As a result of these alterations, the values of the oxidation index in the studied nuclear preparations also changed accordingly. During the combined use of cisplatin and dexamethasone there is some antagonism in the action of these drugs. Instead of the supposed summation of the effects of enhancing lipid peroxidation processes, “masking” of the effect of cisplatin with dexamethasone is observed. Thus, it has been assumed that exactly such antagonism revealed during combined action helps mitigate the side effects of cisplatin with dexamethasone.

The influence of diet and nutritional status of milk donors on the nutritional composition of donor human milk (DHM) is unknown. The present study aimed to determine the nutritional profile of DHM and the associations of donors’ dietary intake and nutritional status with micronutrient and lipid composition in DHM. For this purpose, 113 donors completed a food frequency questionnaire, provided a 5-day weighed dietary record, and collected milk for 5 consecutive days. Nutrient determinations in donors’ erythrocytes, plasma, urine, and milk were performed. Multiple linear regressions were conducted for the evaluation of the associations. We highlight the following results: DHM docosahexaenoic acid (DHA) was positively associated with donors’ plasma DHA content and donors’ DHA intake (R2 0.45, p < 0.001). For every 1 g/day of DHA intake, the percentage of DHA in DHM increased by 0.38% (% of total fat) and the percentage of total omega-3 in DHM increased by 0.78% (R2 0.29, p < 0.001). DHM saturated fatty acids were positively associated with erythrocyte dimethyl acetals, plasma stearic acid, trans fatty acids intake, and breastfeeding duration, and negatively associated with erythrocyte margaroleic acid (R2 0.34, p < 0.01). DHM cholecalciferol was associated with plasma cholecalciferol levels and dairy intake (R2 0.57, p < 0.01). Other weaker associations were found for free thiamine, free riboflavin, pyridoxal, dehydroascorbic acid, and lipid profile in DHM. In conclusion, the diet and nutritional status of donors influences the fatty acid profile and micronutrient content of DHM.

Calcium signaling and lipid metabolism are crucial in the infection processes of Apicomplexans parasites. Thus, enzymes involved in these processes can be drug targets against Apicomplexans. For example, in malaria infection, in-depth research into lipid metabolic pathways is crucial in understanding the parasite's infection cycle, particularly during its erythrocytic infection cycle, which has been demonstrated to be a critical stage during the disease progression. Most enzymes that play critical roles in lipid synthesis and calcium signaling have been extensively studied; nonetheless, a vast knowledge gap still exists, especially on specific enzymes and their roles in the transmission and progression of the Apicomplexan parasites. Many types of infections caused by Apicomplexans are life-threatening and hard to treat. These intracellular parasites proliferate within parasitophorous vacuoles in their host cells. As the parasites multiply, they need to meet their high demand for nutrients such as amino acids and lipids. They can acquire nutrients through scavenging and biosynthesis. This review summarizes a few interesting, unique pathways in selected Apicomplexa and how such unique pathways can be targets for drugs.

This study aimed to evaluate the antioxidant activities (AA) of lyophilized rosemary extract and lyophilized sage extract and their effects on the oxidative stability of poultry pátê. For this purpose, four poultry pátê formulations with rosemary, sage, sodium erythorbate, and a control (without antioxidants) were produced. The rosemary and sage were characterized according to total phenolic compounds (TPC), and AA by several methods. The poultry pátês stored at 4°C were evaluated by the lipid oxidation. High concentrations of TPC were detected in rosemary extract and sage extract (46.48 and 41.61 mg GAE/g: Gallic acid equivalent respectively). The AA of rosemary and sage extracts by free radical-scavenging were 4745.72 and 2462.82 µmol Trolox/g, respectively. The high concentration of catechin, rutin, myricetin and p-coumaric acids in these extracts may be responsible for the strong inhibitory action against food pathogens. Besides these compounds can be responsible for the best performance in inhibiting lipid oxidation in poultry pátês during the storage. This study suggests that rosemary and sage extracts may be used as a natural antioxidant in meat products.

Imperatorin is a chemical compound belong to Linear furan coumarins. Imperatorin is attracting considerable attention because of its anti-tumor, antibacterial, anti-inflammatory, anticoagulant and inhibition of myocardial hypetrophy and other pharmacological efficacy. However, imperatorin has limited water solubility and preferable lipid solubility, we decided to design and synthesize imperatorin lipid microsphere, to optimize preparation conditions. The aim was to develop and formulate imperatorin lipid microsphere through nano emulsion technology and apply the response surface-central composite design to optimize the imperatorin lipid microsphere formulation. Influence of content of amount of egg lecithin(A), amount of poloxamer188(B), soybean oil for injection accounted for the total percentage of oil phase(C) were investigated. Integrated effect of dependent variables including particle size(Y₁), polydispersity index(Y₂), Zeta potentials(Y₃), drug loading(Y₄), encapsulation efficiency(Y₅). Data of overall desirabiities were fitted to a second-order polynomial equation, through which three dimensional response surface graphs were described. Optimum experimental conditions were calculated by Design-Expert 8.06. Results indicated that the optimum preparation conditions were as follows: egg lecithin amount 1.39 g, poloxamer188 amount 0.21 g, soybean oil for injection amount 10.57%. Preparation of imperatorin lipid microsphere according to the optimum experimental conditions resulted in an overall desirability of 0.7286, while the particele size (168±0.54) nm, polydispersity index (PDI) (0.138±0.02), Zeta potentials (−43.5±0.5) mV, drug loading (0.833±0.27) mg·mL⁻¹, encapsulation efficiency (90±1.27)%. The difference between observed and predicted values of the overall desirability of the optimum formulation was in range from 2.4% to 4.3%. Subsequently, using the Scanning electron microscopy to observe the micromorphology of imperatorin lipid microsphere, the result shows that round globular of relatively uniform and sizes within 200nm.The proliferation study of imperatorin lipid microsphere on MDA-MB-231 was investigated by MTT method. Furthermore, pharmacokinetics in Sprague Dawley rats were evaluated using orbital bleeding. A sensitive and reliable liquid chromatography with High Performance Liquid Chromatography (HPLC) method was established and validated for the quantification of imperatorin in rat plasma samples. The data were calculated by DAS (Drug and statistics) pharmacokinetic software version3.2.6 (China). Results demonstrated that imperatorin lipid microsphere can significantly enhance the bioavailability of imperatorin and can significantly inhibit MDA-MB-231 cell proliferating. In conclusion, our results suggersted that the response surface-central composite design is suitable for the optimized lipid microspere formulation. Imperatorin Lipid microsphere can improve the bioavailability of imperatorin and inhibit the proliferation of MDA-MB-231 than that of imperatorin.

Autophagy refers to the degradation of cytoplasmic constituents by a lysosomal-mediated pathway, which plays a critical role in maintaining cellular homeostasis. Importantly, dysregulation of autophagy has been implicated in multiple neurodegenerative disorders. Previous studies reported that autophagy affects the processing of amyloid precursor protein (APP), thus stimulating β‐amyloid (Aβ) production in Alzheimer’s disease (AD) eventually. Although the mechanism of autophagy modulation on APP processing and its pathogenesis has not yet been fully elucidated at the molecular level, but modulation of autophagy has received considerable attention as a promising approach for the treatment of AD. In the early stage of AD, Aβ may prompt autophagy to facilitate its removal via mTOR‐independent as well as-dependent pathways. However, a recent study proposed that autophagy processes are not properly regulated as AD continues to progress, and consequently, the production of Aβ tends to accumulate rapidly. Meanwhile, a number of autophagy-related genes (Atg) as well as APP genes are also thought to influence the development of AD, which may serve as a bi‐directional link to autophagy and AD pathology. In this review, we summarized current observations related to autophagy regulation and APP processing, focusing on their dynamic modifications associated with the progression of AD. Recent findings together highlight the essential role of autophagy in the removal and clearance of APP and Aβ deposition in the pathological condition of AD.

Transketolase (TKT) is an essential thiamine diphosphate (ThDP)-dependent enzyme of the non-oxidative branch of pentose phosphate pathway, with the glucose-6P flux through the pathway regulated in various medically important conditions. Here, we characterize the brain TKT regulation by acylation in rats with perturbed thiamine-dependent metabolism, known to occur in neurodegenerative diseases. The perturbations are modelled by administration of oxythiamine inhibiting ThDP-dependent enzymes in vivo, or by reduced thiamine availability in the presence of metformin and amprolium, inhibiting intracellular thiamine transporters. Compared to control rats, chronic administration of oxythiamine does not significantly change the modification level of the two detected TKT acetylation sites (K6 and K102), but doubles malonylation of TKT K499, concomitantly decreasing 1.7-fold the level of demalonylase sirtuin 5. The inhibitors of thiamine transporters do not change average levels of TKT acylation or sirtuin 5. TKT structures indicate that the acylated residues are distant from the active sites. The acylations-perturbed electrostatic interactions may be involved in conformational shifts and/or formation of TKT complexes with other proteins or nucleic acids. Acetylation of K102 may affect the active site entrance/exit and subunit interactions. Correlation analysis reveals that the action of oxythiamine is characterized by significant negative correlations of K499 malonylation or K6 acetylation with TKT activity, not observed upon the action of the inhibitors of thiamine transport. However, the transport inhibitors induce significant negative correlations between the TKT activity and K102 acetylation or TKT expression, absent in the oxythiamine group. Thus, perturbations in the ThDP-dependent catalysis or thiamine transport manifest in the insult-specific patterns of the brain TKT malonylation and acetylations.

Finishing coatings in the wood-based composites industry not only influence the final appearance of the product but also serve to protect against fungi, and molds, and reduce the release of harmful substances, particularly formaldehyde and volatile organic compounds (VOCs). Carbon-rich materials, such as those derived from birch bark extraction, specifically suberin acids, can fulfil this role. Previous research has demonstrated that adding suberin acid residues (SAR) at 20% and 50% by weight significantly enhances the gas barrier properties of surface finishing materials based on poly(lactide) (PLA) and polycaprolactone (PCL), particularly in terms of Total VOC (TVOC) and formaldehyde emissions. This study aims to explore whether these properties can be further improved through the incorporation of nano-zinc oxide (nano-ZnO). Previous research has shown that these nanoparticles possess strong resistance to biological factors and can positively affect the characteristics of nanofilms applied as surface protection. The study employed PLA and PCL finishing layers blended with SAR powder at 10% w/w and included 2% and 4% nano-zinc oxide nanoparticles. The resulting blends were milled to create a powder, which was subsequently pressed into 1 mm thick films. These films were then applied to raw particleboard surfaces. TVOC and formaldehyde emission tests were conducted. Additionally, the fungal resistance of the coated surfaces was assessed. The results showed that PLA/SAR and PCL/SAR composites with the addition of nano-zinc oxide nanoparticles exhibited significantly improved barrier properties, offering a promising avenue for developing biodegradable, formaldehyde-free coatings in the furniture industry with enhanced features. Furthermore, by utilizing SAR as a post-extraction residue, this project aligns perfectly with the concept of upcycling.

Weather conditions appear to be undergoing significant deviations from the long-term average, marked by pronounced extremes of heat, prolonged droughts, and heightened rainfall occurring with greater frequency worldwide. Consequently, new patterns of extreme weather are emerging, like the unusual and unorganized tropical cyclone called "Yaku", that influenced the extreme amount of rain that between March 6th to 10th, 2023 hits more than 1000 districts in the northwestern of Peru. One of the district more affected was Íllimo, in the Lambayeque province, due to the river that pass through the city, so called “La Leche”, after the continuous and intensive rain overflow devastating his surrounding areas and causing victims and damage. This emergency provided and excellent opportunity to apply, on the aforementioned areas, the “change detection” technique, that allows identifying areas of change between data obtained before and after of emergency events. In this research, optical data (Sentinel-2, Landsat, MODIS Terra and Aqua, and PeruSAT-1) and synthetic aperture radar (SAR) data (Sentinel-1 and COSMO SkyMed) were analyzed. A benchmark could also be carried out between open-source and commercial spatial analysis tools. The results indicated that in an extreme rain event the optical data are obscured by clouds and do not allow their use, while SAR data overcome clouds, and can be used for this research. The benchmark indicated that using the Jaccard index score, the Sentinel-1A set showed a 33% of correlation, while COSMO SkyMed demonstrated a 38% of match between the maps. The results obtained could be used to sensitize the population and develop a better management of future emergency events (floods) in different areas of Peru.

LPA3 receptors were expressed in TREx HEK 293 cells, and their signaling and phosphorylation were studied. The agonist, lysophosphatidic acid (LPA), increased intracellular calcium and ERK phosphorylation through pertussis toxin-insensitive processes. Phorbol myristate acetate, but not LPA, desensitizes LPA3-mediated calcium signaling. The agonists and the phorbol ester-induced LPA3 internalization. Pitstop 2 (clathrin heavy chain inhibitor) markedly reduced LPA-induced receptor internalization; in contrast, phorbol ester-induced internalization was only delayed. LPA induced rapid β-arrestin-LPA3 receptor association. The agonist and the phorbol ester induced marked LPA3 receptor phosphorylation, and phosphorylation sites were detected using mass spectrometry. Phosphorylated residues were detected in the intracellular loop 3 (S221, T224, S225, and S229) and in the carboxyl terminus (S321, S325, S331, T333, S335, Y337, and S343). Interestingly, phosphorylation sites are within sequences predicted to constitute β-arrestin binding sites. These data provide insight into LPA3 receptor signaling and regulation.

Cannabinoid metabolites have been reported to be more potent than the parent compounds. Among them, Ajulemic acid (AJA) is a synthetic analogue of Δ9-THC-11-oic which will be a good template structure for discovery of more potent analogues. Herein, we optimized the key allylic oxidation step to introduce the C-11 hydroxy group with high yield. And a series of compounds were prepared with this condition applied including HU-210, 11-Nor-Δ8-Tetrahydrocannabinol-9-carboxylic acid and Δ9-THC-COOH.

Cardiovascular diseases (CVDs) represent the leading cause of global mortality with 1,7 million deaths a year. One of the alternative systems to drug therapy to minimize the risk of CVDs is represented by alpha-linolenic acid (ALA), an essential fatty acid of the Omega-3 series, known for its cholesterol-lowering effect. The main purpose of this review is to analyze the effects of ALA and investigate the relevant n-6/n-3 ratio in order to maintain functionally beneficial effects. Concerning the lipid-lowering preventive effects, ALA may favorably affect the values of LDL-C and triglycerides in either adult and pediatric populations and it has a positive and protective effect against hypertension, suggesting that ALA is an useful diet-related antihypertensive compound. According to the 2009 EFSA statement, dietary ALA may contribute to reducing the risk of CVDs, thanks to anti-hypertensive, anti-atherosclerotic and cardio-protective effects.

Using the techniques of computer-aided drug design, the docking of Survivin and known active small molecules was simulated and then the key amino acid residue fragment of the target protein was analyzed. It led to the discovery of active groups capable of binding to the critical sites. Through the use of the natural product, Oleanolic Acid, as a lead compound, the introduction of the active groups onto the A-ring, and the modification of the carboxyl group at the C-28 position using esterification or amidation, twenty new Oleanolic acid derivatives had been designed and synthesized.A549 and SGC-7901 cells were used to screen the antitumor activity in vitro through the standard MTT method. The compounds, II₃, III₅ and Ⅳ_4, exhibited more potent cytotoxicity than positive drugs.

The supposition is that the usage of fibrin rich in leukocytes and platelets advanced (A-PRF) in ulcerative osteomyelitis of the diabetic foot allows rehabilitation from this critical illness. In this investigation, the focus was to normalize the use of PRF in patients with osteomyelitis not amputated, to use this second generation platelet concentrate as a regeneration enabler. The researchers submitted and utilized A-PRF membranes (1300 g × 8 min) in 7 patients (all diabetics) with osteomyelitis and cutaneous injury for 6 months. The membranes, in combination with the supernatant fluid produced by stress, have been integrated into the skin lesion down to the bone after surgical debridement. The advancement of the lesions after some period of time has been analyzed. All seven subjects had a Probe-to-Bone positive assay; MRI indicated a cortico-periosteal coagulation and/or foci of cortico-spongeous osteolysis contiguous to the lesion. Gram-positive bacterium were identified in our procedures in 52% of cases. Gram+ Cocci, for example, S. Aureus (15.6%), S. Hemolytic (12.1%), S. Viridans (7.1%), and Gram-negative Bacteria, for example, Pseudomonas (10.6%), Proteus (7.8%), Enterobacter (5.7%) are present. Candida Albicans is active in 2.8%. The blood count shows no relevant differences. To date, cutaneous lesions have cured in 6 of the seven subjects treated (one patient for more than five years) without any evidence of infection or recurrence. The results obtained on our subjects indicate that PRF membranes may be a therapeutic option in this problematic disease.

The supposition is that the usage of fibrin rich in leukocytes and platelets advanced (A-PRF) in ulcerative osteomyelitis of the diabetic foot allows rehabilitation from this critical illness. In this investigation, the focus was to normalize the use of PRF in patients with osteomyelitis not amputated, to use this second generation platelet concentrate as a regeneration enabler. The researchers submitted and utilized A-PRF membranes (1300 g × 8 min) in 7 patients (all diabetics) with osteomyelitis and cutaneous injury for 6 months. The membranes, in combination with the supernatant fluid produced by stress, have been integrated into the skin lesion down to the bone after surgical debridement. The advancement of the lesions after some period of time has been analyzed. All seven subjects had a Probe-to-Bone positive assay; MRI indicated a cortico-periosteal coagulation and/or foci of cortico-spongeous osteolysis contiguous to the lesion. Gram-positive bacterium were identified in our procedures in 52% of cases. Gram+ Cocci, for example, S. Aureus (15.6%), S. Hemolytic (12.1%), S. Viridans (7.1%), and Gram-negative Bacteria, for example, Pseudomonas (10.6%), Proteus (7.8%), Enterobacter (5.7%) are present. Candida Albicans is active in 2.8%. The blood count shows no relevant differences. To date, cutaneous lesions have cured in 6 of the seven subjects treated (one patient for more than five years) without any evidence of infection or recurrence. The results obtained on our subjects indicate that PRF membranes may be a therapeutic option in this problematic disease.

This study presents the chemical synthesis, purification, and characterization of a novel non-natural synthetic amino acid. The compound was synthesized in solution, purified, and characterized using NMR spectroscopy, polarimetry, and melting point determination. Dynamic Light 22 Scattering (DLS) analysis demonstrated its ability to form aggregates with an average size of 391 nm, extending to low micrometric sizes. Furthermore, cellular biological assays revealed its ability to enhance fibroblast cell growth, highlighting its potential for tissue regenerative applications. Circular dichroism (CD) spectroscopy showed the ability of the synthetic amino acid to bind serum albumins (using bovine serum albumin (BSA) as a model), and CD deconvolution provided insights into the changes in secondary structures of BSA upon interaction with the amino acid ligand. Additionally, molecular docking using HDOCK software elucidated the most likely binding mode of the ligand inside the BSA structure. We also performed in silico oligomerization of the synthetic compound in order to obtain a model of aggregate to investigate computationally. More in detail, in the dimer formation achieved by molecular self-docking, two distinct poses were observed, corresponding to the lowest and comparable energies, with one pose exhibiting a quasi-coplanar arrangement characterized by a close alignment of two aromatic rings from the synthetic amino acids within the dimer, suggesting the presence of π-π stacking interactions. In contrast, the second pose displayed a non-coplanar configuration, with the aromatic rings oriented in a staggered arrangement, indicating distinct modes of interaction. Both poses were further utilized in the self-docking procedure. Notably, iterative molecular docking of amino acid structures resulted in the formation of higher-order aggregates, with a model of a 512-mer aggregate obtained through self-docking procedures. This model of aggregate presented a cavity capable of hosting therapeutic cargoes and biomolecules, rendering it a potential scaffold for cell adhesion and growth in tissue regenerative applications. Overall, our findings highlight the potential of this synthetic amino acid for tissue regenerative therapeutics and provide valuable insights into its molecular interactions and aggregation behavior.

Treating central giant cell granuloma (CGCG) is challenging due to high recurrence rates and variable therapy responses. This study examines the efficacy of various treatments in reducing CGCG recurrence. A literature review explored outcomes of surgical excision, curettage, intralesional corticosteroid injection, and adjuvant therapy, considering factors like lesion location, size, and histological features. Aggressive surgical techniques such as en bloc resection were found to potentially lower recurrence rates compared to conservative approaches. However, treatment should be tailored to individual patient needs. Further research is needed to confirm these findings and improve treatment strategies. A concise literature review was conducted using PubMed, MEDLINE, and Google Scholar, focusing on papers published from 1986 to 2024. Search terms included "central giant cell granuloma," "recurrence," "treatment modalities," and "surgical excision". Studies reporting recurrence rates and treatment outcomes for CGCG were analyzed. Twenty-nine studies were reviewed, including six studies on surgical excision and curettage, eight studies on intralesional corticosteroid injections, six studies on calcitonin therapy, five studies on interferon alpha therapy and four studies on the therapy with denosumab. Analysis indicated that aggressive surgical treatments like en bloc resection were associated with lower recurrence rates compared to conservative methods. Predictors of recurrence included lesion size (&gt;3 cm), location (mandible), and aggressive histopathological features. Aggressive surgical excision combined with nonsurgical methods may lower recurrence rates, while conservative techniques remain viable in some cases. Further prospective research is needed to validate these findings and enhance CGCG treatment options.

The present study aims to evaluate the antibacterial activity of five commercially available essential oils (EOs): Lavender (LEO), Clove (CEO), Oregano (OEO), Eucalyptus (EEO), and Peppermint (PEO) against the most-known MDR Gram-positive and Gram-negative bacteria - Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 27853) - alone and in various combinations. Gas Chromatography-Mass Spectrometry (GC-MS) analysis established their complex composition. Then, the antibacterial activity was investigated in vitro by diffusimetric antibiogram method, using sterile cellulose discs with Ø 6 mm impregnated with 10 µl of sample and sterile borosilicate glass cylinders loaded with 100 µl of sample; MIC (µg/mL) for each EO was calculated from IZD values (mm) measured after 24 hours. The following EO combinations were evaluated: OEO+CEO, CEO+EEO, CEO+PEO, LEO+EEO, and EEO+PEO. Then, the influence of each dual combination on 3 conventional antibacterial drugs – Neomycin (NEO), Tetracycline (TET), and Bacitracin (BAC) - activity was investigated. The most active EOs against S. aureus and E. coli were LEO and OEO (IZD = 40 mm). They were followed by the CEO and EEO (IZD = 20-27 mm); PEO exhibited the lowest antibacterial activity (IZD = 15-20 mm). EEO alone showed the highest inhibitory activity on P. aeruginosa (IZD = 25-35 mm). It was followed by the CEO, LEO, and EEO (IZD = 7-11 mm), while PEO proved no antibacterial action against it (IZD = 0 mm). Only one synergic action was recorded (OEO+CEO against P. aeruginosa); EEO+PEO revealed partial synergism against S. aureus and CEO+PEO additive behavior against E. coli. Two triple associations with TET showed partial synergism against E. coli, and the other 2 ones (with NEO and TET) evidenced the same behavior against S. aureus; all contained EEO+PEO or CEO+PEO. Most combinations reported indifference. However, numerous cases were of antagonism between constituents included in double and triple combinations, and EOs with the strongest antibacterial activities belong to the highest antagonistic combinations. A consistent statistical analysis supports our results, showing that EOs with moderate antibacterial activities could generate combinations with higher inhibitory effects based on synergistic or additive interactions.

Low dietary intake of calcium, vitamin D, vitamin C and magnesium has been associated with increased risk of osteoporosis. The purpose of the study was to evaluate changes in several bone health indicators and metabolic biomarkers in postmenopausal women, with high osteopenia or osteoporosis, followed by a nutritional intervention program. 115 apparently healthy postmenopausal women (52±8 years old) were randomized into four groups: group I (n=40) received daily 1000 mg vitamin C, 100 mcg vitamin D3, 500 mg calcium(Ca) and 300 mg magnesium (Mg); group II (n=42) received daily 100 mcg vitamin D3, 500 mg Ca and 300 mg Mg; group III (n=18) received daily 5 mg bisphosphonates, 100 mcg vitamin D3, 500 mg Ca and 300 mg Mg; and group IV (n=15) received daily about 364 mg polyphenols via an innovative functional food (50 g olive paste enriched with mountain tea extract) along with 100 mcg vitamin D3, 500 mg Ca and 300 mg Mg. Groups I -III received supplementation for a year whereas group IV for 5 months. Changes in bone health indicators and metabolic biomarkers were assessed at the beginning and at the end of the study. Anthropometric indices and whole-body bone mineral density (BMD) were also evaluated at the beginning and at the end of the intervention period. The results revealed improved elevated levels of 25(OH)D3, in groups II, III and IV (+3,71% and +1.45% and +5.62% respectively). Significant positive changes were recorded, for whole-body BMD, in all four study groups. Significant beneficial changes for total cholesterol were observed in group IV (-2.07%, P&lt;0.05) and positive changes in group I for HDL biomarker (+61.62%, P&lt;0.05). Additional larger-scale clinical trials and intervention studies are considered essential, to fully investigate and elucidate associations between dietary components and biochemical indices of bone health.

Powdery mildew disease, caused by Sphaerotheca fusca, is a major disease affecting cucumbers cultivated in greenhouses. This study was conducted to find defense genes induced by DL-3-amino-butyric acid (BABA) and powdery mildew in cucumber. The 2000 and 5000 mg/L BABA treated cucumber exhibited disease severity of 25% and 5%, respectively, whereas the water treated cucumber leaves were severely infected, with a disease severity of 90%. BABA did not effect spore germination of the powdery mildew pathogen,. showing BABA is not antifungal agent against the pathogen. In quantitative real-time PCR analysis, BABA treated cucumber upregulated transcriptional level of the defense genes CsPAL, CsPR3,CsPR1, CsLOX1, CsLOX23, Cs LecRK6.1, CsWRKY20, and Cupi4 in cucumber to maximum levels at 48 h, whereas CsLecRK6.1 reached maximum expression after 24 h and futher salicylic acid (SA) levels were significantly increased in BABA-treated cucumber plants. In addition, the infected cucumber with powdery mildew enhanced the expression levels from1.6 to 47.3 fold of the defense genes PAL, PR3, PR1, Lox1, Lox 23, LecRK6.1, WRKY20, and Cupi4 compared to heathy cucumber. The results suggests the BABA induced defense response is associated with SA signal pathway-dependent systemic acquired resistance (SAR) in cucumber, which is involved in plant resistance mechanisms.

Epistaxis, particularly in Hereditary Hemorrhagic Telangiectasia (HHT) patients, is a common otolaryngological emergency, often requiring complex management. A hierarchy of increasingly invasive interventions, from external compression of the nasal pyramid to nostril closure, is typically proposed and applied. We conducted a retrospective study on HHT patients to assess the effectiveness and longevity of invasive procedures postoperatively. Data were collected using the Epistaxis Severity Score (ESS) questionnaire. The primary focus was on changes in the frequency and intensity of epistaxis, while the secondary focus was on the overall quality of life. The study found that invasive procedures initially improved the frequency and intensity of epistaxis in HHT patients. However, within one to 9 months postoperatively, these benefits often diminished, with hemorrhagic symptoms recurring at similar or worsened levels. Facial trauma further negated the advantages of these procedures. The findings suggest a need for a gradual and increasingly invasive approach to managing epistaxis in HHT patients. Highly invasive procedures should be reserved for cases where less invasive methods fail, due to their limited temporal effectiveness and the risk of causing anatomical-functional changes in the rhino-sinus area, complicating future management of severe epistaxis.

This work aims to investigate systematically the tecno-economic feasibility of ther-mos-catalytic cracking process for two solid waste materials, a lipid-base material (re-sidual fat/scum from retention box of the University Restaurant of UFPA) and a lig-nin-cellulosic material Açaí seed (Euterpe oleracea. Mart). The thermo-catalytic process-es were carried out in pilot scale (THERMTEK/LEQ/UFPA/IME/RJ), and their economic feasibility analyzed. The yields of biofuels produced by fractional distillation were al-so studied. The physicochemical characteristics of the raw materials, the organic liquid product (bio-oil) and the chemical composition of kerosene, light-diesel and heavy-diesel from the lipid-base material, as well as those of kerosene and light-diesel from the Açaí seed were also determined. The economic indicators for the evaluation of the most viable cracking (pyrolysis) and distillation process of bio-oils were: a) the sim-ple payback criterion, b) discounted payback, c) net present value (NPV), d) internal rate of return (IRR), and e) index of profitability (IP). The analysis of the indicators showed the economic viability of crude palm oil (Elaeis guineensis, Jacq) and unfeasibil-ity for the palm oil neutralization. The minimum fuel selling price (MFSP) obtained is this work for the biofuels was of 1.34 US$/L) and the breakeven point obtained was of 1.28 US$/L. The sensibility analysis demonstrated that the pyrolysis and distillation yields are the most important variables to affect the minimum fuel selling price (MFSP).

7β-(3-ethyl-cis-crotonoyloxy)-1α-(2-methylbutyryloxy)-3,14-dehydro-Z-notonipetranone (ECN), a sesquiterpenoid obtained from a natural origin (Tussilago farfara)has proved to be effective in minimizing various side effects associated with opioids and nonsteroidal anti-inflammatory drugs. The current study focused on investigating the effects of ECN on neuropathic pain induced by partial sciatic nerve ligation (PSNL) by mainly focusing on oxidative stress, inflammatory and apoptotic proteins expression in mice. Neuropathic pain was induced in mice by PSNL surgery performed on day 1 and ECN (1 and 10 mg/kg, i.p.), was administered once daily for 11 days, starting from the third day after surgery. ECN post-treatment was found to reduce hyperalgesia and allodynia in a dose dependent manner. ECN significantly reversed the severity of neuropathic pain by improving distress symptoms and survival rate. ECN remarkably reversed the histopathological abnormalities associated with oxidative stress, apoptosis and inflammation. Furthermore, ECN prevented the suppression of antioxidants (glutathione, glutathione-S-transferase, catalase, superoxide dismutase, NF-E2-related factor-2 (Nrf2), hemeoxygenase-1 and NAD(P)H: quinone oxidoreductase) by PSNL. Moreover, pro-inflammatory cytokines (tumor necrotic factor alpha, interleukin 1 beta, interleukin 6, cyclooxygenase-2 and inducible nitric oxide synthase) expression was reduced by ECN administration. Treatment with ECN was successful in reducing caspase-3 level consistent with the observed modulation of pro-apoptotic proteins. Additionally, ECN showed protective effect on the lipid content of myelin sheath as evident from FTIR spectroscopy which showed the shift of lipid component bands to higher values. Thus, anti-neuropathic potential of ECN might be due to inhibition of oxidative stress, inflammatory mediators and pro-apoptotic proteins.

In this study, we evaluated the effects of Cyclosporine A (CsA) on Lipopolysaccharide (LPS)-induced cytokine production in the genital tract of female rabbits. Twelve sexually mature and healthy female rabbits were randomly divided into four groups (n = 3 each). The rabbits in the LPS group were given an intrauterine infusion of Escherichia coli LPS (4 mg/kg body weight (BW)). Rabbits in the CsA group were given CsA (20 mg/kg BW). Rabbits in the LPS + CsA group were given LPS (4 mg/kg BW) and CsA (20 mg/kg BW). The control group received only LPS and CsA carrier. The gene expression and protein levels of pro- and anti-inflammatory cytokines were observed using qRT-PCR and immuno-histochemical (IHC) assay, respectively. Our study showed that IL-1β, IL-6, IL-8, TNF-α, IFN-γ, IL-4, IL-10, IL-13, and TGF-β were expressed in female genital organs. The LPS challenge increased the mRNA expression of IL-6 and TNF-α in the uterine body and IL-1β in the uterotubal junction compared to the control group. CsA increased the basal mRNA expression of anti-inflammatory cytokines (i.e., IL-4 in the uterine body, uterotubal junction, and oviductal ampulla; IL-10 in the cervix, oviductal isthmus, and ampulla; and TGF-β in the uterotubal junction and oviductal ampulla) and pro-inflammatory cytokines (i.e., IL-6 and IL-8 in the cervix; IL-1β in the oviductal isthmus; TNF-α in the oviductal ampulla; and IFN-γ in the uterine body compared to the control group). In addition, CsA inhibited the mRNA expression of pro-inflammatory cytokines, such as IL-6 in the uterine body, uterotubal junction, and oviductal isthmus; TNF-α in the uterine body; and IFN-γ in the uterotubal junction and oviductal isthmus induced by the LPS challenge. The IHC assay showed the LPS-induced increase in protein production of IL-6 in the uterine body and oviductal isthmus. CsA increased the protein production of IL-10 in the cervix, uterine body, oviductal ampulla, and isthmus. Moreover, CsA decreased the protein production of IL-6 in the uterine body and oviductal isthmus induced by LPS.

We investigated the efficacy of a Rumex crispus and Cordyceps sinensis mixture made using the Beopje (Korea traditional processing method to remove anti-nutrients and enhance phytochemicals) method to regulate immune cell responses toward nitric oxide (NO) production, pro-inflammatory cytokines, and inflammation related genes in mice splenocytes. The six experimental groups were as follows: control (control), Rc-Cs (Rumex crispus (Rc) and Cordyceps sinensis (Cs) mixture, 6:4), TMC (Taemyeongcheong, commercial healthy drink containing Rc-Cs), LPS (lipopolysaccharide), LPS+Rc-Cs, and LPS+TMC. The Rc-Cs mixture reduced nitric oxide (NO) production in LPS-induced splenocytes. Moreover, Rc-Cs enhanced production of the pro-inflammatory cytokines TNF-α, IFN-γ, IL-1β, and IL-6 compared to the control (no treatment). However, Rc-Cs inhibited production of pro-inflammatory cytokines in LPS-induced splenocytes. In addition, LPS+Rc-Cs also significantly suppressed mRNA expression of IL-1β and IL-6 compared to LPS treatment. Interestingly, Rc-Cs did not increase mRNA levels of iNOS and COX-2, which are inflammation related genes compared to the control, while LPS+Rc-Cs reduced mRNA levels of iNOS and COX-2 compared LPS alone (p < 0.05). TMC showed a similar pattern compared to Rc-Cs. Therefore, Rc-Cs treatment in splenocytes enhanced NO production and pro-inflammatory cytokines compared to the control, whereas Rc-Cs treatment in LPS-induced splenocytes reduced NO production, pro-inflammatory cytokines, and inflammation related genes. Thus, Rc-Cs regulated immune cells responses by increasing pro-inflammatory cytokines in splenocytes and reducing toxin (LPS)-induced inflammation. These results indicate that a Rumex crispus and Cordyceps sinensis mixture (Rc-Cs) and TMC containing Rc-Cs promote immune cells responses and anti-inflammatory activities.

To investigate switching from brimonidine and ripasudil, and brimonidine or ripasudil to a fixed combination of brimonidine and ripasudil and evaluate the associated efficacy and safety in glaucoma patients. Glaucoma patients undergoing treatment with at least brimonidine and ripasudil (n = 25) or treatment with at least brimonidine or ripasudil (n = 45) were evaluated in this retrospective study. After switching patients taking brimonidine and ripasudil, or brimonidine or ripasudil to a ripasudil/brimonidine fixed-combination ophthalmic suspension (RBFC), intraocular pressure (IOP), superficial punctate keratopathy (SPK) and conjunctival hyperemia were evaluated at baseline and at 4, 12 and 24 weeks. No significant differences in the IOPs were observed at any of the time points after switching from brimonidine and ripasudil to RBFC. However, at 4, 12 and 24 weeks, a significant decrease was observed in the mean baseline IOP from 17.0 ± 4.4 mmHg to 15.7 ± 3.2 mmHg (P < 0.01), 14.3 ± 3.4 mmHg (P < 0.01) and 14.4 ± 4.1 mmHg (P < 0.01), respectively, after switching from brimonidine or ripasudil to RBFC. No significant changes were noted for the SPK score or conjunctival hyperemia at any time points after switching to RBFC. Throughout the 24-week evaluation period, the IOP was maintained after switching from brimonidine and ripasudil to RBFC. However, there was a significant IOP decrease after switching from brimonidine or ripasudil to RBFC. These results demonstrate that RBFC is safe for use in the treatment of glaucoma patients.

There is sufficient knowledge of the beneficial effect of warm-dry storage on breaking the morpho-logical dormancy of the chincuya (Annona purpurea Moc. & Sessé ex Dunal) seed embryo. Chincuya is an underutilized, tropical wild species native to Mexico, with potential as a biopesticide. The impact of warm-dry storage and gibberellic acid treatment on seed viability and germination was determined to improve that knowledge further. Also, the content and kinetics of fatty acids in chincuya seeds were profiled during warm-dry storage. Seed treatments included storage time (0, 3, 6, 9, and 12 months), seed imbibition for 72 h in gibberellic acid at 350 mg L-1, and distilled water im-bibition for 72 h for the control treatment. Seed viability was determined using the TTZ classic test. Imbibed seeds were germinated on paper towels and incubated at 30 °C during the day and 25 °C at night in a 12:12 h dark:light photoperiod. The lipid profile was obtained by gas chromatography. During the storage treatment, seeds stayed in darkness at 25 ± 3 °C. Results showed that high viability remained up to month 9 in storage when it significantly decreased. Freshly harvested seeds germi-nated at a statistically significantly lower rate (26.1 %) than six-month-old seeds (65.6 %). The profile of fatty acids breaks down as palmitic acid (33.41 %), stearic acid (7.72 %), and arachidic acid (1.30 %), for a total of 42.44 % of saturated fatty acids. The detected unsaturated fatty acids (52.15 %) were palmitoleic acid (1.52 %), oleic acid (43.37 %), and linoleic acid (7.24 %). No significant changes were detected in fatty acid content; however, the highest fatty acid content (92.84 %) occurred with the highest germination rate. Regression analysis showed significant content changes: palmitoleic and palmitic acid increased while oleic acid decreased during dry storage. Arachidic acid showed a slight downward trend. Also, fatty acid content significantly differed between intact seeds (unstored and unincubated) and latent seeds (unstored, incubated, and ungerminated). The total fatty acids content for latent seeds was significantly lower. These results show that Annona purpurea seeds present morphophysiological dormancy. Also, we document the highest germination rate reported (65.6 %) and report the presence of arachidic and palmitoleic acids in chincuya seeds.

To study the fermentation process of biocatalyzing decanoic acid to synthesize trans-2-decenoic acid, this study was based on the engineering E.coli constructed in the laboratory in the early stage and studied the effect of seed liquid culture time, culture temperature, inoculum amount, induction temperature, dissolution effects of substrate solvent, metal ions, and substrate loading on the yield of trans-2-decenoic acid. Based on single-factor experimental optimization, the Box–Behnken design was used to conduct response surface testing using the substrate feeding concentration, inducer concentration, and MnCl2 concentration as response variables and trans-2-decenoic acid production as the response value. The optimal fermentation process was determined through experiments: seed culture time 20 h, culture temperature 37°C, inoculation amount 1%, induction temperature 30°C, substrate flow amount 0.15 g/L, inducer concentration 5.60 g/L, MnCl2 concentration was 0.10 mM. Under these conditions, the average production of trans-2-decenoic acid was 1.982 ± 0.110 g/L. Compared with the basic LB medium, the production of trans-2-decenoic acid increased by 1.042 g/L; compared with the previous period, the yield of trans-2-decenoic acid studied increased by 1.501 ± 0.110 g/L, which provides a reliable basis for further research on the fermentation process of biocatalytic decanoic acid synthesis of trans-2-decenoic acid.

The article delves into the intricate phase transitions of 1-Octadecanol and n-Nonadecane within a binary system, unveiling dynamic structural changes under varying conditions. Through Fouri-er-transform infrared (FTIR) analysis, specific molecular vibrations were identified, shedding light on the molecular composition and interactions. The study highlights the challenges in detecting subtle phase transitions and emphasizes the individuality of molecular behaviours in closely related compounds. The findings underscore the complexity of phase transitions in binary systems and advocate for a nuanced approach to studying molecular structures and behaviours. Addi-tionally, the research contributes valuable insights into the molecular dynamics of Organic Polymer Functional Adsorption Materials, offering implications for synthetic waxy layers in plant epidermis.

Background and Aims Insulin resistance is pivotal in the pathogenesis of Metabolic Syndrome (MetS), which predisposes to both type 2 diabetes mellitus (T2DM) and premature atherosclerotic cardiovascular disease (ASCVD). The triglyceride-glucose index (Ty-G index), a validated measure of insulin resistance also predicts MetS, T2DM, severity of albuminuria and ASCVD. There is scantly data providing mechanistic insights into these sequalae. Accordingly, we investigated the relationship between the TyG index and biomarkers of inflammation, oxidative stress, free fatty acids (FFA) levels and adipokine dysregulation in a cohort comprising both controls and patients with nascent MetS. Patients and Methods Participants included 47 patients with MetS and 41 controls. Persons with diabetes, ASCVD, smoking and macro-inflammation were excluded. Fasting blood was obtained for both plasma and monocyte isolation. Results: Receiver operating Characteristic (ROC) curve analysis revealed that TyG index was an excellent predictor of MetS with an area under the curve of 0.87 and it correlated with both hepatic and adipose tissue insulin ressitance .Both serum FFA levels and non-HDL-cholesterol increased significantly over tertiles of TyG index. Based on TyG index tertiles and or correlations, C reactive protein, endotoxin, chemerin , interleukin-6 levels and monocyte toll-like receptor (TLR)- 4 and TLR-2 and their cellular signaling were significantly associated with TyG index . Conclusion: Increased non-HDL-C and most importantly a pro-inflammatory state evidenced by both circulating and cellular biomarkers could be advanced as potential mechanisms explaining the increased risk for T2DM and ASCVD.

Celiac disease is an autoimmune disease triggered by oral ingestion of gluten, with certain gluten residues resistant to digestive tract enzymes. Within the duodenum, the remaining peptides incite immunogenic responses, including the generation of autoantibodies and inflammation, leading to irreversible damage. Our previous exploration unveiled a glutenase called Bga1903 derived from the Gram-negative bacterium Burkholderia gladioli. The cleavage pattern of Bga1903 indicated its moderate ability to mitigate the toxicity of pro-immunogenic peptides. The crystal structure of Bga1903, along with the identification of subsites within its active site, was determined. To improve its substrate specificity toward prevalent motifs like QPQ within gluten peptides, the active site of Bga1903 underwent site-directed mutagenesis according to structural insights and enzymatic kinetics. Among the double-site mutants, E380Q/S387L exhibits an approximately 38-fold increase in its specificity constant toward the QPQ sequence, favoring glutamines at the P1 and P3 positions compared to the wild type. Not only does the heightened specificity of E380Q/S387L improve the hydrolytic activity against pro-immunogenic peptides, but also holds this version of the enzyme as a promising candidate as an oral therapy enzyme for celiac disease.

Historically, fortified wines originated in Europe, and they have in common a high alcohol content to increase their shelf-life during long journeys to northern Europe and the American continent. Nowadays, the world’s better-known Marsala, Port, Sherry, and Vermouth due to their high alcoholic content, sweet taste, and intense aromatic profile, are designated as dessert wines and sometimes served as aperitifs. This review gives an overview of the traditional vinification process, including the microbiota and autochthonous yeast, the use of aromatic botanicals, and regulatory aspects of the main Italian, Portuguese, and Spanish fortified wines. The wine-making process is essential to defining the volatile organic compounds (VOCs) that characterize the aroma of each fortified wine, giving them an organoleptic fingerprint and “terroir” characteristics. The various volatile and odorous compounds found in fortified wines during oxidative and thermal aging are discussed in the last part of this review.

Searching for bioactive compounds within the huge chemical space is like trying to find a needle in a haystack. Isatin is a unique natural compound which is endowed with different biopertinent activities specially in cancer therapy. Herein, we envisaged that adopting a hybrid strategy of isatin and α,β-unsaturated ketone would afford new chemical entities with strong chemotherapeutic potential. Of interest, compounds 5b and 5g demonstrated significant antiproliferative activities against different cancer genotypes according to NCI assay. Concomitantly, their IC50 against HL-60 cells were 0.38 ± 0.08 and 0.57 ± 0.05, respectively, demonstrating remarkable apoptosis and mod-erate cell cycle arrest at G1 phase. Intriguingly, an impressive safety profile for 5b was reflected by a 37.2 times selectivity against HL-60 over PBMC from a healthy donor. This provoked us to further explore their mechanism of action by in vitro and in silico tools. Conclusively, 5b and 5g stand out as strong chemotherapeutic agents that hold a clinical promise against acute myeloid leukemia.

Under some employment circumstances, individuals in some organizations are willing to engage in unethical behaviors that benefit one’s own supervisors who have a great power to decide the levels of evaluation and compensation for each individual. In this study two hypotheses were examined. First, based on social identification theory, we hypothesized that individuals’ feeling a sense of oneness with one’s own supervisors promote unethical pro-supervisor behaviors (UPSB). Second, based on a person-situation interactionist model, we hypothesized that this positive relationship is strengthen if the individual perceives lower levels of one’s own employability. Data were collected from 185 individuals of various types of organizations in South Korea. A time-lagged field study supported our hypotheses. In particular, supervisor identification was positively related to UPSB. Further, for individuals with a weaker employability perception, supervisor identification was positively related to UPSB.

This study aims to demonstrate the possibility of incorporating a natural antioxidant biomolecule, into polymeric porous scaffolds. To this end, Poly-L-Lactic Acid (PLLA) scaffolds were produced using the Thermally Induced Phase Separation (TIPS) technique and additivated with different amounts of Rosmarinic Acid (RA). The scaffolds, with a diameter of 4 mm and a thickness of 2 mm, were characterized with a multi-analytical approach. Specifically, Scanning Electron Mi-croscopy analyses demonstrated the presence of an interconnected porous network, character-ized by a layer of RA at the level of the pore’s surfaces. Moreover, the presence of RA biomole-cules increased the hydrophilic nature of the sample, as evidenced by the decrease in contact angle with water from 128° to 76°. This approach is cost-effective, and it could be customized with different biomolecules, offering the possibility of producing porous polymeric structures con-taining antioxidant molecules. These scaffolds meet the requirements of tissue engineering and could be offered a potential solution to reduce inflammation associated with scaffold implantation thus improving tissue regeneration.

Chronic hemodialysis (HD) patients have very high cardiovascular risk. Acute vascular changes during dialysis mediated by factors of the endothelium may have a crucial role in this. Aim: To study acute vascular changes during HD. In 29 consecutive chronic HD patients (age: 65.6±10.4 years) pre-, mid-, and post-HD plasma syndecan-1 (SDC-1) and endothelin-1 (ET-1) levels were measured. Applanation tonometry was performed before HD. SDC-1 levels increased during HD (p=0.004). Males had higher ET-1 levels. Patients were divided into 2 groups based on pulse wave velocity (PWV): PWV≥12 m/s and PWV<12 m/s. Pre-HD and mid-HD SDC-1 levels were higher in the group with PWV≥12 m/s (10.174±2.568 vs. 7.928±1.794 ng/ml, p=0.013, and 10.319±3.482 vs. 8.248±1.793 ng/ml, p=0.044, respectively). Post-HD ET-1 levels were higher in the patient group having PWV≥12 m/s (10.88±3.00 vs. 8.05±3.48 pg/l, p=0.027). Patients having PWV≥12 m/s had higher pre-HD peripheral and aortic systolic blood pressure (p<0.05). Total cholesterol correlated with the SDC-1 decrease during HD (r=0.539; p=0.008). Pre-, mid-, and post-HD SDC-1 correlated with the ultrafiltration (r=0.432, p=0.019; r=0.377, p=0.044; and r=0.401, p=0.012, respectively). SDC-1 and ET-1 contribute to vascular changes observed during HD, and they have correlations with some cardiovascular risk factors.

This study aimed to evaluate the positive effect of autumn olive berries (AOB) extract on aging delay by improving the lipid metabolism of middle-aged C. elegans who became obese due to high glucose (GLU) diet. As a result of investigating the total phenol content and DPPH radical scavenging ability of freeze- or spray-dried AOB, freeze-dried AOB showed better antioxidant potential. Afterward, through HPLC analysis, it was confirmed that catechin was the main compound in the polyphenols of AOB. Therefore, we used freeze-dried AOB in subsequent in vivo experiments. AOB inhibited lipid accumulation in both the young adult and middle-aged groups in a concentration-dependent manner under both normal and 2% GLU conditions. Additionally, AOB inhibited ROS accumulation in a concentration-dependent manner under normal and 2% GLU conditions in the middle-aged worms. In particular, AOB also increased the number of body bending and egg production in middle-aged worms. To confirm the intervention of genetic factors related to lipid metabolism in the effect of AOB, body lipid accumulation was confirmed using worms deficient in the daf-16, atgl-1, aak-1, and akt-1. Regarding the effect of AOB on reducing lipid accumulation, the impact was nullified in daf-16 deficient worms under the 2% GLU condition and nullified in both daf-16 and deficient worms under fasting conditions. This means that AOB regulates lipogenesis and lipolysis by mediating daf-16 and atgl-1 in middle-aged worms. Our results suggest that AOB contributes to the aging delay effect by improving lipid metabolism in metabolic impaired middle-aged worms.

Aging and obesity make humans more prone to cardiovascular and metabolic syndrome diseases, leading to several serious health conditions, including dyslipidemia, high blood pressure, and sleep disturbance. Hyperlipidemia means elevated blood lipid levels, including cholesterol and triglycerides. This study aimed to explore the hypolipidemic effect of fermented citrus lemon juice using a hyperlipidemic hamster model. Sugar-free lemon juice’s fermentation was optimized, and the characteristics of fresh and fermented lemon juice (FLJ) were evaluated and compared. In addition, tests were conducted to determine the appropriate hamster feed for the functional animal tests. Then, experiments were conducted to evaluate the hypolipidemic effect of the FLJ, which contained polyphenols and superoxide dismutase-like activity, on a hyperlipidemic hamster model. This study’s pre-fermentation efficiency evaluation found that 21–30 days of bacterial DMS32004 and DMS32005 fermentation of fresh lemon juice provided the best fermentation benefits. In addition, the fermentation evaluation showed that a sugar-free fermentation method provided FLJ with the best benefits. Results showed that the absorption and utilization efficiency of FLJ was higher compared with the unfermented lemon juice. After six weeks of feeding, the total cholesterol and triglyceride values in the blood and liver of the FLJ treatment groups were de-creased compared with the high-fat diet (HFD) group. In addition, the blood low-density lipoprotein cholesterol levels were significantly reduced in the FLJ treatment groups compared with the HFD group. In contrast, the blood high-density lipoprotein to low-density lipoprotein cholesterol ratio increased considerably in the FLJ treatment groups, and the total to high-density lipoprotein ratio was significantly lower than in the HFD group. Compared with the HFD group, the total cholesterol content in the FLJ treatment groups’ feces increased significantly. This study demonstrated that the sugar-free fermentation method and fermentation cycle management provided FLJ with the potential to regulate blood lipids. Further research and verification will be carried out to isolate specific substances from the FLJ and identify their mechanisms of action.

Obesity induces inflammation in the hypothalamus and adipose tissue, resulting in metabolic disorders. A novel hypothalamic neuropeptide, neurosecretory protein GM (NPGM), was previously identified in the hypothalamus of vertebrates. While NPGM plays an important role in lipid metabolism in chicks, its metabolic regulatory effects in mammals remain unclear. In this study, a novel Cre driver line, NPGM-Cre, was generated for cell-specific manipulation. Cre-dependent overexpression of Npgm led to fat accumulation without increased food consumption in NPGM-Cre mice. Chemogenetic activation of NPGM neurons acutely promoted feeding behavior and chronically resulted in a transient increase in body mass gain. Furthermore, the ablated NPGM neurons exhibited a tendency to be glucose intolerant, with infiltration of proinflammatory macrophages into the adipose tissue. These results suggest that NPGM neurons may regulate lipid storage and inflammatory responses, thereby maintaining glucose homeostasis.

Needle abscission in balsam fir has been linked to both cold acclimation and changes in lipid composition. The overall objective of this research is to uncover lipid changes in balsam fir during cold acclimation and link those changes with postharvest abscission. Branches were collected monthly from September to December and assessed for cold tolerance via membrane leakage and chlorophyll fluorescence changes at -5, -15, -25, -35, and -45°C. Lipids were extracted and analyzed using mass spectrometry while postharvest needle abscission was determined gravimetrically. Cold tolerance and needle retention each significantly (P < 0.001) improved throughout autumn in balsam fir. There were concurrent increases in DGDG, PC, PG, PE, and PA throughout autumn and a decrease in MGDG. Those same lipids were strongly related to cold tolerance, though MGDG had the strongest relationship (R2 = 55.0% and 42.7% from membrane injury and chlorophyll fluorescence, respectively). There was a similar, albeit weaker, relationship between MGDG:DGDG and needle retention (R2 = 24.3%). Generally, a decrease in MGDG:DGDG ratio resulted in better cold tolerance and higher needle retention in balsam fir possibly due to increased membrane stability.

Hydrolysate prepared from water hyacinth biomass, containing a considerable amount of solubilised carbohydrate and nutrients, was utilised as a medium for the cultivation of two strains of Chlorella sorokiniana. These strains were isolated from an oxidation pond using two different media, i.e., BG-11 and Knop's media maintained at pH-9. Different light intensities, light-dark cycles, and various concentrations of external carbon sources (monosaccharides and inorganic carbon) were used to optimise the microalgal growth. It was observed that in the presence of organic carbon (glucose), biomass productivity increased significantly (~300 mgL-1day-1) as compared to that in the presence of only inorganic carbon (~100 mgL-1day-1). For the accumulation of stress products (lipids and carbohydrates), the microalgal strains were transferred to nutrient-amended media (N-amended and P-amended). The combined effects of glucose, inorganic carbon, and a 12h:12h light-dark cycle proved to be optimum for biomass productivity. For Chlorella sp. isolated from BG-11, maximum carbohydrate content (22%) was found in the P-amended medium, whereas high lipid content (17.3%) was estimated in the N-amended medium. However, for Chlorella sp. isolated from Knop's medium, both the lipid (17%) and carbohydrate accumulation (12.3%) were found maximum in the N- amended medium. Kinetic modelling of the lipid profile revealed that kinetic coefficients obtained for strain isolated from BG-11 media were statistically significant from each other.

Adeno-associated viral (AAV) vectors can be used for gene delivery. AAV.CAP-Mac was recently developed; it can cross the blood-brain barrier and transduce cells throughout the CNS. However, some brain regions were not transduced in adult rhesus monkeys. Additionally, AAV vectors can only package 5 kb of DNA. Also, AAV vectors may be genotoxic and cytotoxic, especially at high doses. Finally, AAV vectors are very expensive to produce at sufficiently high titers for treatment. Off-the-shelf cell-based delivery systems wherein the cells can infiltrate the target tissue and be hyper-motile would be ideal. Also, mRNA-based gene editing would be a transient treatment, and thus be much safer.

Serendipity favors the prepared mind, but how does the brain make that lucky find? Analyzing the cerebral mechanisms behind an exceptional (albeit trivial) discovery, the author suggests that a combination of ‘concept cells’ and the Global Neuronal Workspace Hypothesis could explain how we make great discoveries.