Neural or mental simulation of actions is a powerful tool for allowing cognitive agents to develop Prospection Capabilities that are crucial for learning and memorizing key aspects for challenging skills. In previous studies we developed an approach based on the animation of the redundant human Body Schema based on the Passive Motion Paradigm (PMP). In this paper we show that this approach can be easily extended to hyper-redundant serpentine robots as well as to hybrid configurations where the serpentine robot is functionally integrated with a traditional skeletal infrastructure. A simulation model is analyzed in detail showing that it incorporates spatio-temporal features discovered in the biomechanical studies of biological hydrostats like the elephant trunk or the octopus tentacles. It is proposed that such generative internal model can be the basis for a cognitive architecture appropriate for serpentine robots, independent of the underlying design and control technologies. Although robotic hydrostats have received a lot of attention in the last decades, the great majority of research activities have been focused on the actuation/sensorial/material technologies that can support the design of hyperredundant soft robots as well as the related control methodologies. The cognitive level of analysis has been limited to motion planning, without addressing synergy formation and metal time travel. This is where the contribution of the paper is focused on.

This study used 10 replicate pens per treatment in a randomized complete block design and each pen contained 8 steers (initial BW = 305 ± 30.4 kg; n=80 steers/treatment) to determine if a phytogenic feed additive (PFA) with essential oils and plant extracts (PHYTOsolvan 200; DOSTOFARM, Westerstede, Germany) influences measures of growth or growth efficiency during the feedlot receiving phase in auction-derived beef steers. No steers were removed from the study; one steer from the control treatment was treated for respiratory disease. No mortality was noted in the present experiment. No appreciable differences were noted for BW, ADG, DMI, or feed conversion efficiency from d 1 to 29, 29 to 53, or during the cumulative receiving period (P ≥ 0.12). Performance based NEm and NEg were not influenced by dietary treatment (P ≥ 0.79). The ratio of observed-to-expected dietary net energy was not impacted by dietary treatment (P ≥ 0.71). These were healthy, high-growth potential Northern Plains steers. There was minimal morbidity (0.63%) and no mortality noted during the 53 d receiving study. Steers performed well and met growth performance expectations (the ratio of observed-to-expected NEm = 1.00), hence, it was not anticipated that the phytogenic compound would appreciably influence growth or health outcomes under the conditions of this experiment.

Long intergenic noncoding (LINC)01270 is a 2278 bp transcript belonging to the intergenic subset of long noncoding (lnc)RNAs. Despite increased reports of LINC01270’s involvement in different diseases, evident research on its effects on inflammation is yet to be achieved. In the present study, we investigated the potential role of LINC01270 in modulating the inflammatory response in the human monocytic leukemia cell line THP-1. Lipopolysaccharide treatment upregulated LINC01270 expression, and siRNA-mediated suppression of LINC01270 enhanced NF-kB activity and the subsequent production of cytokines IL-6, IL-8, and MCP-1. Interestingly, the knockdown of LINC01270 downregulated expression of leucine zipper downregulated in cancer 1 (LDOC1), a novel NF-kB suppressor. An analysis of the LINC01270/micro-RNA (miRNA)/protein interactome profile identified miR-326 as a possible mediator. Synthetic RNA agents that perturb the interaction among LINC01270, miR-326, and LDOC1 mRNA mitigated the changes caused by LINC01270 knockdown in THP-1 cells. Additionally, a luciferase re-porter assay in HEK293 cells further confirmed that LINC01270 knockdown enhances NF-kB activation, while its overexpression has the opposite effect. This study provides insight into LINC01270’s role in modulating inflammatory responses to lipopolysaccharide stimulation in THP-1 cells via miR-326/LDOC1 axis which negatively regulates NF-kB activation.

Epilepsy is known to cause alterations in neural networks. However, many details of these changes remain poorly understood. The objective of this study was to investigate changes in the properties of hippocampal CA1 pyramidal neurons and their synaptic inputs in a rat lithium-pilocarpine model of epilepsy. In the chronic phase of the model, we found a marked loss of pyramidal neurons in the CA1 area. However, the membrane properties of the neurons remained essentially unal-tered. The results of the electrophysiological and morphological studies indicate that the direct pathway from the entorhinal cortex to CA1 neurons is reinforced in epileptic animals, whereas the inputs to them from CA3 are either unaltered or even diminished. In particular, the dendritic spine density in the str. lacunosum moleculare, where the direct pathway from the entorhinal cortex ter-minates, was found to be 2.5 times higher in epileptic rats than in control rats. Furthermore, the summation of responses upon stimulation of the temporoammonic pathway was enhanced by approximately twofold in epileptic rats. This enhancement is believed to be a significant con-tributing factor to the heightened epileptic activity observed in the entorhinal cortex of epileptic rats using an ex vivo 4-aminopyridine model.

The injury causes resistance in human gastric cancer (GC). This Adverse Outcome Pathway (AOP) entitled “Increases in cellular reactive oxygen species (ROS) and chronic ROS leading to human treatment-resistant gastric cancer (GC)” consists of molecular initiating event (MIE) as “Increases in cellular ROS” and “Chronic ROS”, followed by series of key events (KEs); “porcupine-induced Wnt secretion and Wnt signaling activation”, “beta-catenin activation”, “epithelial-mesenchymal transition (EMT), and adverse outcome (AO) as “human treatment-resistant GC” in the sequence. ROS has multiple roles in disease such as development and progression of cancer, or apoptotic induction causing anti-tumor effects. In this AOP, we focus on the role of sustained levels of chronic ROS to induce the therapy-resistance in human GC. EMT, which is cellular phenotypic change from epithelial to mesenchymal-like features, demonstrates cancer stem cell (CSC)-like characteristics in human GC. EMT is induced by Wnt/beta-catenin signaling, providing the rationale to have Wnt secretion and beta-catenin activation as KEs in the AOP.

PARK7, also known as DJ-1, plays a critical role in protecting cells by functioning as a sensitive oxidation sensor and modulator of antioxidants. DJ-1 acts to maintain mitochondrial function and regulate transcription in response to different stressors. In this study, we showed that cell lines vary based on their antioxidation potential at basal conditions. The transcriptome of HEK293 cells was tested following knockdown (KD) of DJ-1 using siRNAs which reduced the DJ-1 transcripts to only 12% of the original level. We compared the expression levels of 14k protein-coding transcripts, and 4.2k non-coding RNAs relative to control cells treated with non-specific siRNAs. Among the coding genes, ~200 upregulated differentially expressed genes (DEGs) signified a coordinated antiviral innate immune response. Most genes were associated with regulation of type 1 interferons (IFN) and induction of inflammatory cytokines. About a quarter of these genes were also induced in cells treated by non-specific siRNAs that were used as a negative control. Beyond the antiviral response, 114 genes were specific to KD of DJ-1 with enrichment in RNA metabolism and mitochondrial functions. A smaller set of downregulated genes (58 genes) were associated with dysregulation in membrane structure, cell viability, and mitophagy. We propose that KD of DJ-1 diminish its protective potency against oxidative stress, rendering the cells labile and responsive to dsRNA signal by activation of a large number of genes, many of which drive apoptosis, cell death, and inflammatory signatures. The KD of DJ-1 highlights its crucial role in regulating genes associated with antiviral responses, RNA metabolism, and mitochondrial functions, apparently through alteration in STAT activity and downstream signaling. Given that DJ-1 is highly expressed in metastatic cancers, targeting DJ-1 could be a promising therapeutic strategy where manipulation of DJ-1 levels may reduce cancer cell viability and enhance the efficacy of cancer treatments.

Cytomegalovirus infection contributes to 10-30% congenital hearing loss in children. Vertebrate peripheral auditory organs include the outer, middle and inner ear. Their development is regulated by multiple signaling pathways. However, most ear diseases due to viral infections are due to congenital infections and reactivation, and affect healthy adults to a lesser extent. This may be due to the fact that viral infections affect signaling pathways that are important for the development of peripheral hearing organs. Therefore, an in-depth understanding of the relationship between viral infections and the signaling pathways involved in the development of peripheral hearing organs is important for the prevention and treatment of ear diseases. In this review, we summaries the effects of viruses on signaling pathways and signaling molecules in development of peripheral auditory organ, with a focus on Human cytomegalovirus as an example.

Natural and sustainable plant-based antioxidants and antimicrobials are highly desirable for improving food quality and safety. The present investigation assessed the antimicrobial and antioxidant properties of active components from Alkanna tinctoria (herb) roots, also known as Ratanjot root. Two methods were used to extract active components: microwave-assisted hot water (MAHW) and ethanol and air-dried. MAHW extract yielded 6.29% while the ethanol yielded 18.27%, suggesting superior Ratanjot root extract powder (RRP) solubility in ethanol over water. The ethanol extract showed significantly higher antioxidant activity than the MAHW extract. Gas chromatography and mass-spec analysis revealed three major phenolic compounds: Butanoic acid, 3-hydroxy-3-methyl-; Arnebin 7, and Diisooctylpthalate. The color attributes (L*, a*, b*, hab, C*ab) for the ethanolic and MAHW extracts revealed significant differences (P < 0.05) in all the above parameters for both types of extracts, except for yellowness (b*) and chroma (C*ab) values. The ethanol extract exhibited antimicrobial activity against 14 bacterial species, with a signifi-cantly higher inhibitory effect against Gram-positive bacteria (Listeria monocytogenes and Staphylococcus aureus) than the Gram-negative bacteria (Salmonella enterica serovar Typhimurium and Escherichia coli). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were both 25 mg/ml for the Gram-negative bacteria, while the MIC and MBC concentrations varied for Gram-positive bacteria (0.049 - 0.098 mg/ml and 0.098 - 0.195 mg/ml) and the antimicrobial effect was bactericidal. The antimicrobial activities of RRP extract remained stable under broad temperature (37-100°C) and pH (2-6) conditions, as well as during refrigerated storage for 30 days. Application of RRP at 1% (10 mg/g) and 2.5% (25 mg/g) levels in a cooked chicken meatball model system prevented lipid oxidation and improved sensory attributes and retarded microbial growth during refrigerated (4°C) storage for 20 days. Furthermore, the RRP extract was non-toxic when tested with sheep erythrocytes and did not inhibit the growth of probiotics, Lacticaseibacillus casei, and Lactiplantibacillus plantarum. In conclusion, the study suggests that RRP possesses excellent antimicrobial and antioxidant activities, thus making it suitable for food preservation.

Climate change has altered the frequency and severity of extreme weather, which can affect vegetation condition and habitat quality for wildlife. Declines in vegetation productivity during droughts and heatwaves can negatively impact animals that depend on vegetation for water and nutrition. The ability to detect such effects on habitat suitability can reveal refugia, which can be prioritised for protection to improve threatened species conservation. We used the normalised difference vegetation index (NDVI) to look at relationships between vegetation productivity and the presence of koalas (Phascolarctos cinereus) in potential habitat throughout much of their range. Using a large, long-term koala presence dataset, we tested the hypothesis that locations where koalas had been observed would exhibit higher NDVI values than a random, representative sample from the same vegetation group (i.e. woodlands, open forests or tall open forests). We also identified the minimum NDVI threshold at which koalas occurred across time for each vegetation group and compared these to the minimum NDVI values observed across potential koala habitat before and during the millennium drought; one of the worst recorded in Australia. Additionally, we investigated whether vegetation above the minimum NDVI thresholds was significantly closer to perennial water than unsuitable vegetation. We found that koalas tend to occur at locations exhibiting higher NDVI than average for all vegetation groups. We also found that 49% of all vegetation groups maintained a minimum NDVI above the koalas’ NDVI threshold before drought, equating to 190,227 km2, which declined to 166,746 km2 during drought (a 12% reduction). We also found that unsuitable vegetation tended to occur farther from perennial water than suitable vegetation for some vegetation groups. Areas that remained above the NDVI thresholds during the drought should be considered potential refugia for populations during an event of similar magnitude and could indicate future core habitat extent.

Serum biochemical indicators serve as vital proxies that reflect the physiological state and functions of different organs. The genetic parameters and molecular mechanisms underlying serum biochemical indicators of sheep (Ovis aries) have not been well understood. Therefore, the aim of the present study was to identify genetic architecture and genomic loci underlying ten serum biochemical indicators in sheep, including alanine transaminase, aspartate transferase, lactate dehydrogenase, cholesterol, glucose, phosphorus, calcium, creatinine, urea concentrations and total protein levels. We implemented genetic parameter estimations and GWAS for each trait in 422 Akkaraman lambs. Overall, low to moderate heritability estimates were found, in the range 0.14–0.55. Additionally, low to high genetic correlations were observed among traits. In total, 23 SNP loci were associated with serum biochemical indicators leading to 19 genes . These are SPTA1, MGST2, CACUL1, IGFBP7, PARD3, PHB1, SLC15A5, TRIM35, RGS6, NUP93, CNTNAP2, SLC7A11, B3GALT5, DPP10, HST2ST1, NRP1, LRP1B, MAP3K9, ENSOARG00020040484.1 as well as LOC101103187, LOC101117162, LOC105611309 and LOC101118029. To our knowledge, these data provide the first association between SPTA1 and serum cholesterol and between ENSOARG00020040484.1 and serum glucose. The current findings provide a comprehensive inventory of the relationships between serum biochemical parameters, genetic variants, and disease-relevant characteristics. This information may facilitate the identification of therapeutic targets and fluid biomarkers and establish a strong framework for comprehending the pathobiology of complex diseases as well as providing targets for sheep genetic improvement programmes.

Decompression sickness (DCS) with neurological disorders is the leading cause of diving accidents. Exposure to high levels of CO2 during diving is a safety concern for occupational , groups at risk of DCS. However, the effects of prior exposure to CO2 have never been evaluated. The purpose of this study was to evaluate the effect of CO2 breathing prior to a provocative dive on the occurrence of DCS in mice. 50 mice were exposed to a maximum CO2 concentration of 70 hPa for one hour at atmospheric pressure. Another 50 mice breathing air under similar conditions served as controls. In the AIR group (controls), 22 out of 50 mice showed post-dive symptoms compared to 44 out of 50 in the CO2 group. We found that CO2 breathing is associated with a decrease in body temperature in mice and that CO2 exposure dramatically increases the incidence of DCS. More unexpectedly, it appears that a lower temperature of the animals even before exposure to the accident-prone protocol leads to an unfavorable prognosis. This study also suggests that the composition of the microbiota may influence thermogenesis and thus accidentology. Depending on prior exposure, some bacteria identified in this work could be perceived as protective or pathogenic.

Hirschsprung disease (HSCR, incidence 1/5000 live births) is caused by failure of neural crest-derived precursors to migrate, survive, proliferate or differentiate during the embryonic development of the Enteric Nervous System (ENS), which could be disrupted by many factors, in-cluding inflammatory processes. The NF-κB family controls several biological processes includ-ing inflammation, neurogenesis and cell migration. With the aim of studying the potential role of NF-κB in HSCR, we have analyzed the expression of the NF-κB main subunits and other NF-κB-related genes by RT-qPCR in HSCR tissue samples (sub-divided in ganglionic and agan-glionic segments). We found a decreased gene expression of the NF-κB main subunit RelA/p65, but also of IkBα, TNF-α, TFGBR2 and ERBB3 in the pathologic distal aganglionic segments com-pared to the proximal ganglionic segments. Moreover, we could also confirm the lower protein expression of RelA/p65 in the aganglionic distal segments by immunofluorescence staining. Fur-ther, we show that the expression of RelA/p65 in the proximal segments concurs with lymphocyte infiltration in the bowel tissue, indicating a pro-inflammatory activation of p65 in the proximal ganglionic HSCR tissue in the patients analyzed. In all, our findings suggest that the modulation of NF-κB signaling in the neuro-enteric system does obviously contribute to the pathological ef-fects in HSCR.

In the Lemongrass (Cymbopogon citratus), the investigations showed a wide range of active molecules their biological properties. However, most of these studies were conducted on the wid varieties, while cultivated plan addressed. This study aimed to characterize the biomolecules and biological activities of Lemongrass growing us African conditions sons in in Marocco. Marocco. Phenolic compound profiles of aqueous (AE) E) ethanol ethanol (EE), (EE), and methanol (ME) extract: fractions were obtained with steric exclusion chromatography on Sephadex 050 gel and identified by LC-MS/MS polyphenols (TPC), flavonoids (TFC), and antioxidant activities (FRAP: scavenging value and TAC: Total Antioxidant C the fraction were evaluated as well as the antimicrobial activity Obtained results showed that the ME contained e compounds (ie. Apigenine-7-0-rutinoside and myricitine-3-0-rutinoside). The AE showed the presence of five mole kaemiferol-3-0-glucuronide), while EE showed the presence of three molecules (Le. Quercetine-3-0-rutinoside). Reg chemical characterization, the rization, e highest value of Total phenolic content (TPC) was obtained in conten btained in AE ΑΕ (25) (4.60-0.29 mg highest value of Total flavonoids content (TFC) was obtained Ined in ME (29) (0.7±0.08 mg/g). Concerning the antioxide the highest FRAP was obtained in ME (29) (97.89%) and the highest total antioxidant capacity (TAC) was obtained (89.89%) Correlation between FRAP, TPC, and TFC was noted poly in fractions of AE and ME. All tested extracts of and their fractions showed a significant antimicrobial effect. The lowest minimum inhibitory concentration (MIC) wa for ME against E. col. Extracts biological activities and their fractions were governed by their active molecules. Ther new and clarify a novel aspect of bioactive molecules in the extracts of cultivated C. citratus Equaly, throughout this we clarified the relationship between identified molecules and their biological properties including antioxidant and comparative studies new activities, which is new for the study area. This study is suggested to be a reference. assays of other biological activities for the study plant

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and communication, anxiety, hyperactivity, and restricted interest for specific subjects. In addition to the genetic factors, multiple environmental factors have been related to the development of ASD. Animal models can serve as crucial tools for understanding the complexity of ASD and identifying potential therapeutic strategies. In this study, a chemical model of ASD has been developed in zebrafish by exposing embryos to valproic acid (VPA) from 4 to 48 hours post-fertilization. After the exposure, embryos were transferred to fish water and the effects on behavior and neurotransmitters profile were analyzed at both larval and adult stages. Larvae from VPA-treated embryos showed hyperactivity and decreased visual and vibrational escape responses, as well as an altered neurotransmitters profile, with increased glutamate and decreased acetylcholine and norepinephrine levels. Adults from VPA-treated embryos exhibited impaired social behavior characterized by larger shoal sizes and a decreased interest for their conspecifics. Neurotransmitter analysis revealed a significant decrease in dopamine and GABA levels in the brain. These results support the interest of this model in the study of ASD.

Purpose: Investigation for the co-occurrence of two unrelated genetic disorders of muscular dystrophy and Prader-Willi syndrome (PWS) (OMIM # 176270) using joint whole genome sequencing (WGS). Methods: Trio WGS joint analysis was performed to investigate the genetic etiology in a proband with PWS, prolonged muscular hypotonia associated hyperCKemia, and early-onset obesity. The parents were unaffected. Results: Results showed maternal isodisomy uniparental disomy (UPD) in chromosome 15 expanding from 15q11.2 to 15q22.2, including PWS regions at 15q11.2-15q13. Maternal heterodisomy was detected from 15q22.2 to 15q26.3. A pathogenic variant, NM_000070.3(CAPN3):c.550del (p.Thr184fs), was identified at 15q15.1 in a heterozygous state in the mother that was homozygous in the proband due to maternal isodisomy. Conclusion: This is the first study of the concurrent molecular etiology of PWS and calpainopathy (OMIM # 253600) in the same patient. This report highlights the utility of joint analysis and need for the assessment of autosomal recessive disease in regions of isodisomy in patients with complex and unexplained phenotype.

Chikungunya (CHIKV) and Mayaro (MAYV) viruses are arthritogenic alphaviruses that promote an incapacitating and long-lasting inflammatory muscle-articular disease. Despite studies pointing out the importance of skeletal muscle (SkM) in viral pathogenesis, the long-term consequences on its physiology after acute injury and the mechanism of persistence of symptoms are still poorly understood. Combining molecular, morphological, Nuclear Magnetic Resonance Imaging, and histological analysis, we conduct a temporal investigation of CHIKV and MAYV replication in a wild-type mice model, focusing on the impact on SkM composition, structure, and repair in the acute and late phases of infection. We found that viral replication and induced-inflammation promote fast loss of muscle mass and reduction of fibers cross sectional area, by inducing muscle-specific E3 ubiquitin ligases MuRF1 and Atrogin expression, that trigger protein breakdown, resulting in acute SkM fibers atrophy. After temporal reduction of inflammation and clearance of infectious viral particles, SkM atrophy persists until the late phase of infection. The genomic CHIKV and MAYV RNAs were still detected in SkM at the late phase, along with increased levels of chemokines and anti-inflammatory cytokines expression. In agreement with the involvement of inflammatory mediators on induced atrophy, neutralization of TNF and the reduction of oxidative stress using monomethyl fumarate, an agonist of Nrf2, decreases atrogens expression and atrophic fibers, while increasing weight gain in treated mice. Taken together, these data indicate that arthritogenic alphavirus infection could chronically impact body SkM composition and also harm repair machinery, contributing to a better understanding of mechanisms of arthritogenic alphaviruses pathogenesis and with description of potentially new targets of therapeutic intervention.

This study explores the intriguing phenomenon of action potentials reverberating and propagating in high-resistance tissues, such as gliosis, leading to the emergence of short circuits within the brain. Gliosis, characterized by increased tissue resistance, presents a unique environment for electrical signals. My research investigates the possible mechanisms behind these reverberations and their role in the creation of self-empowering short circuits that can potentially affect the entire brain's functionality. Understanding these processes may have significant implications for the treatment and management of neurological disorders associated with gliosis and abnormal electrical activity in the brain.

In this review we aim to address the current status of phage therapy in the management of multidrug-resistant infections, from compassionate use cases to ongoing clinical trials, as well as the challenges this approach presents in the particular context of CF patients.

High temperature stress affects tomato production both in tropical and sub-tropical environments worldwide. To explore genetic variation for heat tolerance in tomato, 329 transcontinental tomato varieties were evaluated at The Ministry of Municipality and Environment (MME) greenhouses near Doha, Qatar. Preliminary phenotypic analysis identified a diverse set of 71 hybrid and pure line tomato varieties for more detailed studies. The selected subset was examined in the greenhouse in a randomized complete block design under heat stress. The materials were phenotyped for fruit size, fruit weight, fruit hardness, fruit locules, fruit set (%), total soluble solids (TSS), and fruit yield. Significant phenotypic differences among genotypes were observed for all the traits assessed. To explore the genetic basis of variation among varieties the subset was genotyped using 104 SNP markers identified in previous heat tolerance genome wide association studies (GWAS). Nineteen QTL associated SNP markers could reliably select heat tolerant varieties in terms of better fruit yield, fruit set, and TSS. These markers are located on Chromosome 1, 5, 6, 8, 9, and 12. Interestingly, two clusters of markers on chromosome 6 were linked to significant effects on yield, fruit set, and TSS under high temperature. Some markers located within these QTL regions were also reported as associated with heat tolerance in other studies. Eighteen out of nineteen SNP markers were mapped within a gene body. Based on the phenotypic and the genotypic analysis, an elite set of five varieties was selected for approval for heat stress environments in Qatar. These findings have significance not only for Qatar, but they are also valuable for wider application at other locations worldwide. The 19 markers presented here could be adopted by breeders for marker-assisted selection (MAS) for heat tolerance.

Since the first reported case of COVID-19 in December 2019, several SARS-CoV-2 variants has evolved and some of them have shown higher transmissibility becoming the prevalent strains. Genomic epidemiological investigations into strains from different time points including the early stages of the pandemic are very crucial for understanding the evolution and transmission patterns. Using whole genome sequences, our study describes the early landscape of SARS-CoV-2 variants in central India retrospectively (including the first known occurrence of SARS-CoV-2 in Madhya Pradesh). We performed amplicon based whole genome sequencing of randomly selected SARS-CoV-2 isolates (n=38) collected between 2020-2022 at state level VRDL, ICMR-NIRTH, Jabalpur from 11899 RT-qPCR positive samples. We observed the presence of five lineages namely B.1, B.1.1, B.1.36.8, B.1.195 and B.6 in 19 genomes from the first wave cases and variants of concern (VOC) lineages i.e. B.1.617.2 (Delta), and BA.2.10 (Omicron) in the second wave cases. There was a shift in mutational pattern of SRAS-CoV-2 strains from the second wave in contrast to the first wave. We have identified five immune escape variants in the S gene: P681R, P681H, L452R, Q57H, and N501Y in the isolates collected during the second wave. Furthermore, these genomes were compared with 2160 complete genome sequences reported from central India that encompass 109 different SARS-CoV-2 lineages. Among them, VOC lineages Delta (28.93%), and Omicron (56.11%) were circulating predominantly in this region. This study provides useful insights into the genetic diversity of SARS-CoV-2 strains over the initial course of the COVID-19 pandemic in central India.

In the contemporary era, youthful and healthy skin is a pivotal determinant of beauty. Choices pertaining to one's dietary and lifestyle practices wield substantial influence over skin health. Currently, the focal point of attention lies in strategies to delay skin aging and maintain skin quality. Remarkably, the skin, the body's largest organ, serves as the primary defense barrier against external elements. Skin aging encompasses intrinsic and extrinsic categories, both susceptible to genetic, lifestyle, and environmental factors. Given the strides in science and technology, the pursuit of effective and safe interventions for skin aging assumes paramount importance. Thus, this review delves into the intricate relationship between diet, lifestyle, and skin aging, culminating in an exploration of the crucial role played by excess iron in this intricate nexus. Understanding these dynamics holds promise for advancing our knowledge of skincare and the quest for timeless vitality.

Salinity stress emerges as an important menace to global food security, particularly affecting susceptible crops such as common bean plants (Phaseolus vulgaris L.). The disruption of ion balances caused by salt stress withing plants cells reduces water and nutrient absorption, and hampers growth and productivity. Sacchorhiza polyschides, a brown macroalga rich in essential elements, and macrominerals, has drawn attention as a natural biostimulant, being a potential remedy to bolster crop resilience against salt stress. This study delves into the effect of water extracts of Sacchorhiza polyschides (SPE) across varying concentrations (1%, 2%, and 5%) in common bean plants under salt stress (68.4 mM NaCl) conditions. Two different methods of application were used: by spraying the aerial part of the plant or by irrigation together with the watering solution. The effects of both systems of application were studied on the aerial parts of the plants. SPE exhibited significant enhancements in morphological parameters, chlorophyll content, carbon-nitrogen activities, and antioxidant enzymatic system activities, alongside increasing osmolyte accumulation, compared to salt-stressed plants without biostimulation. Moreover, SPE reduced reactive oxygen species (ROS) levels caused by salt stress, mitigating lipid peroxidation. The concentrations of 2% and 5% SPE applied by spraying showed the most significant results in most of the parameters analyzed. By shedding light on the underlying science behind this biostimulant effect, this research underscores the potential of SPE to enhance crop resilience and augment food production in salt-challenged environments.

Obesity is a major risk factor for the development of life-threatening malignant ventricular tachyarrhythmias (VT) and sudden cardiac death (SCD). Risks may be highest for patients with high levels of the proinflammatory cytokine interleukin (IL)-6. We used our guinea pig model of high-fat diet (HFD) induced Ventricular arrhythmias, that exhibit heightened proinflammatory-like pathology which is also observed in human obesity VT, as well as immunofluorescence, and confocal microscopy approaches to evaluate the pathological IL-6 trans-signaling function and explore the underlying mechanisms. Using blind-stick and electrocardiogram (ECG) techniques, we tested the hypothesis that heightened IL-6 trans-signaling exhibit enhanced Ventricular arrhythmias /SCD incidence and underlying arrhythmia substrates. Remarkably, compared to low-fat (LFD) diet fed controls, HFD promotes phosphorylation of the IL-6 signal transducer and activator of transcription 4 (STAT4) leading to its activation and enhanced nuclear translocation of pSTAT4/STAT4 more than LFD controls and pSTAT3/STAT3 nuclear expression. Overactivation of IL-6 trans-signaling in guinea pigs prolonged the QT interval that resulted in greater susceptibility to VT/SCD with isoproterenol challenge, as also observed with the downstream Janus kinase (JAK) 2 activator. These findings may have potentially profound implications for more effective VT therapy in the vulnerable obese patient population.

This study investigated the effect of replacing part of the dietary soybean meal with either polymer-coated urea or gelatinized starch urea on the performance, nutrient digestibility, blood biochemical indexes, ruminal fermentation and rumen microflora of Angus heifers. The urea release profiles of two kinds of slow-release urea were evaluated in vitro and indicated a superior nitrogen retention with the polymer-coated urea. 210 purebred Angus cattle (BW = 314.26 kg) were divided into three groups: no urea group (CON), polymer-coated urea group (PCU), gelatinized starch urea group (GSU), 20g/kg polymer-coated urea or 25g/kg gelatinized starch urea was used to replace part of soybean meal in the concentrate feed respectively according to the principle of iso-metabolic energy and iso-nitrogenous. During the whole experiment, the ADG of PCU group was higher than both the GSU group and the CON group. The feed-weight ratio of the PCU group was significantly lower than both the GSU group and the CON group during the 90-day feeding period. The ADF apparent digestibility in the PCU group was significantly higher than that of the CON group, and extremely significantly higher than that of the GSU group. On the 86th day, the ALB content in the PCU group was significantly higher than that in the CON group. The contents of acetic acid and butyric acid, total volatile fatty acid and propionic acid were significantly higher in the PCU group than in the CON group. Bacterial diversity analysis found that the abundance of Firmicutes was higher in the PCU group than that in the GSU group and the CON group at the phylum level, and inverse result was observed in Bacteroidetes. The abundance of Paraprevotella was higher in the PCU group, whereas higher abundance of Prevotella was found in the GSU group at the genus level. These results indicate that both polymer-coated urea and gelatinized starch urea can replace part of soybean meal in the diet, and the amount of substitution in this trial had no diverse effect on the performance of Angus heifers, and the effect and economic benefits brought by polymer-coated urea were better than gelatinized starch urea.

Over the past thirty years, the red gorgonian Paramuricea clavata in the Mediterranean Sea has faced increasing threats, including heat waves and human activities such as fishing and diving. Epibiosis on damaged gorgonian colonies is generally used as an indirect indication of stressed conditions. The density and height of P. clavata and the percentage of colonies affected by epibiosis and entangled in lost fishing gear were studied to investigate the phenomenon and its trend over time in the Ligurian Sea. Analyses were based on transects collected during ROV campaigns between 2015 and 2022 at depths of 33-90 meters. A strong correlation was observed between fishing effort in the study area and the level of epibiosis. Maximal percentages of colonies affected by epibiosis and entanglement were recorded at depths of 50-70 meters. Temporally, marine heat waves before 2019 were identified as the primary cause of damage to P. clavata. The decrease in epibiosis percentages after 2019, despite the 2022 heat wave, may be due to a quick recovery ability of the populations and a reduction in fishing activities during the COVID-19 lockdown in 2020. Long-term monitoring programs are essential to understand the changes in marine benthic communities exposed to different stressors.

Understanding complex biological processes of cells in culture, particularly those related to metabolism, can be biased by culture conditions, since the choice of energy substrate impacts all main metabolic pathways. When glucose is replaced by galactose cells decrease their glycolytic flux, working as an in vitro model of limited nutrient availability. However, the effect of these changes on related physiological processes such as REDOX control is not well documented, particularly in endothelial cells where mitochondrial oxidation is considered to be low. We evaluated the differences in mitochondrial dynamics and function in endothelial cells exposed to galactose or glucose culture medium. We observed that cells maintained in galactose-containing medium show higher mitochondrial oxidative capacity, more fused mitochondrial network, and higher intercellular coupling. These factors are documented to impact the cellular response to oxidative stress. Therefore, we analyzed the levels of two main REDOX regulators and found that Bovine Aortic Endothelial Cells (BAEC) in galactose media had higher levels of FOXO3 and lower levels of Nrf2 than those with glucose in the media. Thus, culture of endothelial cells in galactose containing medium may provide a more suitable condition to study in vitro mitochondrial related processes than glucose media, and deeply influence REDOX signaling in these cells.

Clostridioides difficile is a Gram-positive pathogen known for its toxin production and spore formation. It is primarily responsible for most cases of antibiotic-associated diarrhea. Bacterial persisters are a small subset of the population that exhibits transient tolerance to bactericidal substances, and they are of significant medical concern due to their association with the emergence of antibiotic resistance and difficult-to-treat chronic or recurrent infections. Vancomycin, the predominant antibiotic utilized in the management of C. difficile infection, is extensively applied in the realm of clinical practice. Previous studies have demonstrated a persister-like phenotype with treatments involving this antibiotic. However, the mechanism in C. difficile remains largely unknown, primarily due to the challenge of isolating this small population at any given time. To better characterize C. difficile persister cells, we present a study that enables the enrichment and characterization of persister cells from bacterial cultures in both exponential and stationary phases. Moreover, we could differentiate between triggered (induced by antibiotics, such as vancomycin) and spontaneous (stochastic) persister cells. Additionally, we observed the involvement of toxin-antitoxin systems and Clp proteases in persister cell formation.

In the marine environment, fish parasites are present in most species of seafood. The most com-mon is Anisakis spp. a nematode that can parasitize human tissues causing anisakiasis and al-lergies, in some cases with a strong reaction such as anaphylactic shock in sensitive people. This happens when people ingest live or dead larvae present in the muscles or viscera of a wide range of seafood, fish and cephalopods. Consumer education has been positioned as one of the most ef-fective alternatives for its prevention. This study sought to identify the species that present the greatest risk of anisakiasis for consumers taking into account sex, age and their knowledge about this parasitosis. The objective was to offer recommendations for better consumer information to-wards the prevention of infections by worm larvae. The results revealed that the species most at risk were hake and cod and that young participants know more about the risks of anisakiasis from raw seafood. The gaps detected in the knowledge about the ability of thermal treatments to eliminate parasites, especially in allergic people, must be addressed for better prevention, sug-gesting campaigns adapted by sectors of the population.

An undesirable sensory attribute (“floral taint”) has been recently detected in red wines in some winegrowing jurisdictions in North America (e.g. Ontario, British Columbia, Washington), caused by introduction of frost-killed leaves and petioles [materials-other-than-grapes (MOG)] during mechanical harvest and winemaking. It was hypothesized that terpenes, norisoprenoids, and higher alcohols would be the main responsible compounds. Objectives were to investigate causative volatile compounds for floral taint, and explore threshold concentrations for this problem. Commercial wines displaying varying intensities of floral taints were subjected to GC-MS and sensory analysis. Several odor-active compounds were higher in floral-tainted wines, including terpenes (geraniol, citronellol, cis- and trans-rose oxide), norisoprenoids (β-damascenone, β-ionone), five ethyl esters, and three alcohols. Thereafter, fermentations of Cabernet franc (CF) and Cabernet Sauvignon (CS) (2016, 2017) were conducted. MOG treatments were (wt/wt): 0, 0.5%, 1%, 2% and 5% petioles, and 0, 0.25%, 0.5%, 1%, and 2% leaf blades. Terpenes (linalool, geraniol, nerol, nerolidol, citronellol, citral, cis- and trans-rose oxides, eugenol, myrcene), norisoprenoids (α- and β-ionone), and others (e.g. hexanol, octanol, methyl and ethyl salicylate) increased linearly/quadratically with increasing MOG levels in both cultivars. Principal components analysis separated MOG treatments from the controls with 5% petioles and 2% leaves as extremes. Increasing MOG levels in CF wines increased floral aroma intensity, and were primarily associated with terpenes, higher alcohols, and salicylates. Increased leaf levels in CF were associated with higher vegetal and earthy attributes. Increased petioles in CS were not correlated with floral aromas, but increased leaves increased floral, vegetal and herbaceous attributes. Overall, petioles contributed more to floral taint than leaves through increased terpenes and salicylates (floral notes), while leaves contributed norisoprenoids and C6 alcohols (green notes).

.Halophyte species are rich in bioactive compounds, antioxidant, and antimicrobial properties. However, due to the limited tech-nical-scientific data regarding these properties in the halophyte Salicornia neei, this research aimed to analyze micronutrients, chlorophyll, carotenoids, and activities of S. neei extracts using solvents of different polarities and plant organs (leaf, stem, and root) as free radical scavengers and antimicrobial agents. The fresh plant was collected and subsequently, pigments and micro-nutrients were determined by spectrophotometry and ICP, respectively. From the prepared extracts, antioxidant activity was de-termined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging method and antimicrobial activity by the disc diffusion method for fungi and bacteria. The results obtained demonstrated that the native Brazilian halophyte S. neei can be considered a food rich in minerals and pigments with excellent antioxidant properties, showing inhibition 96.72% and IC50 (4.15 mg/mL). For free radical scavenging capacity, the most effective solvent was ethanol: acetone (1:1) and there was no significant difference (p

Before the Bronze age, when agricultural practices spread throughout the Iberian Peninsula, the diet of natives was based on hunting, fishing and gathering wild plants. On spite of modern agriculture, the popular gathering of wild species for medical use, feeding, craftwork, etc. for centuries, has left a deep knowledge on the use of many of those species. Of the 6.176 Angiosperms native to the Iberian Peninsula and the Balearic Islands, over 200 species were introduced into cultivation from the Neolithic outside the Iberian Peninsula. The name of 30 of the progenitors still popularly used as food, are listed in this paper, together with the name of the derived crops. Special attention is paid to five wild species, including their composition and pharmacological properties, collected as food from ancient times, that in response to their great demand, have been recently introduced into cultivation in Spain and are now harvested and commercialized as new crops.

The prospect of drinking water serving as a conduit for gut bacteria, artificially selected by disinfection strategies and lack of monitoring at the point of use, is concerning. Certain opportunistic pathogens, notably some nontuberculous mycobacteria (NTM), often exceed coliform bacteria levels in drinking water, posing safety risks. NTM and other microbiota resist chlorination and thrive in plumbing systems. When inhaled, opportunistic NTM can infect the lungs of immunocompromised or chronically ill patients, and the elderly, primarily postmenopausal women. When ingested with drinking water, NTM often survive stomach acidity, reach the intestines, migrate to other organs using immune cells as vehicles, potentially colonizing tumor tissue, including in breast cancer. The link between the microbiome and cancer is not new, yet the recognition of intratumoral microbiomes is a recent development. Breast cancer risk rises with age, and NTM infections emerged as a concern among breast cancer patients. In addition to studies hinting at a potential association between chronic NTM infections and lung cancer, NTM have also been detected in breast tumors at levels higher than normal adjacent tissue. Evaluating the risks of continued ingestion of contaminated drinking water is paramount, especially given the ability of various bacteria to migrate from the gut to breast tissue via entero-mammary pathways. This underscores a pressing need to revise water safety monitoring guidelines and delve into hormonal factors, which includes addressing the disproportionate impact of NTM infections and breast cancer on women and examining the potential health risks posed by the cryptic and unchecked microbiota from drinking water.

Protein hydrolysates are plant biostimulants containing amino acids, oligopeptides, and peptides in their composition. When supplied to plants, protein hydrolisates (PH) have been identified to improve nitrogen metabolism, enhance the activity of antioxidant enzymes, boost plant defence response to stresses, and positively impact the quantity and quality of products. Soybean is a crucial global commodity, with nitrogen being the primary nutrient for crop development as it directly affects productivity. This study aimed to evaluate the effect of a HP-based biostimulant on the N metabolism in nodulated soybean plants and their productivity. A greenhouse experiment was conducted to test two modes of application of the 0.20% HP-based biostimulant. Soybean plants, growing in pots, were treated with HP 0.20% either via seed treatment or foliar application (at growth stages V3 and V5). Activities of enzymes and compounds related to N metabolism, gene expression, and productivity components were analysed. It was observed that the mode of application did not significantly influence the results. The application of HP increased the concentration of nitrate, amino acids, and ureides in soybean leaves. It also positively altered the expression of genes such as nitrate reductase, urease, and asparagine. Additionally, it enhanced productivity, resulting in plants with a greater number and weight of pods and grains. Therefore, it is possible to consider HP as a stimulator for increasing soybean productivity, even under non-stressing conditions.

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.

The SARS-CoV-2-induced acute COVID-19 pandemic disorder seems to have begun all of the sudden in 2020, with very little data available regarding prior times in which people experienced mysterious flu-like illness symptoms characteristic of the pandemic disease. The scientific community seems to be divided into a few parts with regards to the belief of the kind of viral origins. A significant number of scientists believe that the virus solely has natural origins and that it underwent a thorough process of zoonosis, independent of laboratory research-based research that would only catalyse zoonosis due to helping the virus gain additional function of transmission and virulence. Many other scientists believe that the virus has wide origins characteristic of “gain-of-function” laboratory research, whilst many other scientists believe that most of the viral genome has natural origins, with the zoonotic process having been artificially catalysed only in its latter part of transmission to humans. Considerable extent of scientific evidence suggests that the virus underwent a restricted, but considerable extent of “gain-of-function” research, prior to having been accidentally leaked into the nearby environment, whilst its process of zoonotic spillover into humans was influenced by such events, given for example the multidimensional pathogenetic process displayed by the virus and its main antigen of action, the spike glycoprotein, causing all kinds of immune pathophysiology - including transient immunosuppression. Investigations into the origins of the novel coronavirus have been lasting for years, seemingly with no concrete end in sight, and the available molecular testing methods to detect SARS-CoV-2 infection displaying less than perfect results have not significantly helped the process. Evidence even started pointing toward the existence of artificial, laboratory research-based viral origins, exposing a probable accidentally-induced artificial process of “accelerated viral evolution”, which could be particularly dangerous because of the nature of the SARS-CoV-2 pathogenic agent. Likewise, it is possible that the prevention of distribution of scientific data regarding scenarios as such in fact constitutes censorship, rather than regulation of data that may be considered not to be significantly evidence based. Simultaneously, it is important not to regard all hypotheses and preliminary reports of scientific research as evidence-based, but to ensure that due diligence is performed in all cases. The integrity of scientific research and ultimately of the innovation process of medical solutions depends on the integrity of democracy and the rule of law, as well as on regulating partnerships with scientific companies from world nations where autocracy rules their society.

Background: Angiogenesis is essential for various physiological and pathological processes, such as embryonic development and cancer cell proliferation, migration, and invasion. Long noncoding RNAs (lncRNAs) play pivotal roles in normal homeostasis and disease processes by regulating gene expression through various mechanisms, including as competing endogenous RNAs (ceRNAs) of target microRNAs (miRNAs). The lncRNA MYU is known to promote prostate cancer proliferation via the miR-184/c-Myc regulatory axis, and to be upregulated in vascular endothelial cells under hypoxic conditions, which often occurs in solid tumors. In the present study, we investigated whether MYU might affect cancer growth by regulating angiogenesis in vascular endothelial cells under hypoxia. Methods: The expression of MYU-regulated miR-23a-3p and interleukin-8 (IL-8) in HUVEC cell lines was examined using qRT-PCR. CCK-8 assay, EdU assay, Wound-healing assay and Tube-formation assay were used to assess the effect of MYU on cell proliferation, migration and tube formation of HUVEC cells in vitro. Dual-luciferase reporter assay was performed to examine the effect of miR-23a-3p on MYU and IL-8 expression. Results: We found that overexpression of MYU and knockdown of miR-23a-3p in human umbilical vein endothelial cells (HUVECs) under hypoxia promoted cell proliferation, migration, and tube formation. Mechanistically, MYU was shown to bind competitively to miR-23a-3p, thereby preventing miR-23a-3p binding to the 3′ untranslated region of IL-8 mRNA. In turn, increased production of pro-angiogenic IL-8 promoted HUVEC proliferation, migration, and tube formation under hypoxia. Conclusion: This study identified a new role for lncRNA MYU as a ceRNA for miR-23a-3p, and uncovered a novel MYU–miR-23a-3p–IL-8 regulatory axis for angiogenesis. MYU and/or miR-23a-3p may thus represent new targets for the treatment of hypoxia-related diseases by promoting angiogenesis.

Background: Fold change is widely used in biomedical research to quantify the magnitude of group differences in omics variables. However, the exact calculation method is often not reported, leading to inconsistent results. This study re-evaluates different fold-change calculation methods and provides a clear preference. Methods: Data scenarios with different distributions of treatment/test and reference data were created to challenge the assumption of interchangeable calculation methods. The main difference lies in the definition of the expected values of the groups used to calculate the log ratio, which is the basis of the fold change calculation. In addition, a multi-omics biomedical dataset was analyzed. Results: Using the arithmetic mean as the expected value for the treatment and reference groups resulted in incorrect fold change values more frequently than other methods, especially when the standard deviations between subgroups differed widely. Conclusions: The inferior arithmetic mean method is often perceived as the standard, although mathematically different equations are possible that differ mainly in the estimation of the expected value. Alternatives that define expectation by median, geometric mean, or paired fold change combinations are less susceptible to violations of equal variances or similar treatment/reference distributions.

Alzheimer’s disease (AD) is a progressive irreversible neurodegenerative disorder that represents a major global public health concern. Traditionally, AD is diagnosed using cerebrospinal fluid biomarker analysis or brain imaging modalities. Recently, less burdensome, more widely available blood biomarker (BBM) assays for amyloid-beta (Aβ42/40) and phosphorylated-tau concentrations have been found to accurately identify the presence/absence of brain amyloid plaques and tau tangles and have helped to streamline AD diagnosis. However, few BBMs have been rigorously analytically validated. Herein, we report the analytical validation of a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying plasma phosphorylated-tau217 (p-tau217) and non-phosphorylated-tau217 (np-tau217) peptide concentrations. We combined the p-tau217/np-tau217 concentrations ratio (%p-tau217) and the previously validated LC-MS/MS assay for plasma Ab42/40 into a new multiple analyte blood test and algorithm (PrecivityAD2™) that identifies brain amyloid status based on brain amyloid positron emission tomography. We found: (a) the %p-tau217 assay is precise, accurate, sensitive, linear over a wide analytical measurement range, and free from carryover and interference; (b) the pre-analytical specimen collection, processing, storage and shipping conditions that maintain plasma tau peptide stability; and (c) using the measured analytical imprecision for plasma Aβ42/40 and p-tau217/np-tau217 levels in a worst-case scenario model, the PrecivityAD2 test algorithm for amyloid pathology classification changed for only 3.5% of participants from brain amyloid positive to negative, or negative to positive. The plasma sample preparation and LC-MS/MS methods underlying the PrecivityAD2 test are suitable for use in the clinical laboratory and valid for the test’s intended purpose: to aid in the diagnostic evaluation of individuals aged 55 and older with signs or symptoms of mild cognitive impairment or dementia.

Objective: This research was aimed to estimate the anti-fatigue effects of arecoline and elucidate its underlying mechanisms using a murine model of central fatigue precipitated by sleep deprivation (SD). Methods: Seventy-two male C57BL/6 mice were randomly allocated into six groups: a control group, a SD-induced fatigue model group, a group receiving Rhodiola Rosea capsules (2.5 mg/kg), and arecoline groups administered low, medium, and high doses (10, 20, and 40 mg/kg, respectively). Following 28 days of continuous administrations, the effects of arecoline on the mouse fatigue-related behaviors was assessed by the behavioral tests, including grip strength, rotarod performance, and weight-bearing swimming endurance. Enzyme-linked immunosorbent assays (ELISAs) were utilized to measure the levels of the relevant biochemical markers. Western blotting was employed to quantify the expression of nuclear factor erythroid 2-related factor (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), heme oxygenase 1 (HO-1), sequestosome-1 (p62), and NADPH quinone oxidoreductase 1 (NQO1) in the gastrocnemius muscle. Results: Arecoline administration notably enhanced grip strength, delayed the onset of fatigue as evidenced by extended latencies in rotarod tests, and increased the duration of weight-bearing swimming in mice. In the elevated plus maze, arecoline significantly reduced both the number of entries and the total distance traveled in the open arms. Arecoline markedly decreased serum levels of creatine kinase, blood urea nitrogen, lactate dehydrogenase, triglycerides, and cholesterol, while elevated total testosterone, lactate dehydrogenase, and immunoglobulin G levels. Furthermore, it significantly increased superoxide dismutase(SOD), catalase(CAT), and glutathione peroxidase activity in the gastrocnemius muscle, reduced malondialdehyde levels, augmented hippocampal SOD and CAT activity, and elevated glycogen stores in both liver and muscle tissues. Neurotransmitter levels were significantly increased, cytokine levels were markedly reduced, and the expression of Nrf2, Keap1, NQO1, p62, and HO-1 in brain tissue was significantly upregulated. Conclusion: The current study for the first time demonstrated that arecoline has significant anti-fatigue activity, and its mechanism of action is related to elevate the levels of glucose and lipid metabolism, relieve oxidative stress damage, inhibit neuroinflammatory response, regulate neurotransmitter levels and Keap1/Nrf2/HO-1 signaling pathway. The current study provides a new insight into the potential of arecoline in prevention and improvement of fatigue.

Divulsuperbac (DSB) is a Service Learning project targeted at the educational community. It started in 2019 and has engaged Biology degree students in a Microbiology-focused initiative in the Valencian Community (Spain), for four academic years. The DSB project comprises various outreach activities intending to raise awareness of the superbugs' threat to pre-university students. We created an exhibition that contained 14 infographics on the topic of antimicrobial resistance which was presented every week in high schools. The infographics were presented by university students, who explained the problem to the pre-university students and subsequently assessed their comprehension of the topic. The surveys conducted yielded satisfactory results, which motivated us to extend this project to other regions of the world.

The MAPK signaling pathway with BRAF mutations has been shown to drive the pathogenesis of 40-60% of melanomas. Inhibitors of this pathway's BRAF and MEK components are currently used to treat these malignancies. However, responses to these treatments are not always successful. Therefore, identifying noninvasive biomarkers to predict treatment responses is essential for personalized medicine of melanoma patients. Using noninvasive 1H magnetic resonance spectroscopy (1H MRS), we previously showed that BRAF inhibition reduces lactate and alanine tumor levels at early stages of effective therapy and could be construed as metabolic imaging biomarkers for drug response. The present work aimed to demonstrate if these metabolic changes and those assessed by 31P MRS are also found in preclinical human melanoma models treated with MEK inhibitors. Apart from 1H and 31P MRS, additional supporting in vitro biochemical analyses are described. Our results indicate significant early metabolic correlations with response levels to MEK inhibition in the melanoma models and are consistent with our previous study of BRAF inhibition. Given these results, our study supports the potential clinical utility of noninvasive MRS to objectively image metabolic biomarkers for early predicting melanoma response to MEK inhibition.

Indolizidines have long been recognized for their valuable bioactivities, their common feature being a bicyclic structure connected via a nitrogen atom. Traditionally, plants have been identified as the primary producers. However, recent discoveries have revealed that certain bacterial strains belonging to the genus of actinomycetes also possess the ability to synthesize various indolizidine-based compounds. Among these strains, Streptomyces sp. HNA39, Saccharopolyspora sp. RL78, and Streptomyces NCIB 11649 have been identified as producers of cyclizidines, characterized by their distinctive cyclopropyl moiety. Additionally, Streptomyces griseus OS-3601 synthesizes a unique class of indolizidine derivatives known as iminimycines, distinguished by their rare imine-cation structure. Protoplast fusion of a Streptomyces griseus strain with Streptomyces tenjimariensis resulted in a new indolizidine named in-dolizomycin. This review aims to provide an overview of known bacterial indolizidine producers, summarize current knowledge regarding the biosynthesis of cyclizidines and iminimycines, and assess their bioactivities.

Animal personalities play a crucial role in invasion dynamics during alien species invasions. The behavioral strategies adopted by native species varied among personalities when facing an invasion by alien species, just as the invasive species exhibited variations in behavior strategies across different personalities during the invasion process. However, the effects of personality interactions between native species and invasive species on behavior and growth are rarely illustrated. We used the globally invasive freshwater turtle Trachemys scripta elegans and the native freshwater turtle Mauremys reevesii to investigate how the personality combinations of native and invasive turtles would impact the foraging strategy and growth of both species. We found that M. reevesii exhibited bolder and more exploratory personalities than T. scripta elegans. The foraging strategy of M. reevesii was mainly affected by the personality of T. scripta elegans, while the foraging strategy of T. scripta elegans was influenced by both their own personality and M. reevesii's personality. In addition, we did not found that the personality combination would affect the growth of either T. scripta elegans or M. reevesii. Difference in foraging strategy may be due to the competitive advantage of invasive species and variations in the exploration-exploitation foraging strategy among different personalities. Overall, our results reveal the mechanisms of personality interaction effects on the foraging behavior of both native and invasive species during alien species invasion and provide empirical evidence to help understand the effects of personality in invasion dynamics.

Tadpole shrimp (Triops longicaudatus) has become a major pest for California rice farmers. Currently, management relies solely on the insecticide lambda-cyhalothrin. However, resistance to this pyrethroid was confirmed in 2016, thus identifying an effective and practical biological control method for TPS is a priority. Field trials were conducted from 2017 to 2018 to: (1) evaluate the efficacy of the predatory fish Gambusia affinis and the predatory beetles, Laccophilus maculosus (Say) and Tropisternus lateralis (Fabricius), in controlling TPS, (2) test the efficacy of several inoculation rates of Gambusia affinis at controlling TPS and (3) to explore early indicators of TPS activity and damage as monitoring tools. Both Gambusia affinis and the predatory beetle treatments were not significantly different from the commercial standard (lambda-cyhalothrin). Both four and five Gambusia per 1 m2 controlled TPS as well as lambda-cyhalothrin, and we observed that Gambusia affinis was able to reproduce in the field. Water turbidity was significantly correlated with TPS counts (R = 0.85, N = 20, P &lt; 0.0001 (2017); R = 0.58, N = 30, P = 0.0007 (2018)). The number of dislodged seedlings was less reliably correlated with TPS count; in 2017 correlations were significant (R = 0.84, N = 20, P &lt; 0.0001), however, in 2018 correlations were not significant (R = 0.18, N = 30, P = 0.35). With further refinement water turbidity could play a valuable role in monitoring TPS populations.

Abiotic stress is a significant factor restricting the normal growth and development of plants. Under abiotic stress, plants maintain their life and continuous growth by reconfiguring transcriptional regulation and metabolic networks. In recent years, with the development of sequencing technology and mass spectrometry technology, transcriptomics and metabolomics have emerged as new disciplines following genomics and proteomics, which are conducive to identifying metabolites and regulatory genes in plants under abiotic stress. In this review, we mainly analyzes the technical characteristics, advantages, and disadvantages of transcriptomics and metabolomics, focusing on reviewing the research progress in the field of plant responses to abiotic stress (temperature stress, salt stress, water stress, and heavy metal stress) using transcriptomics and metabolomics both domestically and internationally in recent years. It also provides a prospective view on current issues, which helps accelerate the understanding of the mechanisms of plant responses to abiotic stress and provides new ideas for breeding stress-resistant varieties in the future.

Rutin, a flavonoid compound found in various plants, has gained attention for its potential applications in the cosmetic industry due to its antioxidant, anti-inflammatory, and potential photoprotective properties. Our review explored the use of rutin (rutoside, 3-O-rutinoside-quercetin) in cosmetics/dermocosmetics, focusing on its physicochemical properties and stability, cutaneous permeability, and efficacy in sunscreen systems, involving in vitro tests and the current state of clinical trials. Rutin's ability to scavenge free radicals, prevent peroxidation, and reduce vascular fragility makes this flavonoid a promising ingredient for photoprotection. Studies have shown that rutin can enhance the sun protection factor (SPF) of sunscreen formulations, especially when combined with organic UV filters. The encapsulation of rutin in nanostructures has also been investigated to improve its applicability. Overall, rutin shows potential as a safe and effective ingredient in cosmetic/dermocosmetic formulations, offering protection against the harmful effects of UV radiation and oxidative stress on the skin.

Dairy farming dates to the early Neolithic era in Europe, Middle East, Asia, and Africa. Over time, the industry has evolved from small ranches and farmhouses milk processing units to large, intensive dairy farms and big, high-tech processing units. Despite the industry’s contribution to the economy and food production, multiple studies have tainted cattle farming as a main contributor to climate change. This study explores literature in dairy farming and sustainable development goals (SDGs) to identify current scholarly developments since the formulation and adoption of SDGs in 2015 and themes for future research. This paper argues that dairy animals are not the source of sustainability shortfalls as depicted by multiple scholarly articles, but human processes associated with dairy farming. Data was analyzed using R package, Excel, NVIVO, and VoS Viewer. A review of literature shows that dairy farming and its contribution to sustainability has gained more intensive scientific interest since 2015. Moreover, livestock management, feed production and management, stakeholder’s management, logistics and supply chain management, and waste management are the sources of environmental adversities associated with dairy farming. Notably, these are human processes developed from commercialization of dairy farming and involve multiple stakeholders across the supply chain. While solutions are embedded within these processes, innovation emerges as a key driver of sustainability and source of opportunities to strengthen sustainability in dairy farming sector and achieve the sustainable development goals.

A feeding study was conducted to evaluate the different diets supplemented with vitamin solution effect on broodstock reproduction, growth performances, and the survival rates of larvae and fry of Pangasius catfish during over-spawning season. The experiment of broodstock cultivation was set up as a diet supplement design with six different diets consisting of vitamin solution, each diet fed to triplicate groups of fish, the stocking density of 10 broodstock fish (07 females and 03 males) per hapa net. Fish larvae and fry were reared in the hatchery for 45 days after hatching to evaluate growth performances and survival rates of fish fingerling. The growth and reproductive performances of breeders fed with different test diets showed that there were differences among the six tested diets (P < 0.05). The highest final body weight (FBW), weight gain (WG), daily weight gain (DWG), specific growth rate (SGR) of broodstock and survival rate of Pangasius fingerlings were found in Treatment 5, which contained 0.6% H-OVN for Pangasius Broodstock mixed with 12.6% algal oil and Treatment 3, which contained 0.6% vitamin premix H-OVN for Pangasius Broodstock compared to other Treatments. With these test diets, the Gonadosomatic index (GSI), relative fecundity index (RFI), fertilized egg, hatching rates of eggs, and survival rate of fingerling ranged between a 6.7–12.8%, 104,267–199,512 eggs/kg, 62.2–93.6%, 43.5–76.2%, and 45.3–66.3%, respectively (P < 0.05). The findings of this study showed that the diet containing 35% CP contents supplemented with 0.6% vitamin premix H-OVN mixed with algal oils showed the highest results in terms of growth, reproductive performance indices, and survival rates of Pangasius catfish fingerling.

Brazil became a major player in the global beef market, after the market liberalization in the 1990’s, and experiencing a substantial development. Nonetheless, the environmental impact of beef production associated with land use and greenhouse gas emissions has been under discussion. The necessity of increased adoption of sustainable technologies, however, may preclude some farmers to keep up to date with technological advances. This article describes the major historical changes in beef farming and how they have been shifting production systems toward a sustainable intensification of grass-fed beef, with likely impacts for farmers. We combined an extensive literature review, public data and our own insights, as senior researchers, to achieve that. The trajectory shown here evidenced the substantial technological development underway in Brazilian beef farming, with strong support of public policies for decarbonizing agriculture. Nonetheless, the pace of this sustainable transition may affect small to medium farmers unable to cope. Our recommendations, therefore, involve a broad program of technical assistance and training on sustainable technologies and other supportive practices, including financial and digital literacy. Additionally, we suggest an alternative credit system, with progressive borrowing allowances to ensure financial resources to support a sustainable and inclusive transition of Brazilian beef farming.

Deuterium is a heavy nonradioactive isotope of hydrogen, having a neutron as well as a proton, making it twice as heavy. It is a natural element, present at 156 parts per million in seawater. The ATPase pumps in the mitochondria utilize proton motive force to drive ATP synthesis, and deuterons damage the pumps, producing a stutter that can cause reactive oxygen release and inefficiencies in ATP synthesis. Cellular metabolism incorporates several novel mechanisms to assure low deuterium content in the mitochondria and other organelles. Nicotinamide adenine dinucleotide (NAD) is a major carrier of deuterium depleted (deupleted) protons to supply the mitochondria. Many enzymes, especially flavoproteins, are able to use proton tunneling to fractionate out deuterium. In this paper, we argue that the amino acid proline is able to trap and sequester deuterium, and that peptidyl prolyl isomerases (PPIases) play a central role in facilitating deuterium trapping in proline-rich proteins, most notably collagen. The endothelial glycocalyx also sequesters deuterium in gelled water lining the blood vessels, creating a battery and promoting low deuterium in the circulation. Excess deuterium promotes cancer growth, and cancer cells release large quantities of lactate via aerobic glycolysis to help reverse deuterium overload, systemically.

Even with 100% certainty of a complete cure for breast cancer (BC), there is still a long way to go toward more efficient treatment. This requires sensitive and timely detection and accurate pre/post-clinical characterizations. Despite the availability of advanced diagnostic tools, many cancer patients lack access to efficient diagnostics that are both highly reliable and affordable. The fluorescence-based optical technique aims to make another significant leap forward in improving patient safety. It offers a convenient operation that reduces healthcare costs compared to visual examination tools (VETs). The primary and metastatic stages of BC consider different cancerous cell lines (MDAs), meaning the highest number of cells in this research (up to 300,000) represents the metastatic stages of BC, and 50,000 represents the primary level of BC developments have been studied based on fluorescence-enhanced photodynamic characterizations. The ability to characterize the fluorescence caused by MDA with 50,000 cells compared to the dominant radiation of MDA with 300,000 cells is emphatic proof of the high potential of fluorescence technique in timely BC detections, specifically before it spreads to the axillary lymph nodes. The specific cell numbers of 50,000 and 300,000 were chosen arbitrarily based on the cultivation of common biological limitations. Comparing the outcomes between 50,000 and 300,000 cells allows for evaluating the fluorescence technique’s diagnostic capability across various stages of breast cancer. This assessment provides valuable insights into the effectiveness of the fluorescence-based characterizing approach in detecting cancerous cells at different stages of the disease. Here, we have assessed fluorescence’s spectral shift and intensity difference as a diagnostic approach to distinguish between cancerous and normal breast cells. This study also presents a two-way structure of the 5-aminolevulinic acid (5-ALA) prodrug and Fluorescein Sodium (FS) effect in BC cell characterization from the perspective of photodynamical procedures and the detection side. 5-ALA induces an accumulation of protoporphyrin IX (PpIX) photosensitizer through a biosynthetic pathway, leading to red radiation of fluorescence measurements depending on different factors, such as temperature, incubation time, added glucose of the culturing medium, as well as photosynthesis processes. The presence and progression of breast cancer can be indicated by elevated levels of Reactive Oxygen Species (ROS), which are associated with the production of PpIX in cells following the administration of 5-ALA. Also, nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) fluorophores are recognized as the main factors for fluorescence emissions at around 420-580 nm emission intervals. Considering the MDA’s high metastatic potential, the impact of 5-ALA on MDA’s cellular morphology and viability has been investigated. The molecular fluorophores are the primary probes to MDA’s cellular photodynamic considerations, allowing this widespread pre/post-clinical approach. The fluorescence signal reduction due to decreased cell viability and increased MDA’s cellular death rate after 24 hours of the 5-ALA-induced staining corresponds to the changes in lipid metabolism enzymes of MDAs cultured at different doses, which could be known as a cell death inducer function. Furthermore, statistical concerns have been studied using PCA multivariate component analysis to differentiate MDA cell lines administrated by 5-ALA.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) continues to be a global threat due to its ability to evolve and generate new subvariants, leading to new waves of infection. Additionally, other coronaviruses like Middle East respiratory syndrome coronavirus (MERS-CoV, formerly known as hCoV-EMC) which first emerged in 2012, persists and continues to present a threat of severe illness to humans. The continued identification of novel coronaviruses, coupled with the potential for genetic recombination between different strains, raises the possibility of new coronavirus clades of global concern emerging. As a result, there is a pressing need for pan-CoV therapeutic drugs and vaccines. After extensive optimization of an HCV protease inhibitor screening hit, a novel 3CLPro inhibitor (MK-7845) was discovered and subsequently profiled. MK-7845 exhibited nanomolar in vitro potency with broad spectrum activity against a panel of clinical SARS-CoV-2 subvariants and MERS-CoV. Furthermore, when administered orally, MK-7845 demonstrated a notable reduction of viral burdens by &gt;6 log orders in the lungs of transgenic mice infected with SARS-CoV-2 (K18-hACE2 mice) and MERS-CoV (K18-hDDP4 mice).

The demand for a more sustainable agriculture, coupled with the need for optimized crop productivity, has driven the use of microorganisms for the biocontrol of diseases and pests, as well as for growth promotion. The use of plant growth-promoting rhizobacteria (PGPR) and plant growth-promoting fungi (PGPF) in Brazilian production systems has become increasingly common, with the number of microbial inoculant registrations in the country growing every year. PGPR and PGPF occupy various niches in the rhizosphere, playing a crucial role in soil nutrient cycling, as well as influencing various plant physiological processes. In this review, we address the main mechanisms used by these microbial agents in growth promotion and the use of strain co-inoculation as a strategy to enhance the efficacy of these products. Subsequently, we conduct an analysis of the available inoculants in Brazil, detailing the microorganisms available for the main Brazilian crops, and the prospects of this market regarding research and development of new products for the coming years based on the current challenges faced.

Bacillus subtilis is a model organism used to study molecular processes in Gram-positive bacteria. Sigma factor B, which associates with RNA polymerase, is one of the transcriptional regulators involved in the cell’s response to environmental stress. Experiments have proven that the amounts of free σB (SigB) are controlled by a system of anti- (RsbW) and anti-anti-sigma (RsbV) factors expressed from the same operon as SigB. Moreover, the phosphorylation state of RsbV is controlled by phosphatases RsbP and RsbU, which directly dephosphorylates RsbV. A set of chemical equations describing the network controlling the levels of free SigB was converted to a set of differential equations quantifying the dynamics of the network. The solution of these equations allowed the simulation of the kinetic behavior of the network and its components under real conditions. In this study, the time series of protein expression measured by mass spectrometry were utilized to investigate the role of the phosphatases RsbU/RsbP in transmitting the environmental signal. Additionally, the influence of kinetic constants and the amounts of other network components on the functioning of the network was investigated. A comparison with the same simulation performed using transcriptomic dataset showed that while the time series between the proteomic and transcriptomic datasets) are not correlated, the results are the same. This indicates that when modeling is done within one dataset, it does not matter whether the data come from the mRNA or protein level. In summary, the computational results based on experimental data provide quantitative insight into the functioning of the SigB-dependent circuit and offer a template for the quantitative study of similar systems.

This review investigates links between post-acute sequelae of SARS-CoV-2 infection (PASC), post-infection viral persistence, mitochondrial involvement and aberrant innate immune response and cellular metabolism during SARS-CoV-2 infection. Advancement of proteomic and metabolomic studies now allows deeper investigation of alterations to cellular metabolism, autophagic processes and mitochondrial dysfunction caused by SARS-CoV-2 infection while computational biology and machine learning have advanced methodologies of predicting virus-host gene and protein interactions. Particular focus is given to interaction between viral genes and proteins with mitochondrial function and that of the innate immune system. Finally, the authors hypothesise that viral persistence may be a function of mitochondrial involvement in sequestration of viral genetic material. While further work is necessary to understand the mechanisms definitively, a number of studies now point to resolution of questions regarding the pathogenesis of PASC.

The key factor that enables pathogenic bacteria to establish successful infections lies largely in their ability to escape the host's immune response and adhere to host surfaces. Vitronectin (Vn) is a multi-domain glycoprotein ubiquitously present in blood and extracellular matrix of several tissues, where it plays important roles as regulator of membrane attack complex (MAC) formation and as mediator of cell adhesion. Vn has emerged as intriguing target for several microorganisms. Vn-binding by bacterial receptors confers protection from lysis resulting from MAC deposition. Furthermore, through its Arg-Gly-Asp (RGD) motif, Vn can bind several host cell integrins. Therefore, Vn recruited to the bacterial cell functions as a molecular bridge between bacteria and host surfaces, where it triggers several host signalling events that could promote bacterial internalisation. Each bacterium uses different receptors that recognise specific Vn-domains. In this review, we update the current knowledge of Vn receptors of major bacterial pathogens, emphasising the role they may play in the host upon Vn-binding. Focusing on the structural properties of bacterial proteins, we provide details on the residues involved in their interaction with Vn. Furthermore, we discuss the possible involvement of Vn adsorption on biomaterials in promoting bacterial adhesion on abiotic surfaces.

Foxtail millet (Setaria italica) is an important cereal crop with rich nutritional value. Distinctness, Uniformity, and Stability (DUS) are the prerequisites for the application of new variety rights for foxtail millet. In this study, we investigated 32 DUS test characteristics of 183 foxtail millet resources, studied their artificial selection trends, and identified varieties that conform to breeding trends. The results indicated significant differences in terms of means, ranges, and coefficients of variation for each characteristic. Correlation analysis was performed to determine the correlations between various DUS characteristics. Principal component analysis was conducted on 31 test characteristics to determine their primary characteristics. By plotting PC1 and PC2, all germplasm resources could be clearly distinguished. Trends in foxtail millet breeding were identified through differential analysis of DUS test characteristics between landrace varieties and cultivated varieties. Based on these breeding trends, optimal solution types for multiple evaluation indicators were determined; weight allocation was calculated, and a specific TOPSIS algorithm was designed to establish a comprehensive multi-criteria decision-making model. Using this model, the breeding potential of foxtail millet germplasm resources was ranked. These findings provided important reference for foxtail millet breeding in future.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has acquired multiple mutations since its emergence. Analyses of the SARS-CoV-2 genomes from infected patients exhibit a bias toward C-to-U mutations, which are suggested to be caused by the apolipoprotein B mRNA editing enzyme polypeptide-like 3 (APOBEC3, A3) cytosine deaminase proteins. However, the role of A3 enzymes in SARS-CoV-2 replication remains unclear. To address this question, we investigated the effect of A3 family proteins on SARS-CoV-2 replication in THP-1 cells lacking A3A to A3G genes. The Wuhan, BA.1, and BA.5 variants had comparable viral replication in parent and A3A-to-A3G-null THP-1-ACE2 cells. On the other hand, the replication and infectivity of these variants were abolished in A3A-to-A3G-null THP-1-ACE2 cells in a series of passage experiments over 20 days. In contrast to previous reports, we observed no evidence for A3-induced SARS-CoV-2 mutagenesis in the passage experiments. Furthermore, our analysis of a large number of publicly available SARS-CoV-2 genomes did not reveal conclusive evidence for A3-induced mutagenesis. Taken together, our studies suggest that A3 family proteins can positively contribute to SARS-CoV-2 replication, however this effect is deaminase-independent.

Functional copy number alterations (fCNAs) are DNA copy number changes with concordant differential gene expression. These are less likely to be bystander genetic lesions and could serve as robust and reproducible tumor biomarkers. To identify candidate fCNAs in neuroendocrine tumors (NETs), we integrated chromosomal microarray (CMA) and RNA-seq differential gene expression data from 31 pancreatic (pNET) and 33 small bowel neuroendocrine tumors (sbNET). Tumors were resected from 47 early disease progression (24 months) patients. Candidate fCNAs that accurately differentiated these groups in this discovery cohort were then replicated using fluorescence in situ hybridization (FISH) on formalin-fixed, paraffin-embedded (FFPE) tissues in a larger validation cohort of 60 pNETs and 82 sbNETs (52 early and 65 late disease progression samples). Logistic regression analysis determined the predictive ability of these biomarkers as well as the assay performance metrics of sensitivity, specificity, and area under the curve. Our results indicate that copy number changes at chromosomal loci 4p16.3, 7q31.2, 9p21.3, 17q12, 18q21.2, and 19q12 may be used as diagnostic and prognostic NET biomarkers. This involves a rapid, cost-effective approach to determine primary tumor site for patients with metastatic liver NETs and to guide risk stratified therapeutic decisions.

'Cv 'Doña María' table grape is a high-quality table grape variety included in the Protected Designation of Origin (PDO) of the European Union "The bagged grape of the Vinalopó." The PDO stipulates that grape clusters must be protected with paper bags from inclement weather and insects, which helps enhance the final grape quality. However, 'Doña María' is a variety prone to high shattering in the late stages of ripening on the vine and during postharvest. Inorganic calcium treatments are one of the most commonly used tools to reduce this disorder, but the translocation of this mineral from veraison onward has been questioned. In this study, five applications were performed, from veraison to harvest, using sorbitol-chelated calcium (0.7 % + 1.0 %), Ca(NO3)2 (Ca) at 0.7% and sorbitol at 1%. It was observed that bagged grapes (not wetted with the solutions) only increased the concentration of total and bound calcium when treated with Sorbitol-Ca. This resulted in reduced berry drop during cultivation and postharvest and improved fruit firmness. Additionally, it reduced grape metabolism indicators such as respiration rate, weight loss, malic acid degradation, prevented abscisic acid (ABA) and malondialdehyde (MDA) accumulation, and favored the accumulation of secondary metabolites such as total polyphenols, increased antioxidant activity, and sugar content. The application of sorbitol-chelated calcium is an effective and safe tool that enhances fruit quality and prevents losses due to shattering during postharvest.

Seasonal precipitation variance significantly alters soil water content, potentially inducing water stress and affecting plant transpiration in semiarid deserts. This study explored the effects of environmental variables and hydraulic conductance on whole-tree transpiration (ET) in Mongolian pines (Pinus sylvestris var. mongolica) across different forest stages in the semiarid deserts of northern China. We measured ET using sap flow in mature (MMP), half-mature (HMP), and young (YMP) Mongolian pine plantations. Measurements included soil-leaf water potential difference (ΔΨ), atmospheric conditions, and soil moisture contents on sunny days, both in dry and wet periods. Seasonally variable rainfall distinctly affected soil moisture, correlating ET with photosynthetically active radiation (PAR) and vapor pressure deficit (VPD). Notable nocturnal sap flow occurred during the growing season. During the dry periods, both stomatal and hydraulic conductance influenced ET, whereas during the wet periods, stomatal conductance primarily regulated it. Discrepancies between predicted and measured ET were noticed: compared to the predicted ET, measured ET was lower during dry periods while higher during wet periods. Hydraulic conductance (KT) increased with tree height (H) and ΔΨ, although tall trees exhibited lower KT rates, suggesting that hydraulic compensation had occurred. This compensation, observed between 11:00 and 13:00, aligned with increased hydraulic resistance during dry periods. Decreasing hydraulic conductance intensified leaf water stress in dry periods, especially during the time when PAR and VPD were heightened, potentially increasing stomatal sensitivity to drought, promoting water conservation and plant survival. A linear relationship between predawn and midday leaf water potentials was noticed, indicating extreme anisohydric behavior across forest stages during both dry and wet periods. Although both stomatal and hydraulic conductance influenced ET during the dry period, MMP and YMP were more susceptible to drought conditions. Understanding these dynamics could help evaluate semiarid desert ecological functions for water conservation amidst uneven seasonal precipitation in Northern China.

Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium that remains a prevalent clinical and environmental challenge. Quorum sensing (QS) molecules are effective biomarkers in pinpointing the presence of P. aeruginosa. This study aimed to develop a convenient-to-use whole-cell biosensor using P. aeruginosa reporters individually encapsulated within alginate-poly-L-lysine (alginate-PLL) microbeads to specifically detect the presence of bacterial autoinducers. The PLL-reinforced microbeads were prepared using a two-step method involving ionic crosslinking and subsequent coating with thin layers of PLL. The alginate-PLL beads showed good stability in the presence of a known cation scavenger (sodium citrate), which typically limits the widespread applications of calcium alginate. In media containing synthetic autoinducers, such as N-(3-oxo dodecanoyl) homoserine lactone (3-oxo-C12-HSL) and N-butanoyl-L-homoserine lactone (C4-HSL) or cell-free supernatants of planktonic or flow cell biofilm effluent of wild P. aeruginosa (PAO1), the encapsulated bacteria enabled a dose-dependent detection of the presence of these QS molecules. The prepared bioreporter beads remained stable during prolonged storage at 4 and -80 °C and were ready for on-the-spot sensing without the need for recovery. This whole-cell biosensor demonstrates the practicality of the encapsulated bioreporter for bacterial detection based on specific QS molecules.

Our study explores the role of cancer-derived extracellular exosomes (EXs), particularly focusing on collagen alpha-3 (VI; COL6A3), in facilitating tumor dissemination and metastasis in epithelial ovarian cancer (EOC). We found that COL6A3 is expressed in aggressive ES2 derivatives, SKOV3 overexpressing COL6A3 (SKOV3/COL6A3), and mesenchymal-type ovarian carcinoma stromal progenitor cells (MSC-OCSPCs), as well as their EXs, but not in less aggressive SKOV3 cells or ES2 cells with COL6A3 knockdown (ES2/shCOL6A3). High COL6A3 expression correlates with worse overall survival in EOC patients, as evidenced by TCGA and GEO data analysis. In vitro experiments showed that EXs from MSC-OCSPCs or SKOV3/COL6A3 cells significantly enhance invasion ability in ES2 or SKOV3/COL6A3 cells, respectively (both, P &lt;0.001). In contrast, ES2 cells with ES2/shCOL6A3 EXs exhibit reduced invasion ability (p&lt;0.001). In vivo, the average disseminated tumor numbers in the peritoneal cavity were significantly greater in mice receiving intraperitoneally injected SKOV3/COL6A3 cells than in SKOV3 cells (p&lt;0.001). Furthermore, mice intravenously (IV) injected with SKOV3/COL6A3 cells and SKOV3/COL6A3-EXs showed increased lung colonization compared to mice injected with SKOV3 cells and PBS (p=0.007) or SKOV3/COL6A3 cells and PBS (p=0.039). Knockdown of COL6A3 or treatment with EXs inhibitor GW4869 or rapamycin-abolished COL6A3-EXs may suppress the aggressiveness in EOC.

Liquid biopsy, a non-invasive diagnosis that examines circulating tumor components in body fluids, is increasingly used in cancer management. An overview of relevant literature emphasizes the current state of liquid biopsy applications in cancer care. Liquid biopsy, particularly circulating tumor DNA (ctDNA), circulating tumor RNAs (ctRNA), circulating tumor cells (CTCs), extracellular vesicles, and other cell-free nucleic acids, offers promising opportunities for early cancer diagnosis, treatment selection, monitoring, and disease assessment. The implementation of liquid biopsy in precision medicine has shown significant potential in various cancer types, including lung cancer, colorectal cancer, breast cancer, and prostate cancer. Advances in genomic and molecular technologies, such as next generation sequencing (NGS) and digital polymerase chain reaction (dPCR) have expanded the utility of liquid biopsy, enabling the detection of somatic variants and actionable genomic alterations in tumors. Liquid biopsy has also demonstrated utility in predicting treatment responses, monitoring minimal residual disease (MRD), and assessing tumor heterogeneity. Nevertheless, standardizing liquid biopsy techniques, interpreting results, and integrating them into clinical routine remain challenges. Despite these challenges, liquid biopsy has significant clinical implications in cancer management, offering a dynamic and non-invasive approach to understanding tumor biology and guiding personalized treatment strategies.

The crosstalk between tumor progression and ferroptosis is largely unknown. Here, we identify malate dehydrogenase 2 (MDH2) as a key regulator of ferroptosis. MDH2 deficiency inhibits hepatocellular carcinoma (HCC) cell growth and promotes sensitivity of HCC cells to RSL3-induced ferroptosis. MDH2 knockdown enhances RSL3-induced intracellular reactive oxygen species (ROS), free iron ions and lipid peroxides levels, leading to HCC ferroptotic cell death which is rescued by Ferrostatin-1 and iron chelator Deferiprone. Importantly, inhibition of HCC cell growth caused by MDH2 deficiency is partially rescued by ferroptosis blockade. Mechanistically, MDH2 resists RSL3-induced ferroptosis sensitivity by dependence on GPX4, which is stabilized by MDH2 in HCC. The protein expression of MDH2 and GPX4 is positively correlated with each other in HCC cell lines. Furthermore, through UALCAN website analysis, we find that MDH2 and GPX4 are highly expressed in HCC samples. These findings reveal a critical mechanism by which HCC evades ferroptosis via MDH2-mediated stabilization of GPX4 to promote tumor progression and underscore the potential of MDH2 inhibition in combination with ferroptosis inducers for the treatment of HCC.

Computational neuroscience has undergone a significant transformation in recent years, driven by the exponential growth of neural data and advancements in data science and machine learning. While traditional theoretical models remain valuable, there is a growing emphasis on integrating data-driven approaches to develop more accurate, biologically plausible, and predictive models of neural function. This shift has led to a new equilibrium in the field, where data-driven model development, machine learning techniques, and hybrid approaches that combine data and theory are increasingly prevalent. In this article, we discuss the evolving landscape of computational neuroscience, highlighting the importance of data-driven methods and the emergence of a more integrative approach that leverages both data and theory to unlock the mysteries of the brain. We also explore the implications of this shift for future research and clinical applications, emphasizing the potential for data-driven computational neuroscience to revolutionize our understanding of neural function and pave the way for new treatments for neurological disorders.

Escherichia coli O157:H7, a Shiga toxin-producing E. coli (STEC) is an important pathogen related to foodborne disease that is responsible for a growing number of outbreaks worldwide and has been detected in processed meats, dairy, and fresh vegetables. Although culturing is the gold standard method for detection of this bacteria, molecular methods based on nucleic acid amplification techniques such as PCR are becoming more common because of their rapidity, sensitivity, and specificity. However, to ensure reliable results among the several alternative PCR protocols (e.g., commercial kits and reference methods), different measurement assurance tools, including validated methods, reference materials, and proficiency tests among others, are required. Herein, we present a digital PCR method validation for E. coli O157:H7 detection and quantification using seven gene sequences; this method quantified nucleic acids from different E. coli serotypes, with a detection range between 6.6 to 7,900 copies/µL and a repeatability standard deviation over the concentration range of between 1% to 13.6%. The relative standard uncertainty was 3.5%–14.6%, and the detection limit was 0.27 copies/µL. Subsequently two batches of a candidate reference material based on E. coli O157:H7 genomic DNA were then produced and characterized for evaluation of copy number concentration with the validated dPCR method, with assigned values of 164,770 ± 9,251 and 172 ± 9 copies/μL. Thus, this study demonstrated the development a validated method and reference material for dPCR and qPCR detection of E. coli O157:H7, a key STEC responsible for food poisoning.

(1) Background: Heat stress detrimentally restricted the economic in dairy farming production, therefore, this study was designed to investigate how automatic spraying method on alleviating heat stress on cows. (2) Methods: A total of 1208 multiparous dairy cows were randomly allocated into 6 barns, three barns were equipped with automatic sprinklers (SP), each barn was considered as a replicate. The other three barns were considered as control treatments (CON). Each barn was considered as a replicate. (3) Results: body temperature and milk somatic cell count were significantly decreased, while DMI, milk yield, and milk fat content significantly increased with spraying treatment. ICR was improved from 30% to 35%. Rumen fermentation was enhanced by the increased levels of total VFA, acetate, propionate, and butyrate with the spraying treatment. Rumen microbiota results showed at the phylum level, rumen Fibrobacters abundance significantly increased by the spraying treatment. At the genus level, Eubacterium, Shuttleworthia, Saccharofermentans, Lachnospira, Pseudobutyrivibrio, Selenomonas, and Succinivibrio abundance were significantly increased, while Ruminococcaceae and Rikenellaceae abundance were significantly decreased in the rumen with spraying treatment. (4) Conclusion: this study demonstrated automatic spraying modulated the rumen microbiota composition and fermentation function, and effectively meliorated side-effects of heat stress on dairy cows.

Photosystem I (PSI) serves as a model system for studying fundamental processes such as electron transfer (ET) and energy conversion, which are not only central to photosynthesis but also have broader implications for bioenergy production and biomimetic device design. In this study, we employed electron paramagnetic resonance (EPR) spectroscopy to investigate key light-induced charge separation steps in PSI isolated from several green algal and cyanobacterial species. Following photoexcitation, rapid, sequential ET occurs through either of two symmetric branches of donor/acceptor cofactors embedded within the protein core, termed the A and B branch. Using high-frequency (130 GHz) time-resolved EPR (TR-EPR) and deuteration techniques to enhance spectral resolution, we observed that at low temperatures prokaryotic PSI exhibits reversible ET in the A branch and irreversible ET in the B branch at low temperatures, while PSI from eukaryotic counterparts displays either reversible ET in both branches or exclusively in the B branch. Furthermore, we observed a notable correlation between low-temperature charge separation to the terminal [4Fe-4S] clusters of PSI, termed FA and FB, as reflected in the measured FA/FB ratio. These findings enhance our understanding of the mechanistic diversity of PSI's ET across different species and underscore the importance of experimental design in resolving these differences. Though further research is necessary to elucidate the underlying mechanisms and the evolutionary significance of these variations in PSI charge separation, this study sets the stage for future investigations into the complex interplay between protein structure, ET pathways, and the environmental adaptations of photosynthetic organisms.

Aquaculture contributes to the sustainable development of food security, marine resource conservation, and economy. Shifting aquaculture feed from fish meal and oil to terrestrial plant-derivatives may result in cost savings. However, many carnivorous fish cannot be sustained on plant-derived materials, necessitating the need for the identification of important factors for farmed fish growth and to investigate whether components derived from terrestrial plants can be used in feed. Herein, we focused on the carnivorous fish leopard coral grouper (P. leopardus) to identify the essential growth factors and clarify their intake timing from feeds. Furthermore, we evaluated the functionality of starch, which are easily produced by terrestrial plants. Results reveal that carbohydrates, which are not considered essential for carnivorous fish, can be introduced as a major part of artificial diet. The development of artificial feed using starch offers the possibility of increasing the growth of carnivorous fish in aquaculture.

The spread of multidrug-resistant mycobacterium strains requires the development of new approaches to combat diseases caused by these pathogens. For that, photodynamic inactivation (PDI) is a promising approach. In this study, a tricarbocyanine (TCC) is used for the first time as a near-infrared (740 nm) activatable PDI photosensitizer to kill mycobacteria with deeper light penetration. For better targeting, a novel tricarbocyanine dye functionalized with two trehalose units (TCC2Tre) is developed. The photodynamic effect of the conjugate against mycobacteria, including Mycobacterium tuberculosis, is evaluated. Under irradiation, TCC2Tre causes more effective killing of mycobacteria compared to the photosensitizer without trehalose conjugation, with 99.99% dead vegetative cells of M. tuberculosis and M. smegmatis. In addition, effective photoinactivation of dormant forms of M. smegmatis is observed after incubation with TCC2Tre. Mycobacteria treated with TCC2Tre are more sensitive to 740 nm light than the Gram-positive Micrococcus luteus and the Gram-negative Escherichia coli. For the first time, this study demonstrates the possibility of in vitro PDI of mycobacteria including the fast-growing M. smegmatis and the slow-growing M. tuberculosis using near-infrared activatable photosensitizers. These findings are useful for the development of new efficient alternatives to antibiotic therapy.

Background: The study was conducted to investigate if the mRNA vaccine technology could be adapted for the ectothermic vertebrate Atlantic salmon (Salmo salar). The lipid nanoparticle (LNP) technology has been developed and optimized for mRNA vaccines in mammals, stabilizing mRNA and facilitating delivery into cells. However, its utility at the temperature and specific biological environment in ectotherms remains unclear. In addition, it is unknown if modified mRNA containing non-canonical nucleotides can correctly translate in salmonid cells. Methods: We used an mRNA transcript coding for enhanced green fluorescence protein, flanked by the untranslated regions of the hemagglutinin-esterase gene of infectious salmon anemia virus, and a 120-base-long poly(A) tail. The mRNA was generated by in vitro transcription where uridine residues were replaced with N1-methyl-pseudouridines, and then encapsulated in LNPs. Results: When transfected into the salmonid cell line CHH-1, the mRNA-LNP construct induced expression of EGFP. Furthermore, when mRNA-LNPs were injected intramuscularly into salmon, in vivo protein expression was demonstrated by immunohistochemistry. EGFP was observed in cells infiltrating the space between the muscle cells in a focal inflammatory response. Conclusion: The results indicate that the N1-methyl-pseudouridine modified mRNA encapsulated in LNPs can be used to express antigens of interest in salmonid fish.

Probiotics in cosmetics is a new and burgeoning area of research attracting attention from cosmetic manufacturers and customers looking for natural or additional alternatives in their skincare regimens. Probiotics not only promote beneficial microbiomes to improve skin health but can also modulate the visual, topographical, and mechanical attributes to improve skin quality. This study was conducted in healthy adults to determine the effect of a topical serum formulation containing the live probiotic Micrococcus luteus Q24 on several key cosmetic skin quality parameters and its beneficial impact on the modulation of the skin microbiome. Quantitative changes in various skin parameters were measured using a skin analyzer device and skin swabs were analysed using whole genome sequencing to monitor microbial diversity and levels of probiotic colonisation. Compared to the baseline, a significant reduction in the pore, spots, wrinkles, and impurities scores; and an increase of 101% in the hydration scores were observed. Additionally, 45-80% of participants showed a decrease in pores, spots, wrinkles, and impurities and 90% of participants showed an increase in hydration after 25 days of probiotic serum application. The WGS analysis of the skin swab samples showed a significant increase in the relative abundance of M. luteus Q24. The results from this study indicated that topical application of serum-containing probiotic M. luteus Q24 offers the benefit of improving skin health quality.

Pumpo is a Simmental breed and an essential livestock resource in the nucleus genetic cattle of Peru. This study provides a draft genome sequence of a top bull using a de novo assembly approach on the Illumina Novaseq X platform, yielding 208 GB of raw sequencing data with 150 bp paired-end reads. The final genome assembly resulted in a size of 2.06 Gb with an N50 contig length of 108 Mb and a completeness of 95.7% according to BUSCO analysis. A total of 973,925 simple sequence repeats (SSRs) were identified, with a predominance of mononucleotide repeats. The genome showed low heterozygosity (0.568%) and moderate repeatability (11.5%), aligning with other Bos taurus genomes. Reference-guided scaffolding improved the assembly quality significantly, producing an N50 scaffold value of 108 Mb. The SSR analysis of the Pumpo genome identified 973,925 SSRs with a frequency of 2,808 SSRs per kilobase, predominantly mononucleotide repeats, and 85,453 found in compound formations. Obtaining knowledge of the genome of a breeding Simmental bull is essential to optimize breeding programs and improve productivity.

Many anti-tumor effects of group-specific component-derived macrophage-activating factors (GcMAFs) have been reported; however, the specific mechanisms remain unclear. Controlling tumor-associated macrophages (TAMs) in the tumor microenvironment is essential for cancer treatment. This study assessed the role of GcMAF in macrophage activation, elucidated the mechanisms by which it exerts its anti-tumor effects, and determined its effects on TAMs in the tumor microenvironment. GcMAF-stimulated RAW264.7 macrophages and EMT6 breast tumor cells were co-cultured in a 0.4-µm pore cell culture insert, and gene and protein expression and cell viability were evaluated. DNA microarray analysis of GcMAF-stimulated RAW264.7 cells was conducted. The induction of M2 RAW264.7 cells by interleukin (IL)-4 and IL-13 was analyzed. GcMAF stimulation increased the tumor necrosis factor-α and inducible nitric oxide synthase mRNA and protein levels in RAW264.7 cells but decreased the viability of co-cultured EMT6 cells. These results were confirmed in the M2 RAW264M2.7 cells, suggesting that GcMAF exerts anti-tumor effects by inducing the differentiation of macrophages into the M1 type and reprogramming M2 macrophages to the M1 type. The anti-tumor activity of GcMAF via M2-to-M1 macrophage reprogramming could aid in developing novel cancer immunotherapies.

In the course of our ongoing research targeting the identification of potential biocontrol agents from entomopathogenic fungi (EPF), we explored a solid-state rice fungal extract of Blackwellomyces roseostromatus BCC56290 derived from infected lepidopteran larvae. Chemical and biological prospections afforded four unprecedently reported natural products differentiated into one dimeric naphthopyran bioxanthracene ES-242 derivative (1) and three cyclodepsipeptides (2-4) in addition to two known cyclodepsipeptides, cardinalisamides B (5) and C (6). Chemical structures of the isolated compounds were elucidated through comprehensive 1D/2D NMR and HR-ESI-MS data together with comparisons to the reported literature. The absolute configuration of the isolated cyclodepsipeptide was determined using Marfey’s method. All isolated compounds were assessed for their antimicrobial, cytotoxic and nematicidal activities with some compounds revealed significant activities.

The growing interest in Kv7.2/7.3 agonists originates from the involvement of these channels in several brain hyperexcitability disorders. In particular, Kv7.2/7.3 mutants have been clearly associated with epileptic encephalopathies (DEE) as well as with a spectrum of focal epilepsy disorders, often associated with developmental plateauing or regression. Nevertheless, there is a lack of available therapeutic options, considering that retigabine, the only molecule used in clinic as broad-spectrum Kv7 agonist, has been withdrawn from the market in the late 2016. This is why several efforts have been made both by both academia and industry in the search for suitable chemotypes acting as Kv7.2/7.3 agonists. In this context, in silico methods have played a major role, since the precise structures of different Kv7 homotetramers have been only recently disclosed. In the present review the computational methods used for the design of Kv.7.2/7.3 small molecule agonists and the underlying medicinal chemistry are discussed in the context of their biological and structure-function properties.

Mediterranean countries are a cauldron of cultural exchange, with a strong emphasis on wild plants in cuisine traditions. Many of these plants belong to the family Apiaceae. The common climate determines the common range of distribution. While many plants have wide distribution, the range of distribution of others is restricted to Western Mediterranean or North Africa. This review investigates wild plants from the family Apiaceae traditionally used as food in 13 study sites - 11 countries in the Mediterranean and adjacent territories - the mainland and 3 islands. The aim is to trace patterns of native distribution versus consumption. As a result, 81 wild umbellifers are listed, traditionally used as food. Their consumption and distribution patterns are described and discussed. Interestingly in 8 of the 13 study sites (61.5%) are recorded 50 plants (66.7% of all wild umbellifers, traditionally used as food) which are consumed in only one particular country. These are as follows: 8 taxa in Morocco, 9 taxa in Spain, 2 taxa in Sicily, 3 taxa in Bulgaria 3 taxa in Crete, 8 taxa in Armenia, 14 taxa in Turkey, and 3 taxa in Jordan. However, these 50 restrictedly consumed plants are distributed in more than one country (except 15 taxa, which are endemics). Many of the plants that are used in certain countries are not consumed by the neighboring people. The results of the two statistical tests, namely Jaccard index and heatmap clustering (double dendrogram) are discussed. The presence of an outlier, such as Bulgaria, which shares borders, history, and culture with Greece and Turkey, emphasizes the importance of local climate on plant distribution and consumption over cultural interactions. The same was observed for some pairs of countries, such as Spain and Morrocco and Turkey and Armenia, although they had the highest number of common plants, that are both distributed and consumed as food.

Acting as the most abundant and widely distributed volatile secondary metabolites in plants, terpenoids play crucial roles in diverse physiological regulations and metabolic processes. Terpene synthases occupy a decisive proportion in determining the composition and diversity of terpenoids; though their regulatory effects have been extensively investigated across various plant species, limited studies have focused on the upstream transcriptional regulation of terpene synthases. In this study, we unveil linalool as the predominant volatile compound in Freesia hybrida flowers, demonstrating a gradual release pattern during flower blooming. In the context of the transcriptome, a typical MYB transcription factor, FhMYB108, was screened based on digital expression profile correlation analysis and homologous gene comparison. FhMYB108 is capable of regulating the expression of terpene synthase FhTPS1, and both their expression levels exhibit a gradual increase concomitant with flower opening. Moreover, transcriptional regulation and transient expression assays revealed that FhMYB108 exerts a stimulatory effect on the transcription of A. thaliana AtTPS14, while no significant increase in AtTPS14 expression was observed upon stabilization of FhMYB108 in Arabidopsis. Investigate its reason, the highly expressed AtMYC2 in A. thaliana can interact with FhMYB108 to suppress the activation of AtTPS14 by FhMYB108. The present study not only elucidated the regulatory mechanism underlying linalool synthesis, but also discovered the synergistic effect of MYB and bHLH transcription factors in governing the biosynthesis of volatile terpenoids.

Phytochemicals have a long and successful history in drug discovery. With recent advancements in analytical techniques and methodologies, discovering bioactive leads from natural compounds has become easier. Computational techniques like molecular docking, QSAR modelling and machine learning, and network pharmacology are among the most promising new tools that allow researchers to make predictions concerning natural products' potential targets, thereby guiding experimental validation efforts. Additionally, approaches like LC-MS or LC-NMR speed up compound identification by streamlining analytical processes. Integrating structural and computational biology aids in lead identification, thus providing invaluable information to understand how phytochemicals interact with potential targets in the body. Emerging computational approach is machine learning involving QSAR modelling and deep neural networks that interrelate phytochemical properties with diverse physiological activities such as antimicrobial or anticancer effects.

DNA-methylation clocks inform not only about chronological but also biological age, which brings a high resolution and precise understanding of age-related pathology and physiology. Attempts based on transcriptomic and epigenetic approaches arise as integrative biomarkers linking the quantification of stress response with a given fitness trait and may help to identify biological age markers, also considered welfare indicators. In gilthead sea bream, targeted gene expression and DNA-methylation analyses in white skeletal muscle proved sirt1 as a reliable marker of age-mediated changes of energy metabolism. To complete the list of welfare auditing biomarkers, wide-analyses of gene expression and DNA-methylation in one- and three-year old fish were combined. After discriminant analysis, 668 differentially expressed transcripts were matched with those containing differentially methylated (DM) regions (14,366), and 172 were overlapping. Through enrichment analyses and selection, two sets of genes were retained: 33 showing an opposite trend for DNA-methylation and expression, and 57 down-regulated and hypo-methylated. The first set displayed apparently a more reproducible and reliable pattern and 10 multifunctional genes with DM CpG in regulatory regions (sirt1, smad1, ramp1, psmd2 – up-regulated; col5a1, calcrl, bmp1, thrb, spred2, atp1a2 – down-regulated) were deemed candidate biological age markers for an improved welfare auditing in gilthead sea bream.

The initial valves of two Cymbella species are observed under the scanning electron microscope and the perizonium ultrastructure of Cymbella is revealed for the first time. The perizonium is composed of alternate nodes and internodes and lacks transverse perizonium bands. Four new species, Cymbella apiculatophora sp. nov., C. hunanensis sp. nov., C. juglandis sp. nov. and C. menyuanensis sp. nov., are described using light and scanning electron microscope from epilithon samples collected in rivers from Hunan and Qinghai Provinces, China. Cymbella menyuanensis is a typical Cymbella species that closely resembles species in the group around C. cymbiformis Agardh, the lectotype species of the genus. Cymbella apiculatophora is similar to C. sinensis Metzeltin & Krammer while Cymbella hunanensis is closer to the C. hustedtii Krasske group. The last species, C. juglandis, has a cymbelloid valve outline, obscured intermissio, internal occlusions of areolae, dorsally deflected distal raphe fissures, and a divided APF at each apex, and does not appear to belong to any group. In addition, new observations on C. cf. excisiformis Krammer and C. hustedtii are reported. The current concept of the genus Cymbella does not represent a monophyletic group as shown by molecular phylogenetic analyses. However, these analyses are still at the preliminary stage and are not yet sufficient to support a complete revision of the genus. Thus, although extremely diverse ultrastructural features are observed in the six Cymbella species investigated in this paper, we prefer to keep them within Cymbella at this moment for the sake of nomenclatural stability.

The ethylene-regulated hypocotyl elongation of Arabidopsis thaliana's involves many transcription factors. The specific role of MYC transcription factors in ethylene signal transduction is not completely understood. The results here revealed that two MYCs, MYC2 and MYC3, act as negative regulators in ethylene-suppressed hypocotyl elongation. Etiolated seedlings of the lost-of-function mutant of MYC2 or MYC3 were longer than wild type seedlings. Single- or double-null mutants of MYC2 and MYC3 displayed an enhanced response to ACC(1-aminocyclopropane-1-carboxylate), the ethylene precursor, compared to wild type seedlings. MYC2 and MYC3 directly bind to the promoter zone of ERF1, suppressing its expression. Additionally, EIN3, a key component in ethylene signaling, interacts with MYC2 or MYC3 and suppresses their binding to ERF1’s promoter. MYC2 and MYC3 play crucial roles in the ethylene-regulated expression of functional genes. The results revealed these transcription factors’ novel role and functional mechanism in ethylene signal transduction.

Subacute rumen acidosis (SARA) is a prevalent issue in intensive livestock farming, particularly associated with high-concentrate diets. This study investigates the prevalence and impact of SARA in Greek dairy sheep farming and explores the use of computerized rumen colorimetry as a management and diagnostic tool for SARA in dairy sheep farms. Forty-two dairy sheep flocks were monitored regularly for rumen pH, milk composition, and milk yield over an approximately 9-month milking period. Computerized Rumen Mucosal Colorimetry was applied to 280 culled, aged ewes from these farms, with rumen wall samples taken for histological examination. SARA cases were identified in 19 farms (45%, n=48). Farms with SARA cases had lower milk fat levels, although milk yield was higher in these farms, while milk protein levels did not differ based on the SARA status of the farms. In culled ewes, rumen color was significantly associated with the farm's SARA status. Additionally, ewes from farms with more SARA cases exhibited increased thickness in the ruminal epithelium layers, particularly in the non-keratinized and total epithelium layers. In conclusion, SARA is a common disorder in the Greek dairy sheep industry, lowering the fat content of milk. The study suggests that computerized rumen epithelium colorimetry in aged culled ewes shows promise as a diagnostic tool for SARA in dairy sheep farms.

CRISPR/Cas9 technology is expected to offer novel genome editing-related therapies for various diseases. We previously showed that an adenovirus vector (AdV) possessing eight expression units of multiplex guide RNAs (gRNAs) was obtained with no deletion of these units. Here, we attempted to construct “all-in-one” AdVs possessing expression units of four and eight gRNAs with Cas9 nickase. We expected this to be difficult because extremely high copies of viral genomes during replication may cause severe off-target cleavages of host cells and induce homologous recombination. However, four units in the all-in-one AdV genome were maintained completely intact. For all-in-one AdV containing eight gRNA units, we shortened the U6 promoter of the gRNA expression units and enlarged the E3 deletion in the vector backbone to shorten the AdV genome within the adenovirus packaging limits. The final size of the all-in-one AdV genome containing eight gRNA units still slightly exceeded the reported upper limit. Nevertheless, approximately one-third of the eight units remained intact even upon preparation for in vivo experiments. Although the genome editing efficiency unexpectedly decreased upon enlarging the E3 deletion, our results suggested that all-in-one AdVs containing four and eight intact gRNA units could be obtained if the problems caused by the excessive size of the vector genome are solved.

Keywords: Endodontic microsurgery; Root canal treatment; Isthmus preparation; Short-term outcomes

A fully automated bacteria whole genome sequencing (WGS) assay was evaluated to characterize Mycobacterium tuberculosis (MTB) and non-tuberculosis Mycobacterium (NTM) clinical isolates. Results generated were highly reproducible with 100% concordance in species and sub-lineage classification, and 92% concordance between antimicrobial resistance (AMR) genotypic and phenotypic profiles. These findings demonstrate that a fully automated WGS assay, with a short turnaround time of 24.5 hours, provides timely and valuable insights into MTB outbreak investigation while providing reliable genotypic AMR profiling consistent with traditional antimicrobial susceptibility tests (AST). This study establishes a favorable proposition in the adoption of an end-to-end fully automated WGS solutions for decentralized TB diagnostics, thereby aiding in WHO’s vision of tuberculosis eradication.

For the World Health Organization, and specifically for the International Coordination Committee, the need to bring forward discussions on non-clinical trials in human models, such as vaccine trials in pregnant women, with the aim of demonstrating immunity in newborns, has been addressed. This literature review seeks to investigate the relationship between mothers and newborns in terms of the transfer of IgG antibodies against SARS-CoV-2. Most of the literary evidence shows that the substantial transfer of transplacental and lactational antibodies to infants confers protection even when the baby is exposed to the disease. However, accurate and conclusive evidence on the safety and efficacy of COVID-19 vaccines during pregnancy will be a key factor in facilitating the decision-making process for pregnant women to ensure the safety of mother and baby.

C. albicans Dfg5 and Dcw1 are homologous cell wall alpha-1,6-mannosidases with important functions. Our past studies have shown that Dfg5 and Dcw1 function in cell wall biogenesis via cross-linking of glycoproteins into the cell wall, thus playing a key role in cell wall integrity. Additionally, Dfg5 and Dcw1 are required for hyphal morphogenesis. However, the exact functions of Dfg5 and Dcw1 in cell wall integrity, hyphal morphogenesis, and pathogenesis were not known. In this study, we determined the relation of Dfg5 and Dcw1 with Hog1 MAPK, that plays a key role in cell wall integrity via regulation of chitin synthesis in C. albicans. Additionally, we also determined the effect of dfg5 and dcw1 mutations on gene expression of transcriptional regulators of hyphal morphogenesis. Furthermore, we determined the effects of dfg5 and dcw1 mutations on pathogenesis in a mouse model of oral candidiasis. Our results demonstrate that dfg5 and dcw1 mutations, as well as hog1 knock-out mutation result in dysregulation of chitin synthesis resulting in a cell separation defect. The heterozygous and conditional mutations of dfg5 and dcw1 result in decreased levels of Cst20, a positive regulator of hyphal morphogenesis. However, mutations of dfg5 and dcw1 mutations resulted in increased levels of all the five negative regulators of hyphal morphogenesis – Tup1, Nrg1, Mig1, Rbf1 and Rfg1. However, Tup1 levels were significantly higher than other negative regulators indicating that Dfg5 and Dcw1 function in hyphal morphogenesis by repression of Tup1. Finally, dfg5 and dcw1 mutations affected the ability of C. albicans to cause oral candidiasis in mice. Thus, cell wall glycosidases, Dfg5 and Dcw1, are required for virulence and pathogenesis and represent novel drug targets.

The current design of irrigation and fertilization systems often depends on a single index, leading to irrational systems due to the lack of a comprehensive multi-index evaluation. The aim of this study is to optimize the irrigation and nitrogen fertilizer application levels of spring maize using the TOPSIS method, in order to achieve a balance between growth characteristics, yield, water use efficiency, and soil nitrogen content. In the typical semi-arid region of Northeast China, through precise control experiments from 2022 to 2023, we adopted a two factor quadratic saturation D-optimal design method to study the effects of different irrigation amounts (145.40, 271.70, 348.20, 436.20 mm) and nitrogen fertilizer application amounts (34.80, 185.90, 277.40, 382.80 kg·hm-2) on spring maize. Results indicate that increasing both irrigation and nitrogen application rates can enhance dry matter accumulation by 15.17% to 32.70%. The impact of irrigation and fertilization on the net photosynthetic rate (Pn) of spring maize was found to be greater for irrigation amount than nitrogen application, particularly at 9:00 am and 13:00 pm, and slightly less so at 11:00 am and 15:00 pm. Concurrently, there was a significant increase in total nitrogen (TN1 by 20.85% for 0-20 cm soil layer, TN2 by 33.33% for 20-40 cm soil layer) and alkali-hydrolyzed nitrogen (AHN1 by 14.65% for 0-20 cm, AHN2 by 28.86% for 20-40 cm). Yields improved by 12.02% to 44.09%, and water use efficiency (WUE) saw an increase ranging from 20.08% to 140.07%. The optimal water and fertilizer management mode for spring maize SBDI (shallow buried drip irrigation) in semi-arid areas was determined through comprehensive analysis using TOPSIS entropy weight method. When the irrigation amount is 436.20 mm and the nitrogen fertilizer application amount is 277.40 kg·hm-2, it can significantly promote the accumulation of dry matter, yield, water use efficiency, photosynthetic characteristics, and soil nitrogen content of spring maize. This study provides a theoretical basis for the practical application of SBDI water fertilizer coupling technology for spring maize.

Mango (Mangifera indica L.) is an allotetraploid (2n = 4X= 40) drupe fruit and has high nutritional value belongs to genus Mangifera and family Anacardiaceae. Mango cultivars are used with worldwide acceptance to pharmacological, ethnomedical, and phytochemical industries. Assessment of the genetic distinctiveness of a cultivar through morphological descriptors is an important tool for both the registration and the protection. New mango genotypes have been improved using valuable diverse germplasm resources to ensure food security. DNA fingerprinting based simple sequence repeats (SSR)-markers have been the most broadly used, effective and accurate in evaluation of genetic characterization of a cultivar. Molecular breeding is an effective source of genetic gain after improvement of fruit trees using marker assisted genomic selection. Total genomic DNA (gDNA) was generated using CTAB method from each cultivar. The most effective 50 hyper-variable SSR markers were selected. Highly specific DNA fingerprints were identified in the candidate line ‘Azeem Chaunsa’ compared with three standard cultivars using SSR-PCR. An agglomerative hierarchical clustering method was used to construct dendrogram based on the UPGMA clustering method. Cultivar identification diagram (CID) was constructed to evaluate association among standard cultivars and Azeem Chaunsa. Our results showed that SSR markers could efficiently assess genetic diversity in mango. The genetic similarity coefficients were recorded between the cultivars of mango ranged from 0.49 to 0.67. CID results concluded that cultivar ‘Azeem Chaunsa’ varied significantly from the check cultivar, Sindhri (46.2%), S.B Chaunsa (45%) and Sufaid Chaunsa (46.7%). The results obtained in this study will orient cultivar identification strategies for a successful future.

In our previous papers, we demonstrated that inflammation and aging are the common roots of cancer and Alzheimer’s disease (AD). In both diseases, there is an inhibition of the mitochondria. In cancer, the alkaline intracellular pH (pHi) is associated with cell proliferation; acidic pHi causes apoptosis in AD. This difference is because cancer feeds on chemically neutral glucose, while neurons feed on acidic lactic acid. Increased uptake of lactic acid is responsible for acidic pH and cell death. Similarly, to AD, inflammation is responsible for metabolic shifts in age-related macular degeneration (AMD). In AD, there is hyperosmolarity responsible for increased lactic secretion by glial cells. Increased lactic secretion will cause neo-angiogenesis and neural cell death. Drugs increasing hyperosmolarity (Polyethylene Glycol) cause neo-angiogenesis and drusen-like structures in rodents. The link between AMD and inflammation is reinforced by the fact that treatments aiming at restoring mitochondrial activity, such as lipoic acid and/or methylene blue, have been experimentally shown to be effective in each set of diseases. The role of osmolarity has been demonstrated in the pathologies of the anterior segment of the eye, such as dry eye, corneal ulceration, cataracts, and glaucoma. The role of increased osmolarity in age-related macular degeneration (AMD) has been largely overlooked. We herein suggest that metabolic shift, inflammation, and hyperosmolarity are key players in the pathogenesis of AMD.

The Japanese Genji firefly Nipponoluciola cruciata is famous for geographic variation in flash pattern. Such geographic variation has also been well studied in terms of ecology and molecular phylogeny. However, there are very few studies on geographic variation in morphology of this species. This study focused on morphological characteristics of males of this species in Yamanashi and Gunma Prefectures separated by the Kanto Mountains in central Japan. Previous studies have shown that this species in the two prefectures exhibits different genetic features as well as different flash patterns. This study aimed to explore morphological characteristics of males of this species and performed multivariate analysis using measurements previously published in the literature. As a result, allometric analysis between body length and elytra width suggested that this species exhibits different allometric patterns between the two prefectures. Moreover, cluster analysis of measurements of genitalia suggested that this species is completely separated into two different groups between the two prefectures. These results suggest the importance of further morphological studies to clarify the divergence of this species.

African swine fever virus (ASFV), a highly contagious pathogen characterized by a complex structure and a variety of immunosuppression proteins, causes hemorrhagic, acute, and aggressive infectious disease that severely injure the pork product and industry. However, there is no effective vaccine or treatment. The main reasons are not only the complex mechanisms that lead to immunosuppression, but also the unknown functions of various proteins. This review summarizes the interaction between ASFV and host immune system, along with the involvement of virulence related genes and proteins, as well as the corresponding molecular mechanism of immunosuppression of ASFV, encompassing pathways such as cGAS-STING, NF-κB, JAK/STAT, apoptosis, and other modulation. The aim is to summarize the dynamic process during the ASFV infection and entry into host cell, provide a rational insight into development of vaccine and a better clear knowledge of how ASFV impacts host.

Background: The accelerated ageing of the world's population will lead to an increase in the number of older persons in the workforce. Computerized Cognitive Training (CCT) is effective in improving cognitive outcomes, but its benefits for older workers remain controversial. We investigate the real-world efficacy of CCT in the workplace, focusing on employees aged 50+ years from a public sector agency. Methods: Case managers (N = 82) were randomized to either Intervention group (24 40-minute CCT sessions two times per week) or waiting list passive Control group. Cognitive ability, wellbeing, job satisfaction, and productivity outcome measures were collected assessed before and after CCT or comparable Control wait time. Results: Participants undergoing CCT improved on a task of executive functioning (p = 0.04). There was a trend toward change in work productivity after CCT (p = 0.09) with the Control group showing a significant decrease (p = 0.02), while the Intervention group remained stable. Conclusions: CCT during office hours has a positive effect on cognition and well-being without affecting the productivity among white-collar office workers. CCT could be considered as an intervention to support the older workforce in managing the cognitive and behavioral challenges of changing workplace demands.

The study involved a comparison of the chemical, physical, microbiological, and functional attributes of must extracted from Solaris cultivar grapes cultivated under both conventional and organic farming systems. This study aimed to determine the influence of cultivation methods on various must properties, including the levels of health-promoting polyphenols and health-threatening mycotoxins and pesticide residues. It was observed that the organic grapes hosted a greater diversity and quantity (OTUs) of bacteria and fungi. The predominant bacteria were Sphingomonas (with similar numbers in both crops) and Massilia (more abundant in grapes from the conventional crop). These two bacterial groups collectively accounted, on average, for about 40% of all OTU sequences detected. Lower levels of bacteria of the genera Hymenobacter and Pseudomonas and others colonized the grapes. Among the fungi, Erysiphe and Aureobasidium were dominant, comprising about 50–70% of all detected taxa. Notably, Erysiphe was predominantly found in conventionally grown grapes, while Aureobasidium, Mycosphaerella, and Botryotinia were present in comparable quantities in fruit from both types of crops. No mycotoxins were detected in the must or marc, despite the presence of genes responsible for aflatoxin and ochratoxin biosynthesis in both types of grape juice. The organic must exhibited significantly higher levels of polyphenols and displayed improved antioxidant properties and technological characteristics. Moreover, sulfur and copper used in the protection of the organic plantation passed from the fruit surface into the must. Also, pesticide residues, namely cyprodinil and fludioxonil from conventional cultivation, were detected in the must.

Rice blast is the most harmful disease caused by Magnaporthe oryzae, leading to yield loss. The aim of the work is to improve resistance of rice to blast by introducing and pyramiding genes using conventional breeding technique and modern MAS analysis. Pyramiding is the combination of several resistance genes in one genotype, in this case it improves the resistance of rice to pathogens. MAS analysis revealed that 3 out of 4 studied domestic high-yielding rice cultivars (Bakanasski, Aisaule and Aru) contain 1 blast resistance gene (Pi-2). It was discovered 7 pyramidal lines with the introduction of a combination of 2 blast resistance genes (Pi-1 and Pi-ta) into 6 hybrids and 3 genes (Pi-1, Pi-33 and Pi-ta) into 1 line. Phytopathological test of local cultivars and pyramidal lines of rice showed that 3 out of 7 pyramidal lines have moderate resistance: 2 lines (F2 Bakanasski/7667 (var. vulgaris Koern.) and F2 Aisaule/7664 (var. italica Alef.)), containing 2 resistance genes (Pi-1 and Pi-ta) and 1 line – F2 Aisaule/7689 (var. zeravschanica Brsch.), carrying 3 genes (Pi-1, Pi-33 and Pi-ta), while the local cultivars Bakanasski, Aisaule and Aru are susceptible. As a result, the blast resistance of rice was improved by creating pyramidal lines. Pyramided lines can be used for germplasm exchange and in rice breeding programs to improve blast resistance in rice.

Probiotics are becoming more and more popular in the growing of fin and shellfish because these species are consumed worldwide and because different techniques are employed to maximize the productivity and efficiency of fin and shellfish. Probiotic Bacillus is one of the many types of probiotics that are used, but it stands out due to its superior qualities. For instance, because of its ability to sporulate, it can survive in harsh environments, produce antimicrobial substances, and is safe to feed to fish. The different species of Bacillus used in the farming of fin and shell fish were discussed in this review, along with the benefits of using Bacillus spp. as a good substitute in sustainable aquaculture to improve feed utilization, immune system response, stress adaptation, resistance to infectious diseases, tissue preservation integrity, and water quality. Additionally, we discussed the possible risks to safety that Bacillus poses when raising these significant species. For the purpose of future research and development regarding Bacillus application in aquaculture, a summary of the findings of recent studies about the advantages of applying Bacillus to enhance fin and shellfish aquatic animal culture has been provided.

Pyrops candelaria is one of the common pests of fruit trees, but the research on the pathogenic microorganisms it may carry is very limited. Therefore, it is essential to reveal the pathogenic microbes it carries and their potential hazards. This study found a new virus from the transcriptome of P. candelaria, which was first reported in P. candelaria and named as PyCaV (Pyrops candelaria associated virus). RACE and bioinformatics assay revealed that the full-length of PyCaV is 10855 bp with the polyA tail, containing a single open reading frame (ORF) encoding a polyprotein consisting of 3171 amino acid (aa). The virus has a typical Iflavirus structure, including two rhv domains, a RNA helicase domain (HEL), a 3C cysteine protease domain (Pro), and a RNA-dependent RNA polymerase domain (RdRp). Further phylogenetic analysis revealed that this virus belongs to family Iflaviridae and sequence alignements analysis suggedted PyCaV is new member in unassigned genus of family Iflaviridae. Further in-depth analysis of virus-infection-part showed that PyCaV is distributing in the whole longan lanternfly, including its head, chest, and abdomen, but more PyCaV was identified in the chest. The distribution of PyCaV in different parts of P. candelaria was further explored, which showed that more PyCaV were detected in its piercing-sucking mouthparts and chest viscera. Statistical analysis showed that the PyCaV infection was affected by time and locations.

Amino acid sequences of native proteins are generally not palindromic. The protein molecule obtained as a result of reading the amino acid sequence backwards, i.e., a retro-protein, having the same amino acid composition and the same hydrophobicity profile as the native sequence may behave as a different molecule. Here we have used R4, a directed evolution product of Scfv-13, a protein that binds β-galactosidase, and report the properties of the retro-R4 (rR4). rR4 remains a binding protein and its new target is Glutamine-fructose-6-phosphate aminotransferase (GLMS), a native E. coli protein. Additionally, a tight junction immunoglobulin domain- containing membrane protein, junctional adhesion molecule A (JAMA) retro-protein retains the ability to drive cell-cell interactions. Thus, protein engineering suggests a new potential application to retro-proteins of the immunoglobulin superfamily.