The most common method for establishing bioequivalence (BE) is to demonstrate similarity of concentration-time profiles in the systemic circulation, as a surrogate to the site of action. However, the similarity, or otherwise, of profiles from two different formulation in the gastrointestinal tract (GIT) may not be associated with same conclusions based on systemic circulation. Here, we have explored the concordance of BE conclusions (or otherwise) for a set of hypothetical formulations based on drug concentration-profiles in various segments of gut vs those in systemic circulation using virtual trials powered by physiologically-based (PBPK) models. Moreover, by changing physiological and biological attributes of the GIT, the impact of Crohn’s Disease on the BE conclusions was explored. The virtual BE (VBE) was applied to an Entocort EC, a pH/time-dependent release formulation of budesonide, as model drug that is targeted at ileum and colon. Substantial “discordance” between the local and systemic outcomes of VBE was observed. Upper GIT segments were much more sensitive to formulation changes than systemic circulation, where the latter led to false conclusions for BE. The ileum and colon showed a lower frequency of discordance with systemic-derived VBE. Nonetheless, a higher f2 value than the default similarity standard (50) was required to achieve local BE. In the case of Crohn’s Disease, a product-specific f2 value might be needed for drugs such as Entocort EC to ensure local BE, knowing the insensitivity of systemic data to show lack of BE. The results, being limited to the single model drug product, Entocort EC, may not provide a a general and conclusive picture. However, for the first time, it demonstrated the potential discordances between the local gut vs systemic BE.

Remote sensing imagery is of great significance for policy decisions, especially for disaster assessment and disaster relief. To ensure the privacy and inviolability of personal buildings, the information containing these buildings must be anonymized during the remote sensing mapping process. Traditional processing methods for these targets in remote sensing mapping are mainly based on manual retrieval and image editing tools, which are inefficient. Deep learning provides a new direction for target hiding. Although the image inpainting method based on deep learning is faster than the manual method, the cost of training calculation is a disadvantage. And the element-wise product operation used in the model increases the risk of vanished or exploded gradients. We propose a Residual Attention Target Hiding (RATH) model for remote sensing target hiding based on deep learning. RATH uses residual attention modules to replace gated convolutions, reducing parameters and mitigating gradient issues. The residual attention module preserves gated convolution performance but provides an adjustable kernel size. RATH retains gated convolutions for dynamic feature selection and balances model depth and width. Furthermore, this paper modifies the contextual attention layer by adjusting the fusion process to enlarge the fusion patch size. Finally, we extend the edge-guided function to preserve the original target information and confound viewers. Ablation studies on an open dataset prove RATH’s efficiency for image inpainting and target hiding. RATH achieves state-of-the-art results with lower complexity. And it has the highest similarity for edge-guided target hiding. RATH enables robust, efficient target hiding for privacy protection in remote sensing imagery while balancing performance and complexity. Experiments show RATH's superiority over existing methods in hiding arbitrary-shaped targets.

Acid stress poses a common challenge for bacteria in diverse environments by the presence of inorganic (e.g., mammals’ stomach) or organic acids (e.g., feed additives; acid-based disinfectants). Limited knowledge exists regarding acid-tolerant strains of specific serotypes, clonal lineages, or sources in human/animal pathogens, namely non-typhoidal Salmonella enterica (NTS) and Enterococcus faecium (Efm). This study evaluated acidic pH and peracetic acid (PAA) susceptibility of Efm (n=72) and NTS (n=60) from diverse epidemiological/genetic backgrounds, and with multiple antibiotic resistance profiles. Efm minimum growth/survival-pH was 4,5-5/3-4 and for NTS 4,0-4,5/3,5-4,0. Among Efm, only those of clade-non-A1 (non-hospital associated) or food chain demonstrated greater tolerance to acidic pH compared to clade-A1 (hospital-associated clones) or clinical isolates (P<0.05). MDR (multidrug-resistant) NTS survived better to acidic pH (P<0.05). The MICPAA/MBCPAA was 70-120/80-150mg/L for Efm and 50-70/60-100mg/L for NTS. Efm-clade-A1 or MDR strains exhibited higher PAA tolerance than clade-non-A1 or non-MDR ones (P<0.05). Higher tolerance was found in non-MDR and clinical NTS than in food chain isolates (P<0.05), but not between different serogroups. This unique study identifies specific NTS or Efm populations more tolerant to acidic pH or PAA, emphasizing the need for further research to tailor control measures of public health and food safety within a One Health framework.

Background: Post-delivery period could be characterized by psychological distress (e.g., anxiety, sadness, and irritability), leading to post-partum depression (PPD). Objective: The present clinical study assess the effect of probiotic supplementation containing Limosilactobacillus reuteri PBS072 and Bifidobacterium breve BB077 (4x10⁹ CFU/day) on mother’s mood and breastfeeding quality during the first trimester after delivery. Methods: A Randomized Double Blind Controlled (RDBPC) trial has been carried out in 200 healthy new mothers divided into an active group taking a supplement containing Limosilactobacillus reuteri PBS072 and Bifidobacterium breve BB077 (4x10⁹ CFU/day) plus multivitamins, and a control group (multivitamin complex only) for 90 days. Symptoms related to maternal depression and breastfeeding quality were evaluated at days 45 and 90 by Edinburgh Postnatal Depression Scale (EPDS) and Breastfeeding Self-Efficacy Scale Short-Form (BSES-SF). Results: At days 45 and 90, probiotic treatment significantly ameliorated the mothers’ mood compared to the control treatment (p<0.001). Likewise, breastfeeding quality and baby’s cries significantly improved in the probiotic group (p<0.001). Conclusions: Microbiota alterations could influence post-delivery woman’s mental state. According to our results, L. reuteri PBS072 and B. breve BB077 are potential candidates able to improve stress resilience in the post-partum period.

Humans can recombine thousands of different facial expressions. This variability is due to the ability to voluntarily or involuntarily modulate emotional expressions, which, in turn, depends on the existence of two anatomically separate pathways. The Voluntary (VP) and Involuntary (IP) pathways mediate the production of posed and spontaneous facial expressions, respectively, and might also affect the left and right sides of the face differently. This is a neglected aspect in the emotion literature, where posed expressions instead of genuine expressions are often used as stimuli. Two experiments with different induction methods were specifically designed to inves-tigate the unfolding of spontaneous and posed facial expressions of happiness along the facial vertical axis (left, right) with a high-definition 3D optoelectronic system. The results showed that spontaneous expressions were distinguished from posed facial movements as revealed by relia-ble spatial and speed key kinematic patterns in both experiments. Moreover, VP activation pro-duced a lateralization effect: compared with the felt smile, the posed smile involved an initial acceleration of the left corner of the mouth, while an early deceleration of the right corner oc-curred in the second phase of the movement, after the velocity peak.

Idiopathic scoliosis (IS) is an unexplained dysplasia of the spine that can occur at any age, with idiopathic scoliosis making up the largest proportion of the total population worldwide, approximately 2-3%. Scoliosis is not just a cosmetic defect, but the development of the spinal deformity can lead to cardiovascular and respiratory lesions, often resulting in serious health problems. Treatment of the condition usually involves major surgery, which is both a physical and financial burden for patients. In order to clarify the aetiology of IS and provide a theoretical basis for new diagnostic and treatment methods IS, it is important to use different animal models for experiments. Zebrafish is an emerging model animal with a short reproductive cycle, minimal breeding expenses, and other beneficial traits including in vitro fertilisation, in vitro development, and embryo transparency. As a result, genetic alteration and observation are simpler than with traditional model animals. This study examines the history of animal models for IS research, focuses on the benefits and drawbacks of zebrafish as an IS model and the advances it provides to IS research, and anticipates zebrafish application prospects in IS research.

Background: The Covid-19 pandemic has globally impacted the lives of individuals, families, and children. In Italy, measures such as lockdowns and distance learning were implemented in schools, which affected the mental health of children and families. Methods: This article employs qualitative methodology to explore the experiences of children, parents, and teachers during the pandemic and lockdown, as well as the implementation of a death education project aimed at primary school children to help them process emotions and losses experienced during this period. Results: Distance learning posed challenges to the learning process and exacerbated social inequalities. Children suffered from limited social contact with friends and experienced negative emotions, including anger, fear, and concern for the health of their loved ones. The death education project provided a safe space for emotional expression and facilitated the acquisition of coping strategies. Open communication between adults and children about illness and death proved effective in mitigating the psychological impacts of loss and preventing traumatic bereavement. Conclusions: The findings highlight the utility of death education in enhancing children's ability to express their emotions and approach the topic of death morefrankly.

Accidents at mining enterprises, including tailing dumps, pose significant threats to human lives, structures, and the environment. This study focuses on designing, constructing, and operating tailing dumps in Siberia's northern region. To ensure safety and minimize environmental impacts, comprehensive scientific monitoring and research were conducted at all stages, including design, construction, operation, and disposal. The aim was to create a uniform mass within the dam body, requiring understanding of the tailings' structure and technological characteristics during placement. Parameters like particle size, distribution, density, and moisture content were considered to assess tailings' physical and geometric properties. Estimated monitoring was introduced as a permanent model to quickly assess the stability of hydrotechnical constructions. This involved monitoring changes in exploitation properties, structure height, beach length, and water levels. A controlled inwashing technology for subsequent dam layers was developed. Complex research facilitated the formulation of an estimated monitoring methodology and an algorithm for tailing dam formation. Practical application demonstrated high reliability and confirmed load-bearing capacity, allowing for the forecast of dam stability and safe execution. Findings led to alterations in work techniques, ensuring safe and efficient operation of tailing dams.

Food safety and quality are the first steps in the food chain. This work reports a low-cost and easy-to-use optoelectronic measurement system for improving feed chain quality and safety, based on near-infrared spectrometry (NIRS) technology. This is a significant challenge for dairy farm technicians and producers who need rapid and reliable knowledge of forage quality on their farms. In most cases, instrumentation suitable for these specifications is expensive and difficult to operate. The core of the measurement system is Texas Instruments´ NIRscan Nano Evaluation Module (EVM) spectrometer. This module has a large sensing area and high resolution suitable for forage samples. To evaluate the feasibility of the prototype to analyze agrifood samples, different ways of presenting the sample, intact or ground, were tested. The final objective of the research is not just to check the efficiency of the proposed system. It is also to determine the measurement system characteristics and how to improve them.

Zucchini (Cucurbita pepo L.) is an important crash crop for producing seeds in Inner Mongolia, China. In August 2021, the harvest season of seed-producing zucchini, fruit rot symptom (cv. Jindi No.1) was found in the Wuyuan region. The incidence of infected fruits of zucchini ranged from 10% to 30% and symptom consisted in 4 to 5 cm diameter lesions where the fruit was in contact with the soil. Ten isolations from six symptomatic fruits were preliminary classified as Fusarium species based on its morphological characters in potato dextrose agar. Phylogenetic tree was constructed by concatenating TEF-1α and RPB2 gene and exhibited the isolates clustered together with the Fusarium solani f. sp. cucurbitae sequences. Pathogenicity tests revealed that two isolates caused over 3 cm diameter lesions on the fruits while negative-controls remained asymptomatic. The colonies reisolated from the leasions were morphologically identical to the original isolates, thus fulfilling Koch’s postulates. Results demonstrated that F. solani f. sp. cucurbitae was the causal agent of fruit rot observed in the field. To our knowledge, this is the first report of fruit rot of seed-producing zucchini caused by F. solani f. sp. cucurbitae in Inner Mongolia, China.

Two monoclonal antibodies (mAbs) against human epidermal growth factor receptor 2 (HER2), trastuzumab and pertuzumab, were clinically approved. We previously developed a highly sensitive and specific anti-HER2 mAb, H2Mab-139 (mouse IgG1, kappa). In this study, we produced a defucosylated IgG2a version of anti‑HER2 mAb (H2Mab-139-mG2a-f) to enhance ADCC-mediated antitumor activity. H2Mab-139-mG2a-f exhibits a high binding affinity in flow cytometry with the dissociation constant (KD) determined to be 3.9 × 10‑9 M and 7.7 × 10‑9 M against HER2‑overexpressed Chinese hamster ovary (CHO)-K1 (CHO/HER2) and HER2-positive BT-474 cells, respectively. Moreover, we showed that H2Mab-139-mG2a-f exerted ADCC and complement-dependent cytotoxicity against CHO/HER2 and BT-474 cells in vitro and exhibited potent antitumor activities in the xenograft models. These results indicated that H2Mab-139-mG2a-f exerts antitumor effects against HER2-positive human breast cancers and could be useful for an antibody treatment regimen for HER2-positive human cancers.

People from Black and Asian backgrounds are more likely to die from Covid-19 but less likely to be vaccinated, threatening to exacerbate health inequalities already experienced by ethnic minority groups. Literature suggests that mistrust rooted in structural inequality may be a key barrier to Covid-19 vaccine uptake. We need to better understand how structural inequalities influence vaccine confidence. Understanding and addressing these processes is likely to lead to longer-term impacts than information alone. We draw on health and sociological theories of structure and agency to inform our understanding of structural factors. We conducted qualitative interviews and focus groups with 22 people from London and surrounding areas in December 2021 to March 2022. Fifteen participants were members of the public from ethnic minority backgrounds and 7 were professionals working with the public to address concerns and encourage vaccine uptake. Our findings suggest that people from ethnic minority backgrounds make decisions regarding Covid-19 vaccination based on a combination of how they experience external social structures (including political authority, social positioning and racial inequality) and internal processes (what they believe and understand about Covid-19 vaccines). We may be able to support knowledge accumulation through the provision of reliable and accessible information, particularly through primary and community care. But we recommend a number of changes to research, policy and practice which address structural inequalities. These include working with communities to improve ethnicity data collection, increasing funding allocation to health conditions where ethnic minority communities experience poorer outcomes, greater transparency and public engagement in the vaccine development process, and culturally adapted research recruitment processes.

In this world that we share with them, they became unintended sentinels for the consequences of pollutant exposure, developing similar conditions to humans, and even earlier. This review focuses on the human-pet interaction and on the effects of the environment pets share with us. Alongside other species, canine and feline companions are veritable models in human medical research. The latency period for showing chronic exposure effects to pollutants is just a few years in them, compared to considerably more, decades in humans. Comparing the serum values of man's best friends to ours can indicate the degree of poisonous lead-load we are exposed to, for example, and of other substances as well. We can find 2.4 times higher perfluorochemicals from stain- and grease-proof coatings in canine companions, 23 times higher values for PBDEs in cats, and five times more mercury compared to the average levels obtained in humans. All these represent early warning signals. Taking into account all these, and the animal welfare orientation of today’s society, finding non-invasive methods to detect the degree of environmental pollution in our animals becomes paramount, alongside with the need to raise awareness on the risks carried by certain chemicals we knowingly use.

Mango flowering phenostages were recorded under global warming conditions to assess the relationship between environmental cues and flowering time shifts and their consequences on reproductive success. Phenological transition to floral destiny was studied in relation to standard metrological week and weather parameters. Shifting of phenostage was recorded in Bud swelling, which is important for the shoot transitioning from vegetative to flowering meristem. Variations were also recorded for panicle elongation and early anthesis. The critical temperature for Bud burst stage was estimated for Dashehari, Langra, Amrapali and Chausa while Chausa had the propensity for late flowering correlated with higher temperature. The shifting of phenological calendar in response to weather parameters was obvious and needed a bigger range of yearly data for arriving at the climatic drives. In general, the results revealed that flower intensity was positively correlated with temperature, sunshine hours and evaporation while humidity showed a negative correlation. Hermaphrodite Flower % is an important attribute affecting fruit set and yield and was found most variable in the two years in the case of the three alternate bearing cultivars. In conclusion, it can be inferred that weather parameters prevailing in subtropics affect flowering intensity and consequently its fate i.e.; fruit yield.

Simultaneous biofortification of vegetable crops with selenium and iodine is necessary in areas where there is a lack of these two elements. The main reason for lack of selenium and iodine in humans is inadequate intake of these two elements from vegetable crops. Biofortification through various agricultural methods including artificial lighting is a pragmatic way of increasing the concentration of these elements in plants. This research was conducted as a three-factor factorial experiment arranged as completely randomized pots replicated thrice in the greenhouse during year 2022. Three levels of sodium selenate fertilizer (S1: 0, S2: 2, S3: 4 mg/l), three levels of potassium iodate (I1: 0, I2: 2, I3: 4 mg/L) and two additional blue light radiation levels (L1: radiation and L2: no blue light radiation) were applied and data was measured at two growth stages namely 40 and 80-days. The results showed that the highest (11.44 g) and the lowest (9.55 g) shoot dry weight values at the 40-day-stage were observed in the supplementary blue light and sunlight (control), respectively. Moreover,, under complementary blue light conditions, the highest and the lowest (5.85 and 3.38 mg/g leaf fresh weight) of leaf chlorophyll value at the 40-day-stage were recorded at sodium selenate 4 and 0 mg/l, respectively. The highest and the lowest (5.24 and 4.76 mg/g) fresh weight of leaf anthocyanin at the 40-day-growth stage were related to supplementary blue light and sunlight treatment (control), respectively. Under the supplementary blue light and 0 mg/l of selenium , the highest and the lowest value of shoot trigonelline (102.56 and 72.14 mg/100 g fresh weight) were obtained at 4 and 2 mg/L of iodine, respectively. Furthermore, in the same treatment, the highest and the lowest of seed trigonelline amounts (0.99 and 0.74 mg/g dry weight) corresponded with 4 and 0 mg/l of iodine, respectively.

Bond Properties were performed on Ag-2.35Au-0.7Pd-0.2Pt-0.1Cu alloy wire with a diameter of 25 µm under different process parameters. Effects of electrical flaming off (EFO) current and EFO time on deformability of the free air ball (FAB) were investigated using scanning electron microscopy (SEM) as well as the effects of ultrasonic power and bonding force on the bond characteristic. The experimental results showed that, FAB grows from a preheated tip to a small ball, a regular ball and finally to a golf ball with increasing either the EFO current or the EFO time, and the FAB presented optimal shape at 25 mA and 650 μs. Moreover, a nonlinear relationship between FAB diameter and EFO time is obtained at the EFO current of 25 mA, which could be expressed by a cubic equation. Further, at a constant bonding force, as the ultrasonic power increased, the mashed ball diameter grew larger and larger, the capillary hole imprint became more and more obvious, and the tail width also increased larger and larger, and vice versa. The optimal ultrasonic power and bonding force are 70 mW and of 45 gf for ball bond and 90 mW and 75 gf for wedge bond, respectively. Finally, for all the bonded wire samples prepared under optimal process parameters, no ball and wedge bond lifts happened after destructive pull test, and full intermetallic compound coverage with perfect morphology occurred on the bond pad after ball shear test, which meant that the bonded wire samples have high bond strength, and hence improved the reliability of microelectronic products.

This study investigated the effects of flamenco dance on mood and subjective well-being in older women. In a broader context, the question was raised about how participation in dance activities could influence the emotional well-being of this demographic group. Thirty-four older women, aged between 62 and 79 years, with a mean age of 70.11 years (SD = 5.13), voluntarily participated in the study after providing informed consent. All of them were enrolled in a 12-week flamenco dance workshop conducted by the Autoestima Flamenca Association, with one two-hour session per week. Mood measurements (sadness, anxiety, anger, and joy) were taken biweekly before and after each session, and subjective well-being assessments were conducted before and after the intervention. The results revealed significant improvements in the overall mood of the participants, as well as an increase in their subjective well-being. These improvements were observed at both the individual and group levels. In conclusion, participation in flamenco dance demonstrated a positive impact on the mood and subjective well-being of older women. These findings support the idea that physical and artistic activities, such as flamenco dance, can play an important role in promoting emotional well-being in this age group.

Electrospinning is a simple versatile method to generate nanofibres. Remarkable progress has been made in the development of electrospinning process. The production of nanofibers is affected by many parameters, which influence the final material properties. Electrospun fibers have a wide range of applications such as energy storage and biomedical scaffolds. Polyacrylonitrile (PAN) has been widely used in the production of carbon nanofibers. PAN has received increasing interest in recent years, due to its excellent characteristics, such as spinnability, biocompatibility, and commercial viability, opening new applications in the biotechnological field. This paper provides an overview of the electrospinning process, its main parameters, and operation modes that affect nanofibers fabrication. A review of their biological applications is proposed. A focus is made on PAN fibers formation, functionalization, and application as scaffolds to allow cell growth. Overall, nanofibre scaffolds, made of stabilized PAN, appear as a powerful tool in medical applications needing controlled cell culture.

This paper presents an innovative testing framework, testFAILS, designed for the rigorous evaluation of AI Linguistic Systems, with a particular emphasis on various iterations of ChatGPT. Leveraging orthogonal array coverage, this framework provides a robust mechanism for assessing AI systems, addressing the critical question, "How should we evaluate AI?" While the Turing test has traditionally been the benchmark for AI evaluation, we argue that current publicly available chatbots, despite their rapid advancements, have yet to meet this standard. However, the pace of progress suggests that achieving Turing test-level performance may be imminent. In the interim, the need for effective AI evaluation and testing methodologies remains paramount. Our research, which is ongoing, has already validated several versions of ChatGPT, and we are currently conducting comprehensive testing on the latest models, including ChatGPT-4, Bard and Bing Bot, and the LLaMA model. The testFAILS framework is designed to be adaptable, ready to evaluate new bot versions as they are released. Additionally, we have tested available chatbot APIs and developed our own application, AIDoctor, utilizing the ChatGPT-4 model and Microsoft Azure AI technologies

With the rapid development of electronic and communication technology in military radar, the demand for microwave absorbing materials in low-frequency with thin layer is growing increasingly. In this study, flexible Co3O4/CC (carbon cloth) composites derives from Co-MOFs (metal-organic frameworks)/CC are prepared by hydrothermal and thermal treatment processes. The flexible precursors of Co-MOFs/CC are calcined with different calcination temperatures, which the material structure, dielectric properties and microwave absorption performance are changed. With the increase of calcination temperature, the minimum reflection loss of the corresponding Co3O4/CC composites gradually moves to the lower frequency with thinner thickness. In addition, the Co3O4/CC composites with 25 wt% filler loading ratio exhibit the minimum reflection loss (RL) of -46.59 dB at 6.24 GHz with 4.2 mm thickness. When the thickness is 3.70 mm, the effective absorption bandwidth is 3.04 GHz from 5.84 to 8.88 GHz. This study not only proves that the composite Co3O4/CC is a kind of outstanding microwave absorbing material with better flexibility, but also provides a useful inspiration for the low frequency and broadband microwave absorbing material.

This paper presents a comprehensive study and the analysis of a topology of a no isolated DC-DC intituled Double Quadratic Boost converter with high static gain. This converter has the main advantage of high static gain and low voltage stress on its switches. The article will first present the theoretical analysis of the converter operating in an open loop. The objective of the work is the mathematical modeling and the control strategy of the converter, as well as the validation through closed-loop experimental results. Besides, we presented the practice test results to demonstrate the operation of the converter, such as the static gain experimental curve, the practice efficiency of the converter, and the control of the output voltage, as well as the capacitor voltage balance control. The authors designed a prototype for 1 kW, with a switching frequency of fs=50kHz, with FPGA-based command and modulation.

This paper proposes a new battery balancing control strategy based on state of charge (SOC) for addressing the problem of cell-to-cell differences in lithium-ion battery systems. The strategy utilizes a reconfigurable converter system to transfer energy from high-SOC battery modules to low-SOC battery modules and allows balancing the battery modules while they are powering the load. A MATLAB/Simulink simulation model with five batteries was built to validate the effectiveness of the proposed balancing strategy under unloaded and loaded conditions. The simulation results demonstrate that the proposed strategy achieves more efficient and accurate battery module balancing compared to the previous balancing modes, thus increasing the overall lifespan and safety of the battery pack.

Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. GC with peritoneal metastasis exhibits a poor prognosis due to the lack of diagnostic biomarkers and effective therapy. A comprehensive analysis of malignant ascites identified the genomic alterations and significant amplifications of cancer driver genes, including CD44. CD44 and its splicing variants are overexpressed in tumors, and play crucial roles in the acquisition of invasiveness, stemness, and resistance to treatments. Therefore, the development of CD44-targeting monoclonal antibodies (mAbs) is important for GC diagnosis and therapy. In this study, we immunized mice with CD44v3–10-overexpressed PANC-1 cells and established several dozens of clones that produce anti-CD44v3–10 mAbs. One of the clones (C44Mab-94; IgG1, kappa) recognized the variant-8-encoded region and peptide, indicating that C44Mab-94 is a specific mAb for CD44v8. Furthermore, C44Mab-94 could recognize CHO/CD44v3–10 cells, oral squamous cell carcinoma cell line (HSC-3), or GC cell lines (MKN45 and NUGC-4) in flow cytometric analyses. C44Mab-94 could detect the exogenous CD44v3–10 and endogenous CD44v8 in western blotting and stained the formalin-fixed paraffin-embedded gastric cancer cells in immunohistochemistry. These results indicate that C44Mab-94 is useful for detecting CD44v8 in various applications and is expected to be useful for the application of GC diagnosis and therapy.

Vaccines trigger a complicated immunological response that includes B and T cells, with B cells producing antibodies. SARS-CoV-2 immunity weakens over time after vaccination. Discovering key changes in antigen-reactive antibodies over time after vaccination could help improve vaccine efficiency. In this study, we collected data on blood antibody levels in a cohort of healthcare workers vaccinated for COVID-19 and obtained 73 antigens in samples from four groups according to the duration after vaccination, including 104 unvaccinated healthcare workers, 534 healthcare workers within 60 days after vaccination, 594 healthcare workers between 60 and 180 days after vaccination, and 141 healthcare workers over 180 days after vaccination. An efficient machine learning based framework containing four feature selection methods (least absolute shrinkage and selection operator, light gradient boosting machine, Monte Carlo feature selection, and maximum relevance minimum redundancy) and four classification algorithms (decision tree, k-nearest neighbor, random forest, and support vector machine) was designed to screen out essential antigens. Several efficient classifiers with weighted F1 value around 0.75 were constructed. This study revealed that S1+S2, S1.mFcTag, S1.HisTag, S1, S2, Spike.RBD.His.Bac, Spike.RBD.rFc, and S1.RBD.mFc were most highly ranked among all features, where S1 and S2 are the subunits of Spike, and the suffixes represent the tagging information of different recombinant proteins. Meanwhile, the classification rules were extracted from the optimal decision tree to explain quantitatively the roles of antigens in the classification. This study identified antibodies associated with decreased clinical immunity based on populations with different time spans after vaccination. These antibodies have important implications for maintaining long-term immunity to SARS-CoV-2.

Neutrophils are the most abundant immune cells and make up about 70% of white blood cells in human blood and play a critical role as the first line of defense in the innate immune response. They also help regulate the inflammatory environment to promote tissue repair. However, in cancer, neutrophils can be manipulated by tumors to either promote or hinder tumor growth depending on the cytokine pool. Studies have shown that tumor-bearing mice have increased levels of neutrophils in peripheral circulation, and that neutrophil-derived exosomes can deliver various cargos, including lncRNA and miRNA, which contribute to tumor growth and degradation of extracellular matrix. Exosomes derived from immune cells generally possess anti-tumor activities and induce tumor-cell apoptosis by delivering cytotoxic proteins, ROS generation, H2O2 or activation of Fas-mediated apoptosis in target cells. Engineered exosome-like nanovesicles have been developed to deliver chemotherapeutic drugs precisely to tumor cells. However, tumor-derived exosomes can aggravate cancer-associated thrombosis through the formation of neutrophil extracellular traps. Despite the advancements in neutrophil-related research, a detailed understanding of tumor-neutrophil crosstalk is still lacking and remains a major barrier in developing neutrophil-based or targeted therapy. This review will focus on the communication pathways between tumors and neutrophils, and the role of neutrophil-derived exosomes (NDEs) in tumor growth. Additionally, potential strategies to manipulate NDEs for therapeutic purposes will be discussed.

The present study reports on the fabrication and performance of ammonia sensors based on single-walled carbon nanotubes (SWCNTs) coated with gold nanoparticles (AuNPs). The sensors were subjected to controlled concentrations of ammonia at two temperatures, namely 25 oC and 140 oC, and their response was monitored through successive cycles of ammonia exposure and nitrogen purging. The results demonstrate that the sputtering-based deposition of AuNPs on SWCNTs led to the best sensor performance, characterized by a rapid increase in resistance values upon exposure to ammonia, and efficient recovery at 140 oC. By contrast, the sensor with chemically impregnated AuNPs exhibited a slower response time. Furthermore, a novel device was developed that combined MoS2-AuNPs (sputtering)-SWCNTs, and it showed improved sensor performance compared to the devices with only AuNPs. Overall, the study provides valuable insights into the fabrication and optimization of SWCNT-based ammonia sensors for various applications, especially for detecting and quantifying small amounts of ammonia (concentrations below 1 ppm).

Cotton cationization with low molecular-weight/polymeric cationic modifiers allows the effective dyeing of fabrics with reactive dyes under salt-free and more environmentally-friendly conditions. The current work focuses on the spectroscopic study of the intermolecular interactions, which dictate the physicochemical process associated with dyeing. Water-soluble copolymers of vinyl benzyl chloride and vinyl benzyl triethylammonium chloride (VBCTEAM) have been used as cellulose cationic modifiers. Dye uptake was assessed using Remazol Brilliant Blue and Novacron Ruby dyes. The study involves ATR-FTIR, UV-Vis, fluorescence and XPS spectroscopy. The results of binary polymer-rich dye-polymer aqueous solutions or dye-polymer precipitates at stoichiometric charge-ratio revealed that the sulfonate/sulfate anions of the dyes interact with the cationic VBCTEAM units of the polymer via electrostatic interactions. Moreover, the comparative study of unmodified/modified dyed cotton indicates that the dye reactive sites remain unaffected for cationized cotton, suggesting that electrostatic interactions are the main driving force for the high dyeing performance observed.

In current study we have obtained Co2FeSi-glass coated microwires with different geometrical aspect ratio, ρ = d/Dtot (diameter of metallic nucleus, d and total diameter, Dtot). The structure and magnetic properties are investigated at a wide range of temperature. XRD analysis illustrates a notable changing in the microstructure by increasing the aspect ratio of Co2FeSi glass coated microwires. Amorphous structure is detected for the sample with the lowest aspect ratio (ρ = 0.23), whereas a growth of crystalline structure is observed in the other samples (aspect ratio ρ = 0.30 and 0.43). This change at the microstructure properties correlates with dramatic changing in magnetic properties. For the sample with the lowest ρ -ratio, non-perfect square loops are obtained with low normalized remanent magnetization. A notable enhancement in the squareness and coercivity are obtained by increasing ρ -ratio. Changing the internal stresses strongly affects the microstructure, resulting in a complex magnetic reversal process. The thermomagnetic curves show large irreversibility for the Co2FeSi with low ρ -ratio. Meanwhile, if we increase the ρ -ratio, the sample shows perfect ferromagnetic behavior without irreversibility. The current result illustrates the ability to control the microstructure and magnetic properties of Co2FeSi-glass-coated microwires by changing only their geometric properties without performing any addition heat treatment. The modification of geometric parameters of Co2FeSi glass-coated microwires allows to obtain microwires which exhibit an unusual magnetization behavior that offers opportunities to understand the phenomena of various types of magnetic domain structures, which is essentially helpful for designing sensing devices based on thermal magnetization switching.

The COVID-19 pandemic has had a profound impact on the mental health, adjustment, and psychological well-being of young adults. Despite extensive research conducted in this area, eudaimonic well-being, one specific form of psychological well-being focusing on self-knowledge and self-realization within existential challenges, has received comparatively less attention. The current study aimed to investigate the potential linkages between two key psychological factors, psychological inflexibility and fear of death, with eudaimonic well-being among young adults in the context of the Covid-19 pandemic. One year after the outbreak, 317 young Italian adults (18-34 yrs.) participated in an online survey, including measures of psychological inflexibility (AAQ-II), fear of death (CL-FODS), and eudaimonic well-being (PWB). Results showed that psychological inflexibility was negatively associated with all the dimensions of Ryff’s model of eudaimonic well-being, while fear of death of others was found to be associated with three of these dimensions (autonomy, environmental mastery, and self-acceptance). Results also indicated a mediation role of psychological inflexibility in the association between fear of death and eudaimonic well-being. These findings expand our knowledge of the potential factors that may influence eudaimonic well-being and provide insights for clinical work with young adults challenged by uncertain times.

Water is an essential commodity to sustain life. The condition of water in Tiruchirappalli was measured using different Physicochemical parameters like Temperature, pH, TDS, Total Solids, Salinity, Total Hardness, and Electrical Conductivity. Water samples were collected from different places in Tiruchirappalli city, Tamil Nadu. Water samples were examined by different chemical methods. According to the results, Thiruvarambur-1 showed comparatively higher results in the case of every parameter compared to other sampling stations. Obtained results were further interpreted using statistical tools. Considering ECs as a principal component for the regression and correlation analysis with other parameters significant correlation was found. A strong correlation was observed between ECs and TDS, Total Hardness, Turbidity, and Salinity.

Long-span steel structure trusses are widely used in factory buildings, but with the growth of service time and the increase of dynamic load fatigue, a considerable part of the long-span truss with dynamic load appears serious transverse cracks at the bottom of the middle span and oblique deformation of the abdomen in the operation process. The U-shaped cracks at the bottom and belly, as well as the mid-span down deflection of the main truss, reduced the functional function of the factory building truss structure, and had to limit the original crane load, which affected the normal safety and durability of the structure. Therefore, the application principle of the variable axial force cable system in the long-span factory building truss structure and 3D3S software modeling [1] were used. Analyzing and studying the reinforcement method of large-span powerhouse truss can provide practical experience for subsequent similar projects. In view of the above phenomenon, the large-span powerhouse trusses of Hongcheng Powerhouse 1 and No.2 located in Tonglu, Zhejiang Province are used as the research object, and the variable axial force cable method is proposed to strengthen and lift the load. Considering the span of large-span powerhouse truss, the cable system with 22m controlling force of 400kN is proposed to be selected for powerhouse 1, and the cable system with variable axial force of 24m is proposed to be selected for Powerhouse 2. The force model of large-span truss is established by using the finite element method commonly used to analyze the force of truss. Under two working conditions, The influence of reinforcement effect is analyzed and compared from three aspects: stiffness, bearing capacity and stability. And the phenomenon of uneven stress distribution is analyzed. The stress distribution characteristics of each node are understood by simulating the most disadvantageous node plates with the greatest internal force before and after reinforcement.

Pairs of pyrrolysyl-tRNA synthetase (PylRS) and tRNAPyl from Methanosarcina mazei and Methanosarcina barkeri are widely used for site-specific incorporations of non-canonical amino acids into proteins (genetic code expansion). Previously, we achieved full productivity of cell-free protein synthesis for bulky non-canonical amino acids, including Ne-((((E)-cyclooct-2-en-1-yl)oxy)carbonyl)-L-lysine (TCO*Lys), by using Methanomethylophilus alvus PylRS with structure-based mutations in and around the amino acid binding pocket (first-layer and second-layer mutations, respectively). Recently, the PylRS•tRNAPyl pair from a methanogenic archaeon ISO4-G1 was used for genetic code expansion. In the present study, we determined the crystal structure of the methanogenic archaeon ISO4-G1 PylRS (ISO4-G1 PylRS) and compared it with those of structure-known PylRSs. Based on the ISO4-G1 PylRS structure, we attempted the site-specific incorporation of Ne-(p-ethynylbenzyloxycarbonyl)-L-lysine (pEtZLys) into proteins, but it was much less efficient than that of TCO*Lys with M. alvus PylRS mutants. Thus, the first-layer mutations (Y125A and M128L) of ISO4-G1 PylRS, with no additional second-layer mutations, increased the protein productivity with pEtZLys up to 578% of that with TCO*Lys, at high enzyme concentrations in the cell-free protein synthesis.

Several studies have shown that combining TiO2 and Cu2O enhances the photocatalytic activity of the material by generating a heterojunction capable of extending the light absorption in the visible and reducing the electron-hole recombination rate. Ball milling has been chosen as an alternative methodology for photocatalyst preparation, among the several techniques documented in the literature review. The results of a previously reported investigation enabled the identification of the most effective photocatalyst that can be prepared for hydrogen generation by combining Cu2O and TiO2 (i.e., 1%wt Cu2O in TiO2 photocatalyst prepared by ball-milling method at 200 rpm and 1 min milling time). To optimize photocatalytic hydrogen generation in the presence of the greatest photocatalyst, the effects of (i) sacrificial species and their concentration, (ii) temperature, and (iii) pH of the system are taken into account, resulting in a light-to-chemical energy efficiency of 8% under the best-tested conditions. Last but not least, the possibility of using the present photocatalytic system under direct solar light irradiation is evaluated: the results indicate that nearly 60% of the hydrogen production recorded under sunlight can be attributed to the visible component of the solar spectrum, while the remaining 40% can be attributed to the UV component.

Alzheimer’s disease (AD) represents the most prevalent type of dementia in elderly people, primarily characterized by brain accumulation of beta-amyloid (Aβ) peptides, derived from Amyloid Precursor Protein (APP), in the extracellular space (amyloid plaques) and intracellular deposits of the hyperphosphorylated form of the protein tau (p-tau; tangles or neurofibrillary aggregates). The Nerve growth factor receptor (NGFR/p75NTR) represents a low-affinity receptor for all known mammalians neurotrophins (i.e., pro-NGF, NGF, BDNF, NT-3 e NT-4/5) and it is involved in pathways that determine both survival and death of neurons. Interestingly, also Aβ peptides can blind to NGFR/p75NTR making it the “ideal” candidate in mediating Aβ-induced neuropathology. Besides pathogenesis and neuropathology, several data indicated that NGFR/p75NTR could play a key role in AD also from a genetic perspective. Other studies suggested that NGFR/p75NTR could represent a good diagnostic tool, as well as a promising therapeutic target for AD. Here, we comprehensively summarize and review the current experimental evidence on this topic.

CD44 is a cell surface glycoprotein, and its isoforms are produced by the alternative splicing with the standard and variant exons. The CD44 variant exon containing isoforms (CD44v) are overexpressed in carcinomas. CD44v6 is one of the CD44v, and its overexpression predicts poor prognosis in colorectal cancer (CRC) patients. CD44v6 plays critical roles in CRC adhesion, proliferation, stemness, invasiveness, and chemoresistance. Therefore, CD44v6 is a promising target for cancer diagnosis and therapy for CRC. In this study, we established anti-CD44 monoclonal antibodies (mAbs) by immunizing mice with CD44v3-10-overexpressed Chinese hamster ovary-K1 (CHO) cells. We then characterized them using enzyme-linked immunosorbent assay, flow cytometry, western blotting, and immunohistochemistry. One of the established clones (C44Mab-9; IgG1, kappa) reacted with a peptide of variant 6-encoded region, indicating that C44Mab-9 recognizes CD44v6. Furthermore, C44Mab-9 reacted with CHO/CD44v3-10 cells or CRC cell lines (COLO201 and COLO205) by flow cytometry. The apparent KD of C44Mab-9 for CHO/CD44v3-10, COLO201, and COLO205 was 8.1 × 10−9 M, 1.7 × 10−8 M, and 2.3 × 10−8 M, respectively. C44Mab-9 detected the CD44v3-10 in western blotting, and partially stained the formalin-fixed paraffin-embedded CRC tissues in immunohistochemistry. Collectively, C44Mab-9 is useful for detecting CD44v6 in various applications.

The effect of Gymnema Sylvestre supplementation on beta cell and hepatic activity was explored in an alloxan-induced hyperglycemic rat model. Adult rats were made hyperglycemic via a single inj. (i.p) of Alloxan (120mg/kg b.w). Gymnema Sylvestre was supplemented @250mg/kg and 500mg/kg b.w. Blood glucose levels were constantly monitored. After 21 days, rats were euthanized, and blood and tissues (pancreas and liver) were collected for biochemical, expression, and histological analysis. One-way ANOVA was used to compare the means of different treatment groups. Gymnema Sylvestre significantly reduced blood glucose levels with a subsequent increase in plasma insulin levels in a dosage-dependent manner. Total oxidant status (TOS), malondialdehyde, LDL, VLDL, ALT, AST, triglyceride, total cholesterol, total protein, C-reactive protein, and cortisol levels were reduced significantly in alloxan-treated hyperglycemic rats supplemented with Gymnema Sylvestre as compared to control. Significantly raised paraoxonase, arylesterase, albumin, and HDL levels were also observed in Gymnema Sylvestre supplemented hyperglycemic rats. Increased mRNA expression of Ins-1, Ins-2, Gck, Pdx1, Mafa, and Pax6 were observed, while decreased expression of Cat, Sod1, Nrf2, and NF-kB was observed in the pancreas. Whereas increased mRNA expression of Gck, Irs1, SREBP1c, and Foxk1 and decreased expression of Irs2, ChREBP, Foxo1, and FoxA2 were observed in the liver. The current study indicates the potent effect of Gymnema Sylvestre on the transcription modulation of the insulin gene in the alloxan-induced hyperglycemic rat model. Enhanced plasma insulin levels further help to improve hyperglycemia-induced dyslipidemia through transcriptional modulation of hepatocytes.

We studied the effect of annealing and the applied magnetic field from 50 Oe to 20 kOe on the magneto-structural behavior of Ni2FeSi-based Heusler microwires fabricated by using Taylor-Ulitovsky technique. Using the XRD analysis, a strong effect of annealing, manifested as the development of the crystallization process, was observed. The average grain size and crystalline phase content of annealed sample increase from 21.3 nm and 34 % to 32.8 nm and 79%, respectively, as-compared to the as-prepared one. In addition, upon annealing phase transforms into a monoclinic martensitic structure with modulation 10M were observed, which cannot be found in the as-prepared sample. Concerning the magnetic properties, both samples show ferromagnetic behavior below and above the room temperature, where the Curie temperature of Ni2FeSi is higher than room temperature. The induced secondary phases have a noticeable effect on the magnetic behavior of the annealed sample, where a high normalized saturation magnetization (NMs) and low normalized reduced remenance (Mr = M/M5K), compared to the as- prepared have been detected. Additionally, the coercivity of annealed sample shows one flipping point at 155 K where it behavior with temperature is changed. Meanwhile, the as-prepared sample show two flipped point at 205 K and 55 K. A mismatch between field cooling (FC) and field heating (FH) magnetization curves with temperature has been detected for annealed sample at low applied magnetic field. In addition the FC and FH curves shows different slopes with variation the temperature and the magnetic field. By increasing the external magnetic field higher than 200 Oe and up to 20 kOe a gradual changing in the magnetic behavior has been detected, where the mismatch and different slopes disappeared at applying magnetic field about 20 kOe. The difference in magnetic and structure behavior of Ni2FeSi microwires sample is discussed considering the effect of induced internal stresses by the presence of a glass coating and the recrystallization and stresses relaxation upon annealing.

Canola is the major oilseed crop of Canada. The de-oiled material is an important by-product due to its rich phenolic profile and high protein content. This co-processing stream from canola is primarily utilized as animal feed but represents an invaluable source of nutraceuticals. Microwave-assisted solvent extraction (MAE), as a green extraction method, has received considerable attention in recent times. The ease of use and application of many solvents at the same time makes the MAE one of the best methods for studying multiple solvents at the same time. The formation of canolol, from sinapine and sinapic acid, is primarily dependant on temperature which favors the decarboxylation reaction. Hence, MAE using green extractants can be used to enhance the yield of canolol. This study examined the effects of different pre-treatment temperature-time combinations of 140, 150, 160, and 170℃ for 5, 10, 15, 20 and 30 minutes on the extraction of canolol and other canola endogenous phenolic compounds. Three antioxidant assays assessed the antioxidant activity of the different extracts obtained by MAE confirming the microwave as a novel and versatile instrument for enhancing the yield of canolol. Improvements in the antioxidant activity of the different extracts further established the efficacy of the current method for isolating important natural phenolic derivatives for utilization by the nutraceutical industry.

The solid particle erosion at room and elevated temperatures of pure and filled hot-curing epoxy resin on anhydride hardener was experimentally tested using accelerated method on special bench. Micro-sized dispersed industrial wastes were used as fillers: fly-ash from a power plant and spent filling material from a copper mining and processing plant. The results showed that the unfilled resin wear significantly decreases with increasing temperature, while the dependence on the temperature of the wear intensity at an impingement angle of 45o is linear inversely proportional, and at an angle of 90o non-linear. The decrease in wear intensity is probably due to an increase in elasticity (an increase in the fracture strain limit) because of heating. Solid particle erosion of the examined filled epoxy compounds is considerably higher than that of unfilled compounds at impingement angles of 90o and 45o. Filled compounds showed ambiguous dependences of intensity of wear from temperature (especially at an angle of attack 45o), probably, character of dependence is defined by a filler share and the structural features of the samples caused by distribution of particles of the filler. Intensity of wear of the considered compounds at impingement angles 90o and 45o has high direct correlation with density and the modulus of elasticity (i.e., increases with their increase), and low correlation with bending strength of the considered materials. The data set for determining the correlation between mechanical properties and wear included characteristics due to both compound filling and test temperature.

The fruits and leaves of the black currant (BC, Ribes nigrum) contain phytochemicals with thera-peutic benefits. The current paper reports on a standardized BC gemmotherapy extract (BC-GTE) prepared from fresh buds, and details the extract specific flavonoid content, antioxidant, and an-ti-inflammatory properties, respectively. The main HPLC identified aglyka flavonoids were lute-olin, quercetin, apigenin and kaempferol, while all together, at about 133 phytonutrients could be detected in the reported BC-GTE, so that the BC specific presence of many compounds was re-ported for the first time. We also demonstrated that in adult male Wistar rats pretreated with BC-GTE, and assessed after the LPS injection, the body size modifications of the activated microglial cells in the hippocampal CA1 region were not apparent, and no elevated serum specific TNF-α levels were seen under such LPS induced inflammatory conditions. The specific flavonoid content, and the LPS induced in-flammatory model based experimental data are all suggesting that the assessed BC-GTE seems to feature anti-neuroinflammatory property, holding the promise of a novel GTE based comple-mentary therapeutic approach.

Micromobility has gained attention from policymakers, industry stakeholders, and academia; however, a comprehensive conceptualization of micromobility is still missing. Existing definitions are largely vehicle-centric: either listing modes or detailing vehicle characteristics. This paper addresses this gap by developing a ‘beyond vehicles’, multi-dimensional conceptualization of micromobility, accompanied by a novel socio-technical definition. Through a review of related concepts, combined with an analysis of the use and definitions of the term micromobility in publications, this study establishes a new conceptualization of micromobility. It incorporates human, social, and cultural dimensions, considers environmental, economic, infrastructure, vehicle technology, regulatory and policy aspects, and considerations for public health. Our definition of micromobility encompasses a wide range of mobility options typically used for shorter trips and manoeuvrable by an individual without motor assistance, at least for short distances. These modes are characterized by their ‘micro’ attributes, including low energy demand, environmental impact, and road space use relative to automobility. The conceptualization incorporates a range of micromobility modes, including fully human-powered (including walking), partially motor-assisted, and fully powered options. These modes typically operate at speeds not exceeding 25 to 32 kilometres per hour (or 45 km/h for faster options), weigh (typically substantially) below 350 kilograms and often yield significant (public) health benefits. Trip length is generally less than 15 kilometres, and daily distances under 80 kilometres. Importantly, our definition includes the practices, policies, cultures, and infrastructures that emerge around the use of micromobility options and shape their uptake. This proposed conceptualization significantly broadens the prevailing vehicle-focus in micromobility debates towards a socio-technical perspective. Embracing a widely accepted conceptualisation of micromobility would offer several advantages, including robust design standards, legislation, and evaluation metrics and methods. Additionally, this paper highlights the pivotal role micromobilities can play in transcending the limitations of automobility, towards more sustainable and equitable mobility futures.

For the soil in different regions, the nutrient fertility contained in it is different, and the detection and zoning management of soil nutrients before tillage every year can improve grain yield. In this paper, an integrated learning strategy model based on black soil hyperspectral data is designed for rapid classification of organic matter content classification of black soil. Soil hyperspectral image dataset of Xiangyang Experimental Base was collected; by changing the internal structure of the stacking model, an LSVM-stacking model with (MLP, SVC, DTree, XGBl, kNN) five classifiers as the L1 layer was built, and the simulated annealing algorithm was used for hyperparameter optimization. Compared to other stacking models, the LSVM-stacking metrics are significantly improved. The accuracy rate of hyperparameter optimization is improved by 38.6515%, the accuracy rate of the independent test data set is 0.9488, and the comparison of individual learners can improve the recognition classification accuracy of label"1" to 1.0.

Ischemia/reperfusion (I/R) injury results in cell death by inducing apoptosis. During I/R, early generation of mitochondrial reactive oxygen species (mtROS) can induce neighboring mitochondria to release additional ROS, a toxic cycle resulting in significant mitochondrial and cellular injury. Oxidative damage in the mitochondria contributes to various pathologies, including I/R injury. Accordingly, preventing mitochondrial oxidative damage should be therapeutically relevant for many disorders, including cardiovascular diseases. We recently discovered an Indole-Peptide-Tempo Conjugate (IPTC) that served as a novel bifunctional agent with both antioxidant and autophagy-modulating capacity. Here, we demonstrate that IPTC can protect H9C2 cardiomyocytes from hypoxia/reoxygenation (H/R) injury that results from mtROS overproduction due to impaired mitophagy and resultant mitochondrial dysfunction. We hypothesize that the mechanism of action of IPTC involves the capacity to decrease mtROS combined with induction of mitophagy.

The pulsating flow is one of the techniques which can enhance heat transfer, therefore leading to energy saving in tubular heat exchangers. This paper investigates the heat transfer and flow characteristics in a two-dimensional in-line tube bundle with the pulsating flow by a numerical method using the Ansys Fluent. Numerical simulation is performed for Reynolds number Re = 500 with different frequencies and amplitude of pulsation. Heat transfer enhancement was estimated from the central tube of the tube bundle. Pulsation velocity had an asymmetrical character with a reciprocating flow. The technique developed by the authors to obtain asymmetric pulsations was used. This technique allows simulating an asymmetric flow in heat exchangers equipped with a pulsation generation system. Increase in both the amplitude and the frequency of the pulsations has a significant effect on heat transfer enhancement. Heat transfer enhancement is mainly observed in the front and back of the cylinder. At a steady flow in these areas, heat transfer is minimal due to the weak circulation of the flow. The increase in heat transfer in the front and back of the cylinder is associated with increased velocity and additional flow mixing in these areas.

3,4-Dihydro-2(1H)-pyridones (3,4-DHPo) and their derivatives are privileged structures present in natural products, which has been increased its relevance due to its biological activity in front of a broad range of targets, but especially for its importance as synthetic precursors of a variety of compounds with marked biological activity. Taking into account the large number of contributions published over the years regarding this kind of heterocycle, here we presented a current view of 3,4-dihydro-2(1H)-pyridones (3,4-DHPo), which include general aspects such as those related to nomenclature, synthesis, and biological activity; but also highlighting the importance of DHPo as building blocks of other relevance structures.

Lumbar support exoskeletons with active and passive actuators are currently the cutting-edge technology for preventing back injuries in workers while lifting heavy objects. However, many challenges still exist in both types of exoskeletons, including rigid actuators, risks of human-robot interaction, high battery consumption, bulky design, and limited assistance. In this paper, the design of a compact, lightweight energy storage device combined with rotary series elastic (ES-RSEA) is proposed for use in a lumbar support exoskeleton to increase the level of assistance and exploit the human bioenergy during the two stages of the lifting task. ES takes the responsibility to store and release passive mechanical energy while RSEA provides excellent compliance and prevents injury from the human body's undesired movement. The experimental tests on the spiral spring showed excellent linear characteristics (above 99%) with an actual spring stiffness of 9.96 Nm/rad. The results demonstrate that ES-RSEA can provide maximum torque assistance in the ascent phase with 66.6 Nm while generating nearly 21 Nm of spring torque during descent without turning on the DC motor. Ultimately, the proposed design can maximize the energy storage of human energy, exploit the biomechanics of lifting tasks, and reduce the burden on human effort to perform lifting tasks.

The main aspects of material research: material synthesis, material structure, and material properties, are interrelated. Acquiring atomic structure information of electron beam sensitive materials by electron microscope, such as porous zeolites, organic-inorganic hybrid perovskites, metal-organic frameworks, is an important and challenging task. The difficulties in characterization of the structures will inevitably limit the optimization of their synthesis methods and further improve their performance. The emergence of integrated differential phase contrast scanning transmission electron microscopy (iDPC-STEM), a STEM characterization technique capable of obtaining images with high signal-to-noise ratio under lower doses, has made great breakthroughs in the atomic structure characterization of these materials. This article reviews the developments and applications of iDPC-STEM in electron beam sensitive materials, and provides an outlook on its capabilities and development.

Policies to require front-of-package labels (FOPLs) on foods may help Indian consumers better identify foods high in nutrients of concern including sugar, saturated fat, and sodium, and discourage their consumption, outcomes critical for preventing rises in diet-related non-communicable disease. The objective was to test whether FOPLs helped Indian consumers identify ‘high-in’ foods and reduce intentions to purchase them. We conducted an in-person randomized experiment (n=2,869 adults between ages 18 and 60 years old) in six states of India in 2022. Participants were randomized to one of five FOPLs: a control label (barcode), warning label (octagon with “High in [nutrient]”), Health Star Warning (HSR), Guideline Daily Amount (GDA), or traffic light label. Participants then viewed a series of foods high in sugar, saturated fat, or sodium with the assigned FOPL, and rated product perceptions and label reactions. Fewer than half of participants in the control group (39.1%) correctly identified all products high in nutrient(s) of concern. All FOPLs led to an increase in this outcome, with the biggest differences observed for the warning label (60.8%, p<0.001) followed by the traffic light label (54.8%, p<0.001), GDA (55.0%, p<0.001), and HSR (45.0%, p<0.01). Relative to the control, only the warning label led to a reduction in intentions to purchase the products. The results suggest that warning labels are the most effective FOPL to help Indian consumers identify and avoid unhealthy foods.

Previous studies reported the physical, transcriptomics and metabolomics changes in in-vitro acute heat stressed bovine granulosa cells. Granulosa cells exhibited transient proliferation senescence, oxidative stress, increased rate of apoptosis, and decline in steroidogenic activity. This study performs joint integration and network analysis of metabolomics and transcriptomics data to further narrow down and elucidate the role of differentially expressed genes, important metab-olites and relevant cellular and metabolic pathways in acute heat-stressed granulosa cells. Among significant (Raw P-value <0.05) metabolic pathways where metabolites and genes did converge, this study found Vitamin B6 metabolism, Glycine, serine and threonine metabolism, Phenylalanine metabo-lism, Arginine biosynthesis, Tryptophan metabolism, Arginine and proline metabolism, Histidine metabolism, and Glyoxylate and dicarboxylate metabolism. Important significant convergent bio-logical pathways included, ABC transporters and Protein digestion and absorption, while func-tional signaling pathways included cAMP, mTOR, and AMPK signaling pathways together with Ovarian steroidogenesis pathway. Among caner pathways, the most important pathway was Central carbon metabolism in cancer. Through multiple analysis query, Progesterone, Serotonin, citric acid, Pyridoxal, L-Lysine, Succinic acid, L-Glutamine, L-Leucine, L-Threonine, L-Tyrosine, Vitamin B6, Choline, and CYP1B1, MAOB, VEGFA, WNT11, AOX1, ADCY2, ICAM1, PYGM, SLC2A4, SLC16A3, HSD11B2 and NOS2 appeared to be important enriched metabolites and genes, respectively. These genes, metabolites, metabolic, cellular and cell signaling pathways com-prehensively elucidate the mechanisms underlying the intricate fight between death and survival in acute heat-stressed bovine granulosa cells, and essentially help further our understanding and future quest of research in this direction.

SGLT2 inhibitors act to induce glucosuria and have been shown to be efficacious in the treatment of type II diabetes mellitus but have also been shown to positively affect cardiovascular conditions and some benefitting kidney function. SGLT2i have shown to be effective in more advanced conditions but may eventually be a treatment in more general metabolic dysfunction. Metabolic syndrome is a clinical diagnosis for establishing risk for ischemic heart disease and diabetes. The prevalence of type II diabetes mellitus, heart disease, and severe vascular events steadily increased over recent decades. In addition to the established benefits of diet and exercise, SGLT2 inhibitor therapy may be able to aid in the treatment of metabolic syndrome from its proven cardiovascular and anti-hyperglycemic benefits. Pharmacologic modeling in canines is also considered, as they present with similar diagnoses and offer a model that shares many of the characteristics of humans in metabolic dysfunction.

In this review, photoinduced electron transfer processes in specifically designed assembled ar-chitectures have been investigated on the basis of recent results reported from our laboratories. A convenient and useful way to study these kinds of systems has been described in order to under-stand the rules that drive to a light induced charge separation and its subsequent decay to the ground state, also with the aim of offering a tutorial for young researchers. Assembled systems of covalent or supramolecular nature have been presented and some functional multicomponent systems for the conversion of light energy into chemical energy have been discussed.

The location and number data of individual fruit trees are critical for planting area investigation, fruit yield prediction, and smart orchard management and planning. These data are conventionally obtained through manual investigation and statistics with time-consuming and laborious effort. Object detection models in deep learning used widely in computer vision could provide an opportunity for accurate detection of individual fruit trees, which is essential for rapidly obtaining the data and reducing human operations errors. This study proposes an approach to detecting individual fruit trees and mapping their spatial distribution by integrating deep learning with unmanned aerial vehicle (UAV) remote sensing. UAV remote sensing collected high-resolution true-color images of fruit trees in the experimental pomelo tree orchards in Meizhou city, South China. An image dataset of deep learning samples of individual pomelo trees (IPTs) was constructed through visual interpretation and field investigation based on the fruit tree images captured by UAV remote sensing. Four different scales of YOLOv5 (YOLOv5s, YOLOv5m, YOLOv5l, and YOLOv5x) for object detection were selected to train, validate, and test on the image dataset of pomelo trees. The results show that the average precision (AP@0.5) of the four YOLOv5 models for validation reach 87.8%, 88.5%, 89.1%, and 90.7%, respectively. The larger the model scale, the higher the average accuracy of the detection result of validation. It suggests that YOLOv5x is a preferred high-accuracy model among the YOLOv5 family and is suitable to realize the detection of IPTs. The number of the IPTs in the study area was counted using YOLOv5x, and their spatial distribution map was made using the non-maximum suppression method and ArcGIS software. This study will provide primary data and technical support for smart orchard management in Meizhou city and other fruit-producing areas.

The Covid-19 pandemic caused a shift in teaching practice towards blended learning for many Higher Education institutions. This led to the rapid adoption of certain digital technologies within existing teaching structures as a means to meet student access needs and facilitate learning. Integration of these technologies caused numerous challenges for practitioners and often provided mixed results. This paper is an attempt to summarise and extend pre-Covid pedagogical research to leverage digital immersive technologies for blended teaching in the post-pandemic era. Focus is given towards the evolution of Virtual Learning Environments through elements of immersive audio-visual technologies, which are shown to be effective when coupled in a blended approach. It is both a review of these methodologies and a case study of the I-Ulysses: Virtual Learning Environment as a point of comparison for evaluating the review.

CD44 is a cell surface glycoprotein, which is widely expressed on normal and cancer cells. CD44 is involved in cell adhesion, migration, proliferation, survival, stemness, and chemo-resistance. Therefore, CD44 is thought to be a promising target for cancer diagnosis and therapy. In this study, we established anti-CD44 monoclonal antibodies (mAbs) by immunizing mice with CD44v3-10 ectodomain and screening using enzyme-linked immunosorbent assay. We then characterized them using flow cytometry, western blotting, and immunohistochemistry. One of the established clones (C44Mab-46; IgG1, kappa) reacted with CD44s-overexpressed Chinese hamster ovary-K1 cells (CHO/CD44s) or esophageal squamous cell carcinoma (ESCC) cell lines (KYSE70 and KYSE770). The KD of C44Mab-46 for CHO/CD44s, KYSE70, and KYSE770 was 1.1×10-8 M, 4.9×10-8 M, and 4.1×10-8 M, respectively. C44Mab-46 detected CD44s of CHO/CD44s and KYSE70, and CD44v of KYSE770 in western blot analysis. Furthermore, C44Mab-46 strongly stained esophageal squamous carcinoma cells in immunohistochemistry using formalin-fixed paraffin-embedded ESCC tissues. Taken together, C44Mab-46 is very useful for detecting CD44 in various applications.

The extracts of Garcinia mangostana L. (mangosteen) are traditionally used for medicinal purposes in Asia. Phenols and xanthones are the two main phenolic compounds with anti-inflammatory activities in the pericarps of mangosteen. A simple and economic reverse-phase high-performance liquid chromatography (RP-HPLC) method has been developed for the simultaneous quantification of phenols (catechin, epicatechin, and procyanidin B2) in mangosteen. The mobile phase was acetonitrile: water (12:88) at 30°C, the flow rate was 1 mL/min, and the detection wavelength was 230 nm. The results showed good linear relationships for catechin from 50-250 ng and for epicatechin and procyanidin B2 from 250-1250 ng. The RP-HPLC fingerprint determination method of total xanthones in mangosteen was also established to provide a new method for quality control of mangosteen extract. The mobile phase was a methanol-water gradient elution at 30°C, the flow rate was 1 mL/min, and the detection wavelength was 320 nm. The similarity of fingerprints of 10 batches of total xanthones was more than 0.90. These methods had good precision, reproducibility, and stability and can be applied in the quality control of mangosteen extracts for medicinal purposes.

The unavoidable progression of EGFR-mutated NSCLC on EGFR-TKIs forces us to discover solutions for further therapies. Herein, we discuss the necessity of accurate genomic mapping of progressive disease illustrated by a patient case. Tumor rebiopsies at progression are strongly needed to characterize acquired resistance to EGFR-TKI. The necessary data, however, may be reliably obtained only by deep targeted next generation sequencing (NGS) of both DNA and RNA. The reported case is a patient with EGFR-mutant NSCLC, who progressed during second line Osimertinib with subsequent targeted treatment determined by the detection of an acquired intergenic ANK3-RET-fusion with concomitant PTEN-mutation and MDM2-amplification. These three acquired gene alterations represent potential mechanisms of TKI-resistance, not previously reported on second line Osimertinib. Yet, while PTEN-mutations and MDM2-amplification are currently undruggable, the ANK3-RET fusion allowed further personalized treatment by combining continuation of Osimertinib with the RET-TKI Pralsetinib, which resulted in objective partial response, so far for 7 months, and significant clinical improvement. Hence, complementary DNA- and RNA-based targeted NGS may be of importance in clinical routine to better reveal the current molecular state of the disease and contribute to the identification of further targeted therapy strategies. Indeed, further cases with acquired RET-fusions, including ANK3-RET, should be investigated to fully determine the effectiveness of RET-TKI-Osimertinib combinations.

The current study evaluates the selection signals in the evolution of mitochondrial DNA of voles, subfamily Arvicolinae, during the colonization of subterranean environments. The comparative sequence analysis of mitochondrial protein-coding genes of eight subterranean vole species (Prometheomys schaposchnikowi, three species of the genus Ellobius: E. talpinus, E. fuscocapillus and E. lutescens, two species of the genus Terricola: T. subterraneus and T. daghestanicus, Lasiopodomys mandarinus and Hyperacrius fertilis) and their closest aboveground relatives using codon-substitution models was applied. The highest number of selection signatures was detected in genes ATP8 and CYTB. The relaxation of selection was observed in most mtDNA protein-coding genes. In mole voles (genus Ellobius) the signatures of adaptive evolution of mitochondrial genes related to subterranean niche were most pronounced. The number of selection signatures was found to be independent of the evolutionary age of the lineage but fits the degree of specialization to the subterranean niche. The common trends of selective pressures were observed among the evolutionary ancient and highly specialized subterranean rodent families and phylogenetically young lineages of voles. It suggests that the signatures of adaptations in individual mitochondrial protein-coding genes associated with the colonization of the subterranean niche may appear within a rather short evolutionary timespan.

Abstract: The effect of collagen type 1 (Col I) oxidation on Adipose Tissue-Derived Mesenchymal Stem Cells (ADMSCs) remodeling is described as a model for acute oxidative stress. Morphologically, remodeling was presented by a mechanical rearrangement of adsorbed FITC-Col I and a trend for its organization in a fibril-like pattern - a process strongly abrogated in oxidized samples, but without visible changes in cell morphology. The cellular proteolytic activity was quantified in multiple samples utilizing fluorescence de-quenching (FRET effect). In the presence of ADMSCs a significant increase of native FITC-Col I fluorescence was observed, almost absent in the oxidized samples. Parallel studies in cell-free systems confirmed the enzymatic de-quenching of native FITC-Col I by Clostridial collagenase, again showing significant inhibition in oxidized samples. The structural changes in the oxidized Col I was further studied by Differential Scanning Calorimetry: an additional endotherm at 33.6°C along with the typical for native Col I at 40.5°C with sustained enthalpy (∆H) was observed in oxidized samples. Collectively, it has been evidenced that remodeling of Col I by ADMSCs is altered upon oxidation due to the intrinsic changes in the protein structure, thus presenting a novel mechanism for the control of stem cells' behavior toward collagen.

Importance: p53 is an unequivocal tumor suppressor altered in half cancers. The immune system produces systemic p53 autoantibodies (p53 Abs) in many cancer patients. Objective: The focus of this systemic review and meta-analysis is on the prognostic value of p53 Abs expressed in the serum of patients with solid tumors. Data Sources: All the clinical investigations were searched on PubMed, MBase and Cochrane from 1993 reporting the first study until May 2021. Study Selection: Studies were included that met the following criteria: 1) participants with cancer; 2) outcome results expressed in relation to the presence of a p53 antibody; 3) a primary outcome (disease free survival, overall survival or progression free survival) expressed as hazard ratio (HR). The following exclusion criteria were used: 1) insufficient data available to evaluate outcomes; 2) animal studies; 3) studies with less than 10 participants. 1333 potentially relevant articles; studies as duplicates, non-patients studies or reviews were excluded. After viewing the titles and abstracts of the 52 remaining studies, the full texts of 34 studies were retrieved and 12 studies were included in the analysis. Data Extraction and Synthesis: PRISMA guidelines were used for abstracting and assessing data quality and validity by three independent observers. The summary estimates were generated using a fixed-effect model (Mantel–Haenszel method) or a random-effect model (DerSimonian–Laird-method) depending on the absence or presence of heterogeneity (I2). Main Outcome(s) and Measure(s): The primary study outcome was to determine the prognostic value of p53 Abs from a large population size of patients with solid tumors, as determined before data collection. Results: In total 12 clinical studies and of which 2094 patients were included and it was determined that p53-wt Abs expression in the serum significantly correlated with a worse survival of cancer patients (95% CI 1.48 [1.24, 1.77]; p<0.00001). On the contrary, data from literature indicated that there was a potential association between p53-mut Abs antibodies with better survival. Conclusions and Relevance: This is the first meta-analysis proving the diagnostic utility of p53-Abs for cancer patients, predicting a worse outcome. The serum-p53 value (s-p53-value) could be useful for future theranostics.

In this manuscript we use an exactly solvable stochastic binary model for regulation of gene expression to analyse the dynamics of response to a treatment aiming to modulate the number of transcripts of RKIP gene. We demonstrate the usefulness of our method simulating three treatment scenarios aiming to reestablish RKIP gene expression dynamics towards pre-cancerous state: i. to increase the promoter’s ON state duration; ii. to increase the mRNAs’ synthesis rate; iii. to increase both rates. We show that the pre-treatment kinetic rates of ON and OFF promoter switching speeds and mRNA synthesis and degradation will affect the heterogeneity and time for treatment response. Hence, we present a strategy for reducing drug dosage by simultaneously targeting multiple kinetic rates. That enables a reduction of treatment response time and heterogeneity which in principle diminishes the chances of emergence of resistance to treatment. This approach may be useful for inferring kinetic constants related to expression of antimetastatic genes or oncogenes and on the design of multi-drug therapeutic strategies targeting master regulatory genes.

Farmers and seed companies constantly require high-quality seeds with excellent agronomic performance. However, faced with environmental adversity, limited natural resources and increasing food demand around the globe, more attention has turned to improving crop plant production by implementing efficient strategies. Seed priming technology has shown promising biological improvements leading to suitable agronomic performance in crop plants under adverse environmental conditions. Seeds are subjected to controlled conditions that are conducive to complex physiological, biochemical, and molecular changes, conferring specific stress tolerance to subsequent germination and growth conditions. In this review paper, we aimed to study the recent approaches in the efficiency of hydropriming, osmopriming, chemopriming, hormopriming, nanopriming, matrix priming, biopriming, physical priming and hybrid priming procedures in the production of crop plants under environmental adversity, as well as their biological mechanism changes. All priming methods demonstrated relevant changes in the biological mechanism related to crop plant production by mitigating salinity effects, heavy metals, and flooding stress and enhancing chilling, heat, drought and phytopathogen tolerance. We strongly recommend that researchers combine multiple priming methods, known as hybrid priming, in their investigations to provide novel technologies and additional biological approaches to enhance the knowledge of crop plant science. Thus, the findings shed light on the use of seed priming technology as a key strategy to increase crop plant production under environmental adversity by acquiring stress tolerance and enhancing agronomic traits to meet the global food demand.

Since the exploitation of mineral resources results in the release of radionuclides, and consuming radionuclides affects public health in the short and long term. A case study of the environmental radiation impact from coal mining and germanium processing was carried out in southwest China. The coal mines contain germanium and uranium and have been exploited for more than 40 years. The farmlands around the site of coal mining and germanium processing have been contaminated by the solid waste and mine water in some extend since then. Samples of crops have been collected from contaminated farmlands in research area. The research area covers a radius of 5 km, in which there are 2 coal mines located. 210Pb and 210Po have been analyzed as the key radionuclides during monitoring program. The average activity concentrations of 210Pb and 210Po in the crops were 1.38 and 1.32 Bq/kg in cereals, 4.07 and 2.19 Bq/kg in leafy vegetables and 1.63 and 1.32 Bq/kg in root vegetables. The annual effective doses due to the ingestion of 210Pb and 210Po in consumed crops have been estimated for adult residents living in research area. The average annual effective dose was 0.336mSv/a, while the minimum was 0.171 mSv/a and the maximum was 0.948 mSv/a. The results show that crops grown on contaminated farmland contained an enhanced level of radioactivity concentration. Ingestion doses of local residents in research area were significantly higher than the China average level of 0.112 mSv/a, and the world average level of 0.042 mSv/a through 210Pb and 210Po in crops intake respectively.

The emergence of multi-drug resistant E. coli is an important matter of increasing considerable concern to global public health. The aim of this study was to investigate the incidence, antibiotic resistance pattern, phylogroups and genetic variation of E. coli isolates from raw milk, vegetable salad and ground meat samples. Methods: Culture-based techniques, Kirby-Bauer disk diffusion susceptibility testing, PCR and RAPD assays were used to determine the incidence rate, antimicrobial resistance pattern, phylogenetic groups and genetic diversity of the E. coli isolates. Results: E. coli isolates were highly resistant to amoxicillin (79.16%), trime-thoprim-sulfamethoxazole (70.83%), amoxicillin-clavulanic acid (62.50%), tetracycline (54.16%), chloramphenicol (54.16%), nitrofurantoin (54.16%), ampicillin (45.83%), streptomycin (45.83%), and kanamycin (33.33%); and completely susceptible to norfloxacin and azithromycin. 70.83% of the isolates were multi-drug resistant. Most E. coli isolates (46%) belonged to phylogroup A. RAPD with UBC245 primer categorized the isolates into 11 clusters. A high level of genetic di-versity was found among the isolates; however, 33.3% of the isolates were grouped in a major cluster (R5). Conclusions: Antibiotic resistance patterns are randomly distributed among the ge-netic clusters. Novel, practical, efficient food safety control and surveillance systems of multi-drug resistant foodborne pathogens are required to control the foodborne pathogen contamina-tion.

Black horehound (Ballota nigra L.) is one of the important medicinal plants, which is a rich source of health-promoting essential oils. Salinity stress affects plant development and alters the quality and quantity of plants extracts and their composition. This study was aimed to investigate the effect of salinity on morphological, physiological characteristics, and secondary metabolites of B. nigra under greenhouse, and in vitro culture conditions. The plants were treated with different concentrations of NaCl (25, 50, 75, 100 mM) and fresh and dry weight of leaf and stem were measured as well as morphological characteristics of the plant. Plant growth was reduced with the increased salinity concentrations. The results showed that all growth-related traits and SPAD were decreased both in vivo and in vitro. Additionally, increased salt concentration affected the cell membrane integrity. Total phenolics content of plants growing in the greenhouse, increased by 21% at 50 mM NaCl, but at higher stress levels (100 mM NaCl), the amounts were decreased significantly. Total flavonoids contents followed similar patterns, with a slight difference. In addition, the maximum and minimum total phenolics contents of plants growing under in vitro condition were observed at 50 mM NaCl and control treatments, respectively. Increasing the salt concentration significantly affected the total flavonoids content, and as a result, the highest amount was observed in 50 and 75 mM NaCl treatments. Antioxidant activity was also measured. Among the NaCl treatments, the highest DPPH scavenging activities (IC50) under greenhouse and in vitro conditions were detected at 50 mM and 25 mM concentrations, respectively. In general, based on the results, with increasing the salinity level to 75 mM, the activities of CAT and APX were significantly upregulated in both greenhouse and in vitro culture conditions. A correlation between total phenolics and flavonoids contents as well as antioxidant activity were obtained. With shifting salinity stress, the type and the amount of the identified essential oil compounds changed. Compounds such as styrene, tridecanol, germacrene-D, beta-Ionone, beta-bisabolene, and caryophyllene oxide increased compared to the controlled treatment.

Climate change has had a significant impact on many ecosystems worldwide, prompting native population species to adapt to the current weather patterns eventually. Pre-existing genetic variation in populations explains part of this adaptation. Still, recent studies have shown that new stable phenotypes can be generated through epigenetic modifications in just a few generations, thereby contributing to the stability and survival of plants in their natural habitat as they eventually adjust to the surrounding impacts. The state of chromatin inside plant cells varies, allowing cells to fine-tune their transcriptional profiles to better adapt to stimuli from the external environment. Within a cell, chromatin state changes such as post-transcriptional histone modifications and variations, DNA methylation, and non-coding RNA activity are all examples of chromatin state alterations that may epigenetically dictate certain transcriptional outputs. Recent advances in the field of ‘Omics’ in major crops has made it easier to identify epigenetic changes and their impact on plant responses to environmental stresses. These epigenetic mechanisms thus play an important role in improving crop adaptation and resilience to changing environments. This variation that has emerged can thus be exploited in crop breeding, ultimately leading to the generation of stable climate-resilient genotypes.

p53 is among the most frequently mutated tumor suppressor genes given its prevalence in >50% of all human cancers, including high grade serous endometrial cancers and ovarian cancers. In addition to loss of tumor suppression function, many mutated p53 (Mutp53) proteins acquire gain-of-function (GOF) activities as oncogenes to promote cancer progression, which manifest through aberrant expression of p53. As we have come to see, statins induce CHIP-mediated degradation of mutp53 by blocking the interaction between mutp53 and DNAJA1. Therefore, targeting critical downstream pathways of mutp53 provides an alternative strategy for treating cancers expressing mutp53. In this review, we summarize recent advances with Wee1 inhibitors and mevalonate pathway inhibitors, particularly statins, regarding their use in gynecological cancers with p53 mutations.

Objective: To investigate the protein expression levels of cyclin‑dependent kinase subunit 2 (CKS2) and cluster of differentiation (CD) 47 in gastric cancer (GC) and their clinical significances. Methods: A total of 126 GC patients who underwent radical resection were selected as study subjects. Additionally, 32 patients with benign gastric tumor, 42 patients with low-grade intraepithelial neoplasia (LGIEN), and 49 patients with high-grade intraepithelial neoplasia (HGIEN) who underwent surgery were selected as the control groups. Immunohistochemistry was used to detect the expression of CKS2 and CD47 in surgical specimens. We statistically analyzed the clinical significance of the expression of the two factors. Results: (1) The positivity rates for CKS2 in benign gastric tumor tissue, LGIEN tissue, HGIEN tissue, and GC tissue gradually increased, i.e., 6.3% (2/32), 30.9% (13/42), 38.8% (19/49), and 60.3% (76/126), respectively, and the positivity rates for CD47 were 18.8% (6/32), 38.1% (16/42), 46.9% (23/49), and 65.9% (83/126), respectively. (2) High expression of CKS2 and CD47 were associated with tumor diameter, Lauren classification, number of lymph node metastases, and TNM stage. In addition, the immunohistochemical scores for CKS2 and CD47 were positively correlated (r=0.625, P=0.000). (3) The median follow-up time of 126 patients was 46.5 months, and the overall survival rate was 40.5% (51/126). Survival analysis showed that compared with that in the CKS2 (-) group, the overall survival rate for patients in the CKS2 (+) group was significantly worse (25.0% vs 64.0%, 2=15.67, P=0.000) and that compared with the CD47 (-) group, the CD47 (+) group had significantly worse overall survival (30.1% vs 60.5%, 2=15.67, P=0.000). (4) The overall survival rates of CKS2(+)CD47(+) group, CKS2(+)CD47(-) group, CKS2(-)CD47(+) group, and CKS2 (-)CD47 (-) group were 20.0%(13/65), 58.3%(7/12), 57.1%(8/14), 65.7% (23/35), respectively, the prognosis of patients in CKS2(+)CD47(+) group was significantly poor. Conclusion: High expression levels of CKS2 and CD47 were closely related to the occurrence of GC and can be used as independent risk factors to assess the prognosis of patients.

Artificial Intellignece (AI) is a platform lending immense assistance in discovering and developing drugs and thus, various such approaches have been developed with the intent of simplifying and improving biomedical operations such as drug repurposing and drug discovery. In the past decade, AI-based investigation of nanomedicines, as well as non-nanomedicines has reached the clinical level. In semblance with the traditional methods of therapy, nanomedicine therapy is employed at limited doses. The study of a variety of drugs resulted in the conclusion that the effect of each drug is variable for every patient and, evaluating that perfect drug combination manually is a time-consuming as well as an inefficient treatment method. Therefore, the use of AI simplifies and reduces the time consumption in determining the perfect customized drug combination for nano-therapy. The area with the most potential for meeting this reality is to optimize the drug and dosage parameters. It is a universally known fact that cancer is dangerous and unique because of the exacting challenges it poses during treatment and, to achieve a better treatment, the therapeutic effect on each patient must be delineated even if the volume of data generated is massive. The article aims at analyzing the AI technologies that help yield results much quicker, make the analyses simple, and efficient.

Obesity is a complex chronic disease characterized by excess of body fat. It represents a significant public health problem due to the health-related risk factors. There are growing evidences showing that maternal obesity can program the offspring, which influence neonatal phenotype and predispose offspring to a higher prevalence of metabolic disorders such as obesity. This increased risk may also be epigenetically transmitted across generations. Thus, there is an urgent need to find effective reprogramming approaches in order to resume normal fetal development. Polyphenols are bioactive compounds found in fruits and vegetables that exert their anti-obesity effect through its powerful anti-oxidant and anti-inflammatory activities. Polyphenols supplementation has been proven to counteract the deleterious effects of maternal obesity programming on offspring. Indeed, some polyphenols can cross the placenta and protect the fetal predisposition against obesity. The present review summarizes the effects of dietary polyphenols on obesity-induced maternal reprogramming as an offspring anti-obesity approach.

The nucleosome is a major modulator of DNA accessibility to other cellular factors. Nucleosome positioning has a critical importance in regulating cell processes such as transcription, replication, recombination or DNA repair. The DNA sequence is a major factor influencing the position of nucleosomes on genomes. Different sequence motifs can promote or inhibit the nucleosome formation, thus influencing the accessibility to the DNA. Sequence-encoded nucleosome positioning having functional consequences on cell processes can then be selected or counter-selected during evolution. We review the interplay between sequence evolution and nucleosome positioning evolution. We first focus on the different ways to encode nucleosome positions in the DNA sequence, and to which extent these mechanisms are responsible of genome-wide nucleosome positioning in vivo. Then, we discuss the findings about selection of sequences for their nucleosomal properties. Finally, we illustrate how the nucleosome can directly influence sequence evolution through its interactions with DNA damage and repair mechanisms. This review aims to provide an overview of the mutual influence of sequence evolution and nucleosome positioning evolution, possibly leading to complex evolutionary dynamics.

Triple negative breast cancer (TNBC) is an aggressive subtype of the disease with poor clinical outcomes and limited therapeutic options. Immune checkpoint blockade (CP) has surged to the forefront of cancer therapies with widespread clinical success in a variety of cancer types. However, the percentage of TNBC patients that benefit from CP as a monotherapy is low and clinical trials have shown the need for combined therapeutic modalities. Specifically, there has been interest in combining CP therapy with radiation therapy where clinical studies primarily with external beam have suggested their therapeutic synergy, contributing to the development of anti-tumor immunity. Here, we have developed a therapeutic platform combining radionuclide therapy (RT) and immunotherapy utilizing a radiolabelled biomolecule and CP in an E0771 murine TNBC tumor model. Survival studies show that while neither monotherapy is able to improve therapeutic outcomes, the combination of RT + CP extended overall survival. Histologic analysis showed that RT + CP increased necrotic tissue within the tumor and decreased levels of F4/80+ macrophages. Flow cytometry analysis of the peripheral blood also showed that RT + CP suppressed macrophages and myeloid-derived suppressive cells, both of which actively contribute to immune escape and tumor relapse.

Objective: To study the changes in urine metabolism in female water polo players before and after high-intensity training by using ultra-high performance liquid chromatography-mass spectrometry, and to explore the biometabolic characteristics of urine after training and competition. Methods: Twelve young female water polo players (except goalkeepers) from Shanxi Province were selected. A 4-week formal training was started after one week of acclimatization according to experimental requirements. Urine samples (5 ml) were collected before formal training, early morning after 4 weeks of training, and immediately after 4 weeks of training matches, and labeled as T1, T2, and T3, respectively. The samples were tested by LC-MS after pre-treatment. XCMS, SIMCA-P 14.1, and SPSS16.0 were used to process the data and identify differential metabolites. Results: On comparing the immediate post-competition period with the pre-training period (T3 vs T1), 24 differential metabolites involved in 16 metabolic pathways were identified, among which niacin and niacinamide metabolism and purine metabolism were potential post-competition urinary metabolic pathways in the untrained state of the athletes. On comparing the immediate post-competition period with the post-training period (T3 vs T2), 10 metabolites involved in 3 metabolic pathways were identified, among which niacin and niacinamide metabolism was a potential target urinary metabolic pathway for the athletes after training. Niacinamide, 1-methylnicotinamide, 2-pyridone, L-Gln, AMP, and Hx were involved in two metabolic pathways before and after the training. Conclusion: Differential changes in urine after water polo games are due changes in the metabolic pathways of niacin and niacinamide.

RNA editing involves the insertion, deletion or substitution of single nucleotides within a RNA molecule, without altering the DNA sequence. Adenosine to inosine (A-to-I) editing consists of an RNA modification where single adenosines along the RNA sequence are converted into inosines. Such a biochemical transformation is catalyzed by enzymes belonging to the family of adenosine deaminases acting on RNA (ADARs) and occurs either co- or post-transcriptionally. Initially, the A-to-I RNA editing phenomenon was discovered and studied in messenger RNAs (mRNAs), where it can influence RNA splicing and cause the recoding of codon sequences. The employment of more powerful, high-throughput detection methods has recently revealed that A-to-I editing widely occurs in non-coding RNAs, including microRNAs (miRNAs). MiRNAs are a class of small regulatory non-coding RNAs (ncRNAs) acting as translation inhibitors, known to exert relevant roles in controlling cell cycle, proliferation, and cancer development. Indeed, a growing number of recent researches have evidenced the importance of miRNA editing in cancer biology by exploiting various detection and validation methods. Herein, we briefly overview early and currently available A-to-I miRNA editing detection and validation methods and discuss the significance of A-to-I miRNA editing in human cancer.

During the 1970s, Tunisian durum wheat landraces were replaced progressively by modern cultivars. These landraces are nowadays maintained by smallholder farmers in some ecological niches and are threatened gradually by extinction resulting on the narrowing of the genetic diversity. This study aims to investigate patterns of phenotypic variability using twelve quantitative traits in a panel of 189 durum wheat landraces and seven checks, based on farmer’s population name attribution and genetic structure. Our results showed high phenotypic variability among and within landraces and checks for the majority of the studied traits. The principal components analysis showed similar grouping using farmers name attribution and genetic structure using K = 6, which confirmed the identification of a new gene pool in the oases of Tunisia, represented by the sub-population Jenah Zarzoura and the robustness and high relationships between phenotypic and genome-wide genetic structure using DArTseq method. These findings will enhance the conservation efforts of these landraces and their use in breeding efforts at national and international levels to adapt to dry conditions.

Satellite Image Time Series (SITS) is a data set which includes satellite images across several years with a high acquisition rate. Radiometric normalization is a fundamental and important preprocessing method for remote sensing applications using SITS due to the radiometric distortion caused by noise between images. Normalizing the subject image based on the reference image is a general strategy when using traditional radiometric normalization methods to normalize multi-temporal imagery (usually two scenes or three scenes in different time phases). However, these methods are not suitable for calibrating SITS because they cannot minimize the radiometric distortion between any pair of images in SITS. The existing relative radiometric normalization methods for SITS are based on linear assumptions which cannot effectively reduce nonlinear radiometric distortion caused by continuously changing noise in SITS. To overcome this problem and obtain a more accurate SITS, this study proposed a Nonlinear Radiometric Normalization Model (named NMAG) for SITS based on Artificial Neural Networks (ANN) and Greedy Algroithm (GA) . In this method, GA was used to determine the correction order of SITS and calculate the error between the image to be corrected and normalized images, which avoided the selection of a single reference image. ANN was used to obtain the optimal solution of error function, which minimized the radiometric distortion between different images in SITS. SITS composed of 21 Landsat-8 images in Tianjin City from October 2017 to January 2019 were selected to test the method. We compared NMAG with other two contrasting method (refered as CM1 and CM2), and found that the average of root mean square error $(\mu_{RMSE})$ of NMAG $(497.22)$ was significantly smaller than those of CM1 $(641.39)$ and CM2 $(543.47)$, and the accuracy of normalized SITS obtained by using NMAG has increased by 22.4\% and 8.5\% toward CM1 and CM2, respectively. These experimental results confirmed the effectiveness of NMAG in the reduction of radiometric distortion caused by continuously changing noise between images in SITS.

To sustain water-dependent economic and socio-ecological systems, natural capital and its interactions with other capitals is gaining attention, but a clear understanding of how to manage natural capital sustainably and how to make decisions relevant to water-related ecosystem services is yet to be achieved. In this study, we extended the framing of water-related ecosystem service flows as a cycle, integrating water quantity and quality and capturing the flows of ecosystem services (i.e., green phase) and ecosystem disservices (i.e., red phase), and connecting natural capital, built capital, and beneficiaries. We applied this framework to the Jiulong River watershed in China, using hydrological models to model water quantity and quality based on historical observations and experimental data. Our results showed that, during the green phase, the interactions of natural capital and built capital significantly improved water quality in downstream areas with higher flows. During the red phase, built capital reduced ecosystem disservices by ~10% while natural capital further reduced it by over one half. Our framework can provide information for natural capital management, eco-compensation, and pollutant management relevant to water-related ecosystem services.

Protein oligomerzation is key to countless physiological processes, but also to abnormal amyloid conformations implicated in over 25 mortal human diseases. Angiogenin (h-ANG), a ribonuclease A family member, produces RNA fragments that regulate ribosome formation, the creation of new blood vessels and stress granule function. Too little h-ANG activity leads abnormal protein oligomerization resulting in Amyotrophic Lateral Sclerosis (ALS) or Parkinson’s disease. While a score of disease linked h-ANG mutants has been studied by X-ray diffraction, some elude crystallization. There is also debate regarding the structure that RNA fragments adopt after cleavage by h-ANG. Here, to better understand the beginning of the process that leads to aberrant protein oligomerization, the solution secondary structure and residue-level dynamics of WT h-ANG and two mutants: H13A and R121C, are characterized by multidimensional heteronuclear NMR spectroscopy under near physiological conditions. All three variants are found to adopt well folded and highly rigid structures in solution, although the elements of secondary structure are somewhat shorter than those observed in cystallography studies. R121C alters the environment of nearby residues only. By constrast, the mutation H13A affects local residues as well as nearby active site residues residues K41 and H119. The conformation characterization by CD and 1D 1H NMR spectroscopies of tRNAAla before and after h-ANG cleavage reveals a retention of most duplex structure and little or no G-quadruplex formation.

BioPBS is gaining attention in the biodegradable polymer market due to their promising properties such as high biodegradability and processing versatility representing a potential sustainable replacement for fossil oil-based commodities. However, there is still a need to enhance its properties for certain applications, being aesthetical and mechanical properties a challenge. The aim of the present work is to improve these properties by adding selected additives that will confer bioPBS with comparable properties to that of current counterparts such as polypropylene (PP) for specific applications in the automotive and household appliances sectors. A total of thirteen materials have been studied and compared, being twelve biocomposites containing combinations of three different additives: a commercial red colourant, itaconic acid (IA) to enhance colour fixation and zirconia (ZrO2) nanoparticles to maintain at least native PBS mechanical properties. Results show that the combination of IA and the colouring agent tends to slightly yellowish the blend due to the absorbance spectra of IA and also to modify the gloss due to the formation of IA nanocrystals that affects light scattering. In addition, for low amounts of IA (4wt.%), young modulus seems to be kept while elongation at break is even raised. Unexpectedly, a strong aging affect was found after 4 weeks. IA increases the hydrophilic behaviour of the samples and thus seems to accelerate the hydrolisation of the matrix, which is accompanied by an accused disaggregation of phases and an overall softening and rigidization effect. The addition of low amounts of ZrO2 (2wt.%) seems to provide the desired effect for hardening the surface while almost not affecting the other properties; however, higher amounts tends to form aggregates saturating the compounds. As a conclusion, IA might be a good candidate for colour fixing in biobased polymers.

Molluscan aquaculture is a major contributor to global seafood production, but is hampered by infectious disease outbreaks which can cause serious economic losses. Selective breeding has been widely used to improve disease resistance in major agricultural and aquaculture species, and has clear potential in molluscs, albeit its commercial application remains at a formative stage. Advances in genomic technologies, especially development of cost-efficient genomic selection, have potential to accelerate genetic improvement. However, tailored approaches are required due to the distinctive reproductive and lifecycle characteristics of molluscan species. Transgenesis and genome editing, in particular CRISPR/Cas systems, have been successfully trialled in molluscs, and may further understanding and improvement of genetic resistance to disease through targeted changes to the host genome. Whole organism genome editing is achievable on a much greater scale compared to other farmed species, making genome-wide CRISPR screening approaches plausible. This review discusses the current state and future potential of selective breeding, genomic tools, and genome editing approaches to understand and improve host resistance to infectious disease in molluscs.

The way in which the human being learns certain complex contents has always been a focus of interest and a challenge for researchers. Given the fact that children's cognitive abilities do not fully develop until a certain age, this topic is particularly important in the young children's learning scope as they do not correctly and easily learn some content of abstract nature, such as contents in math class. This work presents the results of the use of an application called "Mathematics Learning System with Augmented Reality based on Kinect" (SAM-RAK by its acronym in Spanish), which was designed to cover basic topics of mathematics in the Basic General Education level (EGB by its acronym in Span-ish) in Ecuador. The research was carried out under an experimental quantitative approach with 30 children (18 girls and 12 boys), who study in third grade of EGB level, from 2 different educational in-stitutions in Riobamba city. In order to obtain the results that evaluate the developed application, a pre-test and a post-test were applied, which were contrasted with the student’s t-test for paired samples. The statistical evidence suggests that the proposed computer system had a positive effect on children's performance, when it was used as a support tool in the classroom. The system was more effective in low performance children compared to those of high performance. It was also proved that children were motivated and showed positive attitudes when using the proposed System.

Bulgaria and North Macedonia have a long history of production and use of honey, however, there is an obvious lack of systematic and in-depth research on honey from both countries. Of particular interest is the oak honeydew honey, highly valued by consumers because of its health benefits. Aim of this study was to characterize honeydew and floral honeys from Bulgaria and North Macedonia based on their NMR profiles. 1D and 2D 1H and 13C NMR spectra were measured of 16 North Macedonian and 22 Bulgarian honey samples. 25 individual substances were identified, including quinovose, which was found for the first time in honey. Chemometric methods (PCA - principal component analysis, PLS-DA - partial least squares discriminant analysis, ANOVA) were used to detect similarities and differences between samples, as well as to determine their botanical and geographical origin. Semiquantitative data on individual sugars and some other constituents were obtained; which allowed reliable classification of honey samples by botanical and geographical origin, based on chemometric approaches. The results enabled to distinguish oak honeydew honey from other honey types, and to determine the country of origin. NMR was a rapid and convenient method, avoiding the need for other more time-consuming analytical techniques.

Learning disorders (LD) are diagnosed in children whose academic skills of reading, writing or mathematics are impaired and lagged according to their age, schooling and intelligence. Children with LD experience substantial working memory (WM) deficits, even more pronounced if more than one of the academic skills is affected. We compared the task-related EEG power spectral density of children with LD (n= 23), with a control group of children with good academic achievement (n= 22), during the performance of a WM task. sLoreta was used to estimate the current distribution at the sources, and 18 brain regions of interests (ROIs) were chosen with an extended version of the eigenvector centrality mapping technique. In this way, we lessen some drawbacks of the traditional EEG at the sensor space by an analysis at the brain sources level over data-driven selected ROIs. Results: The LD group showed fewer correct responses at the WM task, an overall slower EEG with more theta activity in all ROIs, less upper-alpha power at posterior areas, and less high-frequency beta activity in frontal areas. We explain these EEG patterns in LD children as indices of an inefficient neural resource management related with a delay in the neural development.

Today is the era of nanoscience and nanotechnology, which finds applications in the field of medicine, electronics, or environmental cleanup. Even though the nanotechnology is in its emerging phase, but still it provides solutions to numerous challenges. Nanotechnology and nanoparticles are found very effective because of their unique chemical and physical properties, high surface area, but their high cost is one of the major hurdles in its wider application. So, the synthesis of nanomaterials especially 2D nanomaterials from the industrial, agricultural and other biological activities could provide a cost-effective technique. The nanomaterials synthesized from such waste not only minimizes the pollution but also provides an eco-friendly approach towards the utilization of the waste. In the present review work, the emphasis has been given on the types of nanomaterials, different methods for the synthesis of 2D nanomaterials from the waste generated from industries, agriculture and their application in electronics, medicine and catalysis.

Bovine tuberculosis (bTB) outbreaks, caused by Mycobacterium bovis infection, are a costly animal health challenge. Understanding factors associated with the duration of outbreaks, known as breakdowns, could lead to better disease management policy development. We undertook a retrospective observational study (2012-2018) and employed Finite Mixture Models (FMM) to model the outcome parameter, and to investigate how factors were associated with duration for differing subpopulations identified. In addition to traditional risk factors (e.g. herd size, bTB history), we also explored farm geographic area, parcels/farm fragmentation, metrics of intensity via nitrogen loading, and whether herds were designated controlled beef finishing units (CBFU) as potential risk factors for increased duration. The final model fitted log-normal distributions, with two latent classes (k) which partitioned the population into a subpopulation around the central tendency of the distribution, and a second around the tails of the distribution. The latter subpopulation included longer breakdowns of policy interest. Increasing duration was positively associated with recent (<3 yrs) TB history and the number of reactors disclosed, (log) herd size, beef herd-type relative to other herd types, number of land parcels, area, and being designated a controlled finishing unit (“feedlot”), and having high annual inward cattle movements within the “tails” subpopulation. Breakdown length was negatively associated with year of commencement of breakdown (i.e. a decreasing trend) and non-significantly with the organic nitrogen produced on the farm (N kg/hectare), a measure of stocking density. The latter finding may be due to confounding effects with herd size and area. Most variables contributed only moderately to explaining variation in breakdown duration, that is, they had moderate size effects on duration. Herd-size and CBFU had greater effect sizes on the outcome. The findings contribute to evidence-based policy formation in Ireland.

In the process of transcription initiation by RNA polymerase, promoter DNA sequences affect multiple reaction pathways determining the productivity of transcription. However, the question of how the molecular mechanism of transcription initiation depends on sequence properties of promoter DNA remains poorly understood. Here, combining the statistical mechanical approach with high-throughput sequencing results, we characterize abortive transcription and pausing during transcription initiation by Escherichia coli RNA polymerase at a genome-wide level. Our results suggest that initially transcribed sequences enriched with thymine bases represent the signal inducing abortive transcription. On the other hand, certain repetitive sequence elements broadly embedded in promoter regions constitute the signal inducing pausing. Both signals decrease the productivity of transcription initiation. Based on solution NMR and in vitro transcription measurements, we also suggest that repetitive sequence elements of promoter DNA modulate the rigidity of its double-stranded form, which profoundly influences the reaction coordinates of the productive initiation via pausing.

A newly identified novel coronavirus named as severe acute respiratory syndrome-related coronavirus2 (SARS‐CoV 2) has given rise to the global pandemic. SARS-CoV2 which causes coronavirus disease 2019 (COVID-19), is a positive-stranded RNA virus with nucleocapsid. It binds to host angiotensin-converting enzyme2 (ACE2) receptor through surface glycoprotein (S protein). These ACE 2 receptors are attached to the cell membranes of many organs. Thus, COVID-19 does not only result in acute respiratory distress syndrome but also affects multiple organ systems, requiring a multidisciplinary approach to manage this disease. COVID-19 can damage the myocardial cells and result in fulminant myocarditis, acute cardiac injury, cardiomyopathy, heart failure, cardiogenic shock, or arrhythmia. COVID-19 seeds harmful immune response through cytokine storm leading to indirect organ damage. In this literature review, the available data is comprehended regarding cardiovascular complications in COVID-19, and the correlation of biomarkers with the disease activity is discussed. This literature review also highlights the important treatment options and outcomes of the individual study.

Ethnomedicine refers to the use of medicinal plants by a society, ethnic group or tribe for health benefits and for the prevention, treatment, and cure of different ailments. The healthy relationship between plants and humans has been continuing since the start of human civilization. The present study aims to document the medicinal information about plants used by ethnic people in different wards of Suryabinyak Municipality, Bhaktapur district, to conserve and utilize the traditional knowledge. Ethnomedicinal data were collected by a Rapid Rural Appraisal (RRA) method such as door to door surveys, direct observation. Individual interviews, field visits, and a questionnaire survey with the guidance of key informants. The present study has documented 107 medicinal plant species under 60 families which are used for prevention and treatment of 39 different diseases like Jaundice, diarrhea, dysentery, and cancer and 46 distinct health benefits like cough, cold, anti-bleeding, stomachache, diarrhea, fever, blood pressure, fracture, toothache, etc. Suryabinayak Municipality has a rich diversity in culture, ethnic groups, and medicinal plants, along with a wide geographic and climatic condition. However, with modernization, urbanization, deforestation, and increasing residential areas, the occurrence and use of medicinal plants have been diminished. Thus, documentation of this research is vital for further pharmaceutical research and enhancement and preservation of traditional knowledge of local people living in Suryabinayak Municipality and Nepal.

Great Britain’s stocks of coal, natural gas, and petroleum have seen major changes to the levels of stored energy over the years 2005 to 2019, a reduction of 200 TWh (35%) from 570 TWh to 370 TWh. The transformation of its electrical system over this timeframe saw a reduction in coal generation, leading to a corresponding reduction of the levels of stockpiled coal of 85 TWh (68%), partially offset by an increase in the stocks of biomass for electrical generation. The reduction in natural gas storage of 24 TWh (44%) was primarily due to the closure of Britain’s only long-term seasonal natural gas storage facility in January 2018. This was partially offset by the construction of medium-term natural gas storage facilities and the use of LNG storage in the years preceding its closure. For stocks of crude oil and oil products the reduction was 35 TWh (21%), linked to the overall reduction in demand.

SARS-CoV-2 is a newly emerging, highly transmissible, and pathogenic coronavirus in humans, which has caused global public health emergency and economic crisis. To date, millions of infections and thousands of deaths have been reported worldwide, and the numbers continue to rise. Currently, there is no specific drug or vaccine against this deadly virus; therefore, there is a pressing need to understand the mechanism through which this virus enters the host cell. Viral entry into the host cell is a multistep process in which SARS-CoV-2 utilizes the receptor binding domain of the spike glycoprotein (S) to recognize ACE2 receptors on the human cells; this initiates host cell entry by promoting viral-host cell membrane fusion through large scale conformational changes in the S protein. Receptor recognition and fusion are critical and essential steps of viral infections and are key determinants of the viral host range and cross-species transmission. In this review, we summarize the current knowledge on the origin and evolution of SARS-CoV-2 and the roles of key viral factors. We discuss the RNA dependent RNA polymerase structure of SARS-CoV-2, its significance in drug discovery, and explain the receptor recognition mechanisms of coronaviruses. We provide a comparative analysis of the SARS-CoV and SARS-CoV-2 S proteins, receptor-binding specificity, and discuss the differences in their antigenicity based on biophysical and structural characteristics.

Over the last decade, the field of Human Attribute Recognition (HAR) has dramatically changed, mainly due to the improvements brought by deep learning solutions. This survey reviews the progress obtained in HAR, considering the transition from the traditional hand-crafted to deep-learning approaches. The most relevant works on the field are analyzed concerning the advances proposed to address the HAR's typical challenges. Furthermore, we outline the applications and typical evaluation metrics used in the HAR context. Finally, we provide a comprehensive review of the publicly available datasets for the development and evaluation of novel HAR approaches.

Gross strap muscle invasion (gSMI) in patients with differentiated thyroid cancer (DTC) was defined as high-risk recurrent group in the 2015 American Thyroid Association guidelines. However, controversy persists because several studies suggested gSMI had little effect on disease outcome. Herein, a systematic review and meta-analysis was conducted to investigate impact of gSMI on outcome of DTC. Methods: A systematic search of electronic databases (PubMed, EMBASE, Cochrane Library, and MEDLINE) for studies published until February 2020 was performed. Case-control studies and randomized controlled trials that studied the impact of gSMI on outcome of DTC were included. Results: Six studies (all retrospective studies) involving 13639 patients met final inclusion criteria. Compared with no extrathyroidal extension (ETE), patients with gSMI were associated with increased risk of recurrence (P=0.0004,OR, 1.46; 95% CI: 1.18 to 1.80) and lymph node metastasis (LNM) (P<0.00001,OR 4.19;95% CI. 2.53 to 6.96). For mortality (P=0.34,OR 1.47;95% CI:0.67 to 3.25), ten-year disease-specific survival (P=0.80, OR 0.91;95% CI:0.44 to 1.88) and distant metastasis (DM) (P=0.21, OR 2.94;95% CI. 0.54 to 15.93), there was no significant difference between gSMI and no ETE group. In contrast with maximal ETE, patients with gSMI were associated with decreased risk of recurrence (P<0.0001,OR, 0.58; 95% CI: 0.44 to 0.76) , mortality (P=0.0003,OR 0.20;95% CI:0.08 to 0.48), LNM (P=0.0003,OR 0.64;95% CI. 0.50 to 0.81) and DM (P=0.0009,OR 0.28;95% CI. 0.13 to 0.59). Conclusions: DTC patients with gSMI had a higher risk of recurrence and LNM than those without ETE. However, in contrast with maximal ETE, a much better prognosis was observed in DTC patients with only gSMI. The findings of our meta-analysis provide supportive evidence for the validity of the T category changes in the 8th edition American Joint Committee on Cancer system. The actual impact of gSMI should be re-evaluated and revised in the recurrent risk stratification system in the future.

The current emergency due to the worldwide spread of the COVID-19 caused by the new SARS-CoV-2 is a great concern for global public health. Already in the past, the outbreak of severe acute respiratory syndrome (SARS) in 2003 and Middle Eastern respiratory syndrome (MERS) in 2012 demonstrates the potential of coronaviruses to cross-species borders and further underlines the importance of identifying new-targeted drugs. An ideal antiviral agent should target essential proteins involved in the lifecycle of SARS-CoV. Currently, some HIV protease inhibitors (i.e., Lopinavir) are proposed for the treatment of COVID-19, although their effectiveness was not yet assessed. The main protease (Mpro) provides a highly validated pharmacological target for the discovery and design of inhibitors. We identified potent Mpro inhibitors employing computational techniques that entail the screening of a Marine Natural Product (MNP) library. MNP library was screened by hyphenated pharmacophore model, and molecular docking approaches. Molecular dynamics and re-docking further confirmed the results obtained by structure-based techniques and allowed to highlight some crucial aspects. Seventeen potential SARS-CoV-2 Mpro inhibitors have been identified among the natural substances of marine origin. As these compounds were extensively validated by a consensus approach and by molecular dynamics, the likelihood that at least one of these compounds could be bioactive is excellent.

Purpose: To evaluate seasonal variation in intra-ocular pressure (IOP) with and without short tear break-up time (SBUT, BUT ≤ 5 s). Methods: This study enrolled 176 patients who visited one of six eye clinics in Japan for IOP measurement at every season. The mean patient age was 67.9 years, including 79 males. We compared the seasonal variation in IOP (mean ± SD) across spring (Mar-May), summer (Jun-Aug), fall (Sep-Nov), and winter (Dec-Feb). Results: The IOP (mmHg) in winter and summer, respectively, was 12.8 ± 3.7 and 12.8 ± 3.1 for non-glaucoma patients without SBUT (n = 47, P = 0.964), 14.8 ± 3.4 and 13.3 ± 3.4 for non-glaucoma patients with SBUT (n = 57, P < 0.001), 14.3 ± 3.2 and 14.1 ± 3.4 for glaucoma patients without SBUT (n = 36, P = 0.489), and 13.3 ± 3.0 and 11.6 ± 2.9 for glaucoma with SBUT (n = 36, P < 0.001). Seasonal variation was largest across the seasons in the glaucoma with SBUT group, and the magnitude of seasonal variation correlated with BUT (β = 0.228, P = 0.003). Conclusions: Seasonal variation tended to be larger in patients with SBUT than those without SBUT.

In this work, TiO₂ QDs modifed NiO nanosheets was employed to imporve the room-temperature NO₂ sensing properties of NiO. The gas-sensing studies showed that the response of nanocomposites with the optimal ratio to 60 ppm NO₂ was nearly 10 times larger than that of bare NiO, exhibiting potential application in gas-sensing. Considering the commonly reported immature mechanism that the effective charge transfer between two phases contribute to enhanced sensitivity, QDs sensitization mechanism was further detailed by designing a seirs of contrast experiments. First, the important role of QDs size effect was revealed by comparing a little enhanced sensitivity of TiO₂ particle-modified NiO with largely enhanced senstivity of TiO₂ QDs-NiO. Second, and more important, the direct evidence of heterointerface charge transfer efficiency was detailed by extracted interface bond (Ti-O-Ni) using XPS peak fitting. We hope this work can provide guideline to design more QDs-modified nanocomposites with the higher sensitivty for practical application.

The origin and significance of the tonalite–trondhjemite–granodiorite (TTG) units and the familiar metabasite xenoliths they host in the Yangtze Craton, China, remain controversial, and resolving these issues is important if we are to understand the evolution of the early Yangtze Craton. We focused on biotite–tremolite schist xenoliths in the Archean TTG units of the Kongling high-grade metamorphic terrane, and U–Pb dating of their zircons yielded ²⁰⁷Pb/²⁰⁶Pb ages of ca. 3.00 Ga, which provides a minimum age for the formation of the pre-metamorphic basic igneous rock. The host TTGs and late intrusive granitic dikes yield three groups of upper intercept ages at 2.87–2.88, 2.91–2.94, and 3.07 Ga, and a concordant age at 2.94 Ga, which suggest that the Yangtze continental nucleus underwent three important metamorphic–magmatic events in the Mesoarchean at ca. 3.00, 2.94, and 2.87 Ga. The biotite–tremolite schists have high ratios of K₂O/Na₂O and high contents of CaO, Cr, and Ni, thus showing the characteristics of high-K calc-alkaline island-arc volcanic rocks (basalt–andesite) that form by the partial melting of subducted oceanic crust. The data also provide further proof that a Mesoarchean metamorphic basement exists in the Yangtze Plate. Derivation of the magmatic protoliths of the biotite–tremolite schist enclaves from an oceanic crust during slab subduction, and the presence of these xenoliths within the TTG suite, indicate the existence of the initiation of plate tectonics during the Mesoarchean (≤2.94 Ga).

Histone Lysine Specific Demethylase 1 (LSD1) is overexpressed in many cancers and become a new target for anticancer drugs. In recent years, the small molecule inhibitors with various structures targeting LSD1 have been reported. Here we report the binding interaction modes of a series of thieno[3,2-b]pyrrole-5-carboxamides LSD1 inhibitors using molecular docking, three dimensional quantitative structure-activity relationship (3D-QSAR). Comparative molecular field analysis (CoMFA q²=0.783, r²=0.944, r²_pred=0.851) and Comparative molecular similarity indices analysis (CoMSIA q²=0.728, r²=0.982, r²_pred=0.814) were used to establish 3D-QSAR models, which had good verification and prediction capabilities. Based on the contour maps and the information of molecular docking, 8 novel small molecules were designed in silico, among which compounds D4, D5 and D8 with high predictive activity were subjected to further molecular dynamics simulations (MD), and their possible binding modes were explored. It was found that Asn535 plays a crucial role in stabilizing the inhibitors. Furthermore, the ADME and bioavailability prediction for D4, D5 and D8 were carried out. The results would provide valuable guidance for designing new reversible LSD1 inhibitors in the future.

Genetic activation of the class I PI3K pathway is very common in cancer. This mostly results from oncogenic mutations in PIK3CA, the gene encoding the ubiquitously expressed PI3Kα catalytic subunit, or from inactivation of the PTEN tumour suppressor, a lipid phosphatase which opposes class I PI3K signalling. The clinical impact of PI3K inhibitors in solid tumours, aimed at dampening cancer-cell-intrinsic PI3K activity, has thus far been limited. Challenges include poor drug tolerance, incomplete pathway inhibition and pre-existing or inhibitor-induced resistance. The principle of pharmacologically targeting cancer-cell-intrinsic PI3K activity also assumes that all cancer-promoting effects of PI3K activation are reversible, which might not be the case. Emerging evidence suggests that genetic PI3K pathway activation can induce and/or allow cells to tolerate chromosomal instability, which – even if occurring in a low fraction of the cell population – might help to facilitate and/or drive tumour evolution. While it is clear that such genomic events cannot be reverted pharmacologically, a role for PI3K in the regulation of chromosomal instability could be exploited by using PI3K pathway inhibitors to prevent those genomic events from happening and/or reduce the pace at which they are occurring, thereby dampening cancer development or progression. Such an impact might be most effective in tumours with clonal PI3K activation and achievable at lower drug doses than the maximum-tolerated doses of PI3K inhibitors currently used in the clinic.

A new strategy to nanoengineer gold/fluorocarbon multilayer (ML) nanostructures is reported. We have investigated the morphological changes occuring at the metal-polymer interface in multilayer structures with varying volume fraction of gold (Au) and the kinetic growth aspect of the microscale properties of nano-sized Au in plasma polymer fluorocarbon (PPFC). Investigations were carried out at various temperatures and annealing time by means of grazing incidence small-angle and wide-angle X-ray scattering (GISAXS and GIWAXS). We have fabricated a series of multilayers with variying volume fraction (0.12, 0.27, 0.38) of Au and bilayer periodicity in ML structure. They show an interesting granular structure consisting of nearly spherical shaped nanoparticles within the polymer layer. The nanoparticle (NP) morphology changes due to the collective effects of NPs diffusion within ensembles in the in-plane vicinity and inter-layer with increasing temperature. The in-plane NPs size distinctly increases (from 1.9 to 4 nm) with increasing temperature. The NPs become more spherical thus reducing the surface energy. Linear growth of NPs with temperature and time shows diffusion-controled growth of NPs in the ML structure. The structural stability of the multilayer is controlled by the volume ratio of the metal in polymer. At room temperature UV-Vis shows a blueshift of the plasmon peak from 560 nm in ML Au/PTFE_1 to 437 nm in Au/PTFE_3. We have identified the fabrication and post-deposition annealing conditions to limit the Local Surface Plasmon resonance (LSPR) shift (from 〖∆λ〗_LSPR=180 nm (Au/PTFE_1) to 〖∆λ〗_LSPR=67 nm (Au/PTFE_3 ML)) and their optical response over a wide visible wavelength range. A variation in the dielectric constant of the polymer in precence of varying Au inclusion is found to be the main factor affecting the LSPR frequency. Our finding may provide insights in Nano engineering ML structure can be useful to systematically control the growth of NPs in polymer matrix.

Wnt pathway is involved in breast cancer (BC) progression. Our aim was to evaluate the expression of some components of the Wnt pathway (β-catenin, FZD4, LRP5, LRP6 and TCF1) in order to detect potential associations with NHERF1 protein. In addition, we assessed their impact on patients’clinical outcome. We evaluated 220 primary BC samples by immunohistochemistry (IHC) and protein localization by immunofluorescence. We found a significant correlation between NHERF1 and FZD4, LRP5, LRP6 and TCF1. Univariate analysis showed that β-catenin (p<0.0001), FZD4 (p=0.0001), LRP5, LRP6 and TCF1 over-expression (p<0.0001 respectively) was related to poor disease free survival (DFS). A Kaplan-Meier analysis confirmed univariate data and showed a poor DFS for cNHERF1+/FZD4+ (p=0.0007), cNHERF1+/LRP5+ (p=0.0002), cNHERF1+/LRP6+ (p<0.0001) and cNHERF1+/TCF1+ phenotypes (p=0.0034). In multivariate analysis, TCF1 and β-catenin expression were independent prognostic variable of worse DFS (p=0.009 and p=0.027, respectively). In conclusion, we found that β-catenin, FZD4, LRP5, LRP6 and TCF1 overexpression was associated to poor prognosis. Furthermore, we first identified TCF1 as independent prognostic factor of poor outcome, indicating it as a new potential biomarker for BC patients management. In addition, Wnt pathway proteins expression, both alone and in association with NHERF1, suggests original associations of biological significance for new studies.

Background: Biomarkers are essential for identification of individuals at high risk of mild cognitive impairment (MCI) for potential prevention of dementia. We investigated DNA methylation in the ApoE gene and plasmatic apolipoprotein E (ApoE) levels as MCI biomarkers in Colombian subjects with MCI and controls. Methods: 100 participants were included (71% women, average age, 70 yrs., range 43-91). MCI was diagnosed by neuropsychological testing, medical and social history, activities of daily living, cognitive symptoms and neuroimaging. Multivariate logistic regression models adjusted by age and gender were performed to examine the risk association of MCI with plasma ApoE and APOE methylation Results: MCI was diagnosed in 41 subjects (average age, 66.5±9.6 yrs.) and compared with 59 controls. Elevated plasma ApoE and APOE methylation of CpGs 165, 190, and 198 were risk factors for MCI (P<0.05). Higher CpG-227 methylation correlated with lower risk for MCI (P=0.002). Only CpG-227 was significantly correlated with plasmatic ApoE levels (correlation coefficient=-0.665; P=0.008). Conclusion: Differential APOE methylation and increased plasma ApoE levels were correlated with MCI. These epigenetic patterns can be used as potential biomarkers to identify early stages of MCI.