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Tin(II) compounds are versatile materials with applications across fields such as catalysis, diagnostic imaging, and therapeutic drugs. However, oxidative stabilization of Sn(II) has remained an unresolved challenge as its reactivity with water and dioxygen results in loss of functionality, limiting technological advancement. Approaches to slow Sn(II) oxidation with chelating ligands or sacrificial electron donors have yielded only moderate improvements. We demonstrate here that the addition of nitrate to pyrophosphate-chelated Sn(II)(aq) suppresses Sn(II) oxidation in water across a broad pH range. Evidence of hydroxyl radical concentration reduction and detection of a radical nitrogen species that only forms in the presence of chelated Sn(II) point to a radical-based reaction mechanism. While this chemistry can be broadly applied, we present that this approach maintains Sn(II)'s antibacterial and anti-inflammatory efficacies as an example of sustained oral chemotherapeutic functionality.

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Sclerotinia sclerotiorum (Lib.) de Bary is the causative agent of stem white mold disease which severely reduces major crop productivity including soybean and rapeseed worldwide. The current study aimed to explore plant growth-promoting traits and biocontrol of new isolated Bacillus subtilis BS-2301 to suppress S. sclerotiorum through various mechanisms. The results indicated that the BS-2301 exhibited strong biocontrol potential against S. sclerotiorum up to 74% both in dual culture and partition plate experiments. The BS-2301 and its crude extract significantly suppressed S. sclerotiorum growth involving excessive reactive oxygen species (ROS) production in mycelia for rapid death. Furthermore, the treated hyphae produced low oxalic acid (OA), a crucial pathogenicity factor of S. sclerotiorum. The SEM and TEM microscopy of S. sclerotiorum showed severe damage in terms of cell wall, cell membrane breakage, cytoplasm displacement, and organelles disintegration compared to control. The pathogenicity of S. sclerotiorum exposed to BS-2301 had less disease progression potential on soybean leaves in the detached leaf assay experiment. Remarkably, the strain also demonstrated broad-range antagonistic activity with 70%, and 68% inhibition rates against Phytophthora sojae and Fusarium oxysporum, respectively. Furthermore, the strain exhibits multiple plant growth-promoting and disease-prevention traits, including the production of indole-3-acetic acid (IAA), siderophores, amylases, cellulases and proteases as well as harboring calcium phosphate decomposition activity. In comparison to the control, the BS-2301 also showed great potential for enhancing soybean seedlings growth for different parameters, including shoot length 31.23%, root length 29.87%, total fresh weight 33.45%, and total dry weight 27.56%. The antioxidant enzymes like CAT, POD, SOD and APX under BS-2301 treatment were up-regulated in S. sclerotiorum infected plants along with the positive regulation of defense-related genes (PR1-2, PR10, PAL1, AOS, CHS, and PDF1.2). These findings demonstrate that the BS-2301 strain possesses a notable broad-spectrum biocontrol potential against different phytopathogens and provides new insight in suppressing S. sclerotiorum through various mechanisms. Therefore, BS-2301 will be helpful in the development of biofertilizers for sustainable agricultural practices.

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Over the years, the production of eggs has increased tremendously, with an estimated global egg production of 9.7 billion by 2050. Further processing of shell eggs to egg products has gained growing popularity. Liquid egg yolks, an innovative form of egg replacement, still suffer from short shelf-life issues, and freezing has been applied to maintain freshness. An undesirable phenomenon called "gelation" was found during the production of frozen egg yolks, which has attracted numerous scholars to study its mechanism and quality control methods. Therefore, we comprehensively reviewed the history of the studies on frozen egg yolks, including the production procedure, the fundamentals of freezing, the gelation mechanism, the factors affecting gelation behaviors, and the techniques to control the gelation behaviors of frozen egg yolks. Reporting the production procedure and freezing fundamentals of frozen egg yolks will give readers a better understanding of the science and technological aspects of frozen egg yolks. Furthermore, a comprehensive summary of the mechanism of egg yolk gel formation induced by freeze-thawing and relevant control techniques will provide insights to researchers and manufacturers in the field of frozen egg processing.

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Particulate matter with a diameter ≤2.5 µm (PM2.5) poses a substantial global challenge, with a growing recognition of pathogens contributing to diseases associated with exposure to PM2.5 Recent studies have focused on PM2.5, which impairs the immune cells in response to microbial infections and potentially contributes to the development of severe diseases in the respiratory tract. Accordingly, changes in the respiratory immune function and microecology mediated by PM2.5 are important factors that enhance the risk of microbial pathogenesis. These factors have garnered significant interest. In this review, we summarise recent studies on the potential mechanisms involved in PM2.5-mediated immune system disruption and exacerbation of microbial pathogenesis in the respiratory tract. We also discuss crucial areas for future research to address the gaps in our understanding and develop effective strategies to combat the adverse health effects of PM2.5.

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Natural products are a valuable resource for the discovery of novel crop protection agents. A series of γ-butyrolactone derivatives, derived from the simplification of podophyllotoxin's structure, were synthesized and assessed for their efficacy against tobacco mosaic virus (TMV). Several derivatives exhibited notable antiviral properties, with compound 3g demonstrating the most potent in vivo anti-TMV activity. At 500 µg/mL, compound 3g achieved an inactivation effect of 87.8%, a protective effect of 71.7%, and a curative effect of 67.7%, surpassing the effectiveness of the commercial plant virucides ningnanmycin and ribavirin. Notably, the syn-diastereomer (syn-3g) exhibited superior antiviral activity compared to the anti-diastereomer (anti-3g). Mechanistic studies revealed that syn-3g could bind to the TMV coat protein and interfere with the self-assembly process of TMV particles. These findings indicate that compound 3g, with its simple chemical structure, could be a potential candidate for the development of novel antiviral agents for crop protection.

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Phosphodiesterases (PDEs) constitute a family of enzymes that play a pivotal role in the regulation of intracellular levels of cyclic nucleotides, including cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Dysregulation of PDE activity has been implicated in diverse pathological conditions encompassing cardiovascular disorders, pulmonary diseases, and neurological disorders. Small-molecule inhibitors targeting PDEs have emerged as promising therapeutic agents for the treatment of these ailments, some of which have been approved for their clinical use. Despite their success, challenges such as resistance mechanisms and off-target effects persist, urging continuous research for the development of next-generation PDE inhibitors. The objective of this review is to provide an overview of the synthesis and clinical application of representative approved small-molecule PDE inhibitors, with the aim of offering guidance for further advancements in the development of novel PDE inhibitors.

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The inherent ambiguity in reconstructed images from coherent diffraction imaging (CDI) poses an intrinsic challenge, as images derived from the same dataset under varying initial conditions often display inconsistencies. This study introduces a method that employs the Noise2Noise approach combined with neural networks to effectively mitigate these ambiguities. We applied this methodology to hundreds of ambiguous reconstructed images retrieved from a single diffraction pattern using a conventional retrieval algorithm. Our results demonstrate that ambiguous features in these reconstructions are effectively treated as inter-reconstruction noise and are significantly reduced. The post-Noise2Noise treated images closely approximate the average and singular value decomposition analysis of various reconstructions, providing consistent and reliable reconstructions.

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In 2023, the European Medicines Agency (EMA) granted approval to 77 new molecular entities (NMEs), consisting of 45 new chemical entities (NCEs) and 32 new biological entities (NBEs). These pharmacological agents encompass a broad spectrum of therapeutic domains, including oncology, cardiology, dermatology, diagnostic medicine, endocrinology, gastroenterology and hepatology, metabolic disorders, and neurology. Among the 77 approved pharmaceuticals, three received accelerated review status, and 17 (22 %) were granted orphan drug designation for the treatment of rare diseases. This review provides an overview of the clinical applications and synthetic routes of 42 newly approved NCEs by the EMA in 2023. The objective is to offer a comprehensive understanding of the synthetic approaches used in the development of these drug molecules, thereby inspiring the creation of novel, efficient, and applicable synthetic methodologies.

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Plant parasitic nematodes (PPNs) pose a significant threat to global crop productivity, causing an estimated annual loss of US $157 billion in the agriculture industry. While synthetic chemical nematicides can effectively control PPNs, their overuse has detrimental effects on human health and the environment. Biocontrol agents (BCAs), such as bacteria and fungi in the rhizosphere, are safe and promising alternatives for PPNs control. These BCAs interact with plant roots and produce extracellular enzymes, secondary metabolites, toxins, and volatile organic compounds (VOCs) to suppress nematodes. Plant root exudates also play a crucial role in attracting beneficial microbes toward infested roots. The complex interaction between plants and microbes in the rhizosphere against PPNs is mostly untapped which opens new avenues for discovering novel nematicides through multi-omics techniques. Advanced omics approaches, including metagenomics, transcriptomics, proteomics, and metabolomics, have led to the discovery of nematicidal compounds. This review summarizes the status of bacterial and fungal biocontrol strategies and their mechanisms for PPNs control. The importance of omics-based approaches for the exploration of novel nematicides and future directions in the biocontrol of PPNs are also addressed. The review highlighted the potential significance of multi-omics techniques in biocontrol of PPNs to ensure sustainable agriculture.

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Introduction: IDH2 mutation is an unfavorable prognostic factor in patients with primary myelofibrosis (PMF) but its effect on myelofibrosis (MF) remains largely unclear. Methods: In this study, we aimed to elucidate the roles of IDH2 mutation in the development and progression of MF by transcriptomic and molecular techniques using the Idh2 R172K transgenic mice. Results: We found that thrombopoietin (TPO)-overexpressed Idh2 R172K (Idh2 R172K + TPO) mice had accelerated progression to MF, compared with TPO-overexpressed Idh2-wild (WT + TPO) mice, showing activation of multiple inflammatory pathways, among which nuclear factor κB (NFκB) was the most significantly enhanced. Single-cell transcriptomes of the marrow cells in early MF showed that S100a8/a9 expression was mainly confined to neutrophil progenitors in the WT + TPO mice, but highly expressed in several types of myeloid precursor cells, including the megakaryocyte progenitors in the Idh2 R172K + TPO group. Furthermore, Idh2 R172K mice at age of 18 months had larger spleens, increased S100a8/a9-Tlr4 expression, and elevated serum S100a8/a9 levels compared with WT mice. PMF patients with IDH2 mutations had higher bone marrow plasma S100A8/A9 levels than those without IDH2 mutations. Conclusion: Overall, our findings showed that IDH2 mutation induced proinflammatory effects, which further exacerbated MF, as evidenced by the increase in S100a8/a9 levels and NFκB hyperactivation in Idh2 R172K + TPO mice.

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High-performance n-type organic mixed ionic-electronic conductors (OMIECs) are essential for advancing complementary circuits based on organic electrochemical transistors (OECTs). Despite significant progress, current n-type OMIECs often exhibit lower transconductance and slower response times compared to their p-type counterparts, limiting the development of OECT-based complementary circuits. Optimizing the conjugated backbone and side chain structures of OMIECs is critical for enhancing both ion and electron transport efficiencies while maintaining a delicate balance between the two. In this study, hydrophilic polyethylene glycol (PEG) side chains were incorporated into the highly conductive n-type polymer poly(3,7-dihydrobenzo[1,2-b:4,5-b']difuran-2,6-dione) (PBFDO) backbone to achieve this goal. The incorporation of PEG chains improved ion accessibility, and by adjusting the PEG content, the electronic and ionic transport properties were fine-tuned, ultimately enhancing the performance of OECTs and related p-n complementary circuits. The n-type OECTs based on PBFDO-PEG50wt% demonstrated exceptional transfer characteristics, including a transient response time (τON) as low as 72 µs, a high geometry-normalized transconductance exceeding 400 S cm-1, and an impressive µC* value surpassing 720 F cm-1 V-1 s-1. Notably, the use of PBFDO-PEG50wt% in a complementary inverter resulted in a voltage gain of 20 V/V, more than five times higher than that achieved with unmodified PBFDO (<4 V/V). These findings highlight the importance of balancing electron and ion transport characteristics in OMIECs to achieve high performance in OECTs and their associated circuits, and they validate PEG decoration as an effective approach.

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Transparent electrodes (TEs) are vital in optoelectronic devices, enabling the interaction of light and charges. While indium tin oxide (ITO) has traditionally served as a benchmark TE, its high cost prompts the exploration of alternatives to optimize electrode characteristics and improve device efficiencies. Conducting polymers, which combine polymer advantages with metal-like conductivity, emerge as a promising solution for TEs. This work introduces a two-in-one electron transport layer (ETL) and TE based on films of polyethylenimine ethoxylated (PEIE)-modified poly(benzodifurandione) (PBFDO). These PEIE-modified PBFDO layers exhibit a unique combination of properties, including low sheet resistance (130 Ω sq-1), low work function (4.2 eV), and high optical transparency (>85% in the UV-vis-NIR range). In contrast to commonly used poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS), the doping level of PBFDO remains unaffected by the PEIE treatment, as verified through UV-vis-NIR absorption and X-ray photoelectron spectroscopy measurements. When employed as a two-in-one ETL/TE in organic solar cells, the PEIE-modified PBFDO electrode exhibits performance comparable to conventional ITO electrodes. Moreover, this work demonstrates all-organic solar cells with record-high power conversion efficiencies of >15.1% under indoor lighting conditions. These findings hold promise for the development of fully printed, all-organic optoelectronic devices.

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Aberrant alternative splicing (AS) contributes to leukemogenesis, but reports on the clinical and biological implications of aberrant AS in acute myeloid leukaemia (AML) remain limited. Here, we used RNA-seq to analyse AS in AML cells from 341 patients, comparing them to healthy CD34+ haematopoietic stem cells (HSCs). Our findings highlight distinct AS patterns in the nuclear transcription factor Y subunit alpha (NFYA) gene, with two main isoforms: NFYA-L (Long) and NFYA-S (Short), differing in exon 3 inclusion. Patients with lower NFYA-L but higher NFYA-S expression, termed NFYA-S predominance, displayed more favourable characteristics and better outcomes following intensive chemotherapy, regardless of age and European LeukemiaNet risk classification, compared to those with higher NFYA-L but lower NFYA-S expression, termed NFYA-L predominance. The prognostic effects were validated using The Cancer Genome Atlas cohort. Transcriptome analysis revealed upregulated cell cycle genes in NFYA-S predominant cases, resembling those of active HSCs, demonstrating relative chemosensitivity. Conversely, NFYA-L predominant cases, as observed in KMT2A-rearranged leukaemia, were associated with relative chemoresistance. NFYA-S overexpression in OCI-AML3 cells promoted cell proliferation, S-phase entry and increased cytarabine sensitivity, suggesting its clinical and therapeutic relevance in AML. Our study underscores NFYA AS as a potential prognostic biomarker in AML.

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Electric discharge occurs ubiquitously in both natural and engineered systems, where the discharge paths provide critical information. However, control and visualization of discharge patterns is a challenging task. Here arrays of liquid metal marbles, droplets of a gallium-indium eutectic alloy with a copper-doped ZnS luminescent coating, are designed for pixelated visualization of electric discharge paths at optical imaging length-scales. The ZnS particles embed themselves into the surface of liquid metal droplets and are anchored by a self-limiting gallium oxide layer. The operation is achieved by generating spark discharges at inter-marble air gaps and reduced voltage drop across highly conducting liquid metal droplets. By taking advantage of the malleability of soft liquid metal marbles, the dynamic visualization platforms allow the manipulation of discharge path selections in configurable marble arrays and the embedding of artificial defect features. The systems are further integrated for characterizing dynamic changes in granular and soft systems, and for enabling logic computing and information encoded display. This demonstration holds promises for creating new-generation electric discharge-based optoelectronics.

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Living kidney donors have been regarded as those people having earned the healthiest status level after having undergone scrutiny. Although one's post-donation GFR is expected to fall to 50% of their pre-donation value, it is well documented that there is a compensatory increase in GFR which subsequently reaches approximately 60-70% of the donor's pre-donation value. Data regarding gout/hyperuricemia in living kidney donors has remained scarce until now. This study involved kidney donors enrolled within the years 2000 to 2017, where those who were selected to be matched to those in group of case cohort by age, year of index date, gender and co-morbidity were considered as the control cohort. During the 17-year study period 2,716 participants were enrolled. Results revealed that kidney donors experienced a risk of new onset gout/ hyperuricemia (adjusted HR = 1.73; 95%CI = 1.27, 2.36), and new onset CKD (adjusted HR = 6.7; 95% CI = 4.4, 10.21) were found to be higher in kidney donors. Our findings suggest that people after kidney donation are significantly associated with a higher risk of new onset gout/hyperuricemia. Clinical professionals therefore need to be cautious of new onset gouy/hyperuricemia after donation surgery.

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This comprehensive review undertakes a meticulous scrutiny of the synthesis and clinical applications pertaining to small-molecule tyrosine kinase inhibitors (TKIs) directed towards the human epidermal growth factor receptor 2 (HER2), a pivotal protagonist in the pathogenesis of cancer. Focused on compounds like lapatinib, neratinib, and tucatinib, the review delves into the intricate synthesis strategies, emphasizing the challenges associated with their structural complexity. The clinical utilization of HER2 TKIs underscores noteworthy strides in the therapeutic landscape for HER2-positive breast and gastric malignancies. Lapatinib, a dual HER2/ epidermal growth factor receptor (EGFR) inhibitor, has demonstrated efficacy in combination therapies, addressing the need for overcoming resistance mechanisms. Neratinib, an irreversible HER2 inhibitor, presents a promising avenue for patients with refractory tumors. Tucatinib, strategically engineered to traverse the blood-brain barrier, epitomizes a groundbreaking advancement in the management of metastatic HER2-positive breast cancer manifesting cerebral involvement. Despite their success, challenges such as resistance mechanisms and off-target effects persist, urging continuous research for the development of next-generation HER2 TKIs. This comprehensive review serves as a valuable resource for pharmaceutical scientists, offering insights into the synthetic intricacies and clinical impact of small-molecule TKIs targeting HER2.

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Whole egg powder (WEP), predominantly utilized as an ingredient in ready-to-eat foods such as bakery items, puffed snacks and other products, necessitates the consideration of appropriate packaging materials to preserve its quality properties during processing and transportation. The quality changes of WEP were evaluated in PA, C-PA and PE-PP-Al packaging for 35 days at 60 °C in accelerated storage. The results indicate that among the three packaging materials, PE-PP-Al exhibits the highest barrier properties, effectively inhibiting moisture loss, caking, reduced solubility, oxidative deterioration, and decreased thermal stability in WEP. The Multivariate Accelerated Shelf-Life Test (MASLT) was carried out using water content, moisture activity, color value, lipid oxidation (PV, TBA, AV) and organoleptic attributes in different packaging methods, and the predicted shelf-life of WEP at room temperature was 421, 470 and 549 days with RMSE (0.171-0.893) using principal component analysis coupled with kinetic modeling.

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BACKGROUND: Systematic reviews (SRs) are being published at an accelerated rate. Decision-makers may struggle with comparing and choosing between multiple SRs on the same topic. We aimed to understand how healthcare decision-makers (eg, practitioners, policymakers, researchers) use SRs to inform decision-making and to explore the potential role of a proposed artificial intelligence (AI) tool to assist in critical appraisal and choosing among SRs. METHODS: We developed a survey with 21 open and closed questions. We followed a knowledge translation plan to disseminate the survey through social media and professional networks. RESULTS: Our survey response rate was lower than expected (7.9% of distributed emails). Of the 684 respondents, 58.2% identified as researchers, 37.1% as practitioners, 19.2% as students and 13.5% as policymakers. Respondents frequently sought out SRs (97.1%) as a source of evidence to inform decision-making. They frequently (97.9%) found more than one SR on a given topic of interest to them. Just over half (50.8%) struggled to choose the most trustworthy SR among multiple. These difficulties related to lack of time (55.2%), or difficulties comparing due to varying methodological quality of SRs (54.2%), differences in results and conclusions (49.7%) or variation in the included studies (44.6%). Respondents compared SRs based on the relevance to their question of interest, methodological quality, and recency of the SR search. Most respondents (87.0%) were interested in an AI tool to help appraise and compare SRs. CONCLUSIONS: Given the identified barriers of using SR evidence, an AI tool to facilitate comparison of the relevance of SRs, the search and methodological quality, could help users efficiently choose among SRs and make healthcare decisions.

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Background: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has resulted in illness, deaths and societal disruption on a global scale. Societies have implemented various control measures to reduce transmission of the virus and mitigate its impact. Individual behavioural changes are crucial to the successful implementation of these measures. One commonly recommended measure to limit risk of infection is frequent handwashing. It is important to identify those factors that can predict the uptake and maintenance of handwashing. Objectives: We aimed to identify and synthesise the evidence on malleable psychological and psychosocial factors that determine uptake and adherence to handwashing aimed at reducing the risk of infection or transmission of COVID-19. Search Methods: We searched various literature sources including electronic databases (Medline ALL, Child Development & Adolescent Studies, ERIC, PsycInfo, CINAHL and Web of Science), web searches, conference proceedings, government reports, other repositories of literature and grey literature. The search strategy was built around three concepts of interest including (1) context (terms relating to COVID-19), (2) behaviour of interest and (3) terms related to psychological and psychosocial determinants of COVID Health-Related Behaviours and adherence or compliance with handwashing, to capture malleable determines. Searches capture studies up until October 2021. Selection Criteria: Eligibility criteria included observational studies (both retrospective and prospective) and experimental studies that measure and report malleable psychological and psychosocial determinants and handwashing at an individual level, amongst the general public. Screening was supported by the Cochrane Crowd. Titles and abstracts were screened against the eligibility criteria by three independent screeners. Following this, all potentially relevant studies were screened at full-text level by the research team. All conflicts between screeners were resolved by discussion between the core research team. Data Collection and Analysis: All data extraction was managed in EPPI-Reviewer software. All eligible studies, identified through full-text screening were extracted by one author. We extracted data on study information, population, determinant, behaviour and effects. A second author checked data extraction on 20% of all included papers. All conflicts were discussed by the two authors until consensus was reached.We assessed methodological quality of all included studies using an adapted version of the Joanna Briggs Institute Quality appraisal tool for cross-sectional studies. Main Results: Our initial searches yielded 23,587 results, of which 56 studies were included in this review. The included studies were cross sectional in design, came from 22 countries and had a combined sample of 199,376 participants. The vast majority of studies had samples from the general public, with eight of the studies focusing on specific samples. All included studies considered people over the age of 18. The quality of the majority of the studies was good (n = 30 rated low risk of bias), with 8 rated high risk of bias, predominately due to lack of reporting of recruitment, sample characteristics and methodology. Thirty-four studies were included in the narrative synthesis and 28 in the meta-analysis.Findings indicated that emotions about COVID-19 (worry [0.381, confidence interval [CI] = 0.270-0.482, I 2 = 92%) and anxiety (0.308, CI = 0.154-0.448, I 2 = 91%]), knowledge of COVID-19 (0.323, CI = 0.223-0.417, I 2 = 94%), and perceived social norms (0.303, CI = 0.184-0.413, I 2 = 92%) were among the malleable determinants most associated with handwashing. Perceived severity (0.006, CI = -0.011-0.023) and susceptibility of COVID-19 (0.041, CI = -0.034 to 0.115) had little to no effect on handwashing behaviour. Authors' Conclusions: Understanding the effects of various malleable determinants on COVID-related handwashing can aid in the development and implementation of interventions and public health campaigns to promote handwashing behaviour in potential new waves of COVID-19 or other respiratory infections. Emotions about COVID, knowledge of COVID and perceived social norms warrant further consideration in future research and policy.