NHPI-Catalyzed Electro-Oxidation of Alcohols to Aldehydes and Ketones.

A practical and recyclable electro-oxidation of alcohols to aldehydes and ketones by using N-hydroxyphthalimide (NHPI) as the catalyst is presented. Through an undivided pool, under constant current conditions, various alcohols can be oxidized to the corresponding aldehydes or ketones in a high yield. Compared with previous methods, this system has the following characteristics: (1) the catalyst, electrode, electrolyte, and solvent (mainly water) are recyclable; (2) it has many advantages such as mild reaction conditions, easy operation, and good tolerance of functional groups; and (3) it can be smoothly scaled up to kilogram-scale production.

Butyl benzyl phthalate induces neurotoxicity in Eisenia fetida: Mechanisms revealed by biochemical and metabolomic analyses.

Phthalates, particularly butyl benzyl phthalate (BBP), are ubiquitous environmental contaminants with potential neurotoxic effects. However, their impact on soil organisms, especially earthworms (Eisenia fetida), remains poorly understood. The current study investigated the neurotoxic effects of BBP on Eisenia fetida in artificial and red soils using an integrated approach combining biochemical assays, metabolomics, and molecular docking. Earthworms were exposed to 0, 1, and 10 mg kg-1 BBP for 14 and 28 days. Biochemical assays revealed significant increases in oxidative stress markers and disruptions in neurotransmission-related enzyme activities. Metabolomic analysis of the cerebral ganglia identified alterations in energy metabolism, lipid metabolism, and neuroactive ligand-receptor interaction signaling pathways. Molecular docking studies corroborated these findings, showing strong interactions between BBP and essential neuronal proteins, particularly the sodium pump. The integration of these data suggests that BBP-induced neurotoxicity in Eisenia fetida is primarily mediated by calcium signaling pathway dysfunction and calcium homeostasis imbalance. Notably, neurotoxic effects were more pronounced in red soil than in artificial soil, highlighting the importance of considering soil type in ecotoxicological assessments. The current study provides novel insights into the mechanisms of BBP-induced neurotoxicity in soil invertebrates and underscores the potential ecological risks associated with phthalate contamination in agricultural environments.

Blockade of endothelin receptors mitigates SARS-CoV-2-induced osteoarthritis.

Joint pain and osteoarthritis can occur as coronavirus disease 2019 (COVID-19) sequelae after infection. However, little is known about the damage to articular cartilage. Here we illustrate knee joint damage after wild-type, Delta and Omicron variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in vivo. Rapid joint injury with cystic lesions at the osteochondral junction was observed in two patients with post-COVID osteoarthritis and recapitulated in a golden Syrian hamster model. SARS-CoV-2-activated endothelin-1 signalling increased vascular permeability and caused viral spike proteins leakage into the subchondral bone. Osteoclast activation, chondrocyte dropout and cyst formation were confirmed histologically. The US Food and Drug Administration-approved endothelin receptor antagonist, macitentan, mitigated cystic lesions and preserved chondrocyte number in the acute phase of viral infection in hamsters. Delayed macitentan treatment at post-acute infection phase alleviated chondrocyte senescence and restored subchondral bone loss. It is worth noting that it could also attenuate viral spike-induced joint pain. Our work suggests endothelin receptor blockade as a novel therapeutic strategy for post-COVID arthritis.

OsRHS Negatively Regulates Rice Heat Tolerance at the Flowering Stage by Interacting With the HSP Protein cHSP70-4.

Heat stress at the flowering stage significantly impacts rice grain yield, yet the number of identified genes associated with rice heat tolerance at this crucial stage remains limited. This study focuses on elucidating the function of the heat-induced gene reduced heat stress tolerance 1 (OsRHS). Overexpression of OsRHS leads to reduced heat tolerance, while RNAi silencing or knockout of OsRHS enhances heat tolerance without compromising yield, as assessed by the seed setting rate. OsRHS is localized in the cytoplasm and mainly expressed in the glume and anther of spikelet. Moreover, OsRHS was found to interact with the HSP protein cHSP70-4, and the knockout of cHSP70-4 resulted in increased heat tolerance. Complementation assays revealed that the knockout of cHSP70-4 could restore the compromised heat tolerance in OsRHS overexpression plants. Additional investigation reveals that elevated temperatures can amplify the bond between OsRHS and cHSP70-4 within rice. Furthermore, our findings indicate that under heat stress conditions during the flowering stage, OsRHS plays a negative regulatory role in the expression of many stress-related genes. These findings unveil the crucial involvement of OsRHS and cHSP70-4 in modulating heat tolerance in rice and identify novel target genes for enhancing heat resilience during the flowering phase in rice.

Global trends and hotpots in standardised patients research in the last 30 years: A bibliometric analysis.

Background: The research trends regarding standardised patients(SPs) in the education of health professions students have not been systematically studied. Methods: All published literature on SPs from January 1994 to January 2024 in Web of Science was screened by two reviewers. Bibliometric analysis and knowledge mapping visualisation analysis were performed using Cite Space software. The country, institution, journal, keyword co-occurrence, and keyword emergence were visualised. Result: A total of 3259 records were analysed. The amount of relevant literature in the past 30 years showed an upward trend involving 109 disciplinary categories, with the United States dominating. The five central research teams were from the United States and Canada. Nursing education is increasingly using SPs, especially in advanced nursing practice. As for the hotspot and trend analysis, the results indicate that there is still continuous attention to the impact of applying standardised patients on improving the communication ability, competence and performance of medical students. Additionally, there is a growing interest in exploring the application of visual simulation or artificial intelligence in standardised patient-related research. Conclusions: Research on SPs' has received continued attention. To cater to the diverse requirements of education and clinical context, there is a need for further exploration of SPs utilisation. AI-relevant SPs might be a new alternative for various scenarios in the future.

Developing a chain mediation model of recurrence risk perception and health behavior among patients with stroke: A cross-sectional study.

PURPOSE: To understand the recurrence risk perception of stroke patients and develop a chain mediation model of recurrence risk perception and health behavior. METHODS: A cross-sectional study and convenience sampling were used. Stroke survivors were recruited from the neurology departments of three tertiary hospitals. Their recurrence risk perception, behavioral decision-making, social support, self-efficacy, recurrence worry and health behavior were measured by relevant tools. Data was analyzed through one-way analysis and regression analysis; and the AMOS 21.0 software was used to explore the mediating relationships between variables. RESULTS: Of the 419 participants, 74.7% were aware of stroke recurrence risk. However, only 28.2% could accurately estimate their own recurrence risk. Recurrence risk perception was significantly correlated with behavioral decision-making, social support, self-efficacy, and health behavior (r = .19 ∼ .50, p < .05). Social support and recurrence risk perception could affect health behavior indirectly through self-efficacy, behavioral decision-making and worry. Behavioral decision-making acted as a main mediator between recurrence risk perception and health behavior, while the path coefficient was .47 and .37, respectively. The chain mediation effect between recurrence risk perception and health behavior was established with a total effect value of .186 (p < .01). CONCLUSION: Most stroke survivors could aware recurrence risk but failed to accurately estimate their individual risk. In the mediation model of recurrence risk perception and health behavior, social support seemed to be an important external factor, while self-efficacy, behavioral decision-making and worry seemed to act as key internal factor. REGISTRATION: The research project was registered on 29 June 2020 (CTR200003XXXX).

Fluxapyroxad induced toxicity of earthworms: Insights from multi-level experiments and molecular simulation studies.

Fluxapyroxad, an emerging succinate dehydrogenase inhibitor fungicide, is widely used due to its excellent properties. Given its persistence in soil with a 50 % disappearance time of 183-1000 days, it is crucial to evaluate the long-term effects of low-dose fluxapyroxad on non-target soil organisms such as earthworms (Eisenia fetida). The present study investigated the impacts of fluxapyroxad (0.01, 0.1, and 1 mg kg-1) on Eisenia fetida over 56 days, focusing on oxidative stress, digestive and nervous system functions, and histopathological changes. We also explored the mechanisms of fluxapyroxad-enzyme interactions through molecular docking and dynamics simulations. Results demonstrated a significant dose-response relationship in the integrated biomarker response of 12 biochemical indices. Fluxapyroxad altered expression levels of functional genes and induced histopathological damage in earthworm epidermis and intestines. Molecular simulations revealed that fluxapyroxad is directly bound to active sites of critical enzymes, potentially disrupting their structure and function. Even at low doses, long-term fluxapyroxad exposure significantly impacted earthworm physiology, with effects becoming more pronounced over time. Our findings provide crucial insights into the chronic toxicity of fluxapyroxad and emphasize the importance of long-term, low-dose studies in pesticide risk assessment in soil. This research offers valuable guidance for the responsible management and application of fungicides.

Inhibiting endothelial Rhoj blocks profibrotic vascular intussusception and angiocrine factors to sustain lung regeneration.

Lung regeneration after fibrosis requires formation of functional new vasculature, which is essential for gas exchange and cellular cross-talk with other lung cells. It remains unknown how the lung vasculature can be regenerated without fibrosis. Here, we tested the role of N6-methyladenosine (m6A) modification of forkhead box protein O1 (Foxo1) mRNA in lung regeneration after pneumonectomy (PNX) in mice, a model for lung regrowth after surgical resection. Endothelial cell (EC)-specific knockout of methyltransferase-like 3 (Mettl3) and Foxo1 caused nonproductive intussusceptive angiogenesis (IA), which impaired regeneration and enhanced fibrosis. This nonproductive IA was characterized by enhanced endothelial proliferation and increased vascular splitting with increased numbers of pillar ECs. Endothelial-selective knockout of Mettl3 in mice stimulated nonproductive IA and up-regulation of profibrotic factors after PNX, promoting regeneration to fibrotic transition. EC-specific mutation of m6A modification sites in the Foxo1 gene in mice revealed that endothelial Mettl3 modified A504 and A2035 sites in the Foxo1 mRNA to maintain pro-regenerative endothelial glycolysis, ensuring productive IA and lung regeneration without fibrosis. Suppression of Mettl3-Foxo1 signaling stimulated a subset of hyperglycolytic and hyperproliferative 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (Pfkfb3)+, Ras homolog family member J (Rhoj)+, and platelet-derived growth factor subunit B (Pdgfb)+ ECs in both human and mouse lungs with fibrosis. Inhibiting this Pfkfb3+Rhoj+Pdgfb+ EC subset normalized IA, alleviated fibrosis, and restored regeneration in bleomycin (BLM)-injured mouse lungs. We found that m6A modification of Foxo1 in the mouse vasculature promoted lung regeneration over fibrosis after PNX and BLM injury.

A non-invasive osteopontin-targeted phase changeable fluorescent nanoprobe for molecular imaging of myocardial fibrosis.

Due to the elevated fatality rate of cardiovascular diseases, myocardial fibrosis emerges as a prominent pathological alteration in the majority of heart ailments and their associated pathologies, thereby augmenting the likelihood of sudden cardiac death. Consequently, the prompt and obligatory identification of myocardial fibrosis assumes paramount importance in averting malignant incidents among patients afflicted with cardiac disorders. Herein, with higher expression osteopontin (OPN) found in cardiac fibrosis tissue, we have developed a dual-modality imaging probe, namely OPN targeted nanoparticles (OPN@PFP-DiR NPs), which loaded perfluoropentane (PFP) for ultrasound (US) and 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR) for near-infrared fluorescence (NIR) of molecular imaging, to investigate the molecular features of cardiac fibrosis using US and NIR imaging. Subsequently, the OPN@PFP-DiR NPs were administered intravenously to a mouse model of myocardial infarction (MI). The US and NIR molecular imaging techniques were employed to visualize the accumulation of the nanoparticles in the fibrotic myocardium. Hence, this research presents a valuable noninvasive, cost-effective, and real-time imaging method for evaluating cardiac fibrosis, with promising clinical applications.

Cytological and metabolomic analysis of Citrus fruit to elucidate puffing disorder.

Puffiness, a physiological disorder commonly observed during the ripening and post-harvest processes of fruits in Citrus reticulata, significantly affects the quality and shelf-life of citrus fruits. The complex array of factors contributing to puffiness has obscured the current understanding of its mechanistic basis. This study examined the puffing index (PI) of 12 citrus varieties at full ripeness, focusing on the albedo layer as a crucial tissue, and investigated the correlation between cellular structural characteristics, key primary metabolites and PI. The findings revealed that the cell gap difference and the number of lipid droplets were closely linked to PI. Chlorogenic acid, Ferulic acid, D-Galacturonic acid, D-Glucuronic acid, (9Z,11E)-Octadecadienoic acid, and 9(10)-EpOME were identified as pivotal primary metabolites for rind puffing. Determination of lignin, protopectin, cellulose and lipoxygenase content further validated the relationship between cell wall, lipid metabolism and rind puffing. This study furnishes novel insights into the mechanisms underlying puffing disorder.

Enantioselective Ni-Catalyzed 1,2-Borylalkynylation of Unactivated Alkenes.

Enantioselective three-component difunctionalization of alkenes with boron reagents represents an attractive strategy for assembling three-dimensional chiral organoboron compounds. However, regio- and enantiocontrol comprise the pivot challenges in these transformations, which predominantly require the use of activated conjugated alkenes. Herein, by utilizing various carbonyl directing groups, including amides, sulfinamides, ketones, and esters, we succeed in realizing a nickel-catalyzed 1,2-borylalkynylation of unactivated alkenes to enable the simultaneous incorporation of a boron entity and an sp-fragment across the double bond. The products contain boryl, alkynyl, and carbonyl functional groups with orthogonal synthetic reactivities, offering three handles for further derivatization to access valuable intermediates. The utility of this ligand-enabled asymmetric protocol has been highlighted through the late-stage decoration of drug-relevant molecules.

Chlorophyll a acts as a natural photosensitizer to drive nitrate reduction in nonphotosynthetic microorganisms.

With the death and decomposition of widely distributed photosynthetic organisms, free natural pigments are often detected in surface water, sediment and soil. Whether free pigments can act as photosensitizers to drive biophotoelectrochemical metabolism in nonphotosynthetic microorganisms has not been reported. In this work, we provide direct evidence for the photoelectrophic relationship between extracellular chlorophyll a (Chl a) and nonphotosynthetic microorganisms. The results show that 10 µg of Chl a can produce significant photoelectrons (∼0.34 A/cm2) upon irradiation to drive nitrate reduction in Shewanella oneidensis. Chl a undergoes structural changes during the photoelectric process, thus the ability of Chl a to generate a photocurrent decreases gradually with increasing illumination time. These changes are greater in the presence of microorganisms than in the absence of microorganisms. Photoelectron transport from Chl a to S. oneidensis occurs through a direct pathway involving the cytochromes MtrA, MtrB, MtrC and CymA but not through an indirect pathway involving riboflavin. These findings reveal a novel photoelectrotrophic linkage between natural photosynthetic pigments and nonphototrophic microorganisms, which has important implications for the biogeochemical cycle of nitrogen in various natural environments where Chl a is distributed.

SARS-CoV-2 infection activates inflammatory macrophages in vascular immune organoids.

SARS-CoV-2 provokes devastating tissue damage by cytokine release syndrome and leads to multi-organ failure. Modeling the process of immune cell activation and subsequent tissue damage is a significant task. Organoids from human tissues advanced our understanding of SARS-CoV-2 infection mechanisms though, they are missing crucial components: immune cells and endothelial cells. This study aims to generate organoids with these components. We established vascular immune organoids from human pluripotent stem cells and examined the effect of SARS-CoV-2 infection. We demonstrated that infections activated inflammatory macrophages. Notably, the upregulation of interferon signaling supports macrophages' role in cytokine release syndrome. We propose vascular immune organoids are a useful platform to model and discover factors that ameliorate SARS-CoV-2-mediated cytokine release syndrome.

A Recyclable Electrochemical Reduction of Aldehydes and Ketones to Alcohols Using Water as the Hydrogen Source and Solvent.

There are several challenging problems such as the usage of combustible and hazardous hydrogen sources and severe environmental pollution in the conventional reduction of aldehydes/ketones to alcohols. We report here a practical, safe, and green electrochemical reduction, which solves these problems to a large extent. Through an undivided cell, Zn(+) and Sn(-) as the electrode, tetrabutylammonium chloride (TBAC) as the electrolyte, water as the solvent and hydrogen source, a wide range of aldehydes and ketones are converted into the corresponding alcohols in mild conditions. Furthermore, the electrolytes and water can be recycled, and reductive deuteration can be achieved by simply using D2O as the solvent. Finally, the reduction can be smoothly scaled up to a kilogram level.

RAB10 Facilitates Colorectal Cancer Progression through Activation of the NF-κB Signaling Pathway.

Background: Colorectal cancer (CRC) is the third most prevalent malignancy globally, ranking as the second leading cause of cancer-related mortality. Emerging evidence highlights RAB10's involvement in the progression of various malignant tumors; however, its specific role in CRC remains unclear. Objective: To explore the oncogenic role of RAB10 in colorectal cancer progression by investigating its impact on NF-κB activation, aiming to identify a novel genetic biomarker for enhanced diagnosis and treatment of CRC. Methods: This study collected CRC tissue samples and utilized The Cancer Genome Atlas (TCGA) database for RAB10 expression verification through Western blot (WB). Cellular phenotype experiments were conducted on CRC cell lines, including quantitative real-time-polymerase chain reaction (qRT-PCR), CCK-8, transwell assay, and wound healing assay (HCT116 and SW480). Additionally, the impact of RAB10 on NF-κB signaling was assessed through qRT-PCR and WB. Results: RAB10 exhibited upregulation in CRC tissue samples compared to normal counterparts. Furthermore, RAB10 promoted the proliferation, migration, and invasion of HCT116 and SW480 cells. Notably, RAB10 induced NF-κB activation in CRC in vitro. Conclusion: This study revealed the oncogenic function of RAB10, explaining its role in activating NF-κB in CRC. The findings present RAB10 as a potential genetic biomarker for CRC diagnosis and treatment.

Correction: Teng et al. Efficacy Assessment of Phage Therapy in Treating Staphylococcus aureus-Induced Mastitis in Mice. Viruses 2022, 14, 620.

In the original publication [...].

Ecotoxicity and trophic transfer of metallic nanomaterials in aquatic ecosystems.

Metallic nanomaterials (MNMs) possess unique properties that have led to their widespread application in fields such as electronics and medicine. However, concerns about their interactions with environmental factors and potential toxicity to aquatic life have emerged. There is growing evidence suggesting MNMs can have detrimental effects on aquatic ecosystems, and are potential for bioaccumulation and biomagnification in the food chain, posing risks to higher trophic levels and potentially humans. While many studies have focused on the general ecotoxicity of MNMs, fewer have delved into their trophic transfer within aquatic food chains. This review highlights the ecotoxicological effects of MNMs on aquatic systems via waterborne exposure or dietary exposure, emphasizing their accumulation and transformation across the food web. Biomagnification factor (BMF), the ratio of the contaminant concentration in predator to that in prey, was used to evaluate the biomagnification due to the complex nature of aquatic food chains. However, most current studies have BMF values of less than 1 indicating no biomagnification. Factors influencing MNM toxicity in aquatic environments include nanomaterial properties, ion variations, light, dissolved oxygen, and pH. The multifaceted interactions of these variables with MNM toxicity remain to be fully elucidated. We conclude with recommendations for future research directions to mitigate the adverse effects of MNMs in aquatic ecosystems and advocate for a cautious approach to the production and application of MNMs.

Copy number variation sequencing for the products of conception: What is the optimal testing strategy.

BACKGROUND: Copy number variation sequencing (CNV-seq) is crucial in prenatal diagnosis, but its limitations in detecting polyploidy, maternal cell contamination (MCC), and uniparental disomy (UPD) restrict its application in the analysis of products of conception (POCs). This study aimed to investigate an optimal genetic testing strategy for POCs in the era of CNV-seq. METHODS: CNV-seq and quantitative fluorescent polymerase chain reaction (QF-PCR) were performed in all 4,211 spontaneous miscarriage cases. Different testing strategies were compared and the optimal testing strategies were proposed. RESULTS: Of the 4,211 cases, 2561 (60.82%) exhibited clinically significant chromosomal abnormalities. CNV-seq alone, without QF-PCR, might misdiagnose 311 (7.39%) cases, including 278 polyploidy, 13 UPD, and 20 MCC. In 20 MCC cases identified by QF-PCR, CNV-seq successfully pinpointed the cause of miscarriage in 13 cases. Furthermore, in cases where QF-PCR suggested polyploidy, CNV-seq improved the diagnostic accuracy in 54 (1.28%) hypo/hypertriploidy cases. After comparing four different strategies, the sequential approach (initiating with CNV-seq followed by QF-PCR if necessary) emerged as advantageous, reducing approximately 70% of the cost associated with QF-PCR while maintaining result accuracy. CONCLUSIONS: We propose an initial CNV-seq followed by QF-PCR if needed-an efficient and cost-effective strategy for the genetic analysis of POCs.