Genome-wide detections for runs of homozygosity and selective signatures reveal novel candidate genes under domestication in chickens.

BACKGROUND: Indigenous chickens were developed through a combination of natural and artificial selection; essentially, changes in genomes led to the formation of these modern breeds via admixture events. However, their confusing genetic backgrounds include a genomic footprint regulating complex traits, which is not conducive to modern animal breeding. RESULTS: To better evaluate the candidate regions under domestication in indigenous chickens, we considered both runs of homozygosity (ROHs) and selective signatures in 13 indigenous chickens. The genomes of Silkie feather chickens presented the highest heterozygosity, whereas the highest inbreeding status and ROH number were found in Luhua chickens. Short ROH (< 1 Mb), were the principal type in all chickens. A total of 291 ROH islands were detected, and QTLdb mapping results indicated that body weight and carcass traits were the most important traits. An ROH on chromosome 2 covering VSTM2A gene was detected in 12 populations. Combined analysis with the Tajima's D index revealed that 18 genes (e.g., VSTM2A, BBOX1, and RYR2) were under selection and covered by ROH islands. Transcriptional analysis results showed that RYR2 and BBOX1 were specifically expressed in the heart and muscle tissue, respectively. CONCLUSION: Based on genome-wide scanning for ROH and selective signatures, we evaluated the genomic characteristics and detected significant candidate genes covered by ROH islands and selective signatures. The findings in this study facilitated the understanding of genetic diversity and provided valuable insights for chicken breeding and conservation strategies.

AS101 regulates the Teff/Treg balance to alleviate rabbit autoimmune dacryoadenitis through modulating NFATc2.

Sjögren's syndrome (SS) dry eye can cause ocular surface inflammation and lacrimal gland (LG) damage, leading to discomfort and potential vision problems. The existing treatment options for SS dry eye are currently constrained. We investigated the possible therapeutic effect and the underlying mechanism of AS101 in autoimmune dry eye. AS101 was injected subconjunctivally into a rabbit model of autoimmune dacryoadenitis and its therapeutic effects were determined by evaluating clinical and histological scores. The expressions of effector T cells (Teff)/regulatory T cells (Treg)-related transcription factors and cytokines, inflammation mediators, and transcription factor NFATc2 were measured by quantitative real-time PCR and/or Western blot both in vivo and in vitro. Additionally, the role of NFATc2 in the immunomodulatory effects of AS101 on T cells was explored by co-culturing activated peripheral blood lymphocytes (PBLs) transfected with NFATc2 overexpression lentiviral plasmid with AS101. AS101 treatment potently ameliorated the clinical severity and reduced the inflammation of LG. Further investigation revealed that AS101 treatment led to decreased expression of Th1-related genes (T-bet and IFN-γ) and Th17-related genes (RORC, IL-17A, IL-17F, and GM-CSF) and increased expression of Treg-related gene Foxp3 in vivo and in vitro. Meanwhile, AS101 suppressed the expression of TNF-α, IL-1ß, IL-23, IL-6, MMP-2, and MMP-9. Mechanistically, AS101 downregulated the expression of NFATc2 in inflamed LGs. Overexpression of NFATc2 in activated PBLs partially blunted the effect of AS101 on Teff suppression and Treg promotion. In conclusion, AS101 is a potential regulator of Teff/Treg cell balance and could be an effective treatment agent for SS dry eye.

Theoretical Study on the Reaction between Carcinogenic 2,5-Dichloro-1,4-benzoquinone and tert-Butyl Hydroperoxide: Self-Catalysis and Water Catalysis.

The potentially carcinogenic halobenzoquinones (HBQs) have been recently identified in drinking water as disinfection byproducts. Several radical intermediates in the reaction of 2,5-dichloro-1,4-benzoquinone (DCBQ) and t-butyl hydroperoxide (t-BuOOH), which may induce DNA damage, were detected experimentally, and metal-independent decomposition reactions of t-BuOOH by DCBQ were proposed. It has not yet been confirmed by theoretical calculations. The theoretical study in this work provides insights into the details of the reaction. An unprecedented self-catalysis mechanism of organic hydroperoxides, that is, the reactant t-BuOOH also has a catalytic effect, was uncovered at the molecular level. Moreover, as the solvent, water molecules also clearly have an efficient catalytic effect. Due to the catalysis of t-BuOOH and water, the metal-independent reaction of t-BuOOH and DCBQ can occur under moderate conditions. Our findings about the novel catalytic effect of organic hydroperoxides t-BuOOH could offer a unique perspective into the design of new catalysts and an understanding of the catalytic biological, environmental, and air pollution reactions. Furthermore, organic hydroperoxide t-BuOOH could serve as a proton shuttle, where the proton transfer process is accompanied by simultaneous charge transfer. Therefore, organic hydroperoxides may disrupt the vital proton transfer process in biological systems and may give rise to unexpected toxicity.

Magnetic resonance imaging with upconversion nanoprobes capable of crossing the blood-cerebrospinal fluid barrier.

The central nervous system (CNS) maintains homeostasis with its surrounding environment by restricting the ingress of large hydrophilic molecules, immune cells, pathogens, and other external harmful substances to the brain. This function relies heavily on the blood-cerebrospinal fluid (B-CSF) and blood-brain barrier (BBB). Although considerable research has examined the structure and function of the BBB, the B-CSF barrier has received little attention. Therapies for disorders associated with the central nervous system have the potential to benefit from targeting the B-CSF barrier to enhance medication penetration into the brain. In this study, we synthesized a nanoprobe ANG-PEG-UCNP capable of crossing the B-CSF barrier with high targeting specificity using a hydrocephalus model for noninvasive magnetic resonance ventriculography to understand the mechanism by which the CSF barrier may be crossed and identify therapeutic targets of CNS diseases. This magnetic resonance nanoprobe ANG-PEG-UCNP holds promising potential as a safe and effective means for accurately defining the ventricular anatomy and correctly locating sites of CSF obstruction.

The Impact of high-performance work system perceived by medical staff on job satisfaction: the mediating role of self-efficacy.

As the mainstay of healthcare, the job satisfaction of medical staff deserves attention. This study aimed to explore the correlation between the perception of the high-performance work system (P-HPWS) and job satisfaction of medical staff in public hospitals and to further investigate the mediating effect of self-efficacy. From November 2019 to January 2020, a cross-sectional survey on working doctors and nurses was conducted in five tertiary public hospitals in China. A total of 520 participants were surveyed. The P-HPWS, job satisfaction, and self-efficacy were assessed using the 25-item self-administered scale, six-item job satisfaction questionnaire, and the General Self-Efficacy Scale, respectively. Linear regression and mediation effects models were used to identify the associations between primary variables. The results showed a significant positive correlation between P-HPWS and job satisfaction (P < 0.01), while self-efficacy played a mediating role between P-HPWS and job satisfaction. This finding reveals the benefits of improving employees' P-HPWS and self-efficacy on their job satisfaction, and that hospitals can improve their management systems by implementing and refining HPWS.

Novel Insights into the Circadian Rhythms Based on Long Noncoding and Circular RNA Profiling.

Circadian rhythm disorders pose major risks to human health and animal production activity, and the hypothalamus is the center of circadian rhythm regulation. However, the epigenetic regulation of circadian rhythm based on farm animal models has been poorly investigated. We collected chicken hypothalamus samples at seven time points in one light/dark cycle and performed long noncoding RNA (lncRNA), circular RNA (circRNA), and mRNA sequencing to detect biomarkers associated with circadian rhythm. We enhanced the comprehensive expression profiling of ncRNAs and mRNAs in the hypothalamus and found two gene sets (circadian rhythm and retinal metabolism) associated with the light/dark cycle. Noncoding RNA networks with circadian expression patterns were identified by differential expression and circadian analysis was provided that included 38 lncRNAs, 15 circRNAs, and 200 candidate genes. Three lncRNAs (ENSGALT00000098661, ENSGALT00000100816, and MSTRG.16980.1) and one circRNA (novel_circ_010168) in the ncRNA-mRNA regulatory network were identified as key molecules influencing circadian rhythm by regulating AOX1 in retinal metabolism. These ncRNAs were predicted to be related to pernicious anemia, gonadal, eye disease and other disorders in humans. Together, the findings of this study provide insights into the epigenetic mechanisms of circadian rhythm and reveal AOX1 as a promising target of circadian rhythm regulation.

Middle-aged and older people's preference for medical-elderly care integrated institutions in China: a discrete choice experiment study.

BACKGROUND: With the continuing impact of the aging population, medical-elderly care integrated institutions, as a way to bear the pressure of medical and elderly care, effectively ensure the quality of life of the elderly in their later years. OBJECTIVES: To explore the preferences of medical-elderly care integrated institutions among Chinese middle-aged and older people and to provide a reference for establishing elderly-oriented development of medical-elderly care integrated institutions. METHODS: In this study, a discrete choice experiment (DCE) was used to investigate the preferences of people aged 45 years and older in medical-elderly care integrated institutions in China from October 20, 2022, to November 10, 2022. A mixed logit regression model was used to analyze the DCE data. Participants' willingness to pay for each attribute was also calculated. RESULTS: Data from 420 participants who provided valid responses were included in the analysis. In terms of the choice preference, moderate service quality (vs. poor service quality: ß = 1.707, p < 0.001, 95% CI 1.343 ~ 2.071) and high medical technology level (vs. low medical technology level: ß = 1.535, p < 0.001, 95% CI 1.240 ~ 1.830) were the most important attributes to middle-aged and older people, followed by monthly cost, environmental facilities, the convenience of transportation, and entertainment activities. Regarding the willingness to pay, participants were more willing to pay for service quality and medical technology level than for other attributes. They were willing to pay $3156 and $2838 more for "poor service quality" and "low medical technology level," respectively, to receive "moderate service quality " (p = 0.007, 95% CI 963 ~ 5349) and "high medical technology level" (p = 0.005, 95% CI 852 ~ 4824). CONCLUSIONS: The state should attach great importance to the development of medical-elderly care integrated services industry, actively optimize the model of the medical-elderly care integrated service, improve the facilities, and create a healthy environment. At the same time, give full play to the role of medical insurance, long-term care insurance, and commercial insurance, so as to improve the comprehensive quality of life of the elderly. PUBLIC CONTRIBUTION: The design of the experimental selection was guided by 10 experts in the field, 5 Chinese government officials, and interviews and focus group discussions, without whose participation this study would not have been possible.

Electrochemiluminescent CdS Quantum Dots Biosensor for Cancer Mutation Detection at Different Positions on Linear DNA Analytes.

PCR-based techniques routinely employed for the detection of mutated linear DNA molecules, including circulating tumor DNA (ctDNA), require large nucleotide sections on both sides of the mutation for primer annealing. This means that DNA fragments with a mutation positioned closer to the extremities are unlikely to be detected. Thus, sensors capable of recognizing linear DNA with characteristic mutations closer to the ends would be advantageous over the state-of-the-art approaches. Here, an electrochemiluminescence-resonance energy transfer (ECL-RET) biosensor comprising capped CdS quantum dots and hairpin DNA probes labeled with Au nanoparticles was developed for the detection of epidermal growth factor receptor (EGFR) ctDNA carrying the critical T790M lung cancer mutation. The ECL-RET system detected different DNA molecules including single-stranded 18-nucleotides (nt) and 40-nt as well as double-stranded 100-nt with the single nucleotide polymorphism (SNP) coding for T790M located either in the middle or only 7 nt from one end. For all target DNA, the sensor's limits of detection (LODs) were in the aM range, with excellent selectivity. It was the case of 100-nt target linear ctDNA fragments with LODs of 8.1 and 3.4 aM when the EGFR T790M SNP was either in the middle or at the end, respectively. These results show that ECL-RET systems can sense mutations in DNA fragments that would remain undetected by standard techniques.

Growing Electrocatalytic Conjugated Microporous Polymers on Self-Standing Carbon Nanotube Films Promotes the Rate Capability of Li-S Batteries.

Lithium-sulfur (Li-S) batteries hold great promise for widespread application on account of their high theoretical energy density (2600 Wh kg-1 ) and the advantages of sulfur. Practical use, however, is impeded by the shuttle effect of polysulfides along with sluggish cathode kinetics. it is reported that such deleterious issues can be overcome by using a composite film (denoted as V-CMP@MWNT) that consists of a conjugated microporous polymer (CMP) embedded with vanadium single-atom catalysts (V SACs) and a network of multi-walled carbon nanotubes (MWNTs). V-CMP@MWNT films are fabricated by first electropolymerizing a bidentate ligand designed to coordinate to V metals on self-standing MWNT films followed by treating the CMP with a solution containing V ions. Li-S cells containing a V-CMP@MWNT film as interlayer exhibit outstanding performance metrics including a high cycling stability (616 mA h g-1 at 0.5 C after 1000 cycles) and rate capability (804 mA h g-1 at 10 C). An extraordinary area-specific capacity of 13.2 mA h cm-2 is also measured at a high sulfur loading of 12.2 mg cm-2 . The underlying mechanism that enables the V SACs to promote cathode kinetics and suppress the shuttle effect is elucidated through a series of electrochemical and spectroscopic techniques.

VRPharmer: bringing virtual reality into pharmacophore-based virtual screening with interactive exploration and realistic visualization.

SUMMARY: Current pharmacophore-based virtual screening (VS) software has limited interactive capabilities and less intuitive screening processes. In this study, a novel tool named VRPharmer is proposed to perform the entire VS workflow in VR environments. VRPharmer enables users to interactively perceive computation processes and immersively observe molecular structures. Besides a typical screening mode (OPT mode), VRPharmer provides a unique interactive screening mode (SCORE mode) for freely exploring the optimal binding poses. Pharmacophore models are editable to study the impact of each feature and further refine the screening results. Moreover, molecular rendering algorithms are improved for precise representations. AVAILABILITY AND IMPLEMENTATION: VRPharmer is open-source software under the MIT license. The released version is available at https://github.com/VRPharmer/VRPharmer. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Cationic Starch Nanoparticles for Enhancing CpG Oligodeoxynucleotide-Mediated Antitumor Immunity.

CpG ODNs demonstrate a significant promise for immunotherapy. However, their application is limited owing to quick DNase digestion and inadequate cellular internalization. Transportation of CpG ODNs into immune cells is crucial. Although viral vectors exhibit high transfection efficiency, safety risks, high cost, and low carrying capacity remain big obstacles. Herein, a novel CpG ODNs vector was fabricated by using starch. Starch was ultrasonicated and simply aminated (NH2-St) through grafting with diethylenetriamine, which was spherical with a diameter of 50 nm. NH2-St possessed good biocompatibility. Cationic NH2-St encapsulated CpG ODNs well and possessed a high loading capacity of 317 µg/mg. NH2-St protected CpG ODNs from nuclease digestion and significantly enhanced their cellular uptake. NH2-St/CpG induced the potent secretion of antitumor cytokines from macrophages and effectively suppressed the growth of tumor cells. This work highlights the promise of starch for CpG ODNs delivery, which brings new hope for cancer immunotherapy.

Mast cell stabilization: new mechanism underlying the therapeutic effect of intense pulsed light on rosacea.

BACKGROUND: Rosacea, a chronic inflammatory disorder of the facial skin, is effectively treated by intense pulsed light (IPL). OBJECTIVE: To explore the potential molecular mechanism underlying the photobiomodulation effect of IPL for rosacea treatment. METHODS: Skin samples from patients with rosacea were subjected to histological and immunohistological staining. Ten patients were followed up after IPL treatment using the VISIA® skin analysis system, and the severity was assessed. In vivo, skin changes in mice with rosacea-like inflammation induced by intradermal injection of 320 µM LL-37 with or without IPL treatment were evaluated using L*a*b colorimetry as well as histological and immunological staining. In vitro, LL-37-stimulated mast cells (MCs) with or without IPL treatment were evaluated for protein expression of matrix metalloproteinase (MMP)-9, kallikrein-related peptidase 5 (KLK5), and cathelicidin using western blotting and qRT-PCR. RESULTS: Profound infiltration of inflammatory cells and evident MC degranulation were found in rosacea skin lesions. The expression of rosacea-related biomarkers and inflammatory cytokines was higher in lesional areas than in non-lesional areas, as demonstrated via immunochemical staining. In all patients, rosacea severity reduced after IPL therapy. In vivo, IPL alleviated inflammation in mice with rosacea-like inflammation, as demonstrated by the significantly decreased MMP-9, KLK5, and cathelicidin expression and reduced percentage of degranulating MCs. In vitro, IPL decreased MMP-9, KLK5, and cathelicidin expression in P815 cells, reducing the release of inflammatory cytokines and inhibiting rosacea-like inflammatory reactions. CONCLUSION: The photobiomodulation effect of IPL for rosacea treatment may inhibit MC degranulation and alleviate inflammatory reactions.

Risk prediction of second primary malignancies in patients after rectal cancer: analysis based on SEER Program.

BACKGROUND: This study will focus on exploring the clinical characteristics of rectal cancer (RC) patients with Second Primary Malignancies (SPMs) and constructing a prognostic nomogram to provide clinical treatment decisions. METHODS: We determined the association between risk factors and overall survival (OS) while establishing a nomogram to forecast the further OS status of these patients via Cox regression analysis. Finally, we evaluated the performance of the prognostic nomogram to predict further OS status. RESULTS: Nine parameters were identified to establish the prognostic nomogram in this study, and, the C-index of the training set and validation set was 0.691 (95%CI, 0.662-0.720) and 0.731 (95%CI, 0.676-0.786), respectively. The calibration curve showed a high agreement between the predicted and actual results, and the receiver operating characteristic (ROC) curves verified the superiority of our model for clinical usefulness. In addition, the nomogram classification could more precisely differentiate risk subgroups and improved the discrimination of SPMs' prognosis. CONCLUSIONS: We systematically explored the clinical characteristics of SPMs after RC and constructed a satisfactory nomogram.

Regional Distribution of Atmospheric Organophosphate Tri-/Diesters in the Pearl River Delta: Possible Emission, Photo-degradation, and Atmospheric Transportation.

The regional characteristics of atmospheric organophosphate triesters (OPEs) and organophosphate diesters (Di-OPs) in the Pearl River Delta (PRD) were investigated by passive air samplers mounting quartz fiber filters. The analytes were found on a regional scale. Atmospheric OPEs, semi-quantified using sampling rates of particulate-bonded PAHs, were in the range of 537-2852 pg/m3 in spring and in the range of 106-2055 pg/m3 in summer, with tris(2-chloroethyl)phosphate (TCEP) and tris(2-chloroisopropyl)phosphate as the main components. While atmospheric Di-OPs were semi-quantified using sampling rates of SO42-, in the range of 22.5-5576 pg/m3 in spring and in the range of 66.9-1019 pg/m3 in summer, with di-n-butyl phosphate and diphenyl phosphate (DPHP) being the main Di-OPs. Our results indicated that OPEs were mainly distributed in the central part of the region, which might be ascribed to the distribution of industry related to OPE-containing products. In contrast, Di-OPs were scattered in the PRD, suggesting local emission from their direct industrial application. Significantly lower levels of TCEP, triphenyl phosphate (TPHP), and DPHP were detected in summer than in spring, implying that these compounds might be partitioned off particles as the temperature increased and due to possible photo-transformation of TPHP and DPHP. The results also suggested the long-distance atmospheric transportation potential of Di-OPs.

Imaging Features of Primary Intraosseous Meningiomas.

OBJECTIVE: To describe the imaging features of primary intraosseous meningiomas (PIMs) to aid an accurate diagnosis. METHODS: Clinical materials and radiological data for 9 patients with pathologically confirmed PIMs were reviewed comprehensively. RESULTS: Most lesions involved inner and outer plates of the calvaria and all were relatively well circumscribed. Upon computed tomography, portions of the solid neoplasm were hyperattenuated or isoattenuated. Hyperostosis was found in many lesions, but calcification was seen rarely. On magnetic resonance imaging, most neoplasms were hypointense on T1-weighted images, hyperintense on T2-weighted images, and heterogeneous on fluid-attenuated inversion recovery images. In most cases, the soft tissue of neoplasms showed hyperintense on diffusion-weighted imaging and hypointense on apparent diffusion coefficient. All lesions were obviously enhanced after gadolinium administration. Each patient accepted surgical treatment and recurrence was not observed during follow-up. CONCLUSIONS: Primary intraosseous meningiomas are very rare tumors that occur usually in later life. They are well-defined and tend to involve the inner and outer plates of the calvaria, with a classic appearance of hyperostosis on computed tomography. Primary intraosseous meningiomas display hypointense on T1-weighted images, hyperintense on T2-weighted images, and hyperattenuated or isoattenuated on computed tomography. Hyperintense on diffusion-weighted imaging, hypointense on apparent diffusion coefficient can also be found. Obvious enhancement supplied additional information for an accurate diagnosis. A neoplasm with these features should raise the suspicion of a PIM.

Non-Pharmacological Interventions in Patients With Heart Failure With Reduced Ejection Fraction: A Systematic Review and Network Meta-Analysis.

OBJECTIVE: To determine the effectiveness of non-pharmacologic interventions and the additional benefits of their combination in patients with heart failure with reduced ejection fraction (HFrEF). DATA SOURCES: We searched PubMed, Embase, and the Cochrane Clinical Trials Register from the date of database inception to April 22, 2023. STUDY SELECTION: Randomized controlled trials involving non-pharmacologic interventions conducted in patients with HFrEF were included. DATA EXTRACTION: Data were extracted by 2 independent reviewers based on a pre-tested data extraction form. The quality of evidence was assessed using the Cochrane Risk of Bias tool and the Grading of Recommendations Assessment, Development, and Evaluation method. DATA SYNTHESIS: A total of 82 eligible studies (4574 participants) were included. We performed a random-effects model within a Bayesian framework to calculate weighted mean differences (WMDs) and 95% credibility intervals. High or moderate certainty evidence indicated that high-intensity aerobic interval training (HIAIT) was best on improving 6-minute walk distance (6MWD; 68.55 m [36.41, 100.47]) and left ventricular ejection fraction (6.28% [3.88, 8.77]), while high-intensity aerobic continuous training (HIACT) is best on improving peak oxygen consumption (Peak VO2; 3.48 mL/kg•min [2.84, 4.12]), quality of life (QOL; -17.26 [-29.99, -7.80]), resting heart rate (-8.20 bpm [-13.32, -3.05]), and N-terminal pro-B-type natriuretic peptide (-600.96 pg/mL [-902.93, -404.52]). Moderate certainty evidence supported the effectiveness of inspiratory muscle training to improve peak oxygen consumption and functional electrical stimulation to improve QOL. Moderate-intensity aerobic continuous training (MIACT) plus moderate-intensity resistance training (MIRT) had additional benefits in Peak VO2, 6MWD, and QOL. This review did not provide a comprehensive evaluation of adverse events. CONCLUSIONS: Both HIAIT and HIACT are the most effective single non-pharmacologic interventions for HFrEF. MIACT plus MIRT had additional benefits in improving peak oxygen consumption, 6MWD, and QOL.

Identification of Quinone Outside Inhibitor Fungicide-Resistant Isolates of Parastagonospora nodorum from Illinois and Kentucky.

Stagonospora leaf and glume blotch, caused by Parastagonospora nodorum, is a major disease of winter wheat (Triticum aestivum) in the United States capable of significantly reducing grain yield and quality. Pathogens such as P. nodorum that overwinter in crop residue are often an increased concern in cropping systems that utilize no-till farming. In addition, the lack of wheat cultivars with complete resistance to P. nodorum has led to the reliance on foliar fungicides for disease management. Quinone outside inhibitor (QoI) fungicides (Fungicide Resistance Action Committee group 11) are one of the major classes used to manage foliar diseases in wheat. Use of the QoI class of fungicides tends to select isolates of fungal pathogens with resistance due to mutations in the fungal cytochrome b gene. Isolates of P. nodorum were collected from Illinois in 2014 and Kentucky in 2018, 2019, and 2020. Amplification and sequencing of a segment of the cytochrome b gene from these isolates revealed a mutation at codon 143 that confers a change from glycine to alanine in the amino acid sequence (known as the G143A mutation). In vitro plate assays and greenhouse trials were used to confirm and characterize the QoI resistance caused by the G143A mutation. The frequency of the tested isolates with the G143A mutation was 46% (57 of 123 isolates) and 5% (3 of 60 isolates) for Kentucky and Illinois, respectively. This research is the first to identify the G143A mutation in P. nodorum isolates with resistance to QoI fungicides in Illinois and Kentucky.

Ternary Mixture of Azoxystrobin, Boscalid and Pyraclostrobin Disrupts the Gut Microbiota and Metabolic Balance of Honeybees (Apis cerana cerana).

There is a growing risk of pollinators being exposed to multiple fungicides due to the widespread use of fungicides for plant protection. A safety assessment of honeybees exposed to multiple commonly used fungicides is urgently required. Therefore, the acute oral toxicity of the ternary mixed fungicide of ABP (azoxystrobin: boscalid: pyraclostrobin = 1:1:1, m/m/m) was tested on honeybees (Apis cerana cerana), and its sublethal effect on foragers' guts was evaluated. The results showed that the acute oral median lethal concentration (LD50) of ABP for foragers was 12.6 µg a.i./bee. ABP caused disorder of the morphological structure of midgut tissue and affected the intestinal metabolism; the composition and structure of the intestinal microbial community was perturbed, which altered its function. Moreover, the transcripts of genes involved in detoxification and immunity were strongly upregulated with ABP treatment. The study implies that exposure to a fungicide mixture of ABP can cause a series of negative effects on the health of foragers. This work provides a comprehensive understanding of the comprehensive effects of common fungicides on non-target pollinators in the context of ecological risk assessment and the future use of fungicides in agriculture.

Four Meroterpenoids with Novel Aminoglycoside Moiety from the Basidiomycete Clitocybe clavipes with Cytotoxic Activity.

Four new meroterpenoids, Clavilactone M-P, possessing novel aminoglycoside moiety (1-4) and a 10-membered carbocycle fused with an α,ß-epoxy-γ-lactone, were isolated from Clitocybe clavipes, a basidiomycete. Their structures with absolute configurations were determined by extensive analysis of their spectroscopic data, and the ECD method. All the isolated compounds (1-4) were evaluated for their antitumor activity against three human cancer cell lines using the MTT assay. Compound 1 and 2 exhibited a significant suppression of cell viability in the Hela (IC50 = 22.8 and 19.7 µM) cell line.

Divergent and Selective Light Alkene Cross-Coupling.

Light olefins are abundantly manufactured in the petroleum industry and thus represent ideal starting materials for modern chemical synthesis. Selective and divergent transformations of feedstock light olefins to value-added chemicals are highly sought-after but remain challenging. Herein we report an exceptionally regioselective carbonickelation of light alkenes followed by in situ trapping with three types of nucleophiles, namely a reductant, base, or Grignard reagent. This protocol enables efficient 1,2-hydrofunctionalization, dicarbofunctionalization, and branched-selective Heck-type cross-coupling of light alkenes with aryl and alkenyl reagents to streamline access to diverse alkyl arenes and complex alkenes. Harnessing bulky N-heterocyclic carbene ligands with acenaphthyl backbones for nickel catalysts is crucial to attain high reactivity and selectivity. This strategy provides a rare, modular, and divergent platform for upgrading feedstock alkenes and is expected to find broad applications in medicinal chemistry and industrial processes.