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To simultaneously detect 13 illegally added chemical drugs, a high performance liquid chromatography (HPLC) analytical method applicable to health food products for improving sexual function and prostate function was established. The samples were processed by vortex shaking for 1 min, followed by methanol extraction for 10 min under the ultrasonic condition. Then, the sample was separated on an Agilent 5 HC-C18 (2) column (250 mm×4.6 mm, 5 µm) with a gradient separation using methanol-phosphate-triethylamine buffer as the mobile phase. The detection wavelengths were of 218 nm and 245 nm, the column temperature was 30 ℃, and the sample size was 10 µL. Results showed that the correlation coefficients (r) in the linear range were all greater than 0.999, the detection limits were 0.76～4.61 mg/kg, the average recoveries were 92.4%~100.7%, and the relative standard deviations were 0.44%~1.06%. The method was applied to the rapid screening of 65 batches of health foods for improving sexual and prostate function, and results indicated that paroxetine hydrochloride was detected in 2 batches of samples (15.26 mg/tablet, 6.34 mg/pellet, respectively) and yohimbine hydrochloride was detected in 1 batch of samples (10.12 mg/pellet). In summary, the method is easy to conduct and characterized with high sensitivity and reliability, which is suitable for daily supervision and inspection of illegal added drugs in health foods for improving sexual and prostate function.

Abstract The harmonic problems caused by non‐linear factors of the grid connected inverter (GCI) system are more complicated, including both non‐characteristic harmonics emitted by the dead‐time and the changes in harmonic impedance characteristics. Harmonics interact with the changing impedance, and even cause harmonic amplification and resonance. The harmonic deterioration of the multiple GCIs system is serious. To analyse the mechanism and way of harmonic deterioration in grid‐connected system caused by nonlinear factors, the active impedance models of single inverter and multiple GCIs system including dead‐time effect and digital control delay are established first. In view of this, the influence mechanism of non‐linear factors on system stability is explored. The improved modal analysis method is used to traverse the network series parallel resonance caused by nonlinear factors. The results show that both the dead‐time effect and digital control delay reduce phase margin of the system, resulting in the resonant frequency shift and the resonant peak increase. When the harmonic excitation source interacts with the complex network under the influence of nonlinear factors, it will lead to further deterioration of harmonics. Finally, based on the MATLAB and RT‐LAB hardware‐in‐the‐loop simulation platforms, a multiple GCIs system model is built to verify the correctness of the established active impedance model and harmonic deterioration analysis.

Abstract Background Aside from the canonical role of PDL1 as a tumour surface-expressed immune checkpoint molecule, tumour-intrinsic PDL1 signals regulate non-canonical immunopathological pathways mediating treatment resistance whose significance, mechanisms, and therapeutic targeting remain incompletely understood. Recent reports implicate tumour-intrinsic PDL1 signals in the DNA damage response (DDR), including promoting homologous recombination DNA damage repair and mRNA stability of DDR proteins, but many mechanistic details remain undefined. Methods We genetically depleted PDL1 from transplantable mouse and human cancer cell lines to understand consequences of tumour-intrinsic PDL1 signals in the DNA damage response. We complemented this work with studies of primary human tumours and inducible mouse tumours. We developed novel approaches to show tumour-intrinsic PDL1 signals in specific subcellular locations. We pharmacologically depleted tumour PDL1 in vivo in mouse models with repurposed FDA-approved drugs for proof-of-concept clinical translation studies. Results We show that tumour-intrinsic PDL1 promotes the checkpoint kinase-2 (Chk2)-mediated DNA damage response. Intracellular but not surface-expressed PDL1 controlled Chk2 protein content post-translationally and independently of PD1 by antagonising PIRH2 E3 ligase-mediated Chk2 polyubiquitination and protein degradation. Genetic tumour PDL1 depletion specifically reduced tumour Chk2 content but not ATM, ATR, or Chk1 DDR proteins, enhanced Chk1 inhibitor (Chk1i) synthetic lethality in vitro in diverse human and murine tumour models, and improved Chk1i efficacy in vivo. Pharmacologic tumour PDL1 depletion with cefepime or ceftazidime replicated genetic tumour PDL1 depletion by reducing tumour Chk2, inducing Chk1i synthetic lethality in a tumour PDL1-dependent manner, and reducing in vivo tumour growth when combined with Chk1i. Conclusions Our data challenge the prevailing surface PDL1 paradigm, elucidate important and previously unappreciated roles for tumour-intrinsic PDL1 in regulating the ATM/Chk2 DNA damage response axis and E3 ligase-mediated protein degradation, suggest tumour PDL1 as a biomarker for Chk1i efficacy, and support the rapid clinical potential of pharmacologic tumour PDL1 depletion to treat selected cancers.

Abstract Background Fertilization practices control bacterial wilt-causing Ralstonia solanacearum by shaping the soil microbiome. This microbiome is the start of food webs, in which nematodes act as major microbiome predators. However, the multitrophic links between nematodes and the performance of R. solanacearum and plant health, and how these links are affected by fertilization practices, remain unknown. Results Here, we performed a field experiment under no-, chemical-, and bio-organic-fertilization regimes to investigate the potential role of nematodes in suppressing tomato bacterial wilt. We found that bio-organic fertilizers changed nematode community composition and increased abundances of bacterivorous nematodes (e.g., Protorhabditis spp.). We also observed that pathogen-antagonistic bacteria, such as Bacillus spp., positively correlated with abundances of bacterivorous nematodes. In subsequent laboratory and greenhouse experiments, we demonstrated that bacterivorous nematodes preferentially preyed on non-pathogen-antagonistic bacteria over Bacillus. These changes increased the performance of pathogen-antagonistic bacteria that subsequently suppressed R. solanacearum. Conclusions Overall, bacterivorous nematodes can reduce the abundance of plant pathogens, which might provide a novel protection strategy to promote plant health. Video Abstract

Abstract Background Spiroplasma eriocheiris has been proved to be a pathogen causing tremor disease of Eriocheir sinensis, it is also infectious to other aquatic crustaceans, resulting in a serious threat on the sustainable development of the aquaculture industry. S. eriocheiris is a helical-shaped microbe without a cell wall, and its motility is related to the cytoskeleton protein MreB which belongs to the actin superfamily and has five MreB homologs. Results In this study, we purified MreB3, MreB4 and MreB5, and successfully prepared monoclonal antibodies. After S. eriocheiris treated with actin stabilizator Phalloidin and inhibitors A22, we found that Phalloidin and A22 affect the S. eriocheiris morphology by altering MreB expression. We confirmed that the ability of S. eriocheiris to invade E. sinensis was increased after treatment with Phalloidin, including that the morphology of E. sinensis blood lymphocytes was deteriorated, blood lymphocytes viability was decreased, peroxidase activity and cell necrosis were increased. On the contrary, the pathogenicity of S. eriocheiris decreased after treatment with A22. Conclusions Our findings suggest that the MreB protein in S. eriocheiris plays a crucial role in its morphology and pathogenicity, providing new insights into potential strategies for the prevention and control of S. eriocheiris infections.

Abstract Protein aggregation plays key roles in age-related degenerative diseases, but how different proteins coalesce to form inclusions that vary in composition, morphology, molecular dynamics and confer physiological consequences is poorly understood. Here we employ a general reporter based on mutant Hsp104 to identify proteins forming aggregates in human cells under common proteotoxic stress. We identify over 300 proteins that form different inclusions containing subsets of aggregating proteins. In particular, TDP43, implicated in Amyotrophic Lateral Sclerosis (ALS), partitions dynamically between two distinct types of aggregates: stress granule and a previously unknown non-dynamic (solid-like) inclusion at the ER exit sites (ERES). TDP43-ERES co-aggregation is induced by diverse proteotoxic stresses and observed in the motor neurons of ALS patients. Such aggregation causes retention of secretory cargos at ERES and therefore delays ER-to-Golgi transport, providing a link between TDP43 aggregation and compromised cellular function in ALS patients.

Abstract. Tuberculosis (TB) is a prominent infectious disease globally that imposes a substantial health burden. Genital TB (GTB), an extrapulmonary manifestation, leads to complications such as tubal adhesions, blockage, and diminished ovarian function, culminating in infertility, and is recognized as a prevalent cause of infertility in nations with high-burden TB. In regions with low TB rates, infertility and active TB during pregnancy have been reported to be most common among female immigrants from countries with high-burden TB. In the context of TB, pregnant women often exhibit exacerbated symptoms after in vitro fertilization-embryo transfer (IVF-ET), heightening the risk of dissemination. Miliary pulmonary TB and tuberculous meningitis pose a serious threat to maternal and fetal health. This article integrates recent epidemiological data and clinical research findings, delineating the impact of TB on infertility and assisted reproduction and particularly focusing on the diagnosis and treatment of GTB, underscored by the imperative of TB screening before IVF-ET. Our objective is to increase awareness among respiratory and reproductive health professionals, promoting multidisciplinary management to enhance clinical vigilance. This approach seeks to provide patients with judicious reproductive plans and scientifically rigorous pregnancy management, thereby mitigating adverse pregnancy outcomes related to TB activity.

The exploration of the first member of Permian Maokou Formation (Maokou 1) in the Weiyuan area of southern Sichuan Basin has been limited. Previous analyses of cast thin sections and argon ion electron microscopy based on earlier drilling data suggested that talc pores were the primary reservoir spaces, with talc formation significantly contributing to the reservoir. However, the latest drilling data shows substantial differences in the types of reservoir spaces and the genesis of the Maokou 1 marlstone reservoirs compared to earlier understanding. It is necessary to further clarify the main controlling factors for the development of these reservoirs in the Maokou 1 member. Through core observation, thin section identification, physical property analysis, nitrogen adsorption, argon ion polishing scanning electron microscopy, and quantitative pore characterization, the primary reservoir spaces and types of the Maokou 1 marlstone were analyzed from both qualitative and quantitative perspectives. The main controlling factors for the development of these reservoirs were identified by combining total organic carbon (TOC) content determination, rare earth element analysis, and whole rock X-ray diffraction. High-quality reservoirs in the Maokou 1 member of the Weiyuan area are developed in marlstone, characterized by low porosity and permeability fractures and pore-type reservoirs, predominantly Type Ⅲ with some Type Ⅱ reservoirs. The main reservoir spaces include corroded pores, organic matter pores, and talc pores and fractures, with pore development closely related to TOC content. Talc formation, dolomitization, and silicification did not significantly contribute to secondary reservoir spaces, and their contribution to porosity is minimal. The development of marlstone reservoirs is jointly controlled by early dissolution, sedimentary facies, and organic matter abundance. Early dissolution is the key to the formation of corroded pores and fractures, while high primary productivity and high organic matter settling rate of the inner gentle slope shallow water environment provided the material basis for the formation of organic matter pores. This understanding provides theoretical support for the exploration of similar oil and gas reservoirs in the basin.

Background: A Delphi consensus was conducted to formulate an expert opinion on the definition of in-vitro fertilization (IVF) success, to provide a reference basis for clinical practice. Methods: Chinese experts in assisted reproductive technology (ART) were surveyed using the Delphi method. Based on the literature related to IVF success, eight experts developed a framework of statements and items. A questionnaire was then distributed to 23 experts to canvas their opinions on these statements. If consensus was not achieved, the statement was revised and revoted upon until a consensus was reached. Results: Consensus was reached for 19 statements related to the definition of IVF success, the most relevant of which are summarized as follows: (1) Goal of IVF treatment ([Formula: see text] statement): to attain a healthy live birth in the shortest possible time and with the lowest possible risks; (2) Definition of IVF success ([Formula: see text] statements): effectiveness, safety, and efficiency of IVF treatment should be included in the definition of success, with the cumulative live birth rate per ovarian stimulation cycle within 2 years being a performance indicator (PI) of success, and IVF success should be measured from a patient-centered perspective, including the patient’s burden and satisfaction. (3) Assurance of IVF success ([Formula: see text] statements): to provide evidence-based treatment and avoid the introduction of IVF add-ons into routine clinical practice without any clear evidence of benefit, optimize treatment quality by establishing and monitoring key PIs, and improving quality control systems. (4) Hurdles of IVF success ([Formula: see text] statements): cycle cancellation before oocyte pickup and treatment discontinuation after failed cycles are hurdles of success to IVF. Conclusions: Based on the Delphi method, the expert opinion on the definition of IVF success has been formed, which could complement guidelines and may help improve treatment outcomes.

Abstract Background Soil nutrient status and soil-borne diseases are pivotal factors impacting modern intensive agricultural production. The interplay among plants, soil microbiome, and nutrient regimes in agroecosystems is essential for developing effective disease management. However, the influence of nutrient availability on soil-borne disease suppression and associated plant-microbe interactions remains to be fully explored. T his study aims to elucidate the mechanistic understanding of nutrient impacts on disease suppression, using phosphorous as a target nutrient. Results A 6-year field trial involving monocropping of tomatoes with varied fertilizer manipulations demonstrated that phosphorus availability is a key factor driving the control of bacterial wilt disease caused by Ralstonia solanacearum. Subsequent greenhouse experiments were then conducted to delve into the underlying mechanisms of this phenomenon by varying phosphorus availability for tomatoes challenged with the pathogen. Results showed that the alleviation of phosphorus stress promoted the disease-suppressive capacity of the rhizosphere microbiome, but not that of the bulk soil microbiome. This appears to be an extension of the plant trade-off between investment in disease defense mechanisms versus phosphorus acquisition. Adequate phosphorus levels were associated with elevated secretion of root metabolites such as L-tryptophan, methoxyindoleacetic acid, O-phosphorylethanolamine, or mangiferin, increasing the relative density of microbial biocontrol populations such as Chryseobacterium in the rhizosphere. On the other hand, phosphorus deficiency triggered an alternate defense strategy, via root metabolites like blumenol A or quercetin to form symbiosis with arbuscular mycorrhizal fungi, which facilitated phosphorus acquisition as well. Conclusion Overall, our study shows how phosphorus availability can influence the disease suppression capability of the soil microbiome through plant-microbial interactions. These findings highlight the importance of optimizing nutrient regimes to enhance disease suppression, facilitating targeted crop management and boosting agricultural productivity. Video Abstract

Daphnetin, a coumarin derivative isolated from Daphne odorifera, has anti-tumor effects. The MAPK, STAT3, and NF-κB signaling pathways are closely related to the pathogenesis of lung cancer. To investigate the effect of daphnetin on anti-lung adenocarcinoma A549 cells and its mechanism. The anti-tumor effects of daphnetin on the proliferation, clone formation, migration, and invasion of A549 lung adenocarcinoma cells were investigated. The results showed that daphnetin inhibited the proliferation, colony formation, migration, and invasion of A549 cells through the MAPK/STAT3/NF-KB pathway, and mainly inhibited the clonal formation and migration of A549 cells through the JNK pathway. These results provide a new research direction and theoretical basis for the use of daphnetin in the inhibition of lung adenocarcinoma.

Concerning the issue of illegal access and malicious destruction of video data during transmission and storage, a review on encryption techniques under the high efficiency video coding (HEVC) standard was conducted, starting with the HEVC standard and encryption technology. The development history of video coding technology was reviewed, and the HEVC standard was introduced. Common attack methods on video encryption technology and performance evaluation indicators were discussed. The performance, advantages, and disadvantages of different video encryption technologies were comprehensively analyzed and detailed. The development trends of video encryption technology was summarized and anticipated in order to provide reference for the research and application of video encryption technology.

Abstract Background The relationship between Helicobacter pylori (H. pylori) infection and metabolic dysfunction-associated steatotic liver disease (MASLD) has attracted increased clinical attention. However, most of those current studies involve cross-sectional studies and meta-analyses, and experimental mechanistic exploration still needs to be improved. This study aimed to investigate the mechanisms by which H. pylori impacts MASLD. Methods We established two H. pylori-infected (Cag A positive and Cag A negative) mouse models with 16 weeks of chow diet (CD) or high-fat diet (HFD) feeding. Body weight, liver triglyceride, blood glucose, serum biochemical parameters, inflammatory factors, and insulin resistance were measured, and histological analysis of liver tissues was performed. Mouse livers were subjected to transcriptome RNA sequencing analysis. Results Although H. pylori infection could not significantly affect serum inflammatory factor levels and serum biochemical parameters in mice, serum insulin and homeostatic model assessment for insulin resistance levels increased in CD mode. In contrast, H. pylori Cag A + infection significantly aggravated hepatic pathological steatosis induced by HFD and elevated serum inflammatory factors and lipid metabolism parameters. Hepatic transcriptomic analysis in the CD groups revealed 767 differentially expressed genes (DEGs) in the H. pylori Cag A + infected group and 1473 DEGs in the H. pylori Cag A- infected group, and the “nonalcoholic fatty liver disease” pathway was significantly enriched in KEGG analysis. There were 578 DEGs in H. pylori Cag A + infection combined with the HFD feeding group and 820 DEGs in the H. pylori Cag A- infected group. DEGs in the HFD groups were significantly enriched in “fatty acid degradation” and “PPAR pathway.” Exploring the effect of different Cag A statuses on mouse liver revealed that fatty acid binding protein 5 was differentially expressed in Cag A- H. pylori. DEG enrichment pathways were concentrated in the “PPAR pathway” and “fatty acid degradation.” Conclusions Clinicians are expected to comprehend the impact of H. pylori on MASLD and better understand and manage MASLD. H. pylori infection may exacerbate the development of MASLD by regulating hepatic lipid metabolism, and the H. pylori virulence factor Cag A plays a vital role in this regulation.

Abstract Osteosarcoma is an aggressive form of bone cancer and affects the health in children and adolescents. Although conventional treatment improves the osteosarcoma survival, some patients have metastasis and drug resistance, leading to a worse prognosis. Therefore, it is necessary to explore the molecular mechanism of osteosarcoma occurrence and progression, which could discover the novel treatment for osteosarcoma. Long noncoding RNAs (lncRNAs) have been reported to regulate osteosarcoma occurrence and malignant progression. LncRNA HOXA-AS3 facilitates the tumorigenesis and progression in a variety of human cancers. However, the underlying mechanism of lncRNA HOXA-AS3-induced oncogenesis is poorly determined in osteosarcoma. To address this point, we utilized several cellular biological strategies and molecular approaches to explore the biological functions and mechanisms of lncRNA HOXA-AS3 in osteosarcoma cells. We found that lncRNA HOXA-AS3 facilitates cell proliferation and invasion via targeting miR-218-5p/FOXP1 axis in osteosarcoma. In conclusion, lncRNA HOXA-AS3 could be a promising target for osteosarcoma treatment.

Abstract Background The utilization of a double trigger, involving the co-administration of gonadotropin-releasing hormone agonist (GnRH-a) and human chorionic gonadotropin (hCG) for final oocyte maturation, is emerging as a novel approach in gonadotropin-releasing hormone antagonist (GnRH-ant) protocols during controlled ovarian hyperstimulation (COH). This protocol involves administering GnRH-a and hCG 40 and 34 h prior to ovum pick-up (OPU), respectively. This treatment modality has been implemented in patients with low/poor oocytes yield. This study aimed to determine whether the double trigger could improve the number of top-quality embryos (TQEs) in patients with fewer than three TQEs. Methods The stimulation characteristics of 35 in vitro fertilization (IVF) cycles were analyzed. These cycles were triggered by the combination of hCG and GnRHa (double trigger cycles) and compared to the same patients’ previous IVF attempt, which utilized the hCG trigger (hCG trigger control cycles). The analysis involved cases who were admitted to our reproductive center between January 2018 and December 2022. In the hCG trigger control cycles, all 35 patients had fewer than three TQEs. Results Patients who received the double trigger cycles yielded a significantly higher number of 2PN cleavage embryos (3.54 ± 3.37 vs. 2.11 ± 2.15, P = 0.025), TQEs ( 2.23 ± 2.05 vs. 0.89 ± 0.99, P

Abstract Background Endometriosis is considered as a systemic disease with the presence of proinflammatory cytokines in the circulation, which drives hypercoagulable state of endometriosis. Currently, endometriosis is classified into four stages: I (minimal), II (mild), III (moderate) and IV (severe). The aim of this study is to investigate the correlations between inflammatory markers and coagulation factors in patients diagnosed of endometriosis with stage IV. Methods This retrospective case–control study included 171 endometriosis patients with stage IV and 184 controls. Continuous data were expressed by mean ± standard deviation. Mann–Whitney U and χ2 tests were used to compare the medians and frequencies among the groups. Spearman analysis was conducted to determine the correlation among the measured parameters. The diagnostic values of the parameters differentiating endometriomas were tested by receiver operating characteristic (ROC) curve. Results The time of activated partial thromboplastin time (APTT) was decreased and the concentration of fibrinogen (FIB) and neutrophil-to-lymphocyte ratio (NLR) were increased in women of endometriosis with stage IV. The APTT were negatively correlated with NLR while the concentrations of FIB were positively correlated with NLR. The ROC analysis showed that the Area under the curve (AUC) of FIB was 0.766 (95% confidence interval:0.717–0.814) with sensitivity and specificity reaching 86.5 and 60.9%, respectively. The AUC of CA125 and CA199 was 0.638 (95% confidence interval: 0.578–0.697), 0.71 (95% confidence interval: 0.656–0.763) with sensitivity and specificity reaching 40.9 and 91.8%, 80.7 and 56.5% respectively. The combination of these factors showed the highest AUC of 0.895 (0.862–0.927) with sensitivity of 88.9% and specificity of 77.7%. Conclusion In the present study, we found that inflammatory factors showed significant correlation with APTT or FIB in endometriosis with stage IV. Moreover, the coagulation factors combined with CA125 and CA199 were more reliable for identifying the endometriosis with stage IV.

In order to investigate the influence of the structural properties of amine functionalized zeolite adsorbents support on their CO2 adsorption performance and further explore effective methods for low-cost preparation of efficient CO2 adsorbents, different post-treatment methods were used to modify the pore structure of MCM–41 zeolite, and tetra-ethylenepentamine (TEPA) was loaded onto these zeolites to prepare amine functionalized adsorbents. The properties of the zeolite support were characterized using the methods such as N2 adsorption-desorption experiment, scanning electron microscopy, X-ray diffraction and flourier transform infrared spectroscopy. The adsorption performance of the adsorbent was evaluated using a thermogravimetric analyzer (TGA). The structural properties of the support, effects of active amine loading and adsorption temperature on CO2 adsorption performance were systematically studied, and the adsorption kinetics and activation energy of the adsorbent was calculated. Finally, the stability of the adsorbent was evaluated through cyclic adsorption and desorption experiments. The results indicate that by designing the structure of the support reasonably, the CO2 adsorption performance of adsorbents based on different adsorption principles can be effectively improved. The microporous zeolites are more favorable for the physisorption process, while the hierarchical mesoporous zeolites with a wide pore size distribution exhibit a better chemisorption performance than the microporous zeolites after loading with active amines. At 80 ℃ and 15% CO2, the maximum adsorption capacity of the adsorbent (M–N−T60) which modified in structure and loaded with TEPA reached 4.04 mmol/g. After 10 adsorption and desorption cycles, the adsorption capacity of M–N−T60 only decreased by 8.4%, demonstrating good cycling stability, indicating that the M–N−T60 is a potential material for capturing CO2 from flue gas.

To improve the mechanical properties of casting aluminum-copper alloy, the mixed rare earth (RE) was added to ZL206 and its properties and the enhanced mechanism of alloy were researched. The results showed that the strength and hardness of the composite were improved by 10.2% and 6.2%, respectively. After adding mixed RE, which was led by the heterogeneous enrichment area blocking the growth of the α-Al phase and making grain refinement during the solidification process. The simulation results of RE surface adsorption models by first principles also showed that the elastic constant calculation improved the bulk modulus, shear modulus, and Young's modulus of the material. The addition of mixed RE enhances the strength and hardness, although it adversely affects toughness and reduces the machining index. Also, the work function decreased, and the Fermi level increased, reflecting that the electron locality on each band was strong and the bonding state of the alloy system was covalent, which showed that the corrosion resistance was enhanced after adding mixed RE. It provides a new method for the mechanism of RE-modified aluminum-copper alloys and expands the direction of cast aluminum-copper alloy modification.

Abstract Background Jasmonate ZIM-domain (JAZ) proteins, which act as negative regulators in the jasmonic acid (JA) signalling pathway, have significant implications for plant development and response to abiotic stress. Results Through a comprehensive genome-wide analysis, a total of 20 members of the JAZ gene family specific to alfalfa were identified in its genome. Phylogenetic analysis divided these 20 MsJAZ genes into five subgroups. Gene structure analysis, protein motif analysis, and 3D protein structure analysis revealed that alfalfa JAZ genes in the same evolutionary branch share similar exon‒intron, motif, and 3D structure compositions. Eight segmental duplication events were identified among these 20 MsJAZ genes through collinearity analysis. Among the 32 chromosomes of the autotetraploid cultivated alfalfa, there were 20 MsJAZ genes distributed on 17 chromosomes. Extensive stress-related cis-acting elements were detected in the upstream sequences of MsJAZ genes, suggesting that their response to stress has an underlying function. Furthermore, the expression levels of MsJAZ genes were examined across various tissues and under the influence of salt stress conditions, revealing tissue-specific expression and regulation by salt stress. Through RT‒qPCR experiments, it was discovered that the relative expression levels of these six MsJAZ genes increased under salt stress. Conclusions In summary, our study represents the first comprehensive identification and analysis of the JAZ gene family in alfalfa. These results provide important information for exploring the mechanism of JAZ genes in alfalfa salt tolerance and identifying candidate genes for improving the salt tolerance of autotetraploid cultivated alfalfa via genetic engineering in the future.

Abstract Objectives The purpose of this study was to investigate fatigue, mental workload, and burnout among health care workers (HCWs) and explore the possible underlying factors. Materials and methods An online cross-sectional survey design was used to collect data from HCWs in Chongqing, China. The online survey included the Fatigue Severity Scale, NASA Task Load Index, and Chinese version of the Maslach Burnout Inventory-General Survey to assess fatigue, mental workload, and burnout, respectively, and was conducted from February 1 to March 1, 2023. Results In this study, the incidence of fatigue and burnout among HCWs was 76.40% and 89.14%, respectively, and the incidence of moderate to intolerable mental workloads was 90.26%. Work–family conflict, current symptoms, number of days of COVID-19 positivity, mental workload, burnout and reduced personal accomplishment were significantly associated with fatigue. Mental workload was affected by fatigue and reduced personal accomplishment. Furthermore, burnout was influenced by marital status and fatigue. Moreover, there was a correlation among mental workload, fatigue, and burnout. Conclusions Fatigue, mental workload and burnout had a high incidence and were influenced by multiple factors during COVID-19 public emergencies in China.

Background: The paclitaxel liposome formulation, encapsulating paclitaxel within a phospholipid bilayer, addresses the insolubility of traditional paclitaxel formulations, thereby reducing toxicity without compromising its antitumor efficacy. Methods: This multicenter, open-label, non-inferiority randomized controlled trial (ChiCTR2000038555) evaluates the efficacy and safety of paclitaxel liposome in comparison to the standard regimen of paclitaxel combined with carboplatin (PLC vs. PC) as first-line therapy in patients with epithelial ovarian cancer. Results: An analysis of median progression-free survival (PFS) revealed non-inferior outcomes between 263 patients in the PLC group and 260 patients in the PC group (32.3 vs. 29.9 months, hazard ratio [HR], 0.89 [95% CI, 0.64−1.25]), using a non-inferior margin of 1.3. Although the overall incidence of treatment-related adverse events was comparable between groups, the PLC group experienced significantly fewer non-hematologic toxicities than those treated with the PC regimen. Conclusion: The findings affirm the non-inferiority of paclitaxel liposome compared to the combination of paclitaxel and carboplatin regarding therapeutic efficacy, with an enhanced safety profile marked by reduced non-hematologic toxicities.

Abstract Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by mitochondrial dysfunction and accumulation of alpha-synuclein (α-Syn)-containing protein aggregates known as Lewy bodies (LB). Here, we investigated the entry of α-Syn into mitochondria to cause mitochondrial dysfunction and loss of cellular fitness in vivo. We show that α-Syn expressed in yeast and human cells is constitutively imported into mitochondria. In a transgenic mouse model, the level of endogenous α-Syn accumulation in mitochondria of dopaminergic neurons and microglia increases with age. The imported α-Syn is degraded by conserved mitochondrial proteases, most notably NLN and PITRM1 (Prd1 and Cym1 in yeast, respectively). α-Syn in the mitochondrial matrix that is not degraded interacts with respiratory chain complexes, leading to loss of mitochondrial DNA (mtDNA), mitochondrial membrane potential and cellular fitness decline. Importantly, enhancing mitochondrial proteolysis by increasing levels of specific proteases alleviated these defects in yeast, human cells, and a PD model of mouse primary neurons. Together, our results provide a direct link between α-synuclein-mediated cellular toxicity and its import into mitochondria and reveal potential therapeutic targets for the treatment of α-synucleinopathies.

Abstract Background To analyze the risk factors for the development of avascular necrosis (AVN) of the femoral head after reduction surgery in children with developmental hip dysplasia (DDH), and to establish a prediction nomogram. Methods The clinical data of 134 children with DDH (169 hips) treated with closure reduction or open reduction from December 2016 to December 2019 were retrospectively analyzed. Independent risk factors for AVN after DDH reduction being combined with cast external immobilization were determined by univariate analysis and multivariate logistic regression and used to generate nomograms predicting the occurrence of AVN. Results A total of 169 hip joints in 134 children met the inclusion criteria, with a mean age at surgery of 10.7 ± 4.56 months (range: 4–22 months) and a mean follow-up duration of 38.32 ± 27.00 months (range: 12–94 months). AVN developed in 42 hip joints (24.9%); univariate analysis showed that the International Hip Dysplasia Institute (IHDI) grade, preoperative development of the femoral head ossification nucleus, cartilage acetabular index, femoral head to acetabular Y-shaped cartilage distance, residual acetabular dysplasia, acetabular abduction angle exceeding 60°, and the final follow-up acetabular index (AI) were associated with the development of AVN (P

Abstract Older livers are more prone to hepatic ischaemia/reperfusion injury (HIRI), which severely limits their utilization in liver transplantation. The potential mechanism remains unclear. Here, we demonstrate older livers exhibit increased ferroptosis during HIRI. Inhibiting ferroptosis significantly attenuates older HIRI phenotypes. Mass spectrometry reveals that fat mass and obesity-associated gene (FTO) expression is downregulated in older livers, especially during HIRI. Overexpressing FTO improves older HIRI phenotypes by inhibiting ferroptosis. Mechanistically, acyl-CoA synthetase long chain family 4 (ACSL4) and transferrin receptor protein 1 (TFRC), two key positive contributors to ferroptosis, are FTO targets. For ameliorative effect, FTO requires the inhibition of Acsl4 and Tfrc mRNA stability in a m6A-dependent manner. Furthermore, we demonstrate nicotinamide mononucleotide can upregulate FTO demethylase activity, suppressing ferroptosis and decreasing older HIRI. Collectively, these findings reveal an FTO-ACSL4/TFRC regulatory pathway that contributes to the pathogenesis of older HIRI, providing insight into the clinical translation of strategies related to the demethylase activity of FTO to improve graft function after older donor liver transplantation.

Although characterized by high reactive oxygen species (ROS) generation, cancer cells maintain redox homeostasis to avoid severe damage (e.g., DNA, protein, and plasma membrane dysfunction) and facilitate cancer progression. Emerging evidence has indicated that targeting the regulation of redox homeostasis to amplify oxidative stress is of value in cancer therapy. However, therapeutic agents like nucleic acids, small molecular inhibitors, and chemotherapeutic drugs fail to exert effective cancer inhibition due to their low bioavailability, susceptibility to serum enzymes, and inefficiency in cell membrane penetrating. Therefore, specific delivery vectors are required to facilitate the intracellular delivery of anti-tumor drugs. In the past few decades, various engineered nanomaterials have been designed and developed for drug delivery. In particular, rational nanoparticles (NPs) have garnered more attention due to their splendid long circulation ability, modification capacity, and stimulation-responded release. In this review, the methods of ROS generation and ROS-regulated signaling in cancer development were firstly briefly introduced. The anti-oxidant system, including the metabolism shifting and anti-oxidant genes, were next reviewed, and the strategies of NPs-mediated targeted regulation of redox homeostasis were emphatically discussed. The main strategies include NPs-induced delivery of nucleic acids, small molecule inhibitors, chemotherapeutic agents, radiosensitizers, and NPs-induced ROS generation and GSH depletion. The future development of NP-mediated redox dyshomeostasis in cancer therapy and their challenges in clinical translation were finally discussed.

BackgroundComplicated intra-abdominal infections (cIAIs), often caused by multidrug-resistant bacteria such as carbapenem-resistant A. baumannii (CRAB) and carbapenem-resistant Enterobacteriaceae (CRE) are a critical challenge in ICUs. Owing to their high mortality and treatment failure rates, there is an urgent need for effective therapies. This trial will compare eravacycline to tigecycline for treating cIAIs in patients in the ICU, aiming to provide a superior treatment option.MethodsThis is a multicenter, single-blind, parallel randomized controlled trial. Adult patients in the ICU with complex abdominal infections who meet the eligibility criteria will be included. The main outcome is the all-cause 30-day mortality of patients in clinically evaluable and microbiologically evaluable populations. Secondary outcomes include the proportion of total responsive patients in the clinically evaluable population at the end of treatment and test of cure visits; the proportion of total responsive patients in the microbiologically evaluable population at the end of treatment and test of cure visits; and ICU hospitalization time and costs. Safety assessments include the incidence of various adverse events and changes in clinical laboratory test results. The subjects will be randomly assigned to receive treatment with either eravacycline or tigecycline at a 1:1 ratio. The all-cause mortality rates of patients treated with eravacycline and TGC were 17.7 and 18.7%, respectively, with an estimated actual mortality rate of 0.95. A total sample size of 262 subjects is required to reach 80% power with an α of 0.05. Considering a 10% loss rate, 292 patients will be enrolled and randomly assigned to the three groups in equal proportions.Ethics and communicationThis trial was approved by the Ethics Committee of Ansteel Group General Hospital. The communication plan includes presentations at scientific conferences, scientific publications, and presentations to the public through nonprofessional media.Clinical trial registrationhttps://clinicaltrials.gov/, ChiCTR2300078646.

Abstract Magnesium‐based batteries have garnered significant attention due to their high energy density, excellent intrinsic safety, and low cost. However, the application process has been hindered by the high Mg2+ ions diffusion barrier in solid‐state structures and solid‐liquid interphase. To address this issue, a hybrid battery technology based on Mg anode and Fe‐based Prussian Blue Analogue cathode doped with functional transition metal ions and N═O bonds is proposed. Combined multiscale experimental characterizations with theoretical calculations, the subtle lattice distortion can create an asymmetric diffusion path for the active ions, which enables reversible extraction with significantly reduced diffusion barriers achieved by synergistic doping. The optimized cathode exhibits a working potential of 2.3 V and an initial discharge capacity of 152 mAh g−1 at 50 mA g−1. With the preferred electrolyte combined with equivalent concentration [Mg2(µ‐Cl)2(DME)4][AlCl4]2 and NaTFSI salt solution, the hybrid system demonstrates superior cycling performance over 200 cycles at a high current density of 200 mA g−1, maintaining ≈100% coulombic efficiency with superior ion dynamic. The findings are expected to be marked an important step in the further application of high‐voltage cathodes for Mg‐based hybrid batteries.

BackgroundThe majority of elderly individuals prefer to spend their final days in the Intensive Care Unit (ICU). ICU nurses are key providers in hospice care, and their attitudes toward death influence the quality of end-of-life nursing. Positive psychology emphasizes promoting positive attitudes toward death. A sense of meaning in life and resilience are critical aspects of positive psychology, which are essential for shaping ICU nurses’ attitudes toward death.ObjectiveThis study aims to investigate whether a sense of meaning in life indirectly affects attitudes toward death through the mediation of resilience.MethodA total of 212 ICU nurses from four tertiary general hospitals in Guangdong and Fujian provinces, China, participated in this study. They completed an online questionnaire, including the Death Attitude Profile-Revised, the Connor-Davidson Resilience Scale, and the China Meaning in Life Questionnaire for ICU nurses.ResultsICU nurses scored highest in natural acceptance (3.26 ± 0.53), followed by escaping acceptance (2.54 ± 0.59), and fear of death (2.53 ± 0.78). The proposed model fit the data well. Both the presence of meaning and the search for meaning were positive predictors of resilience (β = 0.313, p

Objectives: Efforts to shorten rifampicin-resistant tuberculosis (RR-TB) treatment have led to concerns about hepatotoxicity in shorter regimens. We evaluated hepatotoxicity in two novel regimens against the standard shorter regimen recommended by the World Health Organization (WHO). Methods: Participants from the TB-TRUST and TB-TRUST plus trials were assigned to the WHO shorter regimen, a levofloxacin (Lfx)-based regimen, or a bedaquiline (Bdq)-based regimen. Liver function was tested bi-weekly in the first month, then monthly until treatment ended. Eligibility required receiving at least one drug dose and undergoing at least two liver function tests. Results: Of 429 patients, hepatotoxicity was most prevalent in the WHO shorter group (26.7% of 169), compared to 4.7% in the Lfx group (172 patients), and 5.7% in the Bdq group (88 patients). The median peak alanine aminotransferase levels were 1.67 × upper limit of normal (ULN) for WHO, 0.82 × ULN for Lfx, and 0.88 × ULN for Bdq groups. The incidence of drug-induced liver injury was significantly higher in the WHO group (18.3%) than in the Lfx (3.5%) and Bdq (4.6%) groups. The time to significant alanine aminotransferase elevation was about 2.8 months, with no differences between groups. Conclusions: Two novel regimens demonstrated lower hepatotoxicity compared to the WHO's shorter regimen. Entire course management monitoring is recommended in RR-TB treatment.

High-resolution column-averaged dry air mole fraction of CO2 (XCO2) data is crucial for understanding the spatiotemporal patterns of XCO2 and for mitigating carbon emissions. Due to the limited scanning range of sensors and strict inversion conditions, satellite-retrieved XCO2 data are often significantly incomplete. Machine learning models are widely used to fill these gaps in satellite XCO2 data. However, the limitations of individual machine learning models and the complexity of the spatial distribution of XCO₂ mean that the accuracy of XCO2 predictions still needs improvement. In this study, a new spatiotemporal stacked ensemble learning model (STEL) was developed by combining random forest (RF), extremely randomized trees (ERT), extreme gradient boosting (XGBoost), optical gradient boosting (LightGBM), and categorical boosting (CatBoost) using the stacking ensemble learning methodology. Considering the spatiotemporal heterogeneity of XCO2, a novel spatiotemporal weighting feature was constructed as part of the model's input parameters. Finally, the XCO2 observed by Orbiting Carbon Observatory 2 (OCO-2) was reconstructed using STEL, and a monthly mean XCO2 dataset covering China from 2015 to 2020 was generated at a spatial resolution of 0.1°. The results show that STEL exhibits superior performance and generalization capabilities compared to individual machine-learning models. R2 RMSE and MAPE were 0.9624, 1.0023 ppm, and 0.1583 % on the test set, and 0.8970, 1.4213 ppm, and 0.2475 % for R2, RMSE, and MAPE in ground validation, respectively. In 10-fold cross-validation, STEL's RMSE was reduced by 9.52 % compared to the best-performing single model (RF). The spatiotemporal trend of CO2 in China from 2015 to 2020 was analyzed using STEL XCO2 data. The results indicate that this dataset accurately reflects the spatiotemporal heterogeneity of XCO2 distribution at a fine scale. Overall, XCO2 exhibited a spatiotemporal pattern of “high in the east and low in the west” and “high in spring and low in summer.” Except in summer, high XCO₂ values were mainly distributed in the North China Plain. XCO2 trends and hotspots showed considerable spatial variation. The Pearl River Delta and Yangtze River Delta urban agglomerations have the fastest XCO2 growth rates, and the distribution of XCO2 hotspots is consistent with the distribution of population and economic centers. In the sparsely populated northwest of China, XCO2 is growing rapidly due to increased thermal power generation and coal mining. XCO2 hotspots in Northwest China are mainly located in Xinjiang, Ningxia, and Inner Mongolia. The methodology and data presented are useful for further research on carbon emissions, carbon sinks, and climate change.

ABSTRACT When a virus crosses from one host species to another, the consequences can be devastating. However, animal models to empirically evaluate cross-species transmission can fail to recapitulate natural transmission routes, physiologically relevant doses of pathogens, and population structures of naturally circulating viruses. Here, we present a new model of cross-species transmission where deer mice (Peromyscus maniculatus) are exposed to the natural virome of pet store mice (Mus musculus). Using RNA sequencing, we tracked viral transmission via fecal–oral routes and found the evidence of transmission of murine astroviruses, coronaviruses, and picornaviruses. Deep sequencing of murine kobuvirus revealed tight bottlenecks during transmission and purifying selection that leaves limited diversity present after transmission from Mus to Peromyscus. This work provides a structure for studying viral bottlenecks across species while keeping natural variation of viral populations intact and a high resolution look at within-host dynamics that occur during the initial stages of cross-species viral transmission.IMPORTANCEViral spillover events can have devastating public health consequences. Tracking cross-species transmission in real-time and evaluating viral evolution during the initial spillover event are useful for understanding how viruses adapt to new hosts. Using our new animal model and next generation sequencing, we develop a framework for understanding intrahost viral evolution and bottleneck events, which are very difficult to study in natural transmission settings.

Abstract Neurodegenerative diseases are global health challenges characterized by the progressive degeneration of nerve cells, leading to cognitive and motor impairments. The brain–gut–bone axis, a complex network that modulates multiple physiological systems, has gained increasing attention owing to its profound effects on the occurrence and development of neurodegenerative diseases. No comprehensive review has been conducted to clarify the triangular relationship involving the brain–gut–bone axis and its potential for innovative therapies for neurodegenerative disorders. In light of this, a new perspective is aimed to propose on the interplay between the brain, gut, and bone systems, highlighting the potential of their dynamic communication in neurodegenerative diseases, as they modulate multiple physiological systems, including the nervous, immune, endocrine, and metabolic systems. Therapeutic strategies for maintaining the balance of the axis, including brain health regulation, intestinal microbiota regulation, and improving skeletal health, are also explored. The intricate physiological interactions within the brain–gut–bone axis pose a challenge in the development of effective treatments that can comprehensively target this system. Furthermore, the safety of these treatments requires further evaluation. This review offers a novel insights and strategies for the prevention and treatment of neurodegenerative diseases, which have important implications for clinical practice and patient well‐being.

Dysregulation of cholesterol metabolism is an important feature of cancer development. There are limited reports on the involvement of lncRNAs in hepatocellular carcinoma (HCC) progression via the cholesterol metabolism pathway. The present study explored the effect of LINC00618 on HCC growth and metastasis, and elucidated the underlying mechanisms involved in cholesterol metabolism. Here, we found that LINC00618 expression was upregulated in cancerous tissues from 30 patients with HCC compared to that in adjacent normal tissues. High expression of LINC00618 was detected in metastatic HCC tissues. LINC00618 is predominantly localized in the nucleus and overexpression of LINC00618 facilitated HCC cell proliferation, migration and EMT progression by promoting cholesterol biosynthesis. Mechanistically, the 1–101nt region of LINC00618 bound to NSUN2. LINC00618 inhibited ubiquitin-proteasome pathway-induced NSUN2 degradation. NSUN2 stabilized by LINC00618 increased m5C modification of SREBP2 and promoted SREBP2 mRNA stability in a YBX1-dependent manner, thereby promoting cholesterol biosynthesis in HCC cells. Moreover, mouse HCC xenograft and lung metastasis models were established by subcutaneous and tail vein injections of MHCC97 cells transfected with or without sh-LINC00618. Silencing LINC00618 impeded HCC growth and metastasis. In conclusion, LINC00618 promoted HCC growth and metastasis by elevating cholesterol synthesis by stabilizing NSUN2 to enhance SREBP2 mRNA stability in an m5C-dependent manner.

IntroductionFemale infertility is a global issue that impacts on public health seriously and many mental disorders are observed in infertility groups.MethodsTo investigate the casual relationship between those, genome-wide association studies summary data of anxiety disorder (n=9,897), broad depression (n=322,580), major depressive disorder (n=480,359 and n=500,199), bipolar disorder (n=51,710), insomnia (n= 462,341), and female infertility (n=126,342) were extracted from the existing datasets and was analyzed through the two-sample mendelian randomization study. The following heterogeneity and sensitivity test were applied to ensure the robustness of results.ResultsBased on inverse variance weighted results, major depressive disorder was associated with female infertility (P = 0.0001, odds ratio 1.396, 95 % confidence interval 1.175–1.658). No causal relationship was identified between the other four mental disorders and infertility. was found. Additionally, reverse mendelian randomization did not indicate a causal relationship among these disorders.DiscussionThe early identification and management of anxiety symptoms in women of reproductive age, in conjunction with the effective treatment of major depressive disorder, may be crucial for preserving female fertility.

BackgroundWhile several studies have noted a higher SII correlates with multiple diseases, research on the association between SII and cataract remains limited. Our cross-sectional study seeks to examine the association between SII and cataract among outpatient US adults.MethodsThis compensatory cross-sectional study utilized NHANES data from 1999 to 2008 cycles, conducting sample-weighted multivariate logistic regression and stratified analysis of subgroups.ResultsAmong 11,205 adults included in this study (5,571 [46.2%] male; 5,634 [53.8%] female), 2,131 (15.2%) had cataract and 9,074 (84.8%) did not have cataract. A fully adjusted model showed that SII higher than 500 × 109/L was positively correlated with an increased risk of cataracts among women (OR, 1.27; 95% CI, 1.02–1.59) (p = 0.036). However, no difference was found in the men subgroup, and there was no significant interaction between SII and sex.ConclusionOur results indicated that a SII higher than 500 × 109/L was positively correlated with an increased risk of cataracts in women. This study is the first to specifically investigate the impact of a high SII on cataract risk in outpatient adults in the United States. By effectively addressing inflammation, it is possible to mitigate cataract progression and significantly enhance patient outcomes.

To solve the problem of complex and difficult to quantify factors affecting investment returns and risks in clean energy power grids, this study comprehensively applies the interpretive structural model and Monte Carlo model to the analysis of investment risk-returns in clean energy power grid projects. The interpretive structural model is utilized to analyze project investment returns, while the Monte Carlo model is used to analyze project investment risks. The project investment risk is based on the factor analysis of project investment returns, and key risk factors are identified through 1000 simulations, and the impact of these risks on project returns is quantified. By combining the two, the investability of the project is analyzed. The results showed that grid electricity prices, kilowatt hour subsidies, technology learning rates, total annual sunshine hours, and system power generation efficiency were key factors driving investment returns. The average expected value of investment return was about 20%, and the probability of investment return below 6% was close to 0. The overall project is worth investing in. From this, it can be seen that the research designed investment risk-return analysis methods for clean energy grid projects can effectively distinguish the main factors affecting investment returns and risks, and pre simulate the risk situation of returns. This study can provide reference for investor decision-making.

BackgroundBullous pemphigoid (BP) is the most common autoimmune blistering skin disease in humans, characterized by tense blisters, erosions, urticarial lesions, and itching on normal or erythematous skin. Many autoimmune diseases are considered comorbidities of BP, but clinical case reports of BP complicated by Sjögren’s syndrome are very scarce. Furthermore, cases of central nervous system infection secondary to both autoimmune diseases are even rarer.Case presentationWe report a 74-year-old woman diagnosed with bullous pemphigoid, who showed relief of active lesions after treatment with methylprednisolone and dupilumab injections. However, she was admitted for pulmonary infection during which she was diagnosed with Sjögren’s syndrome (SS). Subsequently, the patient developed altered consciousness, indicating a central nervous system infection. Adjustment of steroid dosage and aggressive antimicrobial therapy led to alleviation of symptoms.ConclusionThe coexistence of autoimmune subepidermal blistering diseases and SS is rare. The role of SS in the pathogenesis of skin lesions is unclear, and the relationship between these blistering diseases and SS remains elusive. Further research is needed to determine whether there are common pathological mechanisms between the two conditions.

The characteristics of elements, isotopes, and small shelly fossils were investigated for Late Ediacaran to Early Cambrian stratigraphy division and to discuss their geological implications in the northwestern Sichuan Basin. The results reveal that small shelly fossils can be detected in the high-phosphorous section, with the concentration of phosphorus mainly ranging from 2% to 8%, suggesting that this interval belongs to the Early Cambrian, which is also consistent with the carbon isotopic composition results. In addition, the Early Cambrian is denudated in the Sichuan Basin due to tectonic movement, and the characteristics of some isotopes and small shell fossils are different from those in other basins. It can be proposed that P content can support the recognition of lithological boundaries, and the high phosphorus content can be used as a reference to identify the top and bottom boundaries of the Maidiping Formation in the study area. According to the elemental compositions in the Ediacaran Dengying Formation, the variations in Si, Al, Fe, and K contents are similar in the platform area and rift area, suggesting that the third and fourth member of the Dengying Formation are also developed in the Deyang–Anyue Rift. The results suggest that both the Deng-4 member and Maidiping Formation feature contemporaneous deposition of different facies in the northwestern Sichuan Basin. The strata consist of shale intercalated with thin carbonate rock deposits in the Deyang–Anyue Rift, while carbonate rock deposits in the platform. The Deyang–Anyue Rift expanded gradually in the Late Ediacaran and eventually filled in the Early Cambrian. The data in this study illustrate that elemental compositions, isotopes, and small shelly fossils can be combined to correlate the Late Ediacaran to Early Cambrian strata and provide new evidence for Deyang–Anyue Rift evolution. The results offer some new insights for deep oil and gas exploration in the Sichuan Basin and for the tectonic–depositional–environmental–biological synergistic evolution in the Late Ediacaran to Early Cambrian transition.

The spread of antibiotic resistance genes (ARGs) and subsequent soil-borne disease outbreaks are major threats to soil health and sustainable crop production. However, the relationship between occurrences of soil-borne diseases and the transmission of soil ARGs remains unclear. Here, soil ARGs, mobile genetic elements and microbial communities from co-located disease suppressive and conducive banana orchards were deciphered using metagenomics and metatranscriptomics approaches. In total, 23 ARG types, with 399 subtypes, were detected using a metagenomics approach, whereas 23 ARG types, with 452 subtypes, were discovered using a metatranscriptomics method. Furthermore, the metagenomics analysis revealed that the ARG total abundance levels were greater in rhizospheres (0.45 ARGs/16S rRNA on average) compared with bulk (0.32 ARGs/16S rRNA on average) soils. Interestingly, metatranscriptomics revealed that the total ARG abundances were greater in disease-conducive (8.85 ARGs/16S rRNA on average) soils than disease suppressive (1.45 ARGs/16S rRNA on average) soils. Mobile genetic elements showed the same trends as ARGs. Network and binning analyses indicated that Mycobacterium, Streptomyces, and Blastomonas are the main potential hosts of ARGs. Furthermore, Bacillus was significantly and negatively correlated with Fusarium (P < 0.05, r = −0.84) and hosts of ARGs (i.e., Mycobacterium, Streptomyces, and Blastomonas). By comparing metagenomic and metatranscriptomic analyses，this study demonstrated that metatranscriptomics may be more sensitive in indicating ARGs activities in soil. Our findings enable the more accurate assessment of the transmission risk of ARGs. The data provide a new perspective for recognizing soil health, in which soil-borne disease outbreaks appear to be associated with ARG spread, whereas beneficial microbe enrichment may mitigate wilt disease and ARG transmission.

In recent years, natural gas discoveries have been continuously made in the first member of the Permian Maokou Formation in the Sichuan Basin, bringing attention to the genesis mechanism of marlstone reservoir space. Centimeter-scale fracture-cavity type reservoir space is one of the newly discovered types in the first member of the Maokou Formation, and relevant research has not been publicly reported. Taking well A1 in the Sichuan Basin as an example, based on core observation and description, the characteristics and genesis of fracture-cavity fillings were studied through comparative analysis of microscopic petrology, carbon-oxygen isotopes, strontium isotopes, and trace elements. The similar distribution characteristics of carbon-oxygen isotopes and strontium isotopes between calcite cement and mudstone matrix in the fractures of the first member of the Maokou Formation indicated that calcite mainly came from the dissolution and redeposition of surrounding rocks. Compared with marlstone, the fracture calcite cement showed lower contents of valence elements (V, Cr, U, Mo) and rare earth elements (REE), while the content of micronutrient elements (Ni, Cu, Zn) increased, revealing the differential migration pattern of trace elements in this process. The differential variation characteristics of Mn and Sr contents between calcite and marl matrix revealed the marine affinity of diagenetic fluids, further indicating their independence from atmospheric freshwater and deep hydrothermal fluids. Since the Late Jurassic, lateral tectonic thrusting pressure has formed detachment faults and related fold systems in southeastern Sichuan, which potentially caused deformation of the Maokou Formation marlstone and the generation of centimeter-scale fracture spaces. Diagenetic fluids formed during subsequent compaction-dissolution processes (including lateral dissolution) provided material sources for quartz and calcite cement in the fractures.

A strategy for the synthesis of α-carboline derivatives from indole-3-carboxaldehydes and 3-aminocyclohex-2-enones under metal-free conditions has been developed. The combination use of phenyliodine (III) diacetate (PIDA) and benzoic acid could significantly facilitate the corresponding [3 ​+ ​3] annulation process. This newly developed strategy featured unextraordinary chemoselectivity, good functional group tolerance and the preservation of the carbonyl group of the ketone substrates, which offers the possibility for further transformation of the products.

Abstract Biotin, serving as a coenzyme in carboxylation reactions, is a vital nutrient crucial for the natural growth, development, and overall well-being of both humans and animals. Consequently, biotin is widely utilized in various industries, including feed, food, and pharmaceuticals. Despite its potential advantages, the chemical synthesis of biotin for commercial production encounters environmental and safety challenges. The burgeoning field of synthetic biology now allows for the creation of microbial cell factories producing bio-based products, offering a cost-effective alternative to chemical synthesis for biotin production. This review outlines the pathway and regulatory mechanism involved in biotin biosynthesis. Then, the strategies to enhance biotin production through both traditional chemical mutagenesis and advanced metabolic engineering are discussed. Finally, the article explores the limitations and future prospects of microbial biotin production. This comprehensive review not only discusses strategies for biotin enhancement but also provides in-depth insights into systematic metabolic engineering approaches aimed at boosting biotin production.

AIM: To observe the effect of ghrelin, a growth hormone-releasing peptide, on retinal angiogenesis in vitro under high glucose (HG) stress and to explore the possible mechanism of autophagy. METHODS: Human retinal microvascular endothelial cells (HRMECs) were treated with high concentration of glucose alone or in combination with ghrelin. The cell migration, tube formation and the expression of the autophagy-related proteins LC3-II/I, Beclin-1, p62, phosphorylated AKT (p-AKT)/AKT and phosphorylated mammalian target of rapamycin (p-mTOR)/mTOR were detected. Then, to clarify the correlation between ghrelin effect and autophagy, AKT inhibitor VIII was adopted to treat HRMECs, and cell migration, tube formation as well as the protein expressions of LC3-II/I, Beclin-1 and p62 were observed. RESULTS: Under HG stress, ghrelin inhibited migration and tube formation of HRMECs. Ghrelin inhibited the increases in the protein levels of LC3-II/I, Beclin-1 and the decreases in the protein levels of p62, p-AKT/AKT and p-mTOR/mTOR induced by HG stress. Moreover, under the action of AKT/mTOR pathway inhibitors, the effects of ghrelin on migration and tube formation were both reduced. In addition, the expression of LC3-II/I and Beclin-1 were significantly up-regulated and the expression of p62 was down-regulated. CONCLUSION: Retinal angiogenesis under in vitro HG stress can be inhibited by ghrelin through activating AKT/mTOR pathway to inhibit autophagy.

Abstract Background To explore the safety of Neodymium:Yttrium-aluminum-garnet (Nd:YAG) laser vitreolysis based on the histological examination of the retina and the alteration of vitreous cytokines in the rabbits. Methods Nine male New Zealand rabbits underwent Nd:YAG laser vitreolysis of 10 mJ x 500 pulses in the left eyes, while the right eyes were used as controls. Intraocular pressure, color fundus photography, and ultrasound B scan were measured before, as well as 1 day, 4 weeks, and 12 weeks after Nd:YAG laser vitreolysis. Three rabbits were euthanized 1 day, 4 weeks, and 12 weeks after treatment, respectively. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and hematoxylin-eosin (H&E) staining were used to look for pathological changes in the retina. An enzyme-linked immunosorbent assay (ELISA) was utilized to detect the expression of vascular endothelial growth factor (VEGF) and some inflammatory cytokines, including interferon inducible protein 10 (IP-10), monocyte chemoattractant protein 1 (MCP-1) and interlenkin 6 (IL-6) in the vitreous humor. The ascorbic acid (AsA) and total reactive antioxidant potential (TRAP) in the vitreous humor were also measured. Results Following Nd:YAG laser vitreolysis, the levels of VEGF, IP-10, MCP-1, IL6, AsA, and TRAP in the vitreous humor did not change substantially (P > 0.05). There were no detectable pathological changes in the retinal tissues, and no apoptotic signal was found. Conclusions Rabbits tolerate Nd:YAG laser vitreolysis without observable impact on retinal tissue or the microenvironment of the vitreous.

Abstract Background This study investigated the association between Anti-Müllerian Hormone (AMH) and relevant metabolic parameters and assessed its predictive value in the clinical diagnosis of polycystic ovarian syndrome (PCOS). Methods A total of 421 women aged 20–37 years were allocated to the PCOS (n = 168) and control (n = 253) groups, and their metabolic and hormonal parameters were compared. Spearman correlation analysis was conducted to investigate associations, binary logistic regression was used to determine PCOS risk factors, and receiver operating characteristic (ROC) curves were generated to evaluate the predictive value of AMH in diagnosing PCOS. Results The PCOS group demonstrated significantly higher blood lipid, luteinizing hormone (LH), and AMH levels than the control group. Glucose and lipid metabolism and hormonal disorders in the PCOS group were more significant than in the control group among individuals with and without obesity. LH, TSTO, and AMH were identified as independent risk factors for PCOS. AMH along with LH, and antral follicle count demonstrated a high predictive value for diagnosing PCOS. Conclusion AMH exhibited robust diagnostic use for identifying PCOS and could be considered a marker for screening PCOS to improve PCOS diagnostic accuracy. Attention should be paid to the effect of glucose and lipid metabolism on the hormonal and related parameters of PCOS populations.

Abstract Background Chimeric antigen receptor T (CAR-T) cell therapy, as an emerging anti-tumor treatment, has garnered extensive attention in the study of targeted therapy of multiple tumor-associated antigens in hepatocellular carcinoma (HCC). However, the suppressive microenvironment and individual heterogeneity results in downregulation of these antigens in certain patients’ cancer cells. Therefore, optimizing CAR-T cell therapy for HCC is imperative. Methods In this study, we administered FGFR4-ferritin (FGFR4-HPF) nanoparticles to the alpaca and constructed a phage library of nanobodies (Nbs) derived from alpaca, following which we screened for Nbs targeting FGFR4. Then, we conducted the functional validation of Nbs. Furthermore, we developed Nb-derived CAR-T cells and evaluated their anti-tumor ability against HCC through in vitro and in vivo validation. Results Our findings demonstrated that we successfully obtained high specificity and high affinity Nbs targeting FGFR4 after screening. And the specificity of Nbs targeting FGFR4 was markedly superior to their binding to other members of the FGFR family proteins. Furthermore, the Nb-derived CAR-T cells, targeting FGFR4, exhibited significantly enhanced anti-tumor efficacy in both experiments when in vitro and in vivo. Conclusions In summary, the results of this study suggest that the CAR-T cells derived from high specificity and high affinity Nbs, targeting FGFR4, exhibited significantly enhanced anti-tumor efficacy in vitro and in vivo. This is an exploration of FGFR4 in the field of Nb-derived CAR-T cell therapy for HCC, holding promise for enhancing safety and effectiveness in the clinical treatment of HCC in the future.

The Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway play a pivotal role in innate immunity. Among invertebrates, Domeless receptors serve as the key upstream regulators of this pathway. In our study on Bactrocera dorsalis, we identified three cytokine receptors: BdDomeless1, BdDomeless2, and BdDomeless3. Each receptor encompasses five fibronectin-type-III-like (FN III) extracellular domains and a transmembrane domain. Furthermore, these receptors exhibit the increased responsiveness to diverse pathogenic challenges. Notably, only BdDomeless3 is upregulated during symbiont-like viral infections. Moreover, silencing BdDomeless3 enhanced the infectivity of Bactrocera dorsalis cripavirus (BdCV) and B. dorsalis picorna-like virus (BdPLV), underscoring BdDomeless3’s crucial role in antiviral defense of B. dorsalis. Following the suppression of Domeless3 expression, six antimicrobial peptide genes displayed decreased expression, potentially correlating with the rise in viral infectivity. To our knowledge, this is the first study identifying cytokine receptors associated with the JAK/STAT pathway in tephritid flies, shedding light on the immune mechanisms of B. dorsalis.

Abstract Background Ovarian ageing is one of the major issues that impacts female fertility. Mesenchymal stem cell (MSC)-based therapy has made impressive progress in recent years. However, the efficacy and safety of MSCs, as nonautologous components, remain to be further verified. Methods Two common sources of MSCs, umbilical cord-derived MSCs (UC-MSCs) and adipose tissue-derived MSCs (AD-MSCs), were orthotopically transplanted into a mouse model of ovarian ageing to evaluate their therapeutic effects. The safety of the treatment was further evaluated, and RNA sequencing was performed to explore the underlying mechanisms involved. Results After orthotopic transplantation of MSCs into the ovary, the oestrous cycle, ovarian weight, number and proportion of primary follicles, granulosa cell proliferation, and angiogenesis were improved. The effects of AD-MSCs were superior to those of UC-MSCs in several indices, such as post-transplant granulosa cell proliferation, ovarian weight and angiogenesis. Moreover, the tumorigenesis, acute toxicity, immunogenicity and biodistribution of MSCs were evaluated, and both AD-MSCs and UC-MSCs were found to possess high safety profiles. Through RNA sequencing analysis, enhancement of the MAPK cascade was observed, and long-term effects were mainly linked to the activation of immune function. Conclusions Orthotopic transplantation of MSCs displays significant efficacy and high safety for the treatment of ovarian ageing in mice.

Abstract. Background:. High body mass index (BMI) results in decreased fecundity, and women with high BMI have reduced rates of clinical pregnancy and live birth in in vitro fertilization/intra-cytoplasmic sperm injection (IVF/ICSI). Meanwhile, ovarian responses show great heterogeneity in patients with a high BMI. This study aimed to analyze the effects of a high BMI on IVF/ICSI outcomes in the Chinese female with normal ovarian response. Methods:. We performed a retrospective cohort study comprising 15,124 patients from the medical record system of the Reproductive Center of Peking University Third Hospital, with 3530 (23.3%) in the overweight group and 1380 (9.1%) in the obese group, who had a normal ovarian response (5–15 oocytes retrieved) and underwent fresh embryo transfer (ET) cycles from January 2017 to December 2018, followed by linked frozen-thawed embryo transfer (FET) cycles from January 2017 to December 2020. Cumulative live birth rate (CLBR) was used as the primary outcome. Furthermore, a generalized additive model was applied to visually illustrate the curvilinear relationship between BMI and the outcomes. We used a decision tree to identify the specific population where high BMI had the greatest effect on IVF/ICSI outcomes. Results:. High BMI was associated with poor IVF/ICSI outcomes, both in cumulative cycles and in separate fresh ET or FET cycles. In cumulative cycles, compared with the normal weight group, obesity was correlated with a lower positive pregnancy test rate (adjusted odds ratio [aOR]: 0.809, 95% confidence interval [CI]: 0.682–0.960), lower clinical pregnancy rate (aOR: 0.766, 95% CI: 0.646–0.907), lower live birth rate (aOR: 0.706, 95% CI: 0.595–0.838), higher cesarean section rate (aOR: 2.066, 95% CI: 1.533–2.785), and higher rate of large for gestational age (aOR: 2.273, 95% CI: 1.547–3.341). In the generalized additive model, we found that CLBR declined with increasing BMI, with 24 kg/m2 as an inflection point. In the decision tree, BMI only made a difference in the population aged ≤34.5 years, with anti-Mullerian hormone >1.395 ng/mL, and the first time for IVF. Conclusions:. High BMI was related to poor IVF/ICSI outcomes in women with a normal ovarian response, and CLBR declined with increasing BMI, partly due to suppressed endometrial receptivity. A high BMI had the most negative effect on young women with anticipated positive prognoses.