Osr2 functions as a biomechanical checkpoint to aggravate CD8+ T cell exhaustion in tumor.

Alterations in extracellular matrix (ECM) architecture and stiffness represent hallmarks of cancer. Whether the biomechanical property of ECM impacts the functionality of tumor-reactive CD8+ T cells remains largely unknown. Here, we reveal that the transcription factor (TF) Osr2 integrates biomechanical signaling and facilitates the terminal exhaustion of tumor-reactive CD8+ T cells. Osr2 expression is selectively induced in the terminally exhausted tumor-specific CD8+ T cell subset by coupled T cell receptor (TCR) signaling and biomechanical stress mediated by the Piezo1/calcium/CREB axis. Consistently, depletion of Osr2 alleviates the exhaustion of tumor-specific CD8+ T cells or CAR-T cells, whereas forced Osr2 expression aggravates their exhaustion in solid tumor models. Mechanistically, Osr2 recruits HDAC3 to rewire the epigenetic program for suppressing cytotoxic gene expression and promoting CD8+ T cell exhaustion. Thus, our results unravel Osr2 functions as a biomechanical checkpoint to exacerbate CD8+ T cell exhaustion and could be targeted to potentiate cancer immunotherapy.

Discovery of metal-binding proteins by thermal proteome profiling.

Metal-binding proteins (MBPs) have various and important biological roles in all living species and many human diseases are intricately linked to dysfunctional MBPs. Here, we report a chemoproteomic method named 'metal extraction-triggered agitation logged by thermal proteome profiling' (METAL-TPP) to globally profile MBPs in proteomes. The method involves the extraction of metals from MBPs using chelators and monitoring the resulting protein stability changes through thermal proteome profiling. Applying METAL-TPP to the human proteome with a broad-spectrum chelator, EDTA, revealed a group of proteins with reduced thermal stability that contained both previously known MBPs and currently unannotated MBP candidates. Biochemical characterization of one potential target, glutamine-fructose-6-phosphate transaminase 2 (GFPT2), showed that zinc bound the protein, inhibited its enzymatic activity and modulated the hexosamine biosynthesis pathway. METAL-TPP profiling with another chelator, TPEN, uncovered additional MBPs in proteomes. Collectively, this study developed a robust tool for proteomic discovery of MBPs and provides a rich resource for functional studies of metals in cell biology.

Co-evolution-based prediction of metal-binding sites in proteomes by machine learning.

Metal ions have various important biological roles in proteins, including structural maintenance, molecular recognition and catalysis. Previous methods of predicting metal-binding sites in proteomes were based on either sequence or structural motifs. Here we developed a co-evolution-based pipeline named 'MetalNet' to systematically predict metal-binding sites in proteomes. We applied MetalNet to proteomes of four representative prokaryotic species and predicted 4,849 potential metalloproteins, which substantially expands the currently annotated metalloproteomes. We biochemically and structurally validated previously unannotated metal-binding sites in several proteins, including apo-citrate lyase phosphoribosyl-dephospho-CoA transferase citX, an Escherichia coli enzyme lacking structural or sequence homology to any known metalloprotein (Protein Data Bank (PDB) codes: 7DCM and 7DCN ). MetalNet also successfully recapitulated all known zinc-binding sites from the human spliceosome complex. The pipeline of MetalNet provides a unique and enabling tool for interrogating the hidden metalloproteome and studying metal biology.

Targeting Neuronal GPR65 With Delayed BTB09089 Treatment Improves Neurorehabilitation Following Ischemic Stroke.

BACKGROUND: GPR65 (G protein-coupled receptor 65) can sense extracellular acidic environment to regulate pathophysiological processes. Pretreatment with the GPR65 agonist BTB09089 has been proven to produce neuroprotection in acute ischemic stroke. However, whether delayed BTB09089 treatment and neuronal GPR65 activation promote neurorestoration remains unknown. METHODS: Ischemic stroke was induced in wild-type (WT) or GPR65 knockout (GPR65-/-) mice by photothrombotic ischemia. Male mice were injected intraperitoneally with BTB09089 every other day at days 3, 7, or 14 poststroke. AAV-Syn-GPR65 (adenoassociated virus-synapsin-GPR65) was utilized to overexpress GPR65 in the peri-infarct cortical neurons of GPR65-/- and WT mice. Motor function was monitored by grid-walk and cylinder tests. The neurorestorative effects of BTB09089 were observed by immunohistochemistry, Golgi-Cox staining, and Western blotting. RESULTS: BTB09089 significantly promoted motor outcomes in WT but not in GPR65-/- mice, even when BTB09089 was delayed for 3 to 7 days. BTB09089 inhibited the activation of microglia and glial scar progression in WT but not in GPR65-/- mice. Meanwhile, BTB09089 reduced the decrease in neuronal density in WT mice, but this benefit was abolished in GPR65-/- mice and reemerged by overexpressing GPR65 in peri-infarct cortical neurons. Furthermore, BTB09089 increased the GAP43 (growth-associated protein-43) and synaptophysin puncta density, dendritic spine density, dendritic branch length, and dendritic complexity by overexpressing GPR65 in the peri-infarct cortical neurons of GPR65-/- mice, which was accompanied by increased levels of p-CREB (phosphorylated cAMP-responsive element-binding protein). In addition, the therapeutic window of BTB09089 was extended to day 14 by overexpressing GPR65 in the peri-infarct cortical neurons of WT mice. CONCLUSIONS: Our findings indicated that delayed BTB09089 treatment improved neurological functional recovery and brain tissue repair poststroke through activating neuronal GRP65. GPR65 overexpression may be a potential strategy to expand the therapeutic time window of GPR65 agonists for neurorehabilitation after ischemic stroke.

Combined metabolome and transcriptome reveal HmF6'H1 regulating simple coumarin accumulation against powdery mildew infection in Heracleum moellendorffii Hance.

BACKGROUND: Powdery mildew, caused by Eeysiphe heraclei, seriously threatens Heracleum moellendorffii Hance. Plant secondary metabolites are essential to many activities and are necessary for defense against biotic stress. In order to clarify the functions of these metabolites in response to the pathogen, our work concentrated on the variations in the accumulation of secondary metabolites in H. moellendorffii during E. heraclei infection. RESULTS: Following E. heraclei infection, a significant upregulation of coumarin metabolites-particularly simple coumarins and associated genes was detected by RNA-seq and UPLC-MS/MS association analysis. Identifying HmF6'H1, a Feruloyl CoA 6'-hydroxylase pivotal in the biosynthesis of the coumarin basic skeleton through ortho-hydroxylation, was a significant outcome. The cytoplasmic HmF6'H1 protein was shown to be able to catalyze the ortho-hydroxylation of p-coumaroyl-CoA and caffeoyl-CoA, resulting in the formation of umbelliferone and esculetin, respectively. Over-expression of the HmF6'H1 gene resulted in increased levels of simple coumarins, inhibiting the biosynthesis of furanocoumarins and pyranocoumarins by suppressing PT gene expression, enhancing H. moellendorffii resistance to powdery mildew. CONCLUSIONS: These results established HmF6'H1 as a resistance gene aiding H. moellendorffii in combatting E. heraclei infection, offering additional evidence of feruloyl-CoA 6'-hydroxylase role in catalyzing various types of simple coumarins. Therefore, this work contributes to our understanding of the function of simple coumarins in plants' defense against powdery mildew infection.

Thermally recovered mechanoluminescence in Ca6BaP4O17:Eu2.

Stable reproducibility of mechanoluminescence (ML) is of vital importance for trap-controlled ML materials. Photo/electric excitation is usually needed for ML recovery of trap-controlled materials. In this work, it is demonstrated that thermal treatment can be applied to achieve recovery of ML, which is ascribed to the unique trap level configuration. The Ca6BaP4O17:Eu2+ performing robust trap-controlled ML has been proposed, and the corresponding repetitive ML can be realized by thermal treatment. TL spectra reveal that the thermally induced reproducible ML benefits from the dual defect level electronic structure of Ca6BaP4O17:Eu2+. The ML intensity is dependent on the electrons in shallow traps, and the electron transfer from deep traps to shallow traps induced by thermal treatment leads to repetitive ML.

Fluorogenic in-situ Labelling of Gelatin Polymer in Aqueous Solution and Hydrogel.

Gelatin polymers made from partially degraded collagen are important biomaterials, but their in-situ analysis suffers from uncontrollable covalent labelling and poor spatio-temporal imaging resolution. Herein, three tetrazolate-tagged tetraphenylethylene fluorophores (TPE-TAs) are introduced for practical fluorogenic labelling of gelatin in aqueous phase and hydrogels. These probes with aggregation-induced emission characteristics offer negligible background and elicit turn-on fluorescence by simply mixing with the gelatin in aqueous phase, giving a detection limit of 0.15 mg/L over a linear dynamic range up to 100 mg/L. This method does not work for collagens and causes minimal interference with gelatin properties. Mechanistic studies reveal a key role for multivalent electrostatic interactions between the abundant basic residues in gelatin (e.g., lysine, hydroxylysine, arginine) and anionic tetrazolate moieties of the lipophilic fluorophore synergistically in spatially rigid macromolecular encapsulation to achieve fluorogenic labelling. The AIE strategy by forming non-covalent fluorophore-gelatin complexes was developed for novel hydrogels that exhibited reversible fluorescence in response to dynamic microstructural changes in the hydrogel scaffold upon salting-in/out treatments, and enabled high spatio-temporal imaging of the fiber network in lyophilized samples. This work may open up avenues for in-situ imaging analysis and evaluation of gelatin-based biomaterials during processes such as in vivo degradation and mineralization.

Hypoxia-induced SHMT2 protein lactylation facilitates glycolysis and stemness of esophageal cancer cells.

Esophageal cancer (EC) is a familiar digestive tract tumor with highly lethal. The hypoxic environment has been demonstrated to be a significant factor in modulating malignant tumor progression and is strongly associated with the abnormal energy metabolism of tumor cells. Serine hydroxymethyl transferase 2 (SHMT2) is one of the most frequently expressed metabolic enzymes in human malignancies. The study was designed to investigate the biological functions and regulation mechanisms of SHMT2 in EC under hypoxia. We conducted RT-qPCR to assess SHMT2 levels in EC tissues and cells (TE-1 and EC109). EC cells were incubated under normoxia and hypoxia, respectively, and altered SHMT2 expression was evaluated through RT-qPCR, western blot, and immunofluorescence. The biological functions of SHMT2 on EC cells were monitored by performing CCK-8, EdU, transwell, sphere formation, glucose uptake, and lactate production assays. The SHMT2 protein lactylation was measured by immunoprecipitation and western blot. In addition, SHMT2-interacting proteins were analyzed by bioinformatics and validated by rescue experiments. SHMT2 was notably upregulated in EC tissues and cells. Hypoxia elevated SHMT2 protein expression, augmenting EC cell proliferation, migration, invasion, stemness, and glycolysis. In addition, hypoxia triggered lactylation of the SHMT2 protein and enhanced its stability. SHMT2 knockdown impeded the malignant phenotype of EC cells. Further mechanistic studies disclosed that SHMT2 is involved in EC progression by interacting with MTHFD1L. Hypoxia-induced SHMT2 protein lactylation and upregulated its protein level, which in turn enhanced MTHFD1L expression and accelerated the malignant progression of EC cells.

High-Resolution Mass Spectrometry Screening of Quaternary Ammonium Compounds (QACs) in Dust from Homes and Various Microenvironments in South China.

Despite their ubiquitous use, information regarding the presence of quaternary ammonium compounds (QACs) in various microenvironments remains scarce and only a small subset of QACs has been monitored using targeted chemical analysis. In this study, a total of 111 dust samples were collected from homes and various public settings in South China during the COVID-19 pandemic and were analyzed for traditional and emerging QACs using high-resolution mass spectrometry. The total traditional QAC concentrations in residential dust (∑traditional QAC, sum of 18 traditional QACs) ranged from 13.8 to 150 µg/g with a median concentration of 42.2 µg/g. Twenty-eight emerging QACs were identified in these samples, and the composition of ∑emerging QAC (sum of emerging QACs) to ∑QAC (sum of traditional and emerging QACs) ranged from 19 to 42% across various microenvironments, indicating the widespread existence of emerging QACs in indoor environments. Additionally, dust samples from cinemas exhibited higher ∑QAC concentrations compared to homes (medians 65.9 µg/g vs 58.3 µg/g, respectively), indicating heavier emission sources of QACs in these places. Interestingly, significantly higher ∑QAC concentrations were observed in dust from the rooms with carpets than those without (medians 65.6 µg/g vs 32.6 µg/g, p < 0.05, respectively). Overall, this study sheds light on the ubiquitous occurrence of QACs in indoor environments in South China.

Association of individual and combined exposures of 10 metals with periodontitis: Results from a large population-based study.

AIMS: To systematically investigate the association between individual and combined metal exposure and periodontitis. METHODS: Data encompassing complete periodontal examinations and metal detection in blood and urine samples were procured from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Three statistical methods, namely weighted logistic regression, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) regression, were used to evaluate the independent and combined associations between metals and periodontitis. RESULTS: Elevated concentrations of blood cadmium (odds ratio [OR]: 1.73, 95% confidence interval [CI]: 1.15-2.61) and blood lead (OR: 1.17, 95 %CI: 1.02-1.34) exhibited a positive association with periodontitis, even after adjusting for potential confounding factors. The BKMR and WQS regression suggested that the co-exposure of metals was also positively associated with periodontitis. Moreover, estradiol and albumin were identified as potential mediators in the relationship between the WQS index of the 10 metals in blood and periodontitis explaining 25.36% and 2.02% of the relationship, respectively. Furthermore, generally consistent patterns of associations between metals and periodontitis and mediating roles of estrogen and albumin were observed after a series of sensitivity analyses. CONCLUSION: This study provides evidence of positive associations between elevated levels of cadmium, lead or metal mixture and periodontitis, which may be partially mediated by sex hormones and oxidative stress indicators.

A novel selective ERK1/2 inhibitor, Laxiflorin B, targets EGFR mutation subtypes in non-small-cell lung cancer.

Extracellular regulated protein kinases 1/2 (ERK1/2) are key members of multiple signaling pathways, including the ErbB axis. Ectopic ERK1/2 activation contributes to various types of cancer, especially drug resistance to inhibitors of RTK, RAF and MEK, and specific ERK1/2 inhibitors are scarce. In this study, we identified a potential novel covalent ERK inhibitor, Laxiflorin B, which is a herbal compound with anticancer activity. However, Laxiflorin B is present at low levels in herbs; therefore, we adopted a semi-synthetic process for the efficient production of Laxiflorin B to improve the yield. Laxiflorin B induced mitochondria-mediated apoptosis via BAD activation in non-small-cell lung cancer (NSCLC) cells, especially in EGFR mutant subtypes. Transcriptomic analysis suggested that Laxiflorin B inhibits amphiregulin (AREG) and epiregulin (EREG) expression through ERK inhibition, and suppressed the activation of their receptors, ErbBs, via a positive feedback loop. Moreover, mass spectrometry analysis combined with computer simulation revealed that Laxiflorin B binds covalently to Cys-183 in the ATP-binding pocket of ERK1 via the D-ring, and Cys-178 of ERK1 through non-inhibitory binding of the A-ring. In a NSCLC tumor xenograft model in nude mice, Laxiflorin B also exhibited strong tumor suppressive effects with low toxicity and AREG and EREG were identified as biomarkers of Laxiflorin B efficacy. Finally, Laxiflorin B-4, a C-6 analog of Laxiflorin B, exhibited higher binding affinity for ERK1/2 and stronger tumor suppression. These findings provide a new approach to tumor inhibition using natural anticancer compounds.

Dose-response relationship between lung function and chest imaging response to silica exposures in artificial stone manufacturing workers.

BACKGROUND: Occupational exposure to artificial stone, a popular material used for countertops, can cause accelerated silicosis, but the precise relationship between silica dose and disease development is unclear. OBJECTIVES: This study evaluated the impact of silica exposure on lung function and chest imaging in artificial stone manufacturing workers. METHODS: Questionnaire and spirometry assessments were administered to workers in two plants. A high-exposure subset underwent further evaluation, including chest CT and DLco. Weighting factors, assigned as proxies for silica exposure, were based on work tasks. Individual cumulative exposures were estimated using area concentration measurements and time spent in specific areas. Exposure-response associations were analyzed using linear and logistic regression models. RESULTS: Among 65 participants, the mean cumulative silica exposure was 3.61 mg/m3-year (range 0.0001 to 44.4). Each 1 mg/m3-year increase was associated with a 0.46% reduction in FVC, a 0.45% reduction in FEV1, and increased lung function abnormality risk (aOR = 1.27, 95% CI = 1.03-1.56). Weighting factors correlated with cumulative exposures (Spearman correlation = 0.59, p < 0.0001), and weighted tenure was associated with lung function abnormalities (aOR = 1.04, 95% CI = 1.01-1.09). Of 37 high-exposure workers, 19 underwent chest CT, with 12 (63%) showing abnormal opacities. Combining respiratory symptoms, lung function, and chest X-ray achieved 91.7% sensitivity and 75% specificity for predicting chest CT abnormalities. CONCLUSION: Lung function and chest CT abnormalities occur commonly in artificial stone workers. For high-exposure individuals, abnormalities on health screening could prompt further chest CT examination to facilitate early silicosis detection.

Safety and benefit of modified mesohepatectomy in the treatment of bilobar involvement congenital biliary dilatation.

BACKGROUND: The diseased bile duct in bilobar congenital biliary dilatation is extensive and often requires major hepatectomy or liver transplantation associated with a higher risk. We aimed to evaluate the safety and benefit of modified mesohepatectomy, in comparison with trisectionectomy, to treat bilobar congenital biliary dilatation. METHODS: This study included 28 patients with type IV and V bilobar congenital biliary dilatation. An innovative mesohepatectomy comprising the hepatectomy technique beyond the P/U point and bile duct shaping was applied to 14 patients to address the extensively diseased bile duct and difficulty in hepaticojejunostomy. Another 14 patients received trisectionectomy. The perioperative and long-term outcomes of these patients were compared. RESULTS: The ratio of residual liver volume to standard liver volume in the mesohepatectomy group was higher (78.68% vs. 40.90%, p = 0.005), while the resection rate of the liver parenchyma was lower (28.25% vs. 63.97%, p = 0.000), than that in trisectionectomy group. The mesohepatectomy group had a lower severe complication (>Clavein III, 0% vs. 57.70%, p = 0.019) and incidence of posthepatectomy liver failure (7.14% vs. 42.86%, p = 0.038). No significant difference was observed in blood loss and bile leakage (p > 0.05). All the patients in the mesohepatectomy group achieved optimal results in the long-term follow-up. CONCLUSIONS: mesohepatectomy provides an efficient treatment option for bilobar congenital biliary dilatation and can achieve radical resection, retain more liver parenchyma, and reduce the difficulty of hepaticojejunostomy, especially for patients that are not eligible for major hepatectomy and liver transplantation.

Early versus delayed appendicectomy for appendiceal phlegmon or abscess.

BACKGROUND: This is an update of a Cochrane review first published in 2017. Acute appendicitis (inflammation of the appendix) can be simple or complicated. Appendiceal phlegmon and appendiceal abscess are examples of complicated appendicitis. Appendiceal phlegmon is a diffuse inflammation in the bottom right of the appendix, while appendiceal abscess is a discrete inflamed mass in the abdomen that contains pus. Appendiceal phlegmon and abscess account for 2% to 10% of acute appendicitis. People with appendiceal phlegmon or abscess usually need an appendicectomy to relieve their symptoms (e.g. abdominal pain, loss of appetite, nausea, and vomiting) and avoid complications (e.g. peritonitis (infection of abdominal lining)). Surgery for people with appendiceal phlegmon or abscess may be early (immediately after hospital admission or within a few days of admission), or delayed (several weeks later in a subsequent hospital admission). The optimal timing of appendicectomy for appendiceal phlegmon or abscess is debated. OBJECTIVES: To assess the effects of early appendicectomy compared to delayed appendicectomy on overall morbidity and mortality in people with appendiceal phlegmon or abscess. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, two other databases, and five trials registers on 11 June 2023, together with reference checking to identify additional studies. SELECTION CRITERIA: We included all individual and cluster-randomised controlled trials (RCTs), irrespective of language, publication status, or age of participants, comparing early versus delayed appendicectomy in people with appendiceal phlegmon or abscess. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included eight RCTs that randomised 828 participants to early or delayed appendicectomy for appendiceal phlegmon (7 trials) or appendiceal abscess (1 trial). The studies were conducted in the USA, India, Nepal, and Pakistan. All RCTs were at high risk of bias because of lack of blinding and lack of published protocols. They were also unclear about methods of randomisation and length of follow-up. 1. Early versus delayed open or laparoscopic appendicectomy for appendiceal phlegmon We included seven trials involving 788 paediatric and adult participants with appendiceal phlegmon: 394 of the participants were randomised to the early appendicectomy group (open or laparoscopic appendicectomy as soon as the appendiceal mass resolved within the same admission), and 394 were randomised to the delayed appendicectomy group (initial conservative treatment followed by delayed open or laparoscopic appendicectomy several weeks later). There was no mortality in either group. The evidence is very uncertain about the effect of early appendicectomy on overall morbidity (risk ratio (RR) 0.74, 95% confidence interval (CI) 0.19 to 2.86; 3 trials, 146 participants; very low-certainty evidence), the proportion of participants who developed wound infections (RR 0.99, 95% CI 0.48 to 2.02; 7 trials, 788 participants), and the proportion of participants who developed faecal fistulas (RR 1.75, 95% CI 0.36 to 8.49; 5 trials, 388 participants). Early appendicectomy may reduce the abdominal abscess rate (RR 0.26, 95% CI 0.08 to 0.80; 4 trials, 626 participants; very low-certainty evidence), reduce the total length of hospital stay by about two days (mean difference (MD) -2.02 days, 95% CI -3.13 to -0.91; 5 trials, 680 participants), and increase the time away from normal activities by about five days (MD 5.00 days; 95% CI 1.52 to 8.48; 1 trial, 40 participants), but the evidence is very uncertain. 2. Early versus delayed laparoscopic appendicectomy for appendiceal abscess We included one trial involving 40 paediatric participants with appendiceal abscess: 20 were randomised to the early appendicectomy group (emergent laparoscopic appendicectomy), and 20 were randomised to the delayed appendicectomy group (initial conservative treatment followed by delayed laparoscopic appendicectomy 10 weeks later). There was no mortality in either group. The trial did not report on overall morbidity, various complications, or time away from normal activities. The evidence is very uncertain about the effect of early appendicectomy on the total length of hospital stay (MD -0.20 days, 95% CI -3.54 to 3.14; very low-certainty evidence). AUTHORS' CONCLUSIONS: For the comparison of early versus delayed open or laparoscopic appendicectomy for paediatric and adult participants with appendiceal phlegmon, very low-certainty evidence suggests that early appendicectomy may reduce the abdominal abscess rate. The evidence is very uncertain whether early appendicectomy prevents overall morbidity or other complications. Early appendicectomy may reduce the total length of hospital stay and increase the time away from normal activities, but the evidence is very uncertain. For the comparison of early versus delayed laparoscopic appendicectomy for paediatric participants with appendiceal abscess, data are sparse, and we cannot rule out significant benefits or harms of early versus delayed appendicectomy. Further trials on this topic are urgently needed and should specify a set of criteria for use of antibiotics, percutaneous drainage of the appendiceal abscess prior to surgery, and resolution of the appendiceal phlegmon or abscess. Future trials should include outcomes such as time away from normal activities and length of hospital stay.

Mechanism of Cnidii Fructus in the Treatment of Infertility Based on Network Pharmacology and Molecular Docking Analysis Technology.

Infertility is a condition characterized by a low fertility rate, which significantly affects the physical and mental health of women of reproductive age. Typically, the treatment duration is prolonged, and the therapeutic outcomes are often unsatisfactory. Professor Cheng-yao He, a renowned expert in traditional Chinese medicine, commonly uses the herb Cnidii Fructus (SCZ) for the treatment of infertility. However, the exact mechanism remains unclear, and there is limited research available on this topic. The active ingredients of SCZ were obtained from the traditional chinese medicine system pharmacology (TCMSP) database and screened for pharmacokinetics (PK), involving absorption, distribution, metabolism, and excretion (ADME). Target prediction was performed by SwissTargetPrediction database, and infertility-related disease targets were searched in GeneCards, TTD, DrugBank, and OMIM database. The protein-protein interaction (PPI) network was constructed using the STRING database (Version 11.5) and analyzed by Cytoscape software (Version 3.9.1). Additionally, the target genes were subjected to biological enrichment analysis in the Metascape database, including gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, and the "Disease-Ingredient-pathway-target" network was constructed using Cytoscape software. With the assistance of AutoDockVina, Ligplot, and PyMOL software, a validation of Molecular docking results and a visualization of the results were performed. This study identified 11 retained active ingredients of SCZ, 447 drug targets, 233 of which were related to infertility, and 5393 disease targets. GO enrichment analysis mainly involved 221 biological processes such as cellular response to chemical stress and gland development. KEGG enrichment analysis mainly involved 68 pathways such as thyroid hormone signaling pathway, estrogen signaling pathway, FOXO signaling pathway, and PI3K/Akt signaling pathway. Molecular docking showed that the core active ingredients of SCZ, including Ammidin, Diosmetin, Xanthoxylin N, and Prangenidin, had strong binding abilities with core targets such as MDM2, MTOR, CCND1, EGFR, and AKT1. This study preliminarily demonstrated that SCZ may act on the PI3K/Akt signaling pathway, exerting its therapeutic effects on infertility by improving energy metabolism disorders and endometrial receptivity, inducing primordial follicle activation, regulating oocyte proliferation, differentiation, and apoptosis, and promoting the release of dominant follicles.

Xylarkarynone A and B: Two Bioactive Eremophilane Sesquiterpenes from Xylaria sp. HHY-2.

A new compound xylarkarynone A (1), a first reported natural product compound xylarkarynone B (2) and eight known compounds (3-10) were isolated from Xylaria sp. HHY-2. Their structures were elucidated by spectroscopic methods, DP4+ probability analyses and electronic circular dichroism (ECD) calculations. The bioactivities of isolated compounds were assayed. Compound 1 exhibited obvious activity against A549 cells with an IC50 value of 6.12±0.28 µM. Additionally, compound 1 showed moderate antifungal activities against Plectosphaerella cucumerina and Aspergillus niger with minimum inhibitory concentrations (MICs) of both 16 µg/mL, which was at the same grade with positive control nystatin. Most compounds exhibited varying degrees of inhibitory activity against P. cucumerina, indicating that Xylaria sp. has potential as inhibitors against P. cucumerina.

Integrated Automatic Optical Inspection and Image Processing Procedure for Smart Sensing in Production Lines.

An integrated automatic optical inspection (iAOI) system with a procedure was proposed for a printed circuit board (PCB) production line, in which pattern distortions and performance deviations appear with process variations. The iAOI system was demonstrated in a module comprising a camera and lens, showing improved supportiveness for commercially available hardware. The iAOI procedure was realized in a serial workflow of image registration, threshold setting, image gradient, marker alignment, and geometric transformation; furthermore, five operations with numerous functions were prepared for image processing. In addition to the system and procedure, a graphical user interface (GUI) that displays sequential image operation results with analyzed characteristics was established for simplicity. To demonstrate its effectiveness, self-complementary Archimedean spiral antenna (SCASA) samples fabricated via standard PCB fabrication and intentional pattern distortions were demonstrated. The results indicated that, compared with other existing methods, the proposed iAOI system and procedure provide unified and standard operations with efficiency, which result in scientific and unambiguous judgments on pattern quality. Furthermore, we showed that when an appropriate artificial intelligence model is ready, the electromagnetic characteristic projection for SCASAs can be simply obtained through the GUI.

Genome-Wide Analysis of C/S1-bZIP Subfamilies in Populus tomentosa and Unraveling the Role of PtobZIP55/21 in Response to Low Energy.

C/S1 basic leucine zipper (bZIP) transcription factors are essential for plant survival under energy deficiency. However, studies on the responses of C/S1-bZIPs to low energy in woody plants have not yet been reported. In this study, members of C/S1-bZIP subfamilies in Populus tomentosa were systematically analyzed using bioinformatic approaches. Four C-bZIPs and 10 S1-bZIPs were identified, and their protein properties, phylogenetic relationships, gene structures, conserved motifs, and uORFs were systematically investigated. In yeast two-hybrid assays, direct physical interactions between C-bZIP and S1-bZIP members were observed, highlighting their potential functional synergy. Moreover, expression profile analyses revealed that low energy induced transcription levels of most C/S1-bZIP members, with bZIP55 and bZIP21 (a homolog of bZIP55) exhibiting particularly significant upregulation. When the expression of bZIP55 and bZIP21 was co-suppressed using artificial microRNA mediated gene silencing in transgenic poplars, root growth was promoted. Further analyses revealed that bZIP55/21 negatively regulated the root development of P. tomentosa in response to low energy. These findings provide insights into the molecular mechanisms by which C/S1-bZIPs regulate poplar growth and development in response to energy deprivation.

[Prevalence of and risk factors for perceived absence of breast milk supply in Chinese lactating women in 2013].

OBJECTIVE: To investigate the prevalence and influencing factors of postpartum perceived absence of breast milk supply among Chinese mothers in 2013. METHODS: This is a cross-sectional study based on the data collected from children and mothers under 2 years of age in 2013 as part of the nutrition and health surveillance of Chinese residents. In this study, multistage stratified cluster sampling method was used to select subjects from 55 countires/districts in 30 provinces in China. The perceived absence of breast milk supply was defined as the mother's self-reported absence of breast milk and failure to breastfeed. Breastfeeding knowledge, maternal breastfeeding knowledge and general characteristics were collected through a structured questionnaire. Univariate analysis and Logistic regression were used to analyze the factors associated with perceived absence of breast milk supply. RESULTS: A total of 12091 mothers were included in the study, including 419 in the perceived non-breastfeeding group, the prevalence of perceived absence of breast milk supply was 3.5%. Multivariate Logistic regression showed maternal age(OR=1.04, 95%CI 1.02-1.06), postpartum hemorrhage(OR=2.03, 95%CI 1.30-3.16), and belief that breastfeeding should continue beyond 12 months of age(OR=0.27, 95%CI 0.17-0.45), not knowing how to breastfeed(OR=3.31, 95%CI: 2.31-4.74) were the main influencing factors for perceived absence of breast milk supply after delivery. CONCLUSION: Age, postpartum hemorrhage and knowledge level of breastfeeding are the main risk factors for perceived absence of breast milk supply, and knowledge level of breastfeeding is a modifiable factor.

Association between new plasma inflammatory markers and risk of colorectal neoplasms in individuals over 50 years old.

OBJECTIVE(S): The prognostic value of systemic cytokine profiles and inflammatory markers in colorectal cancer were explored by several studies. We want to know more about inflammatory biomarkers in colorectal adenoma and early cancer. METHOD: The level of 38 inflammatory markers in the plasma of 112 adenoma patients, 72 Tis-T1 staging of colorectal carcinoma patients, 34 T2-T4 staging of colorectal carcinoma patients and 53 normal subjects were detected and compared. RESULT(S): Eight inflammatory biomarkers (Eotaxin, GCSF, IL-4, IL-5, IL-17E, MCP-1, TNF-α and VEGF-A) have higher plasma concentrations in colorectal adenoma and cancer patients compared with normal participants over 50 years old. CONCLUSION(S): Inflammatory markers may have the prognostic value for colorectal adenoma and early-stage carcinoma.