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Transmembrane channel-like (TMC) proteins are a highly conserved ion channel family consisting of eight members (TMC1-TMC8) in mammals. TMC1/2 are components of the mechanotransduction channel in hair cells, and mutations of TMC1/2 cause deafness in humans and mice. However, the physiological roles of other TMC proteins remain largely unknown. Here, we show that Tmc7 is specifically expressed in the testis and that it is required for acrosome biogenesis during spermatogenesis. Tmc7 -/- mice exhibited abnormal sperm head, disorganized mitochondrial sheaths, and reduced number of elongating spermatids, similar to human oligo-astheno-teratozoospermia. We further demonstrate that TMC7 is colocalized with GM130 at the cis -Golgi region in round spermatids. TMC7 deficiency leads to aberrant Golgi morphology and impaired fusion of Golgi-derived vesicles to the developing acrosome. Moreover, upon loss of TMC7 intracellular ion homeostasis is impaired and ROS levels are increased, which in turn causes Golgi and endoplasmic reticulum stress. Taken together, these results suggest that TMC7 is required to maintain pH and ion homeostasis, which is needed for acrosome biogenesis. Our findings unveil a novel role for TMC7 in acrosome biogenesis during spermiogenesis., Competing Interests: JW, YY, LY, JQ, ZW, CQ, YG, GL, FG, ZC, XZ, HL, ZL No competing interests declared, (© 2024, Wang et al.)

Different from the reported work focusing on the construction of single P- or C-stereocenter via hydrophosphinylation of unsaturated carbon bonds, the highly diastereo- and enantioselective hydrophosphinylation reaction of allenes, conjugated enynes and 1,3-dienes is achieved via a designed Pd/Co dual catalysis and newly modified masked phosphinylating reagent. A series of allyl motifs bearing both a tertiary C- and P-stereocenter are prepared in generally good yields, >20:1 dr, >20:1 rr and 99% ee. The unprecedented diastereo- and enantioselective hydrophosphinylation of 1,3-enynes is established to generate skeletons containing both a P-stereocenter and a nonadjacent chiral axis. The first stereodivergent hydrophosphinylation reaction is also developed to achieve all four P-containing stereoisomers. The present protocol features the use of only 3-minutes reaction time and 0.1% catalyst, and with the observation of up to 730 TON. A set of mechanistic studies reveal the necessity and roles of two metal catalysts and corroborate the designed synergistic process., (© 2024 Wiley‐VCH GmbH.)

In this multicenter, non-inferiority, randomized trial, we randomly assigned 992 women undergoing in-vitro fertilization (IVF) with a good prognosis (aged 20-40, ≥3 transferrable cleavage-stage embryos) to strategies of blastocyst-stage (n = 497) or cleavage-stage (n = 495) single embryo transfer. Primary outcome was cumulative live-birth rate after up to three transfers. Secondary outcomes were cumulative live-births after all embryo transfers within 1 year of randomization, pregnancy outcomes, obstetric-perinatal complications, and livebirths outcomes. Live-birth rates were 74.8% in blastocyst-stage group versus 66.3% in cleavage-stage group (relative risk 1.13, 95%CI:1.04-1.22; P non-inferiority  < 0.001, P superiority  = 0.003) (1-year cumulative live birth rates of 75.7% versus 68.9%). Blastocyst transfer increased the risk of spontaneous preterm birth (4.6% vs 2.0%; P = 0.02) and neonatal hospitalization >3 days. Among good prognosis women, a strategy of single blastocyst transfer increases cumulative live-birth rates over single cleavage-stage transfer. Blastocyst transfer resulted in higher preterm birth rates. This information should be used to counsel patients on their choice between cleavage-stage and blastocyst-stage transfer (NCT03152643, https://clinicaltrials.gov/study/NCT03152643 )., (© 2024. The Author(s).)

Purpose: The aim of this study was to explore the potential correlation between the nuclear receptor subfamily 3 group C member 2 (NR3C2) and outcomes of colon cancer, along with the mechanisms underlying this association., Method: mRNA (messenger RNA) data and clinical records pertaining to colon cancer were retrieved from The Cancer Genome Atlas (TCGA) database. The analysis of NR3C2 expression discrepancies between normal colon and tumor tissues was conducted using R software. In addition, we also studied the relationship between NR3C2 expression and prognosis, pathological parameters. The relative role of NR3C2 were further predicted through bioinformatics methods and receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of NR3C2 in colon cancer. Single-cell data from colon cancer samples in the GEO (Gene Expression Omnibus) database further investigated the mechanism of the lower survival associated with NR3C2 dysregulation. NR3C2 expression in three fresh colon cancer samples and their respective paracancer samples was determined. Furthermore, colon cancer cell models overexpressing NR3C2 and with knockdown NR3C2 were constructed by lentiviral vector transfection. Cell Counting Kit-8 assay, transplantation of tumors in nude mice and transwell assays were used to examine the proliferation, migration and invasion of colon cancer cells. The effect on the Wnt/β-catenin pathway, activities of cellular autophagy and cell apoptosis were examined by assessing the expression levels of several key proteins, including Bcl-2, Bax, and LC3., Results: We found that NR3C2 was found a significantly lower level in colon cancer tissues than in adjacent tissues, which was associated with distant and lymphatic metastases, clinical stage, and poor clinical outcome, and it was an independent prognostic factor and potential marker of colon cancer. Single-cell transcriptome data identified the subset of circulating T and B cells with high expression of NR3C2, which is involved in TNF signaling pathway. Functional experiments show that downregulation of NR3C2 resultsed in the activation of the Wnt/β-catenin signaling pathway, and promotesd the proliferation and invasion of colon cancer cells while suppressing cell autophagy and apoptosis., Conclusion: NR3C2 may regulate Wnt/β-catenin to affect the proliferation, invasion apoptosis and autophagy of colon cancer, and this axis is a potential target for the treatment of colon cancer., (© 2024. The Author(s).)

Aberrant lipid metabolism has been widely recognized as a hallmark of various diseases. However, the comprehensive analysis of distinct lipids is challenging due to the complexity of lipid molecular structures, wide concentration ranges, and numerous isobaric and isomeric lipids. Usually, liquid chromatography-mass spectrometry (LC-MS)-based lipidomics requires a long time for chromatographic separation to achieve optimal separation and selectivity. Ion mobility (IM) adds a new separation dimension to LC-MS, significantly enhancing the coverage, sensitivity, and resolving power. We took advantage of the rapid separation provided by ion mobility and optimized a fast and broad-coverage lipidomics method using the LC-IM-MS technology. The method required only 8 minutes for separation and detected over 1000 lipid molecules in a single analysis of common biological samples. The high reproducibility and accurate quantification of this high-throughput lipidomics method were systematically characterized. We then applied the method to comprehensively measure dysregulated lipid metabolism in patients with colorectal cancer (CRC). Our results revealed 115 significantly changed lipid species between preoperative and postoperative plasma of patients with CRC and also disclosed associated differences in lipid classes such as phosphatidylcholines (PC), sphingomyelins (SM), and triglycerides (TG) regarding carbon number and double bond. Together, a fast and broad-coverage lipidomics method was developed using ion mobility-mass spectrometry. This method is feasible for large-scale clinical lipidomic studies, as it effectively balances the requirements of high-throughput and broad-coverage in clinical studies.

A Pd-catalyzed regioselective H/D exchange at the α-position of pyridines was achieved by employing secondary phosphine oxide as an internal base. The proposed five-membered structure enabled the reaction to overcome its conventional ortho -directing feature, allowing the efficient deuteration of pyridines and quinolines at adjacent sites of N-atoms.

On 9 October 2022, the Large High Altitude Air Shower Observatory (LHAASO) reported the observation of the very early TeV afterglow of the brightest-of-all-time gamma-ray burst 221009A, recording the highest photon statistics in the TeV band ever obtained from a gamma-ray burst. We use this unique observation to place stringent constraints on the energy dependence of the speed of light in vacuum, a manifestation of Lorentz invariance violation (LIV) predicted by some quantum gravity (QG) theories. Our results show that the 95% confidence level lower limits on the QG energy scales are E&#95;{QG,1}>10 times the Planck energy E&#95;{Pl} for the linear LIV effect, and E&#95;{QG,2}>6×10^{-8}E&#95;{Pl} for the quadratic LIV effect. Our limits on the quadratic LIV case improve previous best bounds by factors of 5-7.

Objective: To evaluate whether intergroup differences in the risk of maternal pregnancy complications after in vitro fertilization (IVF) vary with male factor., Design: A post hoc exploratory secondary analysis of data from a multicenter, randomized, controlled noninferiority trial (NCT03118141)., Setting: Academic fertility centers., Patient(s): A total of 1,131 subfertile women with complete recording of their male partner's semen parameters during the trial were enrolled. All participants underwent intracytoplasmic sperm injection followed by frozen embryo transfer (ET) as part of their assisted reproductive technology treatment protocol., Intervention(s): Women were divided into the oligoasthenospermia (n = 405) and normospermia (n = 726) groups according to the quality of male sperm., Main Outcome Measure(s): Pregnancy complications, principally including the incidence of preeclampsia., Result(s): Notably, we found that the risk of maternal preeclampsia was significantly higher in the oligoasthenospermia group than in the normospermia group. After adjustments for confounding factors by multivariate logistic regression analysis, the incidence of preeclampsia in the oligoasthenospermia group was still significantly higher than that in the normospermia group (6.55% vs. 3.60%; odds ratio, 0.529; 95% confidence interval, 0.282-0.992). However, there were no significant differences in terms of embryo quality, cumulative live birth rate, other pregnancy complications, or neonatal outcomes between the 2 groups., Conclusion(s): Oligoasthenospermia was associated with a higher risk of maternal preeclampsia in subfertile couples undergoing IVF-ET treatment. In clinical practice, it is essential to thoroughly evaluate the sperm quality and quantity of male partners before IVF-ET. Further research is needed to establish the causal relationships between semen quality and adverse pregnancy complications, particularly preeclampsia, and explore potential interventions., Competing Interests: Declaration of Interests L.G. has nothing to disclose. A.G. has nothing to disclose. X.L. has nothing to disclose. S.T. has nothing to disclose. F.S. has nothing to disclose. Y.S. has nothing to disclose. Z.-J.C. has nothing to disclose. Y.C. has nothing to disclose. Y.L. has nothing to disclose., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Economical oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) bifunctional catalysts with high activity aimed at replacing precious metal catalysts for rechargeable zinc-air batteries (ZABs) must be developed. In this study, a multiple hierarchical-structural material is developed using a facile dielectric barrier discharge (DBD) plasma surface treatment, solvothermal reaction, and high-temperature carbonization strategy. This strategy allows for the construction of nanosheets using nitrogen-doped carbon (NC) material-encapsulated ternary CoNiFe alloy nanoparticles (NPs) on a network of NC nanotubes (NCNTs), denoted as CoNiFe-NC@p-NCNTs. Precisely, the presence of abundant CoNiFe alloy NPs and the formation of M-N-C active sites created by transition metals (cobalt, nickel, and iron) coupled with NC can provide superior OER/ORR bifunctional properties. Moreover, the prepared NC layers with a multilevel pore structure contribute to a larger specific surface area, exposing numerous active sites and enhancing the uniformity of electron and mass movement. The CoNiFe 0.08 -NC@p-NCNTs show remarkable dual functionality for electrochemical oxygen reactions (ORR half-wave potential of 0.811 V, limiting current density of 5.73 mA cm -2 measured with a rotating disk electrode at a rotation speed of 1600 rpm, and OER overpotential of 351 mV at 10 mA cm -2 ), which demonstrates similar ORR performance to 20 wt% Pt/C and better OER performance than the commercial RuO 2 . A liquid ZAB prepared using the proposed material has excellent bifunctionality with an open-circuit voltage of 1.450 V and long-term cycling stability of 230 h@10 mA cm -2 ., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Aims: Data on the safety and effectiveness of tenofovir alafenamide (TAF) plus peginterferon-alpha (Peg-IFN-α) in children with chronic hepatitis B (CHB) are lacking. The current study aimed to present the characteristics of four pediatric CHB patients who obtained a functional cure by using TAF and Peg-IFN-α., Methods: In this case series study initiated in May 2019, ten children who had no clinical symptoms or signs received response-guided (HBV DNA undetectable, hepatitis B e antigen [HBeAg] loss or seroconversion, and hepatitis B surface antigen [HBsAg] loss or seroconversion) and functional cure-targeted (HBsAg loss or seroconversion) TAF (25 mg/d, orally) plus Peg-IFN-α-2b (180 µg/1.73m 2 , subcutaneously, once weekly) in combination (9/10) or sequential (1/10) therapy. The safety and effectiveness of these treatments were monitored., Results: As of April 2024, four out of ten children obtained a functional cure after a mean of 31.5 months of treatment, and the other six children are still undergoing treatment. These four cured children, aged 2, 4, 8, and 6 years, were all HBeAg-positive and had alanine aminotransferase levels of 80, 47, 114, and 40 U/L; HBV DNA levels of 71200000, 93000000, 8220, and 96700000 IU/mL; and HBsAg levels of 39442.8, 15431.2, 22, and 33013.1 IU/mL, respectively. During treatment, all the children (10/10) experienced mild or moderate adverse events, including flu-like symptoms, anorexia, fatigue, and cytopenia. Notably, growth retardation (8/10) was the most significant adverse event; and it occurred in three cured children (3/4) treated with combination therapy and was present to a low degree in the other cured child (1/4) treated with sequential therapy. Fortunately, all three cured children recovered to or exceeded the normal growth levels at 9 months posttreatment., Conclusions: TAF plus Peg-IFN-α-2b therapy is potentially safe and effective for pediatric CHB patients, which may provide important insights for future clinical practice and study designs targeting functional cures for children with CHB., (© 2024. The Author(s).)

Flueggea virosa (Roxb. ex Willd.) Royle, an evergreen shrub and small tree in the Phyllanthaceae family, holds significant potential in garden landscaping and pharmacological applications. However, the lack of genomic data has hindered further scientific understanding of its horticultural and medicinal values. In this study, we have assembled a haplotype-resolved genome of F. virosa for the first time. The two haploid genomes, named haplotype A genome and haplotype B genome, are 487.33 Mb and 477.53 Mb in size, respectively, with contig N50 lengths of 31.45 Mb and 32.81 Mb. More than 99% of the assembled sequences were anchored to 13 pairs of pseudo-chromosomes. Furthermore, 21,587 and 21,533 protein-coding genes were predicted in haplotype A and haplotype B genomes, respectively. The availability of this chromosome-level genome fills the gap in genomic data for F. virosa and provides valuable resources for molecular studies of this species, supporting future research on speciation, functional genomics, and comparative genomics within the Phyllanthaceae family., (© 2024. The Author(s).)

Derived from enteroendocrine cells (EECs), glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are pivotal incretin hormones crucial for blood glucose regulation. Medications of GLP-1 analogs and GLP-1 receptor activators are extensively used in the treatment of type 2 diabetes (T2D) and obesity. However, there are currently no agents to stimulate endogenous incretin secretion. Here, we find the pivotal role of KCNH2 potassium channels in the regulation of incretin secretion. Co-localization of KCNH2 with incretin-secreting EECs in the intestinal epithelium of rodents highlights its significance. Gut epithelial cell-specific KCNH2 knockout in mice improves glucose tolerance and increases oral glucose-triggered GLP-1 and GIP secretion, particularly GIP. Furthermore, KCNH2-deficient primary intestinal epithelial cells exhibit heightened incretin, especially GIP secretion upon nutrient stimulation. Mechanistically, KCNH2 knockdown in EECs leads to reduced K + currents, prolonged action potential duration, and elevated intracellular calcium levels. Finally, we found that dofetilide, a KCNH2-specific inhibitor, could promote incretin secretion in enteroendocrine STC-1 cells in vitro and in hyperglycemic mice in vivo. These findings elucidate, for the first time, the mechanism and application of KCNH2 in regulating incretin secretion by EECs. Given the therapeutic promise of GLP-1 and GIP in diabetes and obesity management, this study advances our understanding of incretin regulation, paving the way for potential incretin secretagogue therapies in the treatment of diabetes and obesity., (© 2024. The Author(s).)

This work reports a strategy that integrates the carbon nanotube (CNT) supporting, ultrathin carbon coating and oxygen defect generation to fabricate the RuO 2 based catalysts toward the pH-universal hydrogen evolution reaction (HER) with high efficiencies. Specifically, the CNT supported RuO 2 nanoparticles with ultrathin carbon loricae and rich oxygen vacancies at the surface (C@OV-RuO 2 /CNTs-325) have been synthesized. The C@OV-RuO 2 /CNTs-325 shows superior activities and excellent durability for the HER. It only requires overpotentials of 36.1, 18.0, and 19.3 mV to deliver -10 mA cm -2 in the acidic, neutral, and alkaline media, respectively. Its HER activities are comparable to that of the Pt/C in the acidic media but higher than those of the Pt/C in the neutral and alkaline media. The C@OV-RuO 2 /CNTs-325 shows excellent HER durability with no activity losses for > 500 h in the acidic, neutral or alkaline media at -250 mA cm -2 . The density-functional-theory calculations indicate that the CNT supporting, the carbon coating, and the OVs can modulate the d-band centers of Ru, increasing the HER activities of C@OV-RuO 2 /CNTs-325, and stabilize the Ru atoms in the catalyst, increasing the durability of the C@OV-RuO 2 /CNTs-325. More interestingly, the C@OV-RuO 2 /CNTs-325 shows great potential for practical applications toward overall seawater splitting., (© 2024 Wiley‐VCH GmbH.)

In this Letter we try to search for signals generated by ultraheavy dark matter at the Large High Altitude Air Shower Observatory (LHAASO) data. We look for possible γ rays by dark matter annihilation or decay from 16 dwarf spheroidal galaxies in the field of view of the LHAASO. Dwarf spheroidal galaxies are among the most promising targets for indirect detection of dark matter that have low fluxes of astrophysical γ-ray background while having large amount of dark matter. By analyzing more than 700 days of observational data at LHAASO, no significant dark matter signal from 1 TeV to 1 EeV is detected. Accordingly we derive the most stringent constraints on the ultraheavy dark matter annihilation cross section up to EeV. The constraints on the lifetime of dark matter in decay mode are also derived.

Nutritional status and pyroptosis are important for host defence against infections. However, the molecular link that integrates nutrient sensing into pyroptosis during microbial infection is unclear. Here, using metabolic profiling, we found that Yersinia pseudotuberculosis infection results in a significant decrease in intracellular glucose levels in macrophages. This leads to activation of the glucose and energy sensor AMPK, which phosphorylates the essential kinase RIPK1 at S321 during caspase-8-mediated pyroptosis. This phosphorylation inhibits RIPK1 activation and thereby restrains pyroptosis. Boosting the AMPK-RIPK1 cascade by glucose deprivation, AMPK agonists, or RIPK1-S321E knockin suppresses pyroptosis, leading to increased susceptibility to Y. pseudotuberculosis infection in mice. Ablation of AMPK in macrophages or glucose supplementation in mice is protective against infection. Thus, we reveal a molecular link between glucose sensing and pyroptosis, and unveil a mechanism by which Y. pseudotuberculosis reduces glucose levels to impact host AMPK activation and limit host pyroptosis to facilitate infection., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The progression of spermatogenesis along specific developmental trajectories depends on the coordinated regulation of pre-mRNA alternative splicing (AS) at the post-transcriptional level. However, the fundamental mechanism of AS in spermatogenesis remains to be investigated. Here, it is demonstrated that CWF19L2 plays a pivotal role in spermatogenesis and male fertility. In germline conditional Cwf19l2 knockout mice exhibiting male sterility, impaired spermatogenesis characterized by increased apoptosis and decreased differentiated spermatogonia and spermatocytes is observed. That CWF19L2 interacted with several spliceosome proteins to participate in the proper assembly and stability of the spliceosome is discovered. By integrating RNA-seq and LACE-seq data, it is further confirmed CWF19L2 directly bound and regulated the splicing of genes related to spermatogenesis (Znhit1, Btrc, and Fbxw7) and RNA splicing (Rbfox1, Celf1, and Rbm10). Additionally, CWF19L2 can indirectly amplify its effect on splicing regulation through modulating RBFOX1. Collectively, this research establishes that CWF19L2 orchestrates a splicing factor network to ensure accurate pre-mRNA splicing during the early steps of spermatogenesis., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Research Question: What is the association between endometrial thickness (EMT) and the birthweight of singleton infants born from frozen-thawed embryo transfer cycles?, Design: This retrospective cohort study was conducted from January 2016 to December 2019. Participants were categorized into a natural cycle (NC, n = 8132) group and hormone replacement therapy (HRT, n = 4975) group. Only singleton deliveries were included. The primary outcomes were measures of birthweight and relevant indexes. Multivariable logistic regression and multivariable-adjusted linear regression models that incorporated restricted cubic splines were used., Results: In the HRT group, the risk of delivering a small for gestational age (SGA) infant was increased in women with an EMT <8.0 mm (adjusted odds ratio [aOR] 1.85, 95% confidence interval [CI] 1.17-2.91) compared with women with an EMT of 8.0 to <12.0 mm, and increased with an EMT ≥12.0 mm (aOR 1.85, 95% CI 1.03-3.33). An inverted U-shaped relationship was found between EMT and birthweight in women with HRT. No significant differences were shown in birthweight z-score, or being SGA or large for gestational age, in singletons among the three EMT groups in the natural cycles., Conclusions: A thinner endometrium seen in women undergoing HRT cycles was associated with a lower birthweight z-score, as well as a higher risk of SGA. However, no significant association was observed between EMT and birthweight z-score or SGA in the NC group. It is noteworthy that a thicker endometrium was not associated with a higher birthweight in frozen-thawed embryo transfer (FET) cycles. Women with a thin endometrium who achieve pregnancy require specialized attention, particularly if they are undergoing FET with HRT cycles., (Copyright © 2023 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Rationale: The mechanisms underlying major depressive disorder (MDD) in children and adolescents are unclear. Metabolomics has been utilized to capture metabolic signatures of various psychiatric disorders; however, urinary metabolic profile of MDD in children and adolescents has not been studied., Objectives: We analyzed urinary metabolites in children and adolescents with MDD to identify potential biomarkers and metabolic signatures., Methods: Here, liquid chromatography-mass spectrometry was used to profile metabolites in urine samples from 192 subjects, comprising 80 individuals with antidepressant-naïve MDD (AN-MDD), 37 with antidepressant-treated MDD (AT-MDD) and 75 healthy controls (HC). We performed orthogonal partial least squares discriminant analysis to identify differential metabolites and employed logistic regression and receiver operating characteristic analysis to establish a diagnostic panel., Results: In total, 143 and 71 differential metabolites were identified in AN-MDD and AT-MDD, respectively. These were primarily linked to lipid metabolism, molecular transport, and small molecule biochemistry. AN-MDD additionally exhibited dysregulated amino acid metabolism. Compared to HC, a diagnostic panel of seven metabolites displayed area under the receiver operating characteristic curves of 0.792 for AN-MDD, 0.828 for AT-MDD, and 0.799 for all MDD. Furthermore, the urinary metabolic profiles of children and adolescents with MDD significantly differed from those of adult MDD., Conclusions: Our research suggests dysregulated amino acid metabolism and lipid metabolism in the urine of children and adolescents with MDD, similar to results in plasma metabolomics studies. This contributes to the comprehension of mechanisms underlying children and adolescents with MDD., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Polycystic ovary syndrome (PCOS) is a complex disorder. Genome-wide association studies (GWAS) have identified several genes associated with this condition, including DENND1A. DENND1A encodes a clathrin-binding protein that functions as a guanine nucleotide exchange factor involved in vesicular transport. However, the specific role of DENND1A in reproductive hormone abnormalities and follicle development disorders in PCOS remain poorly understood. In this study, we investigated DENND1A expression in ovarian granulosa cells (GCs) from PCOS patients and its correlation with hormones. Our results revealed an upregulation of DENND1A expression in GCs from PCOS cases, which was positively correlated with testosterone levels. To further explore the functional implications of DENND1A, we generated a transgenic mouse model overexpressing Dennd1a (TG mice). These TG mice exhibited subfertility, irregular estrous cycles, and increased testosterone production following PMSG stimulation. Additionally, the TG mice displayed diminished responsiveness to FSH, characterized by smaller ovary size, less well-developed follicles, and abnormal expressions of FSH-priming genes. Mechanistically, we found that Dennd1a overexpression disrupted the intracellular trafficking of follicle stimulating hormone receptor (FSHR), promoting its internalization and inhibiting recycling. These findings shed light on the reproductive role of DENND1A and uncover the underlying mechanisms, thereby contributing valuable insights into the pathogenesis of PCOS and providing potential avenues for drug design in PCOS treatment., (© 2024. Science China Press.)

Purpose: To determine the prevalence of anxiety and depression in patients with nasopharyngeal carcinoma (NPC) and to identify central symptoms and bridge symptoms among psychiatric disorders., Methods: This cross-sectional study recruited patients with NPC in Guangzhou, China from May 2022, to October 2022. The General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were used for screening anxiety and depression, respectively. Network analysis was conducted to evaluate the centrality and connectivity of the symptoms of anxiety, depression, quality of life (QoL) and insomnia., Results: A total of 2806 respondents with complete GAD-7 and PHQ-9 scores out of 3828 were enrolled. The incidence of anxiety in the whole population was 26.5% (depression, 28.5%; either anxiety or depression, 34.8%). Anxiety was highest at caner diagnosis (34.2%), while depression reached a peak at late-stage radiotherapy (48.5%). Both moderate and severe anxiety and depression were exacerbated during radiotherapy. Coexisting anxiety and depression occurred in 58.3% of those with either anxiety or depression. The generated network showed that anxiety and depression symptoms were closely connected; insomnia was strongly connected with QoL. "Sad mood", "Lack of energy", and "Trouble relaxing" were the most important items in the network. Insomnia was the most significant bridge item that connected symptom groups., Conclusion: Patients with NPC are facing alarming disturbances of psychiatric disorders; tailored strategies should be implemented for high-risk patients. Besides, central symptoms (sad mood, lack of energy, and trouble relaxing) and bridge symptoms (insomnia) may be potential interventional targets in future clinical practice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

A series of acylhydrazone-based N,N -chelate half-sandwich iridium complexes have been synthesized through a facile route in good yields. The dehydrogenation of a series of aromatic and aliphatic primary alcohols to corresponding carboxylic acids has been accomplished catalyzed by the prepared air stable iridium complexes under mild reaction conditions. Carboxylic acids were obtained in high yields under open flask condition with broad substrates and good tolerance to sensitive functional groups. Such a half-sandwich iridium catalyst system exhibited high catalytic activity and stability, and a high TOF of 316.7 h -1 could be achieved with a catalyst loading as low as 0.05 mol %. Furthermore, the sustainable catalyst could be reused at least five times without obviously losing its activity, highlighting its potential application in industry. Molecular structure of iridium complex 1 was confirmed by single-crystal X-ray analysis.

This work reports the use of defect engineering and carbon supporting to achieve metal-doped phosphides with high activities and stabilities for the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER) in alkaline media. Specifically, the nitrogen-doped carbon nanofiber-supported Ni-doped CoP 3 with rich P defects (Pv·) on the carbon cloth (p-NiCoP/NCFs@CC) is synthesized through a plasma-assisted phosphorization method. The p-NiCoP/NCFs@CC is an efficient and stable catalyst for the HER and the OER. It only needs overpotentials of 107 and 306 mV to drive 100 mA cm -2 for the HER and the OER, respectively. Its catalytic activities are higher than those of other catalysts reported recently. The high activities of the p-NiCoP/NCFs@CC mainly arise from its peculiar structural features. The density functional theory calculation indicates that the Pv· richness, the Ni doping, and the carbon supporting can optimize the adsorption of the H atoms at the catalyst surface and promote the strong electronic couplings between the carbon nanofiber-supported p-NiCoP with the surface oxide layer formed during the OER process. This gives the p-NiCoP/NCFs@CC with the high activities for the HER and the OER. When used in alkaline water electrolyzers, the p-NiCoP/NCFs@CC shows the superior activity and excellent stability for overall water splitting., (© 2024. The Author(s).)

Papillary adenoma of the lung, a rare and benign tumor, is easily confused with other primary benign or malignant lung tumors and especially with lung adenocarcinoma that has a papillary growth pattern. Enhanced understanding and an accurate diagnosis of papillary adenomas of the lung are crucial for clinical treatment and prognostic assessment. A 61-year-old man who presented with an opportunistic finding in relation to a left lower lobe lung nodule during an examination was admitted to The First Hospital of China Medical University (Shenyang, China) for further treatment. Computed tomography (CT) revealed a well-circumscribed left lower lobe nodule (diameter, ~1 cm), comprising branched papillae with a fibrovascular core and no other structural components. The tumor cells appeared relatively uniform in shape and well arranged with round or oval nuclei. No nucleoli or mitotic figures were observed. Immunohistochemically, the papillary structures of the tumor cells were strongly and diffusely positive for cytokeratin (CK), CK7, Napsin-A and thyroid transcription factor 1. The Ki-67 index was ~1%. A pathological diagnosis of primary papillary adenoma of the lung was made based on these findings. A left lower-lobe wedge resection was performed and the patient's postoperative course was uneventful. Surgical resection is the preferred treatment. Papillary adenoma of the lung is very rare, and its clinical manifestations and CT images are non-specific. It is important to avoid misdiagnosing of papillary adenoma of the lung as another type of lung tumor, especially adenocarcinoma. A clear understanding of the morphological and immunohistochemical features of papillary adenomas is important for the diagnosis of this rare lung tumor., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Chen et al.)

Risk prediction for subsequent cardiovascular events remains an unmet clinical issue in patients with coronary artery disease. We aimed to investigate prognostic metabolic biomarkers by considering both shared and distinct metabolic disturbance associated with the composite and individual cardiovascular events. Here, we conducted an untargeted metabolomics analysis for 333 incident cardiovascular events and 333 matched controls. The cardiovascular events were designated as cardiovascular death, myocardial infarction/stroke and heart failure. A total of 23 shared differential metabolites were associated with the composite of cardiovascular events. The majority were middle and long chain acylcarnitines. Distinct metabolic patterns for individual events were revealed, and glycerophospholipids alteration was specific to heart failure. Notably, the addition of metabolites to clinical markers significantly improved heart failure risk prediction. This study highlights the potential significance of plasma metabolites on tailed risk assessment of cardiovascular events, and strengthens the understanding of the heterogenic mechanisms across different events., (© 2024. The Author(s).)

Out-of-plane polarization is a highly desired property of two-dimensional (2D) ferroelectrics for application in vertical sandwich-type photoferroelectric devices, especially in ultrathin ferroelectronic devices. Nevertheless, despite great advances that have been made in recent years, out-of-plane polarization remains unrealized in the 2D hybrid double perovskite ferroelectric family. Here, from our previous work 2D hybrid double perovskite HQERN ((S3HQ) 4 EuRb(NO 3 ) 8 , S3HQ=S-3-hydroxylquinuclidinium), we designed a molecular strategy of F-substitution on organic component to successfully obtain FQERN ((S3FQ) 4 EuRb(NO 3 ) 8 , S3FQ=S-3-fluoroquinuclidinium) showing circularly polarized luminescence (CPL) response. Remarkably, compared to the monopolar axis ferroelectric HQERN, FQERN not only shows multiferroicity with the coexistence of multipolar axis ferroelectricity and ferroelasticity but also realizes out-of-plane ferroelectric polarization and a dramatic enhancement of Curie temperature of 94 K. This is mainly due to the introduction of F-substituted organic cations, which leads to a change in orientation and a reduction in crystal lattice void occupancy. Our study demonstrates that F-substitution is an efficient strategy to realize and optimize ferroelectric functional characteristics, giving more possibility of 2D ferroelectric materials for applications in micro-nano optoelectronic devices., (© 2024 Wiley-VCH GmbH.)

Oocyte in vitro maturation is a technique in assisted reproductive technology. Thousands of genes show abnormally high expression in in vitro maturated metaphase II (MII) oocytes compared to those matured in vivo in bovines, mice, and humans. The mechanisms underlying this phenomenon are poorly understood. Here, we use poly(A) inclusive RNA isoform sequencing (PAIso-seq) for profiling the transcriptome-wide poly(A) tails in both in vivo and in vitro matured mouse and human oocytes. Our results demonstrate that the observed increase in maternal mRNA abundance is caused by impaired deadenylation in in vitro MII oocytes. Moreover, the cytoplasmic polyadenylation of dormant Btg4 and Cnot7 mRNAs, which encode key components of deadenylation machinery, is impaired in in vitro MII oocytes, contributing to reduced translation of these deadenylase machinery components and subsequently impaired global maternal mRNA deadenylation. Our findings highlight impaired maternal mRNA deadenylation as a distinct molecular defect in in vitro MII oocytes., (© 2024. The Author(s).)

Metal-organic frameworks (MOFs) that exhibit dynamic phase-transition behavior under external stimuli could have great potential in adsorptive separations. Here we report on a zinc-based microporous MOF (JNU-80) and its reversible transformation between two crystalline phases: large pore (JNU-80-LP) and narrow pore (JNU-80-NP). Specifically, JNU-80-LP can undergo a dehydration-induced cluster consolidation under heat treatment, resulting in JNU-80-NP with a reduced channel that allows exclusion of di-branched hexane isomers while high adsorption of linear and mono-branched hexane isomers. We further demonstrate the fabrication of MOF-polymer composite (JNU-80-NP-block) and its application in the purification of di-branched isomers from liquid-phase hexane mixtures (98 % di-branched) at room temperature, affording the di-branched hexane isomers with 99.5 % purity and close to 90 % recovery rate over ten cycles. This work illustrates an interesting dehydration-induced cluster consolidation in MOF structure and the ensuing channel shrinkage for sieving di-branched hexane isomers, which may have important implications for the development of MOFs with dynamic behavior and their potential applications in non-thermal driven separation technologies., (© 2024 Wiley-VCH GmbH.)

A new alkaloid, neohelicomyine A ( 1 ), along with two known alkaloids ( 2 - 3 ), were isolated from the fermentation of Neohelicomyces hyalosporus PF11-1. The structures of these compounds were elucidated by extensive analyses of spectroscopic methods including 1 D and 2 D NMR, HRESIMS and ECD. The bioactivities of all compounds were evaluated using cellular assays, and compounds 2 and 3 displayed moderate cytotoxicities against human cancer (A549, TCA, RD) cells with IC 50 values of 26-87 μg/mL.

MCM8 has emerged as a core gene in reproductive aging and is crucial for meiotic homologous recombination repair. It also safeguards genome stability by coordinating the replication stress response during mitosis, but its function in mitotic germ cells remains elusive. Here we found that disabling MCM8 in mice resulted in proliferation defects of primordial germ cells (PGCs) and ultimately impaired fertility. We further demonstrated that MCM8 interacted with two known helicases DDX5 and DHX9, and loss of MCM8 led to R-loop accumulation by reducing the retention of these helicases at R-loops, thus inducing genome instability. Cells expressing premature ovarian insufficiency-causative mutants of MCM8 with decreased interaction with DDX5 displayed increased R-loop levels. These results show MCM8 interacts with R-loop-resolving factors to prevent R-loop-induced DNA damage, which may contribute to the maintenance of genome integrity of PGCs and reproductive reserve establishment. Our findings thus reveal an essential role for MCM8 in PGC development and improve our understanding of reproductive aging caused by genome instability in mitotic germ cells., (© 2024. The Author(s).)

Objective: To investigate variations in pregnancy outcomes between preimplantation genetic testing for aneuploidy (PGT-A) and conventional in vitro fertilization and embryo transfer (IVF-ET) treatment across distinct groups categorized by oocyte and blastocyst counts. Because the live birth rate (LBR) of assisted reproductive technology treatment is influenced by the number of oocytes and blastocysts retrieved. Our previous study indicated comparable cumulative LBRs (CLBRs) between conventional IVF-ET and PGT-A., Design: A post hoc exploratory secondary analysis of data from a multicenter randomized controlled trial compared the CLBRs between conventional IVF-ET and PGT-A., Setting: Academic fertility centers., Subjects: A total of 1,212 infertile women with a good prognosis for a live birth after PGT-A or conventional IVF-ET were included., Intervention: Women underwent PGT-A or conventional IVF-ET., Main Outcome Measure(s): Cumulative LBR, cumulative clinical pregnancy loss (CPL) rate, and good birth outcome., Result(s): In the study, all participants were divided into 4 groups on the basis of quartiles of the number of oocytes retrieved, or blastocysts. There was an interaction between whether to perform PGT-A and the oocyte numbers category on cumulative CPL and biochemical pregnancy loss. Chi-square analysis revealed that the PGT-A group showed a lower cumulative frequency of CPL compared with the IVF-ET group (PGT-A vs. IVF-ET: 5.9% vs. 13.7%; relative risk = 0.430; 95% confidence interval, 0.243-0.763) when the number of oocytes retrieved was <15. Although there was no interaction on CLBR when the retrieved oocyte count ranged from 19-23 (19≤ oocytes <23) the PGT-A group exhibited a lower CLBR than the conventional IVF-ET group (PGT-A vs IVF-ET: 75.6% vs 87.1%; relative risk = 0.868; 95% confidence interval, 0.774-0.973), and the average body weight of newborns from the PGT-A group was approximately 142 g lower than that of the conventional IVF-ET group (PGT-A vs. IVF-ET: 3,334 ± 479 g vs. 3,476 ± 473 g). However, no statistically significant difference in the CLBR was observed between the PGT-A and IVF-ET groups in the other oocyte or blastocyst groups., Conclusion: When the number of retrieved eggs was <15, the PGT-A group exhibited a lower cumulative CPL rate but no higher CLBR than the conventional IVF-ET group., Clinical Trial Registration Number: NCT03118141., Competing Interests: Declaration of Interests M.H. has nothing to disclose. M.L. has nothing to disclose. S.T. has nothing to disclose. L.G. has nothing to disclose. Z.Z. has nothing to disclose. Z-J.C. has nothing to disclose. Y.L. has nothing to disclose., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

This work utilizes defect engineering, heterostructure, pyridine N-doping, and carbon supporting to enhance cobalt-nickel selenide microspheres' performance in the oxygen electrode reaction. Specifically, microspheres mainly composed of CoNiSe 2 and Co 9 Se 8 heterojunction rich in selenium vacancies (V Se· ) wrapped with nitrogen-doped carbon nanotubes (p-CoNiSe/NCNT@CC) are prepared by Ar/NH 3 radio frequency plasma etching technique. The synthesized p-CoNiSe/NCNT@CC shows high oxygen reduction reaction (ORR) performance (half-wave potential (E 1/2 ) = 0.878 V and limiting current density (J L ) = 21.88 mA cm -2 ). The J L exceeds the 20 wt% Pt/C (19.34 mA cm -2 ) and the E 1/2 is close to the 20 wt% Pt/C (0.881 V). It also possesses excellent oxygen evolution reaction (OER) performance (overpotential of 324 mV@10 mA cm -2 ), which even exceeds that of the commercial RuO 2 (427 mV@10 mA cm -2 ). The density functional theory calculation indicates that the enhancement of ORR performance is attributed to the synergistic effect of plasma-induced V Se· and the CoNiSe 2 -Co 9 Se 8 heterojunction. The p-CoNiSe/NCNT@CC electrode assembled Zinc-air batteries (ZABs) show a peak power density of 138.29 mW cm -2 , outperforming the 20 wt% Pt/C+RuO 2 (73.9 mW cm -2 ) and other recently reported catalysts. Furthermore, all-solid-state ZAB delivers a high peak power density of 64.83 mW cm -2 and ultra-robust cycling stability even under bending., (© 2024 Wiley‐VCH GmbH.)

Kinases, a class of enzymes controlling various substrates phosphorylation, are pivotal in both physiological and pathological processes. Although their conserved ATP binding pockets pose challenges for achieving selectivity, this feature offers opportunities for drug repositioning of kinase inhibitors (KIs). This study presents a cost-effective in silico prediction of KIs drug repositioning via analyzing cross-docking results. We established the KIs database (278 unique KIs, 1834 bioactivity data points) and kinases database (357 kinase structures categorized by the DFG motif) for carrying out cross-docking. Comparative analysis of the docking scores and reported experimental bioactivity revealed that the Atypical, TK, and TKL superfamilies are suitable for drug repositioning. Among these kinase superfamilies, Olverematinib, Lapatinib, and Abemaciclib displayed enzymatic activity in our focused AKT-PI3K-mTOR pathway with IC 50 values of 3.3, 3.2 and 5.8 μM. Further cell assays showed IC 50 values of 0.2, 1.2 and 0.6 μM in tumor cells. The consistent result between prediction and validation demonstrated that repositioning KIs via in silico method is feasible., (© 2024 Wiley-VCH GmbH.)

Aromatic sulfones are the prevailing scaffolds in pharmaceutical and material sciences. However, compared to their widespread application, the selective deuterium labeling of these structures is restricted due to their electron-deficient properties. This study presents two comprehensive strategies for the deuteration of aromatic sulfones. The base-promoted deuteration uses DMSO- d 6 as the deuterium source, resulting in a rapid H/D exchange within 2 h. Meanwhile, a silver-catalyzed protocol offers a much milder option by using economical D 2 O to furnish the labeled sulfones.

An efficient method has been developed for the synthesis of α-deuterated α-amino esters via hydrogen isotope exchange of α-amino esters in D 2 O with 2-hydroxynicotinaldehyde as a catalyst under mild conditions. This methodology exhibits a wide range of substrate scopes, remarkable functional group tolerance, and affording the desired products in good yields with excellent deuterium incorporation. Notably, the ortho-hydroxyl group and the pyridine ring of the catalyst play a crucial role in the catalytic activity, which not only stabilizes the carbon-anion intermediates but also enhances the acidity of the amino esters' α-C-H bond., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: Frozen embryo transfer (FET) has become a widely employed assisted reproductive technology technique. There have historically been concerns regarding the long-term metabolic safety of FET technology in offspring due to pregnancy-induced hypertension and large for gestational age, both of which are well-recognized factors for metabolic dysfunction of children. Therefore, we aimed to compare the metabolic profiles of children born after frozen versus fresh embryo transfer at 2 to 5 years of age., Methods and Findings: This was a prospective cohort study. Using data from the "Assisted Reproductive Technology borned KIDs (ARTKID)," a birth cohort of offspring born from assisted reproductive technology at the Institute of Women, Children and Reproductive Health, Shandong University, China. We included 4,246 singletons born after FET (n = 2,181) and fresh embryo transfer (n = 2,065) enrolled between 2008 and 2019 and assessed the glucose and lipid variables until the age of 2 to 5 years. During a mean follow-up of 3.6 years, no significant differences were observed in fasting blood glucose, fasting insulin, Homeostatic Model Assessment of Insulin Resistance Index, total cholesterol, triglycerides, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol levels between offspring conceived by fresh and frozen embryo transfer in the crude model and adjusted model (adjusted for parental age, parental body mass index, parental education level, paternal smoking, parity, offspring age and sex). These results remained consistent across subgroup analyses considering offspring age, the stage of embryo transfer, and the mode of fertilization. Results from sensitivity analysis on children matched for age within the cohort remains the same. The main limitation of our study is the young age of the offspring., Conclusions: In this study, the impact of FET on glucose and lipid profiles during early childhood was comparable to fresh embryo transfer. Long-term studies are needed to evaluate the metabolic health of offspring born after FET., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4 (SMARCA4)-deficient tumors are rare and highly aggressive tumors characterized by a loss of SMARCA4 expression, and SMARCA4-deficient tumors in the adnexal area of the uterus are particularly rare. The present study describes the case of a 64-year-old woman who was admitted to Weifang People's Hospital (Weifang, China) with abdominal distension, and was observed to have a mass with ascites in the adnexal area of the uterus. Based on clinical, imaging and pathological findings, the patient was diagnosed with a SMARCA4-deficient adnexal tumor with ascites. Biopsy of the left and right adnexal lesions was performed, and the patient was administered chemotherapy. After one cycle of bevacizumab, sindilizumab and carboplatin, no further treatment was administered. After biopsy and chemotherapy, the abdominal distension was alleviated and the general condition of the patient was satisfactory. The patient was followed up and died 3 months after treatment. Notably, it is important to avoid misdiagnosing this tumor as other types of adnexal uterine tumors, and morphological and immunohistochemical features may be useful for diagnosing primary SMARCA4-deficient tumors in the adnexal area of the uterus., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Li et al.)

Accurate and rapid evaluation of density is crucial for evaluating the packing and combustion characteristics of high-energy-density fuels (HEDFs). This parameter is pivotal in the selection of high-performance HEDFs. Our study leveraged a polycyclic compound density data set and quantum chemical (QC) descriptors to establish a correlation with the target properties using the XGBoost algorithm. We utilized a recursive feature elimination method to simplify the model and developed a concise and interpretable density prediction model incorporating only six QC descriptors. The model demonstrated robust performance, achieving coefficients of determination ( R 2 ) of 0.967 and 0.971 for internal and external test sets, respectively, and root-mean-square errors (RMSE) of 0.031 and 0.027 g/cm 3 , respectively. Compared to the other two mainstream methods, the marginal discrepancy between the predicted and actual molecular densities underscores the model's superior predictive ability and more usefulness for energy density calculation. Furthermore, we developed a web server (SesquiterPre, https://sespre.cmdrg.com/#/) that can simultaneously calculate the density, enthalpy of combustion, and energy density of sesquiterpenoid HEDFs, which greatly facilitates the use of researchers and is of great significance for accelerating the design and screening of novel sesquiterpenoid HEDFs., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

The optimization of metal-support interactions is used to fabricate noble metal-based nanoclusters with high activity for hydrogen evolution reaction (HER) in acid media. Specifically, the oxygen-defective Mn 3 O 4 nanosheets supported Pt nanoclusters of ≈1.71 nm in diameter (Pt/V·-Mn 3 O 4 NSs) are synthesized through the controlled solvothermal reaction. The Pt/V·-Mn 3 O 4 NSs show a superior activity and excellent stability for the HER in the acidic media. They only require an overpotential of 19 mV to drive -10 mA cm -2 and show negligible activity loss at -10 and -250 mA cm -2 for >200 and >60 h, respectively. Their Pt mass activity is 12.4 times higher than that of the Pt/C and even higher than those of many single-atom based Pt catalysts. DFT calculations show that their high HER activity arises mainly from the strong metal-support interaction between Pt and Mn 3 O 4 . It can facilitate the charge transfer from Mn 3 O 4 to Pt, optimizing the H adsorption on the catalyst surface and promoting the evolution of H 2 through the Volmer-Tafel mechanism. The oxygen vacancies in the V·-Mn 3 O 4 NSs are found to be inconducive to the high activity of the Pt/V·-Mn 3 O 4 NSs, highlighting the great importance to reduce the vacancy levels in V·-Mn 3 O 4 NSs., (© 2024 Wiley‐VCH GmbH.)

Objective: To provide comprehensive evidence for the anti-cancer cachexia effect of Jianpi Decoction (JP) and to explore its mechanism of anti-cancer cachexia., Methods: A mouse model of colon cancer (CT26)-induced cancer cachexia (CC) was used to investigate the anti-CC effect of JP combined with medroxyprogesterone acetate (MPA). Thirty-six mice were equally divided into 6 groups: normal control, CC, MPA (100 mg•kg -1 •d -1 ), MPA + low-dose (20 mg•kg -1 •d -1 ) JP (L-JP), MPA + medium-dose (30 mg•kg -1 •d -1 ) JP (M-JP), and MPA + high-dose (40 mg•kg -1 •d -1 ) JP (H-JP) groups. After successful modeling, the mice were administered by gavage for 11 d. The body weight and tumor volume were measured and recorded every 2 d starting on the 8th day after implantation. The liver, heart, spleen, lung, kidney, tumor and gastrocnemius muscle of mice were collected and weighed. The pathological changes of the tumor was observed, and the cross-sectional area of the gastrocnemius muscle was calculated. The protein expressions of STAT3 and E3 ubiquitinase in the gastrocnemius muscle were measured by Western blot. In addition, an in vitro C2C12 myotube formation model was established to investigate the role of JP in hindering dexamethasone-induced muscle atrophy. In vitro experiments were divided into control, model, and JP serum groups. After 2-d administration, microscopic photographs were taken and myotube diameters were calculated. Western blot was performed to measure the protein expressions of STAT3 and E3 ubiquitinase., Results: JP combined with MPA restored tumor-induced weight loss (P<0.05, vs. CC) and muscle fiber size (P<0.01, vs. CC). Mechanistically, JP reduced the expression of atrophy-related proteins MuRF1 and MAFbx in tumor-induced muscle atrophy in vivo (P<0.05, vs. CC). In addition, JP reduced the expression of atrophy-related proteins MuRF1 and MAFbx and p-STAT3 phosphorylation (P<0.05 or P<0.01 vs. model group) in C2C12 myotubes treated with dexamethasone in vitro., Conclusions: Administration of JP combined with MPA restores tumor-induced cachexia conditions. In addition, the profound effect of JP combined with MPA on tumor-induced cachexia may be due to its inhibition of muscle proteolysis (E3 ubiquitinase system)., (© 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The systemic immune-inflammation index (SII) showed an extensive link between immunological dysfunction and the activation of systemic inflammation. Several studies have confirmed the application of SII to orthopedic diseases. However, the significance of SII in critically ill elderly individuals with hip fracture who require intensive care unit (ICU) admission is not yet known. This study centered on exploring the relationship between SII and clinical outcomes among critically ill elderly hip fracture individuals., Methods: The study centered around elderly patients experiencing severe illness following hip fractures and requiring admission to the ICU. These patients from the MIMIC-IV database formed the basis of this study's cohort. We stratified them into quartiles according to their SII levels. The results involved the mortality at 30 days and 1 year post-admission. Then we employ Cox proportional hazards regression analysis as well as restricted cubic splines to explore the association between the SII and clinical results in critically ill elderly patients with hip fracture., Results: The study encompassed 991 participants, among whom 63.98% identified as females. Notably, the mortality rates attributed to any cause within 30 days and 1 year after hospitalization stood at 19.68 and 33.40%, respectively. The multivariate Cox proportional hazards model disclosed a significant correlation between an elevated SII and all-cause mortality. Following adjustments for confounding variables, individuals with a high SII showed a notable correlation with 30-day mortality [adjusted hazard ratio (HR), 1.065; 95% confidence interval (CI), 1.044-1.087; p  < 0.001] and 1-year mortality (adjusted HR, 1.051; 95% CI, 1.029-1.074; p  < 0.001). Furthermore, the analysis of restricted cubic splines demonstrated a progressive increase in the risk of all-cause death as the SII value rose., Conclusion: Among critically ill elderly patients with hip fracture, the SII exhibits a non-linear association that positively correlates with both 30-day and 1-year all-cause mortality rates. The revelation indicates that the SII may play a vital role in identifying patients with hip fractures who face an escalated risk of mortality due to any cause., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Li, Wang, Mo, Yang, Shen and Shen.)

Context: Embryo biopsy, which is necessary for preimplantation genetic testing (PGT), has not been fully investigated regarding its potential influences and safety. Previous studies of children born from biopsied embryos (PGT children) have primarily centered around their growth and neuropsychological development, while there remains limited knowledge concerning their endocrine and metabolic parameters., Objective: This study aims to examine the effect of trophectoderm (TE) biopsy on metabolic outcomes for PGT children., Methods: A total of 1267 children from the Center for Reproductive Medicine, Shandong University, who were conceived through in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) with and without PGT, were analyzed in this study. Three sets of measurements pertaining to growth and metabolism were taken at each predetermined follow-up time point. The linear regression models within a generalized estimating equation were employed to examine the associations between the PGT and each outcome measure and the approach of false discovery rate was used to correct for multiple comparisons., Results: After controlling for confounding factors and correcting for multiple comparisons, no statistically significant difference was identified in any of the measured variables between the PGT children and children conceived by IVF alone (IVF children) and children conceived through IVF using ICSI (ICSI children). The same is true also for age- or sex-based subgroup analyses., Conclusion: Between the ages of 1 and 5 years, there are no clinically adverse metabolic outcomes observed in PGT children, and their metabolic profiles are essentially identical to those of IVF children and ICSI children., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Accumulation of aggregated α-synuclein (α-syn) in Lewy bodies is the pathological hallmark of Parkinson's disease (PD). Genetic mutations in lipid metabolism are causative for a subset of patients with Parkinsonism. The role of α-syn's lipid interactions in its function and aggregation is recognized, yet the specific lipids involved and how lipid metabolism issues trigger α-syn aggregation and neurodegeneration remain unclear. Here, we found that α-syn shows a preference for binding to lysophospholipids (LPLs), particularly targeting lysophosphatidylcholine (LPC) without relying on electrostatic interactions. LPC is capable of maintaining α-syn in a compact conformation, significantly reducing its propensity to aggregate both in vitro and within cellular environments. Conversely, a reduction in the production of cellular LPLs is associated with an increase in α-syn accumulation. Our work underscores the critical role of LPLs in preserving the natural conformation of α-syn to inhibit improper aggregation, and establishes a potential connection between lipid metabolic dysfunction and α-syn aggregation in PD., (© The Author(s) 2024. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

By using cyclic (vinyl triflate)iodonium salts, a novel triple Suzuki-Miyaura reaction was accomplished for the synthesis of polyaromatic ethylene derivatives in the presence of palladium catalysts. The reaction exhibits extensive compatibility with a wide range of readily available arylboronic acids, giving triaryl-substituted ethylenes in good yields.

Background: To the best of our knowledge, no study has investigated the potential joint effect of large for gestational age (LGA) and assisted reproductive technology (ART) on the long-term health of children., Methods: This was a prospective cohort study that recruited children whose parents had received ART treatment in the Center for Reproductive Medicine, Shandong Provincial Hospital, affiliated to Shandong University, between January 2006 and December 2017. Linear mixed model was used to compare the main outcomes. The mediation model was used to evaluate the intermediary effect of body mass index (BMI)., Results: 4138 (29.5%) children born LGA and 9910 (70.5%) children born appropriate for gestational age (AGA) were included in the present study. The offspring ranged from 0.4 to 9.9 years. LGAs conceived through ART were shown to have higher BMI, blood pressure, fasting blood glucose, fasting insulin, and homeostatic model assessment of insulin resistance values, even after controlling for all covariates. The odds of overweight and insulin resistance are also higher in LGA subjects. After adjusting for all covariates, LGAs conceived through ART had BMI and BMI z-scores that were 0.48 kg/m 2 and 0.34 units greater than those of AGAs, respectively. The effect of LGA on BMI was identified as early as infancy and remained consistently significant throughout pre-puberty., Conclusions: Compared to AGA, LGA children conceived from ART were associated with increased cardiovascular-metabolic events, which appeared as early as infancy and with no recovery by pre-puberty., (© 2024. The Author(s).)

Environmental pollution caused by persistent organic pollutants has imposed big threats to the health of human and ecological systems. The development of efficient methods to effectively degrade and remove these persistent organic pollutants is therefore of paramount importance. Photocatalytic persulfate-based advanced oxidation technologies (PS-AOTs), which depend on the highly reactive SO 4 - radicals generated by the activation of PS to degrade persistent organic pollutants, have shown great promise. This work discusses the application and modification strategies of common photocatalysts in photocatalytic PS-AOTs, and compares the degradation performance of different catalysts for pollutants. Furthermore, essential elements impacting photocatalytic PS-AOTs are discussed, including the water matrix, reaction process mechanism, pollutant degradation pathway, singlet oxygen generation, and potential PS hazards. Finally, the existing issues and future challenges of photocatalytic PS-AOTs are summarized and prospected to encourage their practical application. In particular, by providing new insights into the PS-AOTs, this review sheds light on the opportunities and challenges for the development of photocatalysts with advanced features for the PS-AOTs, which will be of great interests to promote better fundamental understanding of the PS-AOTs and their practical applications., (© 2024 Wiley-VCH GmbH.)

Taking a city in Guangdong Province as the research area, the concentration and spatial distribution characteristics of heavy metals in the surface soil were studied to clarify the situation of soil heavy metal pollution and priority control factors, providing basic data for the prevention and control of soil heavy metal pollution in the city. The content characteristics of heavy metals in 221 soil samples in the city were analyzed, and the potential health risk assessment and source analysis were carried out through the Monte Carlo model, the potential health risk assessment (HRA) model, and the PMF receptor model. It was found that heavy metals ω (As), ω (Hg), ω (Cd), ω (Pb), ω (Cr), ω (Cu), ω (Ni), and ω (Zn) in the soil of the city were 18.16, 0.43, 1.46, 68.57, 98.34, 64.19, 26.53, and 257.32 mg·kg -1 , respectively, with a moderate to high degree of variation. Except for Ni concentration, the soil concentrations of other heavy metal elements exceeded the background values of soil in Guangdong Province to a certain extent, and the concentrations of Cd and Zn exceeded the national secondary standards, resulting in severe heavy metal pollution; the main sources of heavy metals were industrial sources, and natural parent materials, lead battery manufacturing, transportation, artificial cultivation, and pesticide and fertilizer inputs also had an undeniable impact on the accumulation of heavy metals in the soil. Heavy metals in the soil had a certain degree of tolerable carcinogenic health risk for both children and adults, whereas non-carcinogenic risks could be ignored. The potential health risk of children was greater than that of adults, and the main exposure route was through oral intake. The input sources of pesticides and fertilizers and As should be the main controlling factors for the health risks of heavy metals in the city's soil, followed by mixed sources and Cr. There were differences in the spatial distribution characteristics and relative pollution levels of heavy metals, and it is necessary to deepen zoning monitoring and control, strengthen soil pollution prevention and control, and reduce human input of heavy metals in soil.

Background: A referenced MRI-based classification associated with focused ultrasound ablation surgery (FUAS) outcomes is lacking in adenomyosis., Purpose: To identify an MRI-based classification system for informing the FUAS outcomes., Study Type: Retrospective., Population: Patients with FUAS for adenomyosis, were divided into a training set (N = 643; 355 with post-FUAS gonadotropin-releasing hormone/levonorgestrel, 288 without post-FUAS therapy) and an external validation set (N = 135; all without post-FUAS therapy)., Field Strength/sequence: 1.5 T, turbo spin-echo T2-weighted imaging and single-shot echo-planar diffusion-weighted imaging sequences., Assessment: Five MRI-based adenomyosis classifications: classification 1 (C1) (diffuse, focal, and mild), C2 (intrinsic, extrinsic, intramural, and indeterminate), C3 (internal, adenomyomas, and external), C4 (six subtypes on areas [internal or external] and volumes [<1/3 or ≥2/3]), and C5 (internal [asymmetric or symmetric], external, intramural, full thickness [asymmetric or symmetric]) for FUAS outcomes (symptom relief and recurrence)., Statistical Tests: The optimal classification was significantly associated with the most subtypes of FUAS outcomes. Relating to the timing of recurrence was measured using Cox regression analysis and median recurrence time was estimated by a Kaplan-Meier curve. A P value <0.05 was considered statistically significant., Results: Dysmenorrhea relief and recurrence were only associated with C2 in training patients undergoing FUAS alone. Compared with other subtypes, the extrinsic subtype of C2 was significantly associated with dysmenorrhea recurrence in the FUAS group. Besides, the median dysmenorrhea recurrence time of extrinsic subtype was significantly shorter than that of other subtypes (42.0 months vs. 50.3 months). In the validation cohort, C2 was confirmed as the optimal system and its extrinsic subtype was confirmed to have a significantly shorter dysmenorrhea recurrence time than other subtypes., Data Conclusion: Classification 2 can inform dysmenorrhea relief and recurrence in patients with adenomyosis undergoing FAUS only. Itsextrinsic subtype was associated with an earlier onset of dysmenorrhea recurrence after treatment., Evidence Level: 3 TECHNICAL EFFICACY: Stage 5., (© 2023 International Society for Magnetic Resonance in Medicine.)

Floral patterns are unique to rice and contribute significantly to its reproductive success. SL1 encodes a C2H2 transcription factor that plays a critical role in flower development in rice, but the molecular mechanism regulated by it remains poorly understood. Here, we describe interactions of the SL1 with floral homeotic genes, SPW1, and DL in specifying floral organ identities and floral meristem fate. First, the sl1 spw1 double mutant exhibited a stamen-to-pistil transition similar to that of sl1, spw1, suggesting that SL1 and SPW1 may located in the same pathway regulating stamen development. Expression analysis revealed that SL1 is located upstream of SPW1 to maintain its high level of expression and that SPW1, in turn, activates the B-class genes OsMADS2 and OsMADS4 to suppress DL expression indirectly. Secondly, sl1 dl displayed a severe loss of floral meristem determinacy and produced amorphous tissues in the third/fourth whorl. Expression analysis revealed that the meristem identity gene OSH1 was ectopically expressed in sl1 dl in the fourth whorl, suggesting that SL1 and DL synergistically terminate the floral meristem fate. Another meristem identity gene, FON1, was significantly decreased in expression in sl1 background mutants, suggesting that SL1 may directly activate its expression to regulate floral meristem fate. Finally, molecular evidence supported the direct genomic binding of SL1 to SPW1 and FON1 and the subsequent activation of their expression. In conclusion, we present a model to illustrate the roles of SL1, SPW1, and DL in floral organ specification and regulation of floral meristem fate in rice., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.)