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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.)

Nanocomposite represents the backbone of many industrial fabrication applications and exerts a substantial social impact. Among these composites, metal nanostructures are often employed as the active constituents, thanks to their various chemical and physical properties, which offer the ability to tune the application scenarios in thermal management, energy storage, and biostable materials, respectively. Nanocellulose, as an emerging polymer substrate, possesses unique properties of abundance, mechanical flexibility, environmental friendliness, and biocompatibility. Based on the combination of flexible nanocellulose with specific metal fillers, the essential parameters involving mechanical strength, flexibility, anisotropic thermal resistance, and conductivity can be enhanced. Nowadays, the approach has found extensive applications in thermal management, energy storage, biostable electronic materials, and piezoelectric devices. Therefore, it is essential to thoroughly correlate cellulose nanocomposites' properties with different metallic fillers. This review summarizes the extraction of nanocellulose and preparation of metal modified cellulose nanocomposites, including their wide and particular applications in modern advanced devices. Moreover, we also discuss the challenges in the synthesis, the emerging designs, and unique structures, promising directions for future research. We wish this review can give a valuable overview of the unique combination and inspire the research directions of the multifunctional nanocomposites using proper cellulose and metallic fillers., (© 2024 Wiley-VCH GmbH.)

Background and objective: Cognitive-behavioral therapy (CBT) for somatoform disorders (SFDs) is understudied in China. Western findings may not be applicable to Chinese culture. This preliminary study evaluated the efficacy of CBT for patients in China, relative to treatment-as-usual (TAU). Methods: Seventy patients with SFDs randomly received either combined CBT and TAU (CBT + TAU), or TAU alone between January 2018 to May 2019. The CBT + TAU group received 12 weekly individual 50-minute CBT sessions. Participants were blindly assessed at 4 timepoints (baseline, week 6, end of treatment: week 12; 12 weeks post-treatment: week 24) using the following outcome measures: SQSS (Self-screening Questionnaire for Somatic Symptoms); PHQ-15 (Patient-Health-Questionnaire-15) and the WI (Whiteley Index); GAD-7 (General Anxiety Disorder-7); HAMD-17 (Hamilton Depression Rating Scale-17); Family Burden Interview Schedule (FBIS); Sheehan Disability Scale (SDS); and the Short Form of Quality-of-Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF). The primary endpoint was the difference between the SQSS total score at week 24 and the baseline. A mixed model for repeated measures was used to analyze inter- and intra-group changes from the baseline. Results: At week 24, The least-squares mean (LSM) change of the total score on the SQSS was -18.87 points and -9.69 points, respectively in the CBT + TAU group and in the TAU group (LSM difference, -9.18 points; 95% confidence interval, -15.72 to -2.64; P  = 0.0068). At week 24, the LSM changes from baseline in the WI, HAMD, PHQ15, FBIS and SDS total scores were significantly different between the two groups, however, there was no significant difference in the Q-LES-Q-SF. The SQSS of group effect sizes were 0.63 at 24 weeks. The dropout rates of the CBT + TAU and TAU groups were comparable (22.9% and 19.3%). Conclusions: These preliminary findings suggest that CBT may be helpful for improving the symptoms of patients with SFDs in China.

Four new drimane-type sesquiterpenoids and two new nucleoside derivatives (1-6), were isolated from the fungus Helicoma septoconstrictum. Their structures were determined based on the combination of the analysis of their HR-ESI-MS, NMR, ECD calculations data and acid hydrolysis. All the isolated compounds were detected for their bio-activities against MDA-MB-231, A549/DDP, A2780 and HepG2 cell lines. Helicoside C (4) exhibited superior cytotoxicity against the A2780 cell line with IC 50 7.5 ± 1.5 µM. The analysis of reactive oxygen species (ROS) revealed that Helicoside C induced an increase in intracellular ROS. Furthermore, the flow cytometry and mitochondrial membrane potential (MMP) analyses unveiled that Helicoside C mediated mitochondrial-dependent apoptosis in A2780 cells. The western blotting test showed that Helicoside C could suppress the STAT3's phosphorylation. These findings offered crucial support for development of H. septoconstrictum and highlighted the potential application of drimane-type sesquiterpenoids in pharmaceuticals., 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.)

Competing Interests: Conflict of interest None.

Importance: The safety of exogenous gonadotropin treatment, based on its effect on embryos and pregnancy outcomes, remains inconclusive., Objective: To evaluate the associations of different doses and durations of gonadotropins with embryonic genetic status and pregnancy outcomes after euploid embryo transfer in couples with infertility., Design, Setting, and Participants: This study was a post hoc analysis of a multicenter randomized clinical trial (RCT) conducted at 14 reproductive centers throughout China from July 2017 to June 2018 that evaluated the cumulative live birth rate with or without preimplantation genetic testing for aneuploidy (PGT-A) among couples with infertility and good prognosis. The PGT-A group from the original RCT was selected for secondary analysis. Patients were divided into 4 groups according to the total dosage of exogenous gonadotropins and treatment duration: group 1 (≤1500 IU and <10 days), group 2 (≤1500 IU and ≥10 days), group 3 (>1500 IU and <10 days), and group 4 (>1 500 IU and ≥10 days). Group 1 served as the control group. Data were analyzed from June through August 2023., Interventions: Blastocyst biopsy and PGT-A., Main Outcomes and Measures: The primary outcomes were embryonic aneuploidy, embryonic mosaicism, and cumulative live birth rates after euploid embryo transfer., Results: A total of 603 couples (mean [SD] age of prospective mothers, 29.13 [3.61] years) who underwent PGT-A were included, and 1809 embryos were screened using next-generation sequencing. The embryo mosaicism rate was significantly higher in groups 2 (44 of 339 embryos [13.0%]; adjusted odds ratio [aOR], 1.69 [95% CI, 1.09-2.64]), 3 (27 of 186 embryos [14.5%]; aOR, 1.98 [95% CI, 1.15-3.40]), and 4 (82 of 651 embryos [12.6%]; aOR, 1.60 [95% CI, 1.07-2.38]) than in group 1 (56 of 633 embryos [8.8%]). There were no associations between gonadotropin dosage or duration and the embryo aneuploidy rate. The cumulative live birth rate was significantly lower in groups 2 (83 of 113 couples [73.5%]; aOR, 0.49 [95% CI, 0.27-0.88]), 3 (42 of 62 couples [67.7%]; aOR, 0.41 [95% CI, 0.21-0.82]), and 4 (161 of 217 couples [74.2%]; aOR, 0.53 [95% CI, 0.31-0.89]) than in group 1 (180 of 211 couples [85.3%])., Conclusions and Relevance: In this study, excessive exogenous gonadotropin administration was associated with increased embryonic mosaicism and decreased cumulative live birth rate after euploid embryo transfer in couples with a good prognosis. These findings suggest that consideration should be given to minimizing exogenous gonadotropin dosage and limiting treatment duration to improve embryo outcomes and increase the live birth rate., Trial Registration: ClinicalTrials.gov Identifier: NCT03118141.

The decline in female fertility as age advances is intricately linked to the diminished developmental potential of oocytes. Despite this challenge, the strategies available to enhance the quality of aged oocytes remain limited. Epigallocatechin-3-gallate (EGCG), characterised by its anti-inflammatory, antioxidant and tissue protective properties, holds promise as a candidate for improving the quality of maternally aged oocytes. In this study, we explored the precise impact and underlying mechanisms of EGCG on aged oocytes. EGCG exhibited the capacity to enhance the quality of aged oocytes both in vitro and in vivo. Specifically, the application of EGCG in vitro resulted in noteworthy improvements, including an increased rate of first polar body extrusion, enhanced mitochondrial function, refined spindle morphology and a reduction in oxidative stress. These beneficial effects were further validated by the improved fertility observed among aged mice. In addition, our findings propose that EGCG might augment the expression of Arf6. This augmentation, in turn, contributes to the assembly of spindle-associated F-actin, which can contribute to mitigate the aneuploidy induced by the disruption of spindle F-actin within aged oocytes. This work thus contributes not only to understanding the role of EGCG in bolstering oocyte health, but also underscores its potential as a therapeutic intervention to address fertility challenges associated with advanced age., (© 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

We present the measurements of all-particle energy spectrum and mean logarithmic mass of cosmic rays in the energy range of 0.3-30 PeV using data collected from LHAASO-KM2A between September 2021 and December 2022, which is based on a nearly composition-independent energy reconstruction method, achieving unprecedented accuracy. Our analysis reveals the position of the knee at 3.67±0.05±0.15  PeV. Below the knee, the spectral index is found to be -2.7413±0.0004±0.0050, while above the knee, it is -3.128±0.005±0.027, with the sharpness of the transition measured with a statistical error of 2%. The mean logarithmic mass of cosmic rays is almost heavier than helium in the whole measured energy range. It decreases from 1.7 at 0.3 PeV to 1.3 at 3 PeV, representing a 24% decline following a power law with an index of -0.1200±0.0003±0.0341. This is equivalent to an increase in abundance of light components. Above the knee, the mean logarithmic mass exhibits a power law trend towards heavier components, which is reversal to the behavior observed in the all-particle energy spectrum. Additionally, the knee position and the change in power-law index are approximately the same. These findings suggest that the knee observed in the all-particle spectrum corresponds to the knee of the light component, rather than the medium-heavy components.

Over the past decades, the role of rearranged during transfection (RET) alterations in tumorigenesis has been firmly established. RET kinase inhibition is an essential therapeutic target in patients with RET-altered cancers. In clinical practice, initial efficacy can be achieved in patients through the utilization of multikinase inhibitors (MKIs) with RET inhibitory activity. However, the effectiveness of these MKIs is impeded by the adverse events associated with off-target effects. Recently, many RET-selective inhibitors, characterized by heightened specificity and potency, have been developed, representing a substantial breakthrough in the field of RET precision oncology. This Perspective focuses on the contemporary understanding of RET mutations, recent advancements in next-generation RET inhibitors, and the challenges associated with resistance to RET inhibitors. It provides valuable insights for the development of next-generation MKIs and selective RET inhibitors.

Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) are classified as major mental disorders and together account for the second-highest global disease burden, and half of these patients experience symptom onset in adolescence. Several studies have reported both similar and unique features regarding the risk factors and clinical symptoms of these three disorders. However, it is still unclear whether these disorders have similar or unique metabolic characteristics in adolescents. We conducted a metabolomics analysis of plasma samples from adolescent healthy controls (HCs) and patients with MDD, BD, and SCZ. We identified differentially expressed metabolites between patients and HCs. Based on the differentially expressed metabolites, correlation analysis, metabolic pathway analysis, and potential diagnostic biomarker identification were conducted for disorders and HCs. Our results showed significant changes in plasma metabolism between patients with these mental disorders and HCs; the most distinct changes were observed in SCZ patients. Moreover, the metabolic differences in BD patients shared features with those in both MDD and SCZ, although the BD metabolic profile was closer to that of MDD than to SCZ. Additionally, we identified the metabolites responsible for the similar and unique metabolic characteristics in multiple metabolic pathways. The similar significant differences among the three disorders were found in fatty acid, steroid-hormone, purine, nicotinate, glutamate, tryptophan, arginine, and proline metabolism. Interestingly, we found unique characteristics of significantly altered glycolysis, glycerophospholipid, and sphingolipid metabolism in SCZ; lysine, cysteine, and methionine metabolism in MDD and BD; and phenylalanine, tyrosine, and aspartate metabolism in SCZ and BD. Finally, we identified five panels of potential diagnostic biomarkers for MDD-HC, BD-HC, SCZ-HC, MDD-SCZ, and BD-SCZ comparisons. Our findings suggest that metabolic characteristics in plasma vary across psychiatric disorders and that critical metabolites provide new clues regarding molecular mechanisms in these three psychiatric disorders., (© 2024. The Author(s).)

Retinoic acid receptor-related orphan receptor γ (RORγ) acts as a crucial transcription factor in Th17 cells and is involved in diverse autoimmune disorders. RORγ allosteric inhibitors have gained significant research focus as a novel strategy to inhibit RORγ transcriptional activity. Leveraging the high affinity and selectivity of RORγ allosteric inhibitor MRL-871 ( 1 ), this study presents the design, synthesis, and characterization of 11 allosteric fluorescent probes. Utilizing the preferred probe 12h , we established an efficient and cost-effective fluorescence polarization-based affinity assay for screening RORγ allosteric binders. By employing virtual screening in conjunction with this assay, 10 novel RORγ allosteric inhibitors were identified. The initial SAR studies focusing on the hit compound G381-0087 are also presented. The encouraging outcomes indicate that probe 12h possesses the potential to function as a powerful tool in facilitating the exploration of RORγ allosteric inhibitors and furthering understanding of RORγ function.

Machine learning is gaining momentum in the prediction and discovery of materials for specific applications. Given the abundance of metal-organic frameworks (MOFs), computational screening of the existing MOFs for propane/propylene (C 3 H 8 /C 3 H 6 ) separation could be equally important for developing new MOFs. Herein, we report a machine learning-assisted strategy for screening C 3 H 8 -selective MOFs from the CoRE MOF database. Among the four algorithms applied in machine learning, the random forest (RF) algorithm displays the highest degree of accuracy. We experimentally verified the identified top-performing MOF (JNU-90) with its benchmark selectivity and separation performance of directly producing C 3 H 6 . Considering its excellent hydrolytic stability, JNU-90 shows great promise in the energy-efficient separation of C 3 H 8 /C 3 H 6 . This work may accelerate the development of MOFs for challenging separations.

Spermiogenesis defines the final phase of male germ cell differentiation. While multiple deubiquitinating enzymes have been linked to spermiogenesis, the impacts of deubiquitination on spermiogenesis remain poorly characterized. Here, we investigated the function of UAF1 in mouse spermiogenesis. We selectively deleted Uaf1 in premeiotic germ cells using the Stra8-Cre knock-in mouse strain ( Uaf1 sKO), and found that Uaf1 is essential for spermiogenesis and male fertility. Further, UAF1 interacts and colocalizes with USP1 in the testes. Conditional knockout of Uaf1 in testes results in disturbed protein levels and localization of USP1, suggesting that UAF1 regulates spermiogenesis through the function of the deubiquitinating enzyme USP1. Using tandem mass tag-based proteomics, we identified that conditional knockout of Uaf1 in the testes results in reduced levels of proteins that are essential for spermiogenesis. Thus, we conclude that the UAF1/USP1 deubiquitinase complex is essential for normal spermiogenesis by regulating the levels of spermiogenesis-related proteins., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Premature ovarian insufficiency (POI) is a common reproductive aging disorder due to a dramatic decline of ovarian function before 40 years of age. Accumulating evidence reveals that genetic defects, particularly those related to DNA damage response, are a crucial contributing factor to POI. We have demonstrated that the functional Fanconi anemia (FA) pathway maintains the rapid proliferation of primordial germ cells to establish a sufficient reproductive reserve by counteracting replication stress, but the clinical implications of this function in human ovarian function remain to be established. Here, we screened the FANCI gene, which encodes a key component for FA pathway activation, in our whole-exome sequencing database of 1030 patients with idiopathic POI, and identified two pairs of novel compound heterozygous variants, c.[97C > T];[1865C > T] and c.[158-2A > G];[c.959A > G], in two POI patients, respectively. The missense variants did not alter FANCI protein expression and nuclear localization, apart from the variant c.158-2A > G causing abnormal splicing and leading to a truncated mutant p.(S54Pfs*5). Furthermore, the four variants all diminished FANCD2 ubiquitination levels and increased DNA damage under replication stress, suggesting that the FANCI variants impaired FA pathway activation and replication stress response. This study first links replication stress response defects with the pathogenesis of human POI, providing a new insight into the essential roles of the FA genes in ovarian function., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To investigate the correlation of serum osteopontin levels with disease severity and prognosis in patients with acute cerebral infarction., Methods: This retrospective analysis included forty patients with acute cerebral infarction (ACI) admitted to the Department of Neurology of Baoding Children's Hospital from May, 2019 to May, 2022 within 24 hours of onset were selected as the observation group, while 40 healthy subjects in our hospital during the same period were selected as the control group. The correlation between serum Osteopontin (OPN) levels and risk factors on one day, seven days and 14 days was analyzed. Patients in the observation group were subdivided into the good prognosis group and the poor prognosis group according to mRS score, and the serum OPN levels of the two groups were compared. The correlation between serum OPN and disease severity and prognosis of patients with ACI was analyzed., Results: The serum OPN levels in the observation group were significantly higher than those in control group (P< 0.05), and its level was positively correlated with NIHSS score and infarct size. The proportion of patients with hyperlipidemia, smoking, drinking, hypertension and OPN level on seven day in the poor prognosis group were higher than those in the good prognosis group (P<0.05). The OPN level > 8.720 ng/ml on seven days was an independent risk factor for poor prognosis of cerebral infarction., Conclusion: OPN is involved in the entire pathophysiological process of ACI, and its level can predict the severity of the disease in patients with ACI, and can be used as an important indicator for evaluating their clinical prognosis., Competing Interests: Declaration of conflicting interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)

The development of cost-effective catalysts for oxygen evolution reaction (OER) in acidic media is of paramount importance. This work reports that Sr-doped solid solution structural ultrafine IrMnO 2 nanoparticles (NPs) (≈1.56 nm) on the carbon nanotubes (Sr-IrMnO 2 /CNTs) are efficient catalysts for the acidic OER. Even with the Ir use dosage 3.5 times lower than that of the commercial IrO 2 , the Sr-IrMnO 2 /CNTs only need an overpotential of 236.0 mV to drive 10.0 mA cm -2 and show outstanding stability for >400.0 h. Its Ir mass activity is 39.6 times higher than that of the IrO 2 at 1.53 V. The solid solution and Sr-doping structure of Sr-IrMnO 2 are the main origin of the high catalytic activity and excellent stability of the Sr-IrMnO 2 /CNTs. The density function theory calculations indicate that the solid solution structure can promote strong electronic coupling between Ir and Mn, lowering the energy barrier of the OER rate-determining step. The Sr-doping can enhance the stability of Ir against the chemical corrosion and demetallation. Water electrolyzers and proton exchange membrane water electrolyzers assembled with the Sr-IrMnO 2 /CNTs show superb performance and excellent durability in the acid media., (© 2023 Wiley‐VCH GmbH.)

Background: Excessive hepatic glucose production is a hallmark that contributes to hyperglycemia in type 2 diabetes (T2D). The regulatory network governing this process remains incompletely understood. Here, we demonstrate that TOX3, a high-mobility group family member, acts as a major transcriptional driver for hepatic glucose production., Methods: Tox3-overexpressed and knockout mice were constructed to explore its metabolic functions. Transcriptomic and chromatin-immunoprecipitation sequencing (ChIP-seq) were used to identify downstream targets of TOX3. Both FoxO1 silencing and inhibitor approaches were used to assess the contribution of FoxO1. TOX3 expression levels were examined in the livers of mice and human subjects. Finally, Tox3 was genetically manipulated in diet-induced obese mice to evaluate its therapeutic potential., Results: Hepatic Tox3 overexpression activates the gluconeogenic program, resulting in hyperglycemia and insulin resistance in mice. Hepatocyte-specific Tox3 knockout suppresses gluconeogenesis and improves insulin sensitivity. Mechanistically, integrated hepatic transcriptomic and ChIP-seq analyses identify FoxO1 as a direct target of TOX3. TOX3 stimulates FoxO1 transcription by directly binding to and activating its promoter, whereas FoxO1 silencing abrogates TOX3-induced dysglycemia in mice. In human subjects, hepatic TOX3 expression shows a significant positive correlation with blood glucose levels under normoglycemic conditions, yet is repressed by high glucose during T2D. Importantly, hepatic Tox3 deficiency markedly protects against and ameliorates the hyperglycemia and glucose intolerance in diet-induced diabetic mice., Conclusions: Our findings establish TOX3 as a driver for excessive gluconeogenesis through activating hepatic FoxO1 transcription. TOX3 could serve as a promising target for preventing and treating hyperglycemia in T2D., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: During the human menstrual cycle and pregnancy, the endometrium undergoes a series of dynamic remodeling processes to adapt to physiological changes. Insufficient endometrial remodeling, characterized by inadequate endometrial proliferation, decidualization and spiral artery remodeling, is associated with infertility, endometriosis, dysfunctional uterine bleeding, and pregnancy-related complications such as preeclampsia and miscarriage. Bone morphogenetic proteins (BMPs), a subset of the transforming growth factor-β (TGF-β) superfamily, are multifunctional cytokines that regulate diverse cellular activities, such as differentiation, proliferation, apoptosis, and extracellular matrix synthesis, are now understood as integral to multiple reproductive processes in women. Investigations using human biological samples have shown that BMPs are essential for regulating human endometrial remodeling processes, including endometrial proliferation and decidualization., Objective and Rationale: This review summarizes our current knowledge on the known pathophysiological roles of BMPs and their underlying molecular mechanisms in regulating human endometrial proliferation and decidualization, with the goal of promoting the development of innovative strategies for diagnosing, treating and preventing infertility and adverse pregnancy complications associated with dysregulated human endometrial remodeling., Search Methods: A literature search for original articles published up to June 2023 was conducted in the PubMed, MEDLINE, and Google Scholar databases, identifying studies on the roles of BMPs in endometrial remodeling during the human menstrual cycle and pregnancy. Articles identified were restricted to English language full-text papers., Outcomes: BMP ligands and receptors and their transduction molecules are expressed in the endometrium and at the maternal-fetal interface. Along with emerging technologies such as tissue microarrays, 3D organoid cultures and advanced single-cell transcriptomics, and given the clinical availability of recombinant human proteins and ongoing pharmaceutical development, it is now clear that BMPs exert multiple roles in regulating human endometrial remodeling and that these biomolecules (and their receptors) can be targeted for diagnostic and therapeutic purposes. Moreover, dysregulation of these ligands, their receptors, or signaling determinants can impact endometrial remodeling, contributing to infertility or pregnancy-related complications (e.g. preeclampsia and miscarriage)., Wider Implications: Although further clinical trials are needed, recent advancements in the development of recombinant BMP ligands, synthetic BMP inhibitors, receptor antagonists, BMP ligand sequestration tools, and gene therapies have underscored the BMPs as candidate diagnostic biomarkers and positioned the BMP signaling pathway as a promising therapeutic target for addressing infertility and pregnancy complications related to dysregulated human endometrial remodeling., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Switchable spontaneous polarization is the vital property of ferroelectrics, which leads to other key physical properties such as piezoelectricity, pyroelectricity, and nonlinear optical effects, etc. Recently, organic-inorganic hybrid perovskites with 2D layered structure have become an emerging branch of ferroelectric materials. However, most of the 2D hybrid ferroelectrics own relatively low polarizations (<15 µC cm -2 ). Here, a strategy to enhance the polarization of these hybrid perovskites by using ortho-, meta-, para-halogen substitution is developed. Based on (benzylammonium) 2 PbCl 4 (BZACL), the para-chlorine substituted (4-chlorobenzylammonium) 2 PbCl 4 (4-CBZACL) ferroelectric semiconductor shows a large spontaneous polarization (23.3 µC cm -2 ), which is 79% larger than the polarization of BZACL. This large enhancement of polarization is successfully explained via ab initio calculations. The study provides a convenient and efficient strategy to promote the ferroelectric property in the hybrid perovskite family., (© 2023 Wiley-VCH GmbH.)

The carbon nanotubes (CNTs) supported amorphous Sb doped substoichiometric tin dulfide (Sb─SnS x ) with a carbon coating (the C/Sb─SnS x @CNTs-500) is reported to be an efficient anode material for K + storage. The formation of the C/Sb─SnS x @CNTs-500 is simply achieved through the thermally induced desulfurization of tin sulfide via a controlled annealing of the C/Sb─SnS 2 @CNTs at 500 °C. When used for the K + storage, it can deliver stable reversible capacities of 406.5, 305.7, and 238.4 mAh g -1 at 0.1, 1.0, and 2.0 A g -1 , respectively, and shows no capacity drops when potassiated/depotassiated at 1.0 and 2.0 A g -1 for >3000 and 2400 cycles, respectively. Even at 10, 20, and 30 A g -1 , it can still deliver stable reversible capacities of 138.5, 85.1, and 73.8 mAh g -1 , respectively. The unique structure, which combines the advantageous features of carbon integration/coating, metal doping, and desulfurization-induced amorphous structure, is the main origin of the high performance of the C/Sb─SnS x @CNTs-500. Specifically, the carbon integration/coating can increase the electric conductivity and stability of the C/Sb─SnS x @CNTs-500. The density function theory calculation indicates that the Sb doping and the desulfurization can facilitate the potassiation and increase the electric conductivity of Sb─SnS x . Additionally, the desulfurization can increase the K + diffusivity in Sb─SnS x ., (© 2023 Wiley-VCH GmbH.)

Purpose. Metagenomic next-generation sequencing (mNGS) has been widely used in the diagnosis of infectious diseases, while its performance in diagnosis of tuberculous meningitis (TBM) is incompletely characterized. The aim of this study was to assess the performance of mNGS in the diagnosis of TBM, and illustrate the sensitivity and specificity of different methods. Methods. We retrospectively recruited TBM patients between January 2021 and March 2023 to evaluate the performance of mNGS on cerebrospinal fluid (CSF) samples, in comparison with conventional microbiological testing, including culturing of Mycobacterium tuberculosis (MTB), acid-fast bacillus (AFB) stain, reverse transcription PCR and Xpert MTB/RIF. Results. Of the 40 enrolled, 34 participants were diagnosed with TBM, including 15(44.12 %) definite and 19(55.88 %) clinical diagnosis based upon clinical manifestations, CSF parameters, brain imaging, pathogen evidence and treatment response. The mNGS method identified sequences of Mycobacterium tuberculosis complex (MTBC) in 11 CSF samples. In patients with definite TBM, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of mNGS were 78.57, 100, 100, 66.67 and 85 %, respectively. Compared to conventional diagnostic methods, the sensitivity of mNGS (78.57 %) was higher than AFB (0 %), culturing (0 %), RT-PCR (60 %) and Xpert MTB/RIF (14.29 %). Conclusions. Our study indicates that mNGS of CSF exhibited an overall improved sensitivity over conventional diagnostic methods for TBM and can be considered a front-line CSF test.

Polycystic ovary syndrome (PCOS) is one of the most common reproductive endocrine metabolic disorders. The lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) reportedly can regulate the reproductive system. Despite studies, the alteration of MALAT1 expression in granulosa cells (GCs) from PCOS patients was inconsistent. To evaluate MALAT1 expression in GCs in different PCOS subgroups and its association with PCOS phenotypes, we collected GCs from 110 PCOS cases and 71 controls, and examined MALAT1 expression by quantitative PCR. The results showed MALAT1 expression was upregulated in PCOS cases, especially in insulin resistant (IR) PCOS subgroup, obese PCOS subgroup and non-hyperandrogenic (NHA) PCOS subgroup. MALAT1 expression was positively correlated with BMI and several metabolic parameters in controls. Interestingly, MALAT1 expression was notably associated with some critical endocrine indexes for PCOS, including E2, FSH, LH and LH/FSH ratio. In different PCOS subgroups, we found significant positive correlations with LH/FSH ratio in IR-PCOS and PCOS with normal weight, and with serum T and LH level in NHA-PCOS subgroup. Integrated analysis with lncRNA target databases and PCOS-related databases revealed MALAT1 could participate in PCOS by influencing immune response and lipids metabolism in GCs. In conclusion, MALAT1 was differently expressed in GCs in PCOS, especially in IR, obese and NHA PCOS subgroups. MALAT1 was likely involved in metabolism and immune response in GCs in PCOS. However, more studies are necessary to establish this concept., (© 2024. The Author(s).)

Organic-inorganic hybrid perovskites (OIHPs) have received particular attention due to their characteristic structural tunability and flexibility. These features make OIHPs behave with excellent modifications on macroscopic properties, such as ferroicity or semiconductor performances, etc. Herein, we report two 2D hybrid stibium-based halide perovskite (C 3 H 7 N) 3 Sb 2 X 9 (X = Br, 1 ; Cl, 2 ) ferroelastic semiconductor possessing dual switching properties of dielectric and second harmonic generation (SHG). Notably, these two hybrids exhibit halogen-regulated ferroelasticity and semiconductor properties. There is a significant difference in Curie temperature ( T c ) and X-ray radiation detection sensitivity ( S ), i.e., the Δ T c and Δ S are 38 K and 87 μC Gy air -1 cm -2 , respectively. Meanwhile, crystals 1 and 2 do not show dark current drift in cyclic measurements of different radiation doses with stable switching ratios of 30 and 10, separately. Meanwhile, these results were proven by scientific experimental results and density functional theory (DFT) calculations. Our work presents a facile and practical method to regulate macroproperties on the molecular level, providing a new vision to develop hybrid perovskite ferroic-photoelectric materials.

Context: Both assisted reproductive technology (ART) and obesity are associated with adverse cardiometabolic alterations in offspring. However, the combined effects of paternal obesity and ART on offspring cardiometabolic health are still unclear., Objective: To clarify cardiometabolic changes in offspring of obese fathers conceived using ART., Design: Retrospective cohort study conducted between June 2014 and October 2019., Setting: Center for reproductive medicine., Patients: A total of 2890 singleton visits aged 4-10 years were followed., Intervention(s): None., Main Outcome Measure(s): Age-and sex-specific z-score of body mass index(BMI), blood pressure, insulin resistance and lipid profile were examined., Results: We observed a strong association between paternal BMI categories and offspring BMI, blood pressure, and insulin resistance. Compared to offspring of fathers with normal weight, multivariable-adjusted mean difference for BMI z-score were 0.53 (95%CI: 0.37-0.68) for obese fathers, 0.17 (95%CI: 0.05-0.30) for overweight fathers, and -0.55 (95%CI: -0.95--0.15) for underweight fathers; corresponding values for systolic blood pressure z-score were 0.21(95%CI: 0.07-0.35), 0.10 (95%CI: -0.01-0.21), and -0.24 (95%CI: -0.59-0.11), and corresponding values for HOMA-IR z-score were 0.31(95%CI: 0.16-0.46), 0.09(95%CI: -0.02-0.21), and -0.11 (95%CI: -0.48-0.28), respectively. The mediation analyses suggested that 57.48% to 94.75% of the associations among paternal obesity and offspring cardiometabolic alterations might be mediated by offspring BMI., Conclusions: Paternal obesity was associated with an unfavourable cardiometabolic profile in ART-conceived offspring. Mediation analyses indicated that offspring BMI was a possible mediator of the association between paternal obesity and the offspring impaired metabolic changes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Objective: China is among the 30 countries with a high burden of tuberculosis (TB) worldwide, and TB remains a public health concern. Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China. However, molecular epidemiological studies of Kashgar are lacking., Methods: A population-based retrospective study was conducted using whole-genome sequencing (WGS) to determine the characteristics of drug resistance and the transmission patterns., Results: A total of 1,668 isolates collected in 2020 were classified into lineages 2 (46.0%), 3 (27.5%), and 4 (26.5%). The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid (7.4%, 124/1,668), streptomycin (6.0%, 100/1,668), and rifampicin (3.3%, 55/1,668). The rate of rifampicin resistance was 1.8% (23/1,290) in the new cases and 9.4% (32/340) in the previously treated cases. Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains, respectively: 18.6% vs. 8.7 or 9%, P < 0.001. The estimated proportion of recent transmissions was 25.9% (432/1,668). Multivariate logistic analyses indicated that sex, age, occupation, lineage, and drug resistance were the risk factors for recent transmission. Despite the low rate of drug resistance, drug-resistant strains had a higher risk of recent transmission than the susceptible strains (adjusted odds ratio, 1.414; 95% CI , 1.023-1.954; P = 0.036). Among all patients with drug-resistant tuberculosis (DR-TB), 78.4% (171/218) were attributed to the transmission of DR-TB strains., Conclusion: Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar., (Copyright © 2024 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Background: Polycystic ovary syndrome (PCOS) is one of the most common reproductive endocrine disorders in females of childbearing age. Various types of ovarian cells work together to maintain normal reproductive function, whose discordance often takes part in the development and progression of PCOS. Understanding the cellular heterogeneity and compositions of ovarian cells would provide insight into PCOS pathogenesis, but are, however, not well understood. Transcriptomic characterization of cells isolated from PCOS cases have been assessed using bulk RNA-seq but cells isolated contain a mixture of many ovarian cell types., Methods: Here we utilized the reference scRNA-seq data from human adult ovaries to deconvolute and estimate cell proportions and dysfunction of ovarian cells in PCOS, by integrating various granulosa cells(GCs) transcriptomic data., Results: We successfully defined 22 distinct cell clusters of human ovarian cells. Then after transcriptome integration, we obtained a gene expression matrix with 13,904 genes within 30 samples (15 control vs. 15 PCOS). Subsequent deconvolution analysis revealed decreased proportion of small antral GCs and increased proportion of KRT8 high mural GCs, HTRA1 high cumulus cells in PCOS, especially increased differentiation from small antral GCs to KRT8 high mural GCs. For theca cells, the abundance of internal theca cells (TCs) and external TCs was both increased. Less TCF21 high stroma cells (SCs) and more STAR high SCs were observed. The proportions of NK cells and monocytes were decreased, and T cells occupied more in PCOS and communicated stronger with inTCs and exTCs. In the end, we predicted the candidate drugs which could be used to correct the proportion of ovarian cells in patients with PCOS., Conclusions: Taken together, this study provides insights into the molecular alterations and cellular compositions in PCOS ovarian tissue. The findings might contribute to our understanding of PCOS pathophysiology and offer resource for PCOS basic research., (© 2024. The Author(s).)

Acute myeloid leukemia (AML) is the most common type of blood cancer and has been strongly correlated with the overexpression of Fms-like tyrosine kinase 3 (FLT3), a member of the class III receptor tyrosine kinase family. With the emergence of FLT3 internal tandem duplication alteration (ITD) and tyrosine kinase domain (TKD) mutations, the development of FLT3 small molecule inhibitors has become an effective medicinal chemistry strategy for AML. Herein, we have designed and synthesized two series of 1H-pyrrolo[2,3-b]pyridine derivatives CM1-CM24, as FLT3 inhibitors based on F14, which we previously reported, that can target the hydrophobic FLT3 back pocket. Among these derivates, CM5 showed significant inhibition of FLT3 and FLT3-ITD, with inhibitory percentages of 57.72 % and 53.77 % respectively at the concentration of 1 μΜ. Furthermore, CM5 demonstrated potent inhibition against FLT3-dependent human AML cell lines MOLM-13 and MV4-11 (both harboring FLT3-ITD mutant), with IC 50 values of 0.75 μM and 0.64 μM respectively. In our cellular mechanistic studies, CM5 also effectively induces apoptosis by arresting cell cycle progression in the G0/G1 phase. In addition, the amide and urea linker function were discussed in detail based on computational simulations studies. CM5 will serve as a novel lead compound for further structural modification and development of FLT3 inhibitors specifically targeting AML with FLT3-ITD mutations., 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 Ltd. All rights reserved.)

The exploration of the physical attributes of the recently discovered orthocarbonate Sr 3 CO 5 is significant for comprehending the carbon cycle and storage mechanisms within the Earth's interior. In this study, first-principles calculations are initially used to examine the structural phase transitions of Sr 3 CO 5 polymorphs within the range of lower mantle pressures. The results suggest that Sr 3 CO 5 with the Cmcm phase exhibits a minimal enthalpy between 8.3 and 30.3 GPa. As the pressure exceeds 30.3 GPa, the Cmcm phase undergoes a transition to the I 4/ mcm phase, while the experimentally observed Pnma phase remains metastable under our studied pressure. Furthermore, the structural data of SrO, SrCO 3 , and Sr 3 CO 5 polymorphs are utilized to develop a deep learning potential model suitable for the Sr-C-O system, and the pressure-volume relationship and elastic constants calculated using the potential model are in line with the available results. Subsequently, the elastic properties of Cmcm and I 4/ mcm phases in Sr 3 CO 5 at high temperature and pressure are calculated using the molecular dynamics method. The results indicate that the I 4/ mcm phase exhibits higher temperature sensitivity in terms of elastic moduli and wave velocities compared to the Cmcm phase. Finally, the thermodynamic properties of the Cmcm and I 4/ mcm phases are predicted in the range of 0-2000 K and 10-120 GPa, revealing that the heat capacity and bulk thermal expansion coefficient of both phases increase with temperature, with the constant volume heat capacity gradually approaching the Dulong-Petit limit as the temperature rises.

Background: Excessive energy intake in modern society has led to an epidemic surge in metabolic diseases, such as obesity and type 2 diabetes, posing profound threats to women's reproductive health. However, the precise impact and underlying pathogenesis of energy excess on female reproduction remain unclear., Methods: We established an obese and hyperglycemic female mouse model induced by a high-fat and high-sucrose (HFHS) diet, then reproductive phenotypes of these mice were evaluated by examing sexual hormones, estrous cycles, and ovarian morphologies. Transcriptomic and precise metabolomic analyses of the ovaries were performed to compare the molecular and metabolic changes in HFHS mice. Finally, orthogonal partial least squares discriminant analysis was performed to compare the similarities of traits between HFHS mice and women with polycystic ovary syndrome (PCOS)., Results: The HFHS mice displayed marked reproductive dysfunctions, including elevated serum testosterone and luteinizing hormone levels, irregular estrous cycles, and impaired folliculogenesis, mimicking the clinical manifestations of women with PCOS. Precise metabolomic overview suggested that HFHS diet disrupted amino acid metabolism in the ovaries of female mice. Additionally, transcriptional profiling revealed pronounced disturbances in ovarian steroid hormone biosynthesis and glucolipid metabolism in HFHS mice. Further multi-omics analyses unveiled prominent aberration in ovarian arginine biosynthesis pathway. Notably, comparisons between HFHS mice and a cohort of PCOS patients identified analogous reproductive and metabolic signatures., Conclusions: Our results provide direct in vivo evidence for the detrimental effects of overnutrition on female reproduction and offer insights into the metabolic underpinnings of PCOS., (© 2024. The Author(s).)

In order to comprehensively study the pollution characteristics of polycyclic aromatic hydrocarbons （PAHs） in soils of Guangzhou， 222 topsoil samples were collected and analyzed. The ecological risk of soil PAHs pollution was evaluated using the effect interval low/median method （ERL/ERM） and the （BaP） toxicity equivalent method， and the health risk of soil PAHs pollution was evaluated using the lifelong cancer risk increment model. The source of PAHs was analyzed using the characteristic compound ratio method and PMF model. The results indicated that： the content of surface soil （∑16PAHs） in Guangzhou was 38-11 115 μg·kg -1 ， with an average of 526 μg·kg -1 ， and 16 types of polycyclic aromatic hydrocarbon monomers showed strong variation. There was a certain degree of ecological risk of PAHs in Guangzhou， and there was already a significant ecological risk of PAHs pollution in individual sampling points， which were generally in a state of mild pollution. Based on the results of the health risk assessment， the contribution rates of total cancer risk in both adults and children were presented as follows： skin contact &gt; ingestion of soil &gt; respiratory intake. The health risk of children was greater than that of adults， and the overall health risk was within an acceptable range. Source analysis showed that the main sources of soil PAHs in Guangzhou were coal （37.1%）； diesel （32%）； coking （17.3%）； and mixed sources of traffic emissions， biomass combustion， and petrochemical product volatilization （13.6%）. The overall source of soil PAHs belonged to mixed sources. The research results have enriched our understanding of the pollution status of PAHs in the surface soil of Guangzhou and are helpful in promoting soil pollution prevention and control actions.

Corydalis saxicola , an endangered medicinal plant endemic to karst habitats, is widely used in Traditional Chinese Medicine to treat hepatitis, abdominal pain, bleeding hemorrhoids and other conditions. However, to date, the mitochondrial (mt) genome of C. saxicola has not been reported, which limits our understanding of the genetic and biological mechanisms of C. saxicola . Here, the mt genome of C. saxicola was assembled by combining the Nanopore and Illumina reads. The mt genome of C. saxicola is represented by a circular chromosome which is 587,939 bp in length, with an overall GC content of 46.50%. 40 unique protein-coding genes (PCGs), 22 tRNA genes and three rRNA genes were identified. Codon usage of the PCGs was investigated and 167 simple sequence repeats were identified. Twelve homologous fragments were identified between the mt and ct genomes of C. saxicola , accounting for 1.04% of the entire mt genome. Phylogenetic examination of the mt genomes of C. saxicola and 30 other taxa provided an understanding of their evolutionary relationships. We also predicted 779 RNA editing sites in 40 C . saxicola mt PCGs and successfully validated 506 (65%) of these using PCR amplification and Sanger sequencing. In addition, we transcriptionally profiled 24 core mt PCGs in C. saxicola roots treated with different concentrations of CaCl 2 , as well as in other organs. These investigations will be useful for effective utilization and molecular breeding, and will also provide a reference for further studies of the genus Corydalis ., 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 Li, Liu, Qin, Tan, Ou, Chen, Wei, Zhang and Lei.)

The utilization of black beans as a protein-rich ingredient presents remarkable prospects in the protein food industry. The objective of this study was to assess the impact of germination treatment on the physicochemical, structural, and functional characteristics of a black bean protein isolate. The findings indicate that germination resulted in an increase in both the total and soluble protein contents of black beans, while SDS-PAGE demonstrated an increase in the proportion of 11S and 7S globulin subunits. After germination, the particle size of the black bean protein isolate decreased in the solution, while the absolute value of the zeta potential increased. The above results show that the stability of the solution was improved. The contents of β-sheet and β-turn gradually decreased, while the content of α-helix increased, and the fluorescence spectrum of the black bean protein isolate showed a red shift phenomenon, indicating that the structure of the protein isolate and its polypeptide chain were prolonged, and the foaming property, emulsification property and in vitro digestibility were significantly improved after germination. Therefore, germination not only improves functional properties, but also nutritional content.

Forensic microbiome research is a field with a wide range of applications and a number of protocols have been developed for its use in this area of research. As individuals host radically different microbiota, the human microbiome is expected to become a new biomarker for forensic identification. To achieve an effective use of this procedure an understanding of factors which can alter the human microbiome and determinations of stable and changing elements will be critical in selecting appropriate targets for investigation. The 16S rRNA gene, which is notable for its conservation and specificity, represents a potentially ideal marker for forensic microbiome identification. Gene sequencing involving 16S rRNA is currently the method of choice for use in investigating microbiomes. While the sequencing involved with microbiome determinations can generate large multi-dimensional datasets that can be difficult to analyze and interpret, machine learning methods can be useful in surmounting this analytical challenge. In this review, we describe the research methods and related sequencing technologies currently available for application of 16S rRNA gene sequencing and machine learning in the field of forensic identification. In addition, we assess the potential value of 16S rRNA and machine learning in forensic microbiome science., 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 Yang, Wang, Zhai and Chen.)

Research Question: What are the different characteristics of vaginal microbial composition between patients with endometrial polypoid lesions and controls?, Design: This cohort study compared the pre-operative microbial compositions of vaginal samples in a cohort of 703 women with endometrial polypoid lesions [293 and 410 women diagnosed and not diagnosed with polyps pathologically (polyps group and not-polyps group, respectively] and 703 women in the control group. Bacterial abundance, diversity, differential taxa and microbial network structure were assessed using 16S rRNA gene sequencing. Predictive algorithms were used to determine the functional pathways of vaginal microbiota within the cohort., Results: The control group exhibited higher relative abundance of Lactobacillus crispatus in comparison with the polypoid lesions group (P = 0.0427). Beta diversity of vaginal microbiota differed significantly between the groups (P < 0.05). Comparing the polyps group with the not-polyps group, Leptotrichia spp. and Cutibacterium spp. were more abundant in the polyps group, and Fannyhessea spp., Acinetobacter spp. and Achromobacter spp. were more abundant in the not-polyps group. The control group exhibited higher abundance of Bifidobacterium spp., Achromobacter spp. and Escherichia/Shigella spp. (false discovery rate < 0.05). Furthermore, the polyps group and not-polyps group displayed more complex co-occurrence networks compared with the control group., Conclusions: The results of this study provide compelling evidence supporting associations between vaginal microbiota and endometrial polypoid lesions, highlighting the potential relationship between a well-balanced vaginal microbial ecosystem and a healthy intrauterine environment., (Copyright © 2023. Published by Elsevier Ltd.)

Objective: There is consistent evidence that cognitive behavioral therapies (CBTs) are effective interventions for adult depression. While some evidence has compared these effects in different countries, no prior systematic review and meta-analysis has compared the efficacy of CBTs between Chinese and people from the rest of the world. The current meta-analysis addressed this gap by a systematic review of eligible studies from Chinese and worldwide databases., Method: Hedges' g was calculated using a random-effects model. Subgroup analyses and multilevel meta-analytic models were conducted to examine the relationship among effect sizes and the characteristics in Chinese studies. Metaregression analyses were conducted to explore the difference of the efficacy of CBTs between Chinese studies and non-Chinese studies after controlling for the moderators., Results: A total of 34 ( n = 3,710) studies in China and 307 ( n = 30,333) studies from the rest of the world were included. The effect size of CBTs on depression for Chinese participants was 1.19 (95% CI [0.86, 1.52]), which was higher ( Q = 4.63, p = .03) than the effect size of the rest of the world (0.82, 95% CI [0.74, 0.90]). After controlling for moderators, the effect size of Chinese studies was still higher than non-Chinese studies (β = 0.351, p = .011)., Conclusions: CBTs are effective interventions for adult depression and deserve more attention in China for depression management. Moderators related to study design, clinical features, and cultural factors need to be considered in the interpretation of the results. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Cancer immunotherapies have achieved unprecedented success in clinic, but they remain largely ineffective in some major types of cancer, such as colorectal cancer with microsatellite stability (MSS CRC). It is therefore important to study tumor microenvironment of resistant cancers for developing new intervention strategies. In this study, we identify a metabolic cue that determines the unique immune landscape of MSS CRC. Through secretion of distal cholesterol precursors, which directly activate RORγt, MSS CRC cells can polarize T cells toward Th17 cells that have well-characterized pro-tumor functions in colorectal cancer. Analysis of large human cancer cohorts revealed an asynchronous pattern of the cholesterol biosynthesis in MSS CRC, which is responsible for the abnormal accumulation of distal cholesterol precursors. Inhibiting the cholesterol biosynthesis enzyme Cyp51, by pharmacological or genetic interventions, reduced the levels of intratumoral distal cholesterol precursors and suppressed tumor progression through a Th17-modulation mechanism in preclinical MSS CRC models. Our study therefore reveals a novel mechanism of cancer-immune interaction and an intervention strategy for the difficult-to-treat MSS CRC., (© 2024. The Author(s).)

Surgical removal of the thyroid gland (TG) for treating thyroid disorders leaves the patients on lifelong hormone replacement that partially compensates the physiological needs, but regenerating TG is challenging. Here, an approach is reported to regenerate TG within the spleen for fully restoring the thyroid's functions in mice, by transplanting thyroid tissue blocks to the spleen. Within 48 h, the transplanted tissue efficiently revascularizes, forming thyroid follicles similar to the native gland after 4 weeks. Structurally, the ectopically generated thyroid integrates with the surrounding splenic tissue while maintaining its integrity, separate from the lymphatic tissue. Functionally, it fully restores the native functions of the TG in hormone regulation in response to physiological stimuli, outperforming the established method of oral levothyroxine therapy in maintaining systemic homeostasis. The study demonstrates the full restoration of thyroid functions post-thyroidectomy by intrasplenic TG regeneration, providing fresh insights for designing novel therapies for thyroid-related disorders., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Patients with residual nasopharyngeal carcinoma after receiving definitive treatment have poor prognoses. Although immune checkpoint therapies have achieved breakthroughs for treating recurrent and metastatic nasopharyngeal carcinoma, none of these strategies have been assessed for treating residual nasopharyngeal carcinoma. In this single-arm, phase 2 trial, we aimed to evaluate the antitumor efficacy and safety of toripalimab (anti-PD1 antibody) plus capecitabine in patients with residual nasopharyngeal carcinoma after definitive treatment (ChiCTR1900023710). Primary endpoint of this trial was the objective response rate assessed according to RECIST (version 1.1). Secondary endpoints included complete response rate, disease control rate, duration of response, progression-free survival, safety profile, and treatment compliance. Between June 1, 2020, and May 31, 2021, 23 patients were recruited and received six cycles of toripalimab plus capecitabine every 3 weeks. In efficacy analyses, 13 patients (56.5%) had complete response, and 9 patients (39.1%) had partial response, with an objective response rate of 95.7% (95% CI 78.1-99.9). The trial met its prespecified primary endpoint. In safety analyses, 21 of (91.3%) 23 patients had treatment-related adverse events. The most frequently reported adverse event was hand-foot syndrome (11 patients [47.8%]). The most common grade 3 adverse event was hand-foot syndrome (two patients [8.7%]). No grades 4-5 treatment-related adverse events were recorded. This phase 2 trial shows that combining toripalimab with capecitabine has promising antitumour activity and a manageable safety profile for patients with residual nasopharyngeal carcinoma., (© 2024. The Author(s).)

Background: Extreme ambient temperature has been linked to decline in males' semen quality. Although the temperature-semen quality association has been examined in certain cities of South China, how the effect size of the extreme temperature may lag over critical windows in spermatogenesis and whether the strength of association may vary in North China have yet been adequately explored., Objectives: To quantify the association between air temperature and semen quality, and identify critical exposure windows in a Northern Peninsular Province, China., Materials and Methods: Data on semen quality in 2014-2019 were collected from the Human Sperm Bank of Institute of Women, Children and Reproductive Health, Shandong University, China. Daily meteorological data (0.01°×0.01°) were assigned to each subject's residential address. The linear mixed-effect model combined with the distributed lag nonlinear model was used to estimate the effect of ambient temperature over critical spermatogenesis windows., Results: The temperature-semen quality association was inverted V-shaped, with the maximum lag being 0-45 days before ejaculation and the threshold being 9.2°C. Progressively and total motile sperm number, and total sperm number declined more substantially than other semen quality parameters. Semen quality was more sensitive to cold exposure during the epididymal storage period than the sperm motility development period. By contrast, semen quality was insensitive to heat exposure during both critical spermatogenesis windows. Impairment of certain semen quality parameters was more obvious for males with higher educational attainment and those aged over 35 years., Discussion and Conclusion: Exposure to non-optimal temperature is associated with decreased semen quality in North China, with the epididymal storage and sperm motility development periods more sensitive to cold exposure than heat. Older males and those with higher educations may need particular awareness., (© 2024 American Society of Andrology and European Academy of Andrology.)

In this work, 10 nm scandium-doped aluminum nitride (AlScN) capacitors are demonstrated for the construction of the selector-free memory array application. The 10 nm Al 0.7 Sc 0.3 N film deposited on an 8-inch silicon wafer with sputtering technology exhibits a large remnant polarization exceeding 100 µC/cm 2 and a tight distribution of the coercive field, which is characterized by the positive-up-negative-down (PUND) method. As a result, the devices with lateral dimension of only 1.5 μm show a large memory window of over 250% and a low power consumption of ~40 pJ while maintaining a low disturbance rate of <2%. Additionally, the devices demonstrate stable multistate memory characteristics with a dedicated operation scheme. The back-end-of-line (BEOL)-compatible fabrication process, along with all these device performances, shows the potential of AlScN-based capacitors for the implementation of the high-density selector-free memory array.

Background: During human early placentation, a proportion of extravillous trophoblasts (EVTs) migrate to the maternal decidua, differentiating into endovascular EVTs to remodel spiral arteries and ensure the establishment of blood circulation at the maternal-fetal interface. Inadequate EVT migration and endovascular differentiation are closely associated with adverse pregnancy outcomes such as miscarriage. Activin A and fibronectin are both secretory molecules abundantly expressed at the maternal-fetal interface. Activin A has been reported to regulate EVT biological functions. However, whether fibronectin mediates activin A-promoted EVT migration and acquisition of endothelial-like phenotype as well as the underlying molecular mechanisms remain unknown. Additionally, the role of fibronectin in pregnancy establishment and maintenance warrants further investigation., Methods: Primary and immortalized (HTR8/SVneo) human EVTs were used as in vitro study models. Cultured human first-trimester chorionic villous explants were utilized for ex vivo validation. A local fibronectin knockdown model in ICR mouse uteri, achieved by nonviral in vivo transfection with small interfering RNA (siRNA) targeting fibronectin 1 (si-Fn1), was employed to explore the roles of fibronectin in the establishment and maintenance of early pregnancy., Results: Our results showed that activin A treatment significantly induced fibronectin 1 (FN1) mRNA expression and fibronectin protein production, which is essential for human trophoblast migration and endothelial-like tube formation. Both basal and activin A-upregulated fibronectin expression were abolished by the TGF-β type I receptor inhibitor SB431542 or siRNA-mediated knockdown of activin receptor-like kinase (ALK4) or SMAD4. Moreover, activin A-increased trophoblast migration and endothelial-like tube formation were attenuated following the depletion of fibronectin. Fibronectin knockdown via intrauterine siRNA administration reduced CD31 and cytokeratin 8 (CK8) expression at the maternal-fetal interface, resulting in a decrease in the number of implantation sites and embryos., Conclusions: Our study demonstrates that activin A promotes trophoblast cell migration and acquisition of endothelial-like phenotype via ALK4-SMAD2/3-SMAD4-mediated fibronectin upregulation. Furthermore, through a local fibronectin knockdown model in mouse uteri, we found that the absence of fibronectin at the maternal-fetal interface impedes endovascular migration of trophoblasts and decidual vascularization, thereby interfering with early embryo implantation and the maintenance of pregnancy. These findings provide novel insights into placental development during early pregnancy establishment and contribute to the advancement of therapeutic approaches for managing pregnancy complications related to trophoblast dysfunction., (© 2024. The Author(s).)

Drug discovery and development constitute a laborious and costly undertaking. The success of a drug hinges not only good efficacy but also acceptable absorption, distribution, metabolism, elimination, and toxicity (ADMET) properties. Overall, up to 50% of drug development failures have been contributed from undesirable ADMET profiles. As a multiple parameter objective, the optimization of the ADMET properties is extremely challenging owing to the vast chemical space and limited human expert knowledge. In this study, a freely available platform called Chemical Molecular Optimization, Representation and Translation (ChemMORT) is developed for the optimization of multiple ADMET endpoints without the loss of potency (https://cadd.nscc-tj.cn/deploy/chemmort/). ChemMORT contains three modules: Simplified Molecular Input Line Entry System (SMILES) Encoder, Descriptor Decoder and Molecular Optimizer. The SMILES Encoder can generate the molecular representation with a 512-dimensional vector, and the Descriptor Decoder is able to translate the above representation to the corresponding molecular structure with high accuracy. Based on reversible molecular representation and particle swarm optimization strategy, the Molecular Optimizer can be used to effectively optimize undesirable ADMET properties without the loss of bioactivity, which essentially accomplishes the design of inverse QSAR. The constrained multi-objective optimization of the poly (ADP-ribose) polymerase-1 inhibitor is provided as the case to explore the utility of ChemMORT., (© The Author(s) 2024. Published by Oxford University Press.)