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Abstract Background The postharvest rot of kiwifruit is one of the most devastating diseases affecting kiwifruit quality worldwide. However, the genomic basis and pathogenicity mechanisms of kiwifruit rot pathogens are lacking. Here we report the first whole genome sequence of Pestalotiopsis microspora, one of the main pathogens causing postharvest kiwifruit rot in China. The genome of strain KFRD-2 was sequenced, de novo assembled, and analyzed. Results The genome of KFRD-2 was estimated to be approximately 50.31 Mb in size, with an overall GC content of 50.25%. Among 14,711 predicted genes, 14,423 (98.04%) exhibited significant matches to genes in the NCBI nr database. A phylogenetic analysis of 26 known pathogenic fungi, including P. microspora KFRD-2, based on conserved orthologous genes, revealed that KFRD-2’s closest evolutionary relationships were to Neopestalotiopsis spp. Among KFRD-2’s coding genes, 870 putative CAZy genes spanned six classes of CAZys, which play roles in degrading plant cell walls. Out of the 25 other plant pathogenic fungi, P. microspora possessed a greater number of CAZy genes than 22 and was especially enriched in GH and AA genes. A total of 845 transcription factors and 86 secondary metabolism gene clusters were predicted, representing various types. Furthermore, 28 effectors and 109 virulence-enhanced factors were identified using the PHI (pathogen host-interacting) database. Conclusion This complete genome sequence analysis of the kiwifruit postharvest rot pathogen P. microspora enriches our understanding its disease pathogenesis and virulence. This study establishes a theoretical foundation for future investigations into the pathogenic mechanisms of P. microspora and the development of enhanced strategies for the efficient management of kiwifruit postharvest rots.

Abstract Background The plasma concentrations of acyl coenzyme A binding protein (ACBP, also known as diazepam-binding inhibitor, DBI, or ‘endozepine’) increase with age and obesity, two parameters that are also amongst the most important risk factors for cancer. Methods We measured ACBP/DBI in the plasma from cancer-free individuals, high-risk patients like the carriers of TP53 or BRCA1/2 mutations, and non-syndromic healthy subjects who later developed cancer. In mice, the neutralization of ACBP/DBI was used in models of non-small cell lung cancer (NSCLC) and breast cancer development and as a combination treatment with chemoimmunotherapy (chemotherapy + PD-1 blockade) in the context of NSCLC and sarcomas. The anticancer T cell response upon ACBP/DBI neutralization was characterized by flow cytometry and single-cell RNA sequencing. Results Circulating levels of ACBP/DBI were higher in patients with genetic cancer predisposition (BRCA1/2 or TP53 germline mutations) than in matched controls. In non-syndromic cases, high ACBP/DBI levels were predictive of future cancer development, and especially elevated in patients who later developed lung cancer. In preclinical models, ACBP/DBI neutralization slowed down breast cancer and NSCLC development and enhanced the efficacy of chemoimmunotherapy in NSCLC and sarcoma models. When combined with chemoimmunotherapy, the neutralizing monoclonal antibody against ACBP/DBI reduced the frequency of regulatory T cells in the tumor bed, modulated the immune checkpoint profile, and increased activation markers. Conclusion These findings suggest that ACBP/DBI acts as an endogenous immune suppressor. We conclude that elevation of ACBP/DBI constitutes a risk factor for the development of cancer and that ACBP/DBI is an actionable target for improving cancer immunosurveillance.

Abstract Activating brown adipose tissue (BAT) improves systemic metabolism, making it a promising target for metabolic syndrome. BAT is activated by 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME), which we previously identified to be inversely associated with BMI and which directly improves metabolism in multiple tissues. Here we profile plasma lipidomics from 83 people and test which lipids’ association with BMI replicates in a concordant direction using our novel tool ScreenDMT, whose power and validity we demonstrate via mathematical proofs and simulations. We find that the linoleic acid diols 12,13-diHOME and 9,10-diHOME are both replicably inversely associated with BMI and mechanistically activate calcium influx in mouse brown and white adipocytes in vitro, which implicates this signaling pathway and 9,10-diHOME as candidate therapeutic targets. ScreenDMT can be applied to test directional mediation, directional replication, and qualitative interactions, such as identifying biomarkers whose association is shared (replication) or opposite (qualitative interaction) across diverse populations.

Abstract Introduction The correlation between radiation exposure before pregnancy and abnormal birth weight has been previously proven. However, for large-for-gestational-age (LGA) babies in women exposed to radiation before becoming pregnant, there is no prediction model yet. Material and methods The data were collected from the National Free Preconception Health Examination Project in China. A sum of 455 neonates (42 SGA births and 423 non-LGA births) were included. A training set (n = 319) and a test set (n = 136) were created from the dataset at random. To develop prediction models for LGA neonates, conventional logistic regression (LR) method and six machine learning methods were used in this study. Recursive feature elimination approach was performed by choosing 10 features which made a big contribution to the prediction models. And the Shapley Additive Explanation model was applied to interpret the most important characteristics that affected forecast outputs. Results The random forest (RF) model had the highest average area under the receiver-operating-characteristic curve (AUC) for predicting LGA in the test set (0.843, 95% confidence interval [CI]: 0.714–0.974). Except for the logistic regression model (AUC: 0.603, 95%CI: 0.440–0.767), other models’ AUCs displayed well. Thereinto, the RF algorithm’s final prediction model using 10 characteristics achieved an average AUC of 0.821 (95% CI: 0.693–0.949). Conclusion The prediction model based on machine learning might be a promising tool for the prenatal prediction of LGA births in women with radiation exposure before pregnancy.

Abstract Objective Brachytherapy has been indicated as an alternative option for treating cystic craniopharyngiomas (CPs). The potential benefits of brachytherapy for CPs have not yet been clarified. The purpose of this work was to conduct a meta-analysis to analyze the long-term efficacy and adverse reactions profile of brachytherapy for CPs. Materials and methods The relevant databases were searched to collect the clinical trials on brachytherapy in patients with CPs. Included studies were limited to publications in full manuscript form with at least 5-year median follow-up, and adequate reporting of treatment outcomes and adverse reactions data. Stata 12.0 was used for data analysis. Results According to the inclusion and exclusion criteria, a total of 6 clinical trials involving 266 patients with CPs were included in this meta-analysis. The minimum average follow-up was 5 years. The results of the meta-analysis showed that 1-year, 2–3 years and 5 years progression free survival rates (PFS) are 75% (95%CI: 66-84%), 62% (95%CI: 52-72%) and 57% (95%CI: 22-92%), respectively. At the last follow-up, less than 16% of patients with visual outcomes worser than baseline in all included studies. While, for endocrine outcomes, less than 32% of patients worser than baseline level. Conclusion In general, based on the above results, brachytherapy should be considered as a good choice for the treatment of CP.

The combination of photodynamic therapy (PDT)-immunotherapy has brought much hope for cancer patients. However, the hypoxia tumor microenvironment (TME) can regulate tumor angiogenesis and inhibit immune response, thus limiting the therapeutic effects. In this paper, engineered cyanobacteria-M2-like tumor-associated macrophages (TAMs) targeting peptide modified Fe3O4 nanoparticles hybrid system (ECyano@Fe3O4-M2pep) was constructed for alleviating hypoxia and relieving immune suppression to achieve synergistic cancer PDT-immunotherapy. With the irradiation of red laser, oxygen was produced by the photosynthesis of ECyano to alleviate the hypoxia TME. Then, ECyano could secret 5-aminolevulinic acid (5-ALA) under the induction of theophylline for controllable PDT. In the process of PDT, the disulfide bond between ECyano and Fe3O4-M2pep was broken in response to reactive oxygen species (ROS), and then Fe3O4-M2pep was released to target M2-like TAMs, corresponding by the polarization of M2-like TAMs to M1-like TAMs for the killing of tumor cells. Compared with other groups, ECyano@Fe3O4-M2pep + theophylline + laser (ECyano@Fe3O4-M2pep + T + L) group displayed the lowest tumor volume (159.3 mm3) and the highest M1/M2 ratio (1.25- fold). We believe that this hybrid system will offer a promising way for the biomedical application of bacterial therapy.

ABSTRACT Background Cornelia de Lange syndrome (CdLS) is an uncommon congenital developmental disorder distinguished by intellectual disorder and distinctive facial characteristics, with a minority of cases attributed to RAD21 variants. Methods A patient was admitted to the endocrinology department at Peking Union Medical College Hospital, where 2 mL of peripheral venous blood was collected from the patient and his parents. DNA was extracted for whole‐exome sequencing (WES) analysis, and the genetic variation of the parents was confirmed through Sanger sequencing. Results A 13.3‐year‐old male patient with a height of 136.5 cm (−3.5 SDS) and a weight of 28.4 kg (−3.1 SDS) was found to have typical craniofacial features. WES revealed a pathogenic variant c.1143G>A (p.Trp381*) in the RAD21 gene. He was diagnosed with CdLS type 4 (OMIM #614701). We reviewed 36 patients with CdLS related to RAD21 gene variants reported worldwide from May 2012 to March 2024. Patient's variant status, clinical characteristics, and rhGH treatment response were summarized. Frameshift variants constituted the predominant variant type, representing 36% (13/36) of cases. Clinical features included verbal developmental delay and intellectual disorder observed in 94% of patients. Conclusion This study reported the third case of CdLS type 4 in China caused by a RAD21 gene variant, enriching the genetic mutational spectrum.

Skeletal muscle has a unique ability to remodel in response to stimuli such as contraction and aerobic exercise training. Phenotypic changes in muscle that occur with training such as a switch to a more oxidative fiber type, and increased capillary density contribute to the well-known health benefits of aerobic exercise. The muscle matrisome likely plays an important role in muscle remodeling with exercise. However, due to technical limitations in studying muscle ECM proteins, which are highly insoluble, little is known about the muscle matrisome and how it contributes to muscle remodeling. Here, we utilized two-fraction methodology to extract muscle proteins, combined with multiplexed tandem mass tag proteomic technology to identify 161 unique ECM proteins in mouse skeletal muscle. In addition, we demonstrate that aerobic exercise training induces remodeling of a significant proportion of the muscle matrisome. We performed follow-up experiments to validate exercise-regulated ECM targets in a separate cohort of mice using Western blotting and immunofluorescence imaging. Our data demonstrate that changes in several key ECM targets are strongly associated with muscle remodeling processes such as increased capillary density in mice. We also identify LOXL1 as a novel muscle ECM target associated with aerobic capacity in humans. In addition, publically available data and databases were used for in silico modeling to determine the likely cellular sources of exercise-induced ECM remodeling targets and identify ECM interaction networks. This work greatly enhances our understanding of ECM content and function in skeletal muscle and demonstrates an important role for ECM remodeling in the adaptive response to exercise. The raw MS data have been deposited to the ProteomeXchange with identifier PXD053003.

Abstract Background The vestibular aqueduct (VA) serves an essential role in homeostasis of the inner ear and pathogenesis of Ménière’s disease (MD). The bony VA can be clearly depicted by high-resolution computed tomography (HRCT), whereas the optimal sequences and parameters for magnetic resonance imaging (MRI) are not yet established. We investigated VA characteristics and potential factors influencing MRI-VA visibility in unilateral MD patients. Methods One hundred patients with unilateral MD underwent MRI with three-dimensional sampling perfection with application optimized contrasts using different flip angle evolutions (3D-SPACE) sequence and HRCT evaluation. The imaging variables included MRI-VA and CT-VA visibility, CT-VA morphology and CT-peri-VA pneumatization. Results The most frequent type of MRI-VA and CT-VA visualization was invisible VA and continuous VA, respectively. The MRI-VA visibility was significantly lower than CT-VA visibility. MRI-VA visibility had a weak positive correlation with ipsilateral CT-VA visualization. For the affected side, the MRI-VA visualization was negatively correlated with the incidence of obliterated-shaped CT-VA and positively with that of tubular-shaped CT-VA. MRI-VA visualization was not affected by CT-peri-VA pneumatization. Conclusion In patients with MD, the VA visualization on 3D-SPACE MRI is poorer than that observed on CT and may be affected by its osseous configuration. These findings may provide a basis for further characterization of VA demonstrated by MRI and its clinical significance.

Objective: Patients with growth hormone deficiency (GHD) with inadequate growth hormone levels are often correlated with nonalcoholic fatty liver disease (NAFLD). However, the potential mechanism of how GHD influences liver function remains obscure. In the present study, we aim to perform hepatic metabolomics in Lewis dwarf rats, which were the standard congenital isolated GH-deficient rat, to evaluate the characterizations of hepatic metabolic profiles and explore their relations with liver functions. Methods: Lewis dwarf homozygous (dw/dw) rats at 37 weeks (five females and five males), and Lewis dwarf heterozygous (dw/+) rats at 37 weeks (five females and five males) were analyzed in our study. Body lengths and weights, liver weights, serum alanine transaminase (ALT), and serum aspartate transaminase (AST) were measured. ELISA and RT-qPCR were used to assess IGF-1 levels in serum and liver, respectively. The non-targeted metabolomics was performed in the livers of dw/+ and dw/dw rats. Differential metabolites were selected according to the coefficient of variation (CV), variable importance in the projection (VIP) > 1, and P < 0.05. Hierarchical clustering of differential metabolites was conducted, and the KEGG database was used for metabolic pathway analysis. Results: The body weights, body lengths, liver weights, and IGF-1 levels in the serum and liver of dw/dw rats were significantly decreased compared with dw/+ rats. Dw/dw rats exhibited more obvious hepatic steatosis accompanied by higher serum ALT and AST levels. Hepatic metabolomics showed that a total of 88 differential metabolites in positive ion mode, and 51 metabolites in negative ion mode were identified. Among them, lysophosphatidylcholine (LPC) 16:2, LPC 18:3, LPC 22:6, fatty acid esters of hydroxy fatty acids (FAHFA)18:1 were significantly decreased, while palmitoyl acid, dehydrocholic acid, and 7-ketolithocholic acid were significantly increased in dw/dw rats compared with dw/+ rats. These seven differential metabolites were significantly associated with phenotypes of rats. Finally, KEGG pathway analysis showed that the arginine and proline metabolism pathway and bile secretion pathway were mainly clustered. Conclusion: Lewis dw/dw rats with congenital isolated growth hormone deficiency (IGHD) showed liver steatosis and abnormal liver function, which could be potentially associated with the distinctive hepatic metabolic profiles.

Abstract Applying high stack pressure (often up to tens of megapascals) to solid-state Li-ion batteries is primarily done to address the issues of internal voids formation and subsequent Li-ion transport blockage within the solid electrode due to volume changes. Whereas, redundant pressurizing devices lower the energy density of batteries and raise the cost. Herein, a mechanical optimization strategy involving elastic electrolyte is proposed for SSBs operating without external pressurizing, but relying solely on the built-in pressure of cells. We combine soft-rigid dual monomer copolymer with deep eutectic mixture to design an elastic solid electrolyte, which exhibits not only high stretchability and deformation recovery capability but also high room-temperature Li-ion conductivity of 2×10−3 S cm−1 and nonflammability. The micron-sized Si anode without additional stack pressure, paired with the elastic electrolyte, exhibits exceptional stability for 300 cycles with 90.8% capacity retention. Furthermore, the solid Li/elastic electrolyte/LiFePO4 battery delivers 143.3 mAh g−1 after 400 cycles. Finally, the micron-sized Si/elastic electrolyte/LiFePO4 full cell operates stably for 100 cycles in the absence of any additional pressure, maintaining a capacity retention rate of 98.3%. This significantly advances the practical applications of solid-state batteries.

BackgroundDysnatremia is the most common electrolyte disorder in hospitalized patients. Sodium fluctuation level may be a better parameter in dysnatremia management. We aimed to examine the association between sodium fluctuation level during hospitalization and mortality and to evaluate its value in predicting poor prognosis among general hospitalized patients.MethodsData were collected from patients admitted to Peking Union Medical College Hospital. The generalized estimated equation (GEE) was used to examine the relationship between sodium fluctuation level and mortality. Receiver-operating characteristic (ROC) curve analysis was performed to calculate the optimal cutoff value and the area under the ROC curve (AUC).ResultsSodium fluctuation level showed a dose-dependent association with increased mortality in general hospitalized patients. After adjusting age, sex, length of hospital stay, and Charlson comorbidity index, the ORs of group G2 to G6 were 5.92 (95% CI 5.16–6.79), 26.45 (95% CI 22.68–30.86), 50.71 (95% CI 41.78–61.55), 104.38 (95% CI 81.57–133.58), and 157.64 (95% CI 112.83–220.24), respectively, p trend

Summary: Tissues release microRNAs (miRNAs) in small extracellular vesicles (sEVs) including exosomes, which can regulate gene expression in distal cells, thus acting as modulators of local and systemic metabolism. Here, we show that insulin regulates miRNA secretion into sEVs from 3T3-L1 adipocytes and that this process is differentially regulated from cellular expression. Thus, of the 53 miRNAs upregulated and 66 miRNAs downregulated by insulin in 3T3-L1 sEVs, only 12 were regulated in parallel in cells. Insulin regulated this process in part by phosphorylating hnRNPA1, causing it to bind to AU-rich motifs in miRNAs, mediating their secretion into sEVs. Importantly, 43% of insulin-regulated sEV-miRNAs are implicated in obesity and insulin resistance. These include let-7 and miR-103, which we show regulate insulin signaling in AML12 hepatocytes. Together, these findings demonstrate an important layer to insulin’s regulation of adipose biology and provide a mechanism of tissue crosstalk in obesity and other hyperinsulinemic states.

Abstract As a very prospective solid‐state electrolyte, Li10GeP2S12 (LGPS) exhibits high ionic conductivity comparable to liquid electrolytes. However, severe self‐decomposition and Li dendrite propagation of LGPS will be triggered due to the thermodynamic incompatibility with Li metal anode. Herein, by adopting a facile chemical vapor deposition method, an artificial solid electrolyte interphase composed of Li2S is proposed as a single ionic conductor to promote the interface stability of LGPS toward Li. The good electronic insulation coupled with ionic conduction property of Li2S effectively blocks electron transfer from Li to LGPS while enabling smooth passage of Li ions. Meanwhile, the generated Li2S layer remains good interface compatibility with LGPS, which is verified by the stable Li‐plating/stripping operation for over 500 h at 0.15 mA cm−2. Consequently, the all‐solid‐state Li–S batteries (ASSLSBs) with a Li2S layer demonstrate superb capacity retention of 90.8% at 0.2 mA cm−2 after 100 cycles. Even at the harsh condition of 90 °C, the cell can deliver a high reversible capacity of 1318.8 mAh g−1 with decent capacity retention of 88.6% after 100 cycles. This approach offers a new insight for interface modification between LGPS and Li and the realization of ASSLSBs with stable cycle life.

Under the new demand model of Agriculture 4.0, automated spraying is a very complex task in precision agriculture, which needs to be combined with a computerized vision perception system to distinguish the plant leaf density and execute the spraying operation in real-time accordingly. Aiming at the accurate determination of grape leaf density, an image leaf density determination method based on the lightweight Vision Transformer (ViT) architecture is proposed, which designs a fusion data augmentation method containing a dual augmentation spatial extension and weather data augmentation method, where the former adopts the pixel augmentation and spatial augmentation for the original image processing, and the latter realizes the data augmentation from the empirical point of view adapted to the agricultural operation environment, and fuses the two in order to expand the sample capacity of the grape leaf density image, which then enhances the model's generalization ability and robustness. The lightweight ViT model has self-attention that can automatically and efficiently extract high-frequency local feature representations and use the two-branch structure to mix high-frequency and low-frequency information to form grapevine-leaf density features in the region of interest. The semantic analysis of the feature extraction layer is parsed using t-SNE and histogram methods, which improves the transparency of the model from the multidimensional with frequency domain distribution space. The experimental results show that the fusion data augmentation method can effectively improve the model recognition accuracy, and the accuracy of comparing the included data augmentation methods is improved by 0.55 % and 3.46 %, respectively. The accuracy of recognizing all four types of grape leaf densities exceeded 94 %, and the MCC reached 90.39 %. In addition, the proposed lightweight ViT improves the accuracy by at least 0.34 % with FLOPs of only 0.6 G compared to the popular MobileViT. The proposed method of this work has high recognition speed and accuracy, which can provide practical technical support for plant protection spraying robots and improve the profitability of growers based on the reduction of pesticide residues.

The relationship between the protective performance of flexible polymer material and material parameters (elastic modulus, viscosity coefficient) is explored, an impact collision motion equation between two bodies is established from the viscoelastic material constitutive, and the relationship between the kinematic response and the material parameters is obtained. Based on the Kelvin constitutive model, a theoretical model for impact between the protective body and the protected body is established, then the dynamic response is obtained. The feasibility of the model was verified by drop hammer experiment, and the material parameters (elastic modulus, viscosity coefficient) were obtained by formula. The model is discretized and the relationship between local impact response and material parameters is analyzed. The discussion results on the relationship between the impact response and the protective material performance indicate that adjusting the elastic modulus, viscosity coefficient, and thickness of the protective material can effectively improve protective effect.

Abstract Urban street greening is an important part of urban green infrastructure, and Green View Index (GVI) is widely used to assess urban street quality and ecosystem service value as an important indicator to quantify the perception of green street landscape from a pedestrian perspective. However, the distribution of street greenery is imbalanced. Therefore, to explore the differences in street greening levels within urban cities, we crawled streetscape data using the Internet to assess the spatial distribution patterns of urban street GVI using deep learning and spatial autocorrelation, and combined 11 surrounding environmental features with multi-source geographic data to further analyze the key factors influencing the spatial variation of block GVI using ordinary least squares, geographically weighted regression (GWR) models, and multi-scale geographically weighted regression (MGWR) models. The results show that the mean value of GVI in Fuzhou city is low (23.08%), with large differences among neighborhoods and a significant spatial autocorrelation. Among the regression models, MGWR has the best fit with an R2 of 0.702, where the variables of NDVI, house price, accessibility of water bodies and parks, and the proportion of built-up land have a greater impact on GVI, and the factors do not have the same spatial effect size. The results can provide a scientific basis for promoting green visual equity in different blocks.

Abstract Background Pseudohypoparathyroidism type 1 (PHP1) is a rare disease featuring hypocalcemia and elevated PTH level. Though disturbed calcium and phosphorus metabolism under PTH resistant have been widely studied, glucolipid metabolism abnormalities observed in PHP1 patients have received little attention. The aim of this research is to explore the glucolipid metabolism features in a rather large cohort of PHP1 patient. In the current study, PHP1 patients and primary hyperparathyroidism patients as well as normal control were recruited for the investigation. Glucolipid metabolic indices as well as the level of four adipokines were examined. Results A total of 49 PHP1 patients, 64 PHPT patients and 30 healthy volunteers were enrolled. A trend of higher HOMA-β index was found in PHP1 patients than normal controls (median 97.08% vs 68.19%, p = 0.060). Both the PHP1 and PHPT group presented with significantly lower TNFα level compared to normal controls (average 10.74 pg/ml and 12.53 pg/ml vs 15.47 pg/ml, p = 0.002 and 0.041, respectively). FGF21 level was significantly higher in PHPT group than in PHP1 group (median 255.74 pg/ml vs 167.46 pg/ml, p = 0.019). No significant difference in glucolipid metabolic indices and adipokines was found between PHP1A or PHP1B patients and normal controls, while overweight/obese PHP1 patients tended to have higher leptin than normal-BMI cases (p = 0.055). Multiple linear regression analysis showed BMI rather than PTH or HOMA-IR to be an independent variable of leptin in PHP1. Conclusion Metabolic stress given upon especially overweight PHP1 patients may resulted in possible β-cell compensation. Elevated TNFα may be related with hyper-PTH level regardless of calcium level.

Abstract Background The relationship between the Coronavirus Disease 2019 (COVID-19) pandemic, which is a traumatic event for adolescents, and procrastination is not clear. Mental health may play an important role in this relationship; however, the underlying mechanisms remain unknown. This study aimed to construct chain mediation models to examine whether anxiety and depression symptoms mediate the effects of the COVID-19 pandemic on procrastination in adolescents. Methods A convenience sample of 12 middle and high schools in Harbin, China, with four follow-up online surveys was conducted during the COVID-19 pandemic. A total of 4,156 Chinese adolescents were enrolled in this study, of whom ages 11–18 (Mean = 13.55; SD = 1.18), 50.75% were male, and 93.24% were middle school students. Descriptive demographic analysis and Pearson’s correlation analysis of the effects of the COVID-19 pandemic (T1), anxiety(T2), depression (T3), and procrastination (T4) were performed in SPSS 22.0. Chain mediation analysis performed with Mplus 8.3. Results The effects of the COVID-19 pandemic, anxiety symptoms, depression symptoms, and procrastination were positively correlated (P

ObjectiveDouble pituitary adenomas (DPA) are a rare clinical condition, and our knowledge of them is limited. Missing the second lesion leading to incomplete biochemical remission after surgery is an important challenge in DPA management. This study aims to analyze independent prognostic factors in DPA patients and summarize clinical experiences to prevent surgical failure.MethodsTwo cases of DPA patients with Cushing’s disease diagnosed and surgically treated at Peking Union Medical College Hospital are reported. A literature review was performed on the online database Pubmed, and 57 DPA patients from 22 retrieved articles were included. Demographic characteristics, endocrine manifestations, diagnostic methods, tumor size, and immunohistochemical features of 59 patients were analyzed. Binary logistic regression models were used to identify independent prognostic factors affecting postoperative biochemical remission.ResultsAmong 59 DPA patients, the mean ± SD age was 43.64 ± 14.42 years, with 61.02% being female (n = 36). The most common endocrine manifestations were Cushing’s syndrome (23/59, 38.98%) and acromegaly (20/59, 33.90%). The most prevalent immunohistochemical types were ACTH-immunopositive (31/118, 26.27%) and GH-immunopositive (31/118, 26.27%) tumors. Microadenomas (

Summary: Background: The prevalence and risk factors for failure to thrive (FTT) in pediatric patients with congenital heart disease (CHD) remain ambiguous. We aimed to investigate the prevalence, growth profiles, risk factors, and vulnerable subtypes of CHD associated with FTT in pediatric patients with CHD. Methods: This was a cross-sectional study based on Chinese Database for Congenital Heart Surgery. FTT was defined as either stunting or underweight (height or weight standard deviation score

BackgroundColorectal cancer (CRC) is considered the most prevalent synchronous malignancy in patients with gastric cancer. This large retrospective study aims to clarify correlations between gastric histopathology stages and risks of specific colorectal neoplasms, to optimize screening and reduce preventable CRC.MethodsClinical data of 36,708 patients undergoing gastroscopy and colonoscopy from 2005-2022 were retrospectively analyzed. Correlations between gastric and colorectal histopathology were assessed by multivariate analysis. Outcomes of interest included non-adenomatous polyps (NAP), conventional adenomas (CAs), serrated polyps (SPs), and CRC. Statistical analysis used R version 4.0.4.ResultsOlder age (≥50 years) and Helicobacter pylori infection (HPI) were associated with increased risks of conventional adenomas (CAs), serrated polyps (SPs), non-adenomatous polyps (NAP), and colorectal cancer (CRC). Moderate to severe intestinal metaplasia specifically increased risks of NAP and CAs by 1.17-fold (95% CI 1.05-1.3) and 1.19-fold (95% CI 1.09-1.31), respectively. For CRC risk, low-grade intraepithelial neoplasia increased risk by 1.41-fold (95% CI 1.08-1.84), while high-grade intraepithelial neoplasia (OR 3.76, 95% CI 2.25-6.29) and gastric cancer (OR 4.81, 95% CI 3.25-7.09) showed strong associations. More advanced gastric pathology was correlated with progressively higher risks of CRC.ConclusionPrecancerous gastric conditions are associated with increased colorectal neoplasm risk. Our findings can inform screening guidelines to target high-risk subgroups, advancing colorectal cancer prevention and reducing disease burden.

Background: Manual bone age assessment (BAA) is associated with longer interpretation time and higher cost and variability, thus posing challenges in areas with restricted medical facilities, such as the high-altitude Tibetan Plateau. The application of artificial intelligence (AI) for automating BAA could facilitate resolving this issue. This study aimed to develop an AI-based BAA model for Han and Tibetan children.Methods: A model named “EVG-BANet” was trained using three datasets, including the Radiology Society of North America (RSNA) dataset (training set n = 12611, validation set n = 1425, and test set n = 200), the Radiological Hand Pose Estimation (RHPE) dataset (training set n = 5491, validation set n = 713, and test set n = 79), and a self-established local dataset [training set n = 825 and test set n = 351 (Han n = 216 and Tibetan n = 135)]. An open-access state-of-the-art model BoNet was used for comparison. The accuracy and generalizability of the two models were evaluated using the abovementioned three test sets and an external test set (n = 256, all were Tibetan). Mean absolute difference (MAD) and accuracy within 1 year were used as indicators. Bias was evaluated by comparing the MAD between the demographic groups.Results: EVG-BANet outperformed BoNet in the MAD on the RHPE test set (0.52 vs. 0.63 years, p < 0.001), the local test set (0.47 vs. 0.62 years, p < 0.001), and the external test set (0.53 vs. 0.66 years, p < 0.001) and exhibited a comparable MAD on the RSNA test set (0.34 vs. 0.35 years, p = 0.934). EVG-BANet achieved accuracy within 1 year of 97.7% on the local test set (BoNet 90%, p < 0.001) and 89.5% on the external test set (BoNet 85.5%, p = 0.066). EVG-BANet showed no bias in the local test set but exhibited a bias related to chronological age in the external test set.Conclusion: EVG-BANet can accurately predict the bone age (BA) for both Han children and Tibetan children living in the Tibetan Plateau with limited healthcare facilities.

Abstract Background Despite the growing interest in the impact of the gut microbiome on cancer, the relationship between the lung microbiome and lung cancer has received limited investigation. Additionally, the composition of the oral microbiome was found to differ from that of individuals with lung cancer, indicating that these microorganisms may serve as potential biomarkers for the detection of lung cancer. Methods Forty-three Chinese lung cancer patients were enrolled in the current retrospective study and 16 S rRNA sequencing was performed on saliva, cancerous tissue (CT) and paracancerous tissue (PT) samples. Results Diversity and species richness were significantly different between the oral and lung microbiota. Lung microbiota were largely composed of the phyla Proteobacteria, Firmicutes, Bacteroidetes and Actinobacteria. The relative abundance of Promicromonosporacea and Chloroflexi increased in CT, while Enterococcaceae and Enterococcus were enriched in PT (p

Highlights Fundamental principles underlying the design of oxide catalysts, including the influence of crystal structure, and electronic structure on their performance are summarized and analyzed. Challenges associated with developing oxide catalysts and the potential strategies are discussed.

Highlights This review systematically analyzes the effect of the electrolyte-to-sulfur ratios on battery energy density and the challenges for sulfur reduction reactions under lean electrolyte conditions. The strengths and limitations of different transition metal compounds are systematically presented and discussed from a fundamental perspective. Three promising strategies for sulfur hosts that act as anchors and catalysts are proposed to boost lean electrolyte Li–S battery performance.

Abstract To study the characteristics of bacterial community structure in high-yield and low-yield moso bamboo (Phyllostachys edulis) forests, we collected bamboo rhizome, rhizome root, stem, leaf, rhizosphere soil, and non-rhizosphere soil from high- and low-yield forests in Yong'an City and Jiangle County of Fujian Province, China. The genomic DNA of the samples was extracted, sequenced and analyzed. The results show that: the common differences between the high-yield and low-yield P. edulis forest samples in the two regions were mainly in bacterial community compositions in the bamboo rhizome, rhizome root, and soil samples. Differences in the bacterial community compositions in the stem and leaf samples were insignificant. The bacterial species and diversity in rhizome root and rhizosphere soil of high-yield P. edulis forests were less than those of low-yield forests. The relative abundance of Actinobacteria and Acidobacteria in rhizome root samples of high-yield forests was higher than that in low-yield forests. The relative abundance of Rhizobiales and Burkholderiales in bamboo rhizome samples in high-yield forests was higher than that in low-yield forests. The relative abundance of Bradyrhizobium in bamboo rhizome samples in high-yield forests was higher than that in low-yield forests in the two regions. The change of bacterial community composition in P. edulis stems and leaves showed little correlation with high- or low-yields of P. edulis forests. Notably, the bacterial community composition of the rhizome root system was correlated with the high yield of bamboo. This study provides a theoretical basis for using of microbes to enhance the yields of P. edulis forests.

Postoperative cognitive dysfunction (POCD) commonly occurs after surgery, particularly in elderly individuals. It is characterized by a notable decline in cognitive performance, encompassing memory, attention, coordination, orientation, verbal fluency, and executive function. This reduction in cognitive abilities contributes to extended hospital stays and heightened mortality. The prevalence of POCD can reach 40% within 1 week following cardiovascular surgery and remains as high as 17% 3 months post-surgery. Furthermore, POCD exacerbates the long-term risk of Alzheimer’s disease (AD). As a result, numerous studies have been conducted to investigate the molecular mechanisms underlying POCD and potential preventive strategies. This article provides a review of the research progress on POCD.

Objective: Insulin acts on the liver via changes in gene expression to maintain glucose and lipid homeostasis. This study aimed to the Forkhead box protein K1 (FOXK1) associated gene regulatory network as a transcriptional regulator of hepatic insulin action and to determine its role versus FoxO1 and possible actions of the insulin receptor at the DNA level. Methods: Genome-wide analysis of FoxK1 binding were studied by chromatin immunoprecipitation sequencing and compared to those for IR and FoxO1. These were validated by knockdown experiments and gene expression analysis. Results: Chromatin immunoprecipitation (ChIP) sequencing shows that FoxK1 binds to the proximal promoters and enhancers of over 4000 genes, and insulin enhances this interaction for about 75% of them. These include genes involved in cell cycle, senescence, steroid biosynthesis, autophagy, and metabolic regulation, including glucose metabolism and mitochondrial function and are enriched in a TGTTTAC consensus motif. Some of these genes are also bound by FoxO1. Comparing this FoxK1 ChIP-seq data to that of the insulin receptor (IR) reveals that FoxK1 may act as the transcription factor partner for some of the previously reported roles of IR in gene regulation, including for LARS1 and TIMM22, which are involved in rRNA processing and cell cycle. Conclusion: These data demonstrate that FoxK1 is an important regulator of gene expression in response to insulin in liver and may act in concert with FoxO1 and IR in regulation of genes in metabolism and other important biological pathways.

Background We aimed to investigate the determinant factors of anti-PD-1 therapy outcome in nasopharyngeal carcinoma (NPC). Methods In this retrospective study, we included 64 patients with recurrent/metastatic NPC. The association of patients’ characteristics, C-reactive protein (CRP), neutrophil to lymphocyte ratio (NLR), and lactate dehydrogenase (LDH) with survival benefit of anti-PD-1 therapy were analyzed using Cox regression models and Kaplan-Meier analyses. Patients were divided based on the median value of CRP, NLR or LDH into different subgroups. Results At a median follow-up time of 11.4 months (range: 1-28 months), median progression-free survival (PFS) and overall survival (OS) were 1.9 months (95% CI, .18-3.6) and 15 months (95% CI, 10.9-19.1) months, respectively. Pretreatment metastases numbers was significant predictor of PFS (HR = 1.99; 95% CI 1.10-3.63; P = .024) and OS (HR = 2.77; 95% CI 1.36-5.61; P = .005). Baseline LDH level was independent predictor of OS (HR = 7.01; 95% CI 3.09-15.88; P < .001). Patients with LDH level >435 U/L at the baseline had significantly shorter PFS and OS compared to patients with LDH level ≤435 U/L (median PFS: 1.7 vs 3.5 months, P = .040; median OS: 3.7 vs 18.5 months, P < .001). Patients with non-durable clinical benefit (NDB) had significantly higher LDH level at the baseline compared to patients who achieved durable clinical benefit (DCB) ( P = .025). Post-treatment levels of CRP, LDH, and NLR were decreased compared to baseline in patients with DCB ( P = .030, P = .088, and P = .066, respectively), whereas, there was a significant increase in post-treatment level of LDH compared with baseline in patients with NDB ( P = .024). Conclusions LDH level at the baseline was an independent predictor of OS and pretreatment metastases numbers was a significant predictor of PFS and OS.

ObjectiveTo summarize the clinical characteristics of 4 male prolactinoma patients with severe obesity.MethodsThe clinical data of all the patients were retrospectively analyzed.ResultsAll the patients visited our hospital for severe obesity at the age of 16-30 years old with their body mass index (BMI) of 37.9-55.9 kg/m2. All the patients were obese since childhood, even at birth. Hyperprolactinemia (72.3-273.0 ng/ml) was found during the etiological screening of obesity and MRI revealed pituitary adenomas. Additionally, all of them had multiple obesity related complications, such as hyperinsulinemia and dyslipidemia. Treatment of dopamine agonists (DAs) effectively normalized their prolactin level and the pituitary MRI reexamination after 6 months of DAs treatment showed the shrinkage of the pituitary adenomas in 3 patients. Their weight also decreased in different degrees (2.70~19.03% lower than the baseline) with improved metabolic profiles.ConclusionSerum prolactin level should be screened in obese patients, especially those with severe obesity.

The design methods for gradient coils are mostly based on discrete extrinsic methods (e.g., the Biot–Savart integration calculation), for which the surface normal vector strongly influences any numerical calculation of the discretized surface. Previous studies are mostly based on regular or analytical surfaces, which allow normal vectors to be expressed analytically. For certain applications, design methods for extending current-carrying surfaces from developable or analytic geometries to arbitrary surfaces generated from a scanned point cloud are required. The key task is to correctly express the discretized normal vectors to ensure geometrical accuracy of the designed coils. Mathematically, it has been proven that applying a Delaunay triangulation to approximate a smooth surface can result in the discrete elemental normal vectors converging to those of the original surface. Accordingly, this article uses Delaunay triangulation to expand upon previous design methods so that they encompass arbitrary piecewise continuous surfaces. Two design methods, the stream function and the so-called solid isotropic material with penalization (SIMP) method, are used to design circumvolute and noncircumvolute gradient coils on general surfaces.

Li–CO2 batteries following Li2CO3-product route suffer from low output voltage and severe parasitic reactions. Herein, a soluble binuclear copper(I) complex is introduced as the liquid catalyst to achieve Li2C2O4 products in Li–CO2 batteries, which increases their output voltage to higher than 3.0 V.

The biodiversity and activity of microorganisms are crucial for litter decomposition, but how litter traits at different stages of decomposition drive changes in microbial communities has yet to be thoroughly explored. In the typical alpine hilly area of the Qinghai–Tibet Plateau, three types of litter at different decomposition stages were selected under a natural Picea crassifolia (Picea crassifolia Kom.) forest: undecomposed (A-1), partially decomposed (A-2), and fully decomposed (A-3). By measuring physicochemical indicators, microbial diversity, and the composition of the litter at different decomposition stages, this study investigates the community changes and responses of bacteria to litter characteristic changes at different decomposition levels. The results show that with the increase in decomposition level, bacterial diversity increases, community structure changes, and network complexity gradually increases, while the changes in fungal communities are insignificant. Structural equation modeling indicates that the first principal component (PC1) of litter properties is significantly negatively correlated with bacterial diversity and positively correlated with bacterial community composition. There is no significant correlation between fungal diversity and community composition, indicating a closer relationship between bacteria and litter characteristics than fungi. In summary, with an increase in litter decomposition level, the diversity and network complexity of bacterial and fungal communities will significantly increase, which is related to the changes in various litter characteristics. This study provides a scientific basis for the regulatory mechanism of litter decomposition and turnover in the alpine hilly area of the Qinghai–Tibet Plateau, specifically in Picea crassifolia forests.

Background: Sodium fluctuation is independently associated with clinical deterioration. We developed and validated a prognostic index based on sodium fluctuation for risk stratification and in-hospital monitoring. Methods: This study included 33,323 adult patients hospitalized at a tertiary care hospital in 2014. The first 28,279 hospitalizations were analyzed to develop the model and then the validity of the model was tested using data from 5044 subsequent hospitalizations. We predict in-hospital mortality using age, comorbidity, range of sodium fluctuation, and duration of sodium fluctuation, abbreviated as CARDS. Results: In-hospital mortality was similar in the derivation (0.6%) and validation (0.4%) cohorts. In the derivation cohort, four independent risk factors for mortality were identified using logistic regression: age (66–75, 2 points; >75, 3 points); Charlson comorbidity index (>2, 5 points); range of sodium fluctuation (7–10, 4 points; >10, 10 points); and duration of fluctuation (≤3, 3 points). The AUC was 0.907 (95% CI: 0.885–0.928) in the derivation cohort and 0.932 (95% CI: 0.895–0.970) in the validation cohort. In the derivation cohort, in-hospital mortality was 0.106% in the low-risk group (0–7 points), 1.076% in the intermediate-risk group (8–14 points), and 8.463% in the high-risk group (15–21 points). In the validation cohort, in-hospital mortality was 0.049% in the low-risk group, 1.064% in the intermediate-risk group, and 8.403% in the high-risk group. Conclusions: These results suggest that patients at low, intermediate, and high risk for in-hospital mortality may be identified by CARDS mainly based on sodium fluctuation.

Metastatic PitNETs are a rare life-threatening condition with poor prognosis and documentation. Due to the scarce literature and lack of precise treatment, we hope to better characterise PitNET using the next-generation whole exon sequencing (WES) and RNA sequencing. This case study outlines a 54 years-old man and a 52 years-old woman who were both diagnosed with PitNET and analysis of peripheral blood and tumours were performed by WES and RNA sequencing. Analysis showed that DICER1 mutations in precancerous lesions and LAG3 overexpression were significant in aiding the prognosis and diagnosis of PitNETs. The first case with overexpressed LAG3 and DICER1 mutation died 26 months later, and the second case with LAG3 overexpression achieved partial remission. This study revealed that heightened expression of LAG3 offered promising targets for ICI and mutations in DICER1 could provide markers for effective diagnosis and prognosis.

Nagao et al. show that the insulin receptor can mediate receptor-dependent, but ligand- and tyrosine kinase-independent, events. These are associated with regulation of extracellular matrix, cell cycle, ATM signaling, senescence and apoptosis.

Abstract Metastasis and chemical resistance are the most serious problems in the treatment of highly aggressive uveal melanoma (UM). The newly identified lncRNA OUM1 is overexpressed in UM, functions as a catalyst and regulates protein tyrosine phosphatase (PTP) activity by binding to PTP receptor type Z1 (PTPRZ1), which plays an important role in cell proliferation, metastasis and chemotherapy resistance in the UM microenvironment. Hence, siRNAs that selectively knocking down the lncRNA OUM1 (siOUM1) and its target gene PTPRZ1 (siPTPRZ1) were designed to inhibit the OUM1/PTPRZ1 pathway to reduce PTP activity, and this reduction in activity interrupts protein tyrosine phosphorylation, suppresses UM proliferation and metastasis and improves cisplatin sensitivity in UM cells. Then, to overcome the limitations of the difficulty of drug administration and traditional therapeutics, the indocyanine green (ICG)-labeled manganese metal–organic framework (MOF) nanoparticles (NPs) were fabricated and linked with arginine-glycine-aspartate (RGD) peptide to carry siOUM1/siPTPRZ1 and cisplatin to achieve targeted siRNA interference-mediated therapy, enhanced cisplatin therapy and chemodynamic therapy. This NP system also has a dual-modal imaging ability because ICG is a near-infrared region fluorescent dye and manganese has the potential to be used in magnetic resonance imaging. This study verifies the significance of the newly discovered lncRNA OUM1 as a new therapeutic target for aggressive UM and provides a drug delivery NP system for precise treatment of UM accompanied with a dual-modal imaging ability. Graphical Abstract

Abstract F-box and WD repeat domain containing 7 (FBXW7) acts as a substrate receptor of SKP1-CUL1-F-box (SCF) E3 ubiquitin ligase and plays crucial roles in the regulation of several cellular processes, including cell growth, division, and differentiation, by targeting diverse key regulators for degradation. However, its role in regulating cellular senescence remains elusive. Here, we found that FBXW7 inactivation by siRNA-based knockdown or CRISPR/Cas9-based knockout induced significant cellular senescence in p53 wild-type cells, but not in p53 mutant or null cells, along with activation of both the p53/p21 and p16INK4a/Rb pathways. Simultaneous p53 inactivation abrogated senescence and cell growth arrest induced by FBXW7 deficiency as well as the alteration of both the p53/p21 and p16INK4a/Rb pathways. Moreover, Fbxw7 deletion accelerated replicative senescence of primary mouse embryonic fibroblasts in a p53-dependent manner. In addition, FBXW7 deletion induced the senescence-associated secretory phenotype to trigger secondary senescence. Importantly, in a radiation-induced senescence mouse model, simultaneous deletion of p53 rescued accelerated senescence and aging caused by Fbxw7 loss. Thus, our study uncovered a novel role for FBXW7 in the regulation of senescence by eliminating p53.

Abstract Background Generic medicines substitution is an important means to control rapid growth of pharmaceutical expenditures for the healthcare system in China. Acceptance and utilization of generic medicines is highly influenced by healthcare providers’ perceptions. This study aimed to compare the knowledge, awareness and perceptions of generic medicines between physicians and pharmacists in China. Methods We used an online, cross-sectional survey across China. The questionnaire explored four sections: demographic characteristics, assessment of the participants’ knowledge and awareness of generic medicines, perceptions of generic medicines and generic substitution practices. Chi-square or Mann–Whitney-U tests were applied to compare differences between physicians and pharmacists. P-values

Background Most immunotherapies approved for clinical use rely on the use of recombinant proteins and cell-based approaches, rendering their manufacturing expensive and logistics onerous. The identification of novel small molecule immunotherapeutic agents might overcome such limitations.Method For immunopharmacological screening campaigns, we built an artificial miniature immune system in which dendritic cells (DCs) derived from immature precursors present MHC (major histocompatibility complex) class I-restricted antigen to a T-cell hybridoma that then secretes interleukin-2 (IL-2).Results The screening of three drug libraries relevant to known signaling pathways, FDA (Food and Drug Administration)-approved drugs and neuroendocrine factors yielded two major hits, astemizole and ikarugamycin. Mechanistically, ikarugamycin turned out to act on DCs to inhibit hexokinase 2, hence stimulating their antigen presenting potential. In contrast, astemizole acts as a histamine H1 receptor (H1R1) antagonist to activate T cells in a non-specific, DC-independent fashion. Astemizole induced the production of IL-2 and interferon-γ (IFN-γ) by CD4+ and CD8+ T cells both in vitro and in vivo. Both ikarugamycin and astemizole improved the anticancer activity of the immunogenic chemotherapeutic agent oxaliplatin in a T cell-dependent fashion. Of note, astemizole enhanced the CD8+/Foxp3+ ratio in the tumor immune infiltrate as well as IFN-γ production by local CD8+ T lymphocytes. In patients with cancer, high H1R1 expression correlated with low infiltration by TH1 cells, as well as with signs of T-cell exhaustion. The combination of astemizole and oxaliplatin was able to cure the majority of mice bearing orthotopic non-small cell lung cancers (NSCLC), then inducing a state of protective long-term immune memory. The NSCLC-eradicating effect of astemizole plus oxaliplatin was lost on depletion of either CD4+ or CD8+ T cells, as well as on neutralization of IFN-γ.Conclusions These findings underscore the potential utility of this screening system for the identification of immunostimulatory drugs with anticancer effects.

IntroductionIntracranial germ cell tumors (iGCTs), comprising of germinoma (GE) and non-germinomatous GCT (NGGCT), are a group of heterogenous brain tumors. Immunohistochemical markers, such as placental-like alkaline phosphatase (PLAP), are commonly used in diagnosis but show moderate sensitivity. Organic cation transporter 3/4 (OCT3/4) has been proposed as a novel biomarker for diagnosis and prognosis of iGCTs. This paper aimed to compare OCT3/4 with PLAP as potential immunohistochemical biomarkers in iGCTs diagnosis and clarify the relationship between OCT3/4 and prognosis of patients with iGCTs.MethodsMeta-analyses were performed to estimate pooled percentage point differences in positive rates between OCT3/4 and PLAP, their sensitivities, and correlation between OCT3/4 and prognosis in iGCTs.ResultsNine articles were included representing of 241 patients. A fixed-effects model meta-analysis revealed that OCT3/4s positive rate was 8.6% higher (95% CI, 0.7% lower to 17.9% higher) than that of PLAP. Using fixed-effects models, sensitivities of OCT3/4 as a potential immunohistochemical biomarker in CNS GE and NGGCT were 85% (95% CI, 79% to 89%) and 56% (95% CI, 39% to 71%), respectively. In comparison, PLAP had lower sensitivities in both GE (73%; 95% CI, 64% to 91%) and NGGCT (43%; 95% CI, 27% to 61%). Moreover, OCT3/4 was significantly negatively correlated with 5-year progression free survival in patients with CNS GE (HR = 2.56, 95 % CI 1.47 to 4.44; p = 0.0008). Sensitivity analyses showed similar results.DiscussionThis study provides the first comprehensive assessment of the efficacies of OCT3/4 and PLAP in iGCTs detection and prognosis prediction, indicating OCT3/4 seems to be a more sensitive and reliable immunohistochemical marker in iGCT diagnosis.

Despite the ubiquity and prevalence of lead (Pb) in the environment and industry, the mechanism of lead-induced neurotoxicity in the brain remains unclear, let alone its prevention and treatment. In this study, we hypothesized that exogenous cholesterol supplementation acts as an effective remedy for lead-induced neurodevelopmental impairments caused by lead. Forty 21-day-old male rats were randomly divided into four groups and administered 0.1 % lead water and/or 2 % cholesterol-containing feed for 30 d. Ultimately, rats in the lead group lost weight, accompanied by spatial learning and memory impairments as verified by the Morris water maze test, in which the escape latency of rats was prolonged, and the number of crossings in the target platform and the residence time in the target quadrant were significantly diminished compared to the control group. Hematoxylin-Eosin (H&E) staining and Nissl staining illustrated that typical pathological morphology occurred in the brain tissue of the lead group, where the tissue structure was loose, the number of hippocampal neurons and granulosa cells decreased significantly and were arranged loosely, along with enlarged intercellular space, light matrix staining, and decline in Nissl bodies. In addition, inflammatory response and oxidative stress were significantly induced by lead. Immunofluorescence experiments showed apparent activation of astrocytes and microglia, followed by the enhancement of TNF-α and IL-β levels. Moreover, the MDA content in the lead group was elevated dramatically, whereas the activities of SOD and GSH were significantly inhibited. As for the mechanism, western blot and qRT-PCR experiments were performed, where lead could significantly inhibit the BDNF-TrkB signaling pathway, lowering the protein expression of BDNF and TrkB. Cholesterol metabolism was also affected by lead exposure, in which cholesterol metabolism-related protein expression and gene transcription, including SREBP2, HMGCR, and LDLR, were downregulated. However, cholesterol supplementation efficiently detoxified the negative effects of lead-induced neurotoxicity, reversing the inflammatory response, oxidative stress, inactivation of the BDNF signaling pathway, and imbalance of cholesterol metabolism, thus improving the learning and memory ability of rats. In brief, our study demonstrated that cholesterol supplementation could ameliorate the deficiency of learning and memory induced by lead, which is closely associated with the initiation of the BDNF/TrkB signaling pathway and regulation of cholesterol metabolism.

Abstract Formamidinium lead triiodide (α‐FAPbI3) has been widely used in high‐efficiency perovskite solar cells due to its small band gap and excellent charge‐transport properties. Recently, some additives show facet selectivity to generate a (001) facet‐dominant film during crystallization. However, the mechanism to realize such (001) facet selectivity is not fully understood. Here, the authors attempted to use three ammonia salts NH4X (X are pseudohalide anions) to achieve better (001) facet selectivity in perovskite crystallization and improved crystallinity. After addition, the (001) facet dominance is generally increased with the best effect from SCN− anions. The theoretical calculation revealed three mechanisms of such improvements. First, pseudohalide anions have larger binding energy than the iodine ion to bind the facets including (110), (210), and (111), slowing down the growth of these facets. The large binding energy also reduces nucleation density and improves crystallinity. Second, pseudohalide ions improve phase purity by increasing the formation energies of the δ‐phase and other hexagonal polytypes, retarding the α‐ to δ‐phase transition. Third, the strong binding of these anions can also effectively passivate the iodine vacancies and suppress nonradiative recombination. As a result, the devices show a power conversion efficiency of 24.11% with a Voc of 1.181 V.

Background: The purpose of this study was to elucidate the community structure of rhizosphere soil bacteria and endophytic bacteria during the growth of moso bamboo (Phyllostachys edulis) shoots. Methods: This study collected the rhizospheric soil samples, tissue samples of rhizome roots, shoot buds, winter bamboo shoots, spring bamboo shoots, and samples of forest soil. Their metagenomic DNA was extracted, and the bacterial community structure and diversity characteristics were compared and analyzed using high-throughput sequencing technology. Results: These samples enabled the identification of 32 phyla, 52 classes, 121 orders, 251 families, and 593 genera of bacteria. The phyla primarily included Proteobacteria, Acidobacteria, and Cyanobacteria among others. Proteobacteria was the dominant phylum in the samples of bamboo shoots and rhizome roots, whereas Acidobacteria was dominant in the rhizosphere and forest soil samples. The predominant genera of the rhizome root samples were Acidothermus, Bradyrhizobium and Acidobacterium, and the predominant genera of the soil samples were Acidothermus and Acidobacterium. Conclusions: This study preliminarily revealed the regularity between the growth and development of bamboo shoots and the changes in the community structure of rhizosphere soil and endophytic bacteria, which provides insights into the relationship between growth and the bacterial community structure in different stages of bamboo shoots.

Background: Bacterial communities play an important role in helping plants absorb nutrients, promoting plant development, and preventing diseases. Moso bamboo (Phyllostachys edulis [Carriere] J. Houzeau) has a long history of cultivation and important economic value. Methods: In this study, high-throughput sequencing technology was utilized to analyze the differences in the diversity of endophytic and root zone soil bacterial communities between high-yielding (HY) and low-yielding (LY) P. edulis forests in subtropical China. Results: Notably, the soil conditions and bacterial communities in Yong’an (YA) and Jiangle (JL) differed, but the bacterial community structures in the root zone soil of both regions were similar with the dominant bacterial phyla composed of Proteobacteria, Acidobacteriota, and Actinobacteriota. The Chao1 and Shannon indices of the root zone soil and endophytic bacterial communities in the LY were higher than those in the HY. Moreover, the bacterial community structures of HY and LY were significantly different. Notably, the relative abundances of Actinobacteriota, Myxococcota, and Cyanobacteria were higher in the HY soil samples. The bacterial community differences between the tissues and root zone soil of HY and LY indicated that healthy HY P. edulis plants were enriched with specific bacterial communities, suggesting associations between yield and both endophytic and root zone soil bacterial communities. Conclusions: The findings of this study provide a basis to regulate artificial bacterial communities to benefit the future cultivation of HY P. edulis.

Abstract During their first year of medical residency (internship), 35% of training physicians in the United States suffer at least one depression episode. We assessed whether there is a similar increase of depression among first year residents in China, and identified predictors of depression in the two systems. 1006 residents across three cohorts (2016–2017, 2017–2018 and 2018–2019) at Shanghai Jiao Tong University and Peking Union Medical College were assessed in parallel with three cohorts of 7028 residents at 100 + US institutions. The Patient Health Questionnaire-9 (PHQ-9) depressive symptoms were measured at baseline and quarterly. Demographic, personal and residency factors were assessed as potential predictors of PHQ-9 depression scores. Similar to training interns in the US, the proportion of participants in China who met depression criteria at least once during the first year of residency increased substantially, from 9.1 to 35.1%. History of depression and symptoms at baseline were common factors significantly associated with depression during residency. By contrast, neuroticism, early family environment, female gender and not being coupled were associated with depression risk only in the US, while young age was a predictor of depression only in China. Fear of workplace violence also was a predictor in China. Long duty hours and reduced sleep duration emerged as training predictors of depression in both countries. The magnitude of depression increase and work-related drivers of depression were similar between China and the US, suggesting a need for effective system reforms in both systems.