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Highlights Abnormal changes in P-wave parameters indicative of atrial electrical remodeling often manifest earlier than changes in other indicators reflecting atrial structural remodeling in paroxysmal atrial fibrillation. Preoperative absolute values of Maximum P Wave Duration, P Wave Dispersion, and P Wave Terminal Force of V1, as well as postoperative absolute values of Maximum P Wave Duration, P Wave Duration, P Wave Dispersion, P Wave Terminal Force of V1, and P Wave Area, demonstrate strong predictive value for recurrence risk of paroxysmal atrial fibrillation after Catheter Ablation. The nomogram model based on P-wave parameters before and after catheter ablation exhibits notably strong predictive performance and offers significant clinical benefits.

This study aims to develop and implement standard operating procedures (SOPs) for nursing care during DVSS-Si robot-assisted laparoscopic radical prostatectomy (LRP) and to evaluate the clinical outcomes of these procedures. We included 140 patients who underwent robot-assisted LRP: 70 patients who received routine perioperative nursing care (control group) from July 2021 to February 2022, and 70 patients who were provided perioperative care according to the newly established SOPs (intervention group) from March 2022 to December 2022. Comparative analysis of operational metrics revealed that the intervention group had shorter operation position placement times, reduced robot installation times, decreased robot usage durations and fewer adverse events compared to the control group. Additionally, doctor satisfaction levels were significantly higher in the intervention group. In conclusion, the implementation of nursing SOPs for DVSS-Si robot-assisted LRP effectively standardized nursing practices in the operating room, leading to enhanced operational efficiency and improved quality of nursing services.

Abstract Background Dementia is a major public health challenge in modern society. Early detection of high-risk dementia patients and timely intervention or treatment are of significant clinical importance. Neural network survival analysis represents the most advanced technology for survival analysis to date. However, there is a lack of deep learning-based survival analysis models that integrate both genetic and clinical factors to develop and validate individualized dynamic dementia risk prediction models. Methods and results This study is based on a large prospective cohort from the UK Biobank, which includes a total of 41,484 participants with an average follow-up period of 12.6 years. Initially, 364 candidate features (predictor variables) were screened. The top 30 key features were then identified by ranking the importance of each predictor variable using the Gradient Boosting Machine (GBM) model. A multi-model comparison strategy was employed to evaluate the predictive performance of four survival analysis models: DeepSurv, DeepHit, Kaplan–Meier estimation, and the Cox proportional hazards model (CoxPH). The results showed that the average Harrell's C-index for the DeepSurv model was 0.743, for the DeepHit model it was 0.633, for the CoxPH model it was 0.749, and for the Kaplan–Meier estimator model it was 0.500. In addition, the average D-Calibration Survival Measure was 6.014, 4408.086, 32274.743, and 1.508, respectively. The Brier score (BS) was used to assess the importance of features for the DeepSurv dementia prediction model, and the relationship between features and dementia was visualized using a partial dependence plot (PDP). To facilitate further research, the team deployed the DeepSurv dementia prediction model on AliCloud servers and designated it as the UKB-DementiaPre Tool. Conclusion This study successfully developed and validated the DeepSurv dementia prediction model for individuals aged 60 years and above, integrating both genetic and clinical data. The model was then deployed on AliCloud servers to promote its clinical translation. It is anticipated that this prediction model will provide more accurate decision support for clinical treatment and will serve as a valuable tool for the primary prevention of dementia.

Abstract Background Previous studies have found that the temporal duration required for males to perceive visual motion direction is significantly shorter than that for females. However, the neural correlates of such shortened duration perception remain yet unclear. Given that motion perception is primarily associated with the neural activity of the middle temporal visual complex (MT+), we here test the novel hypothesis that the neural mechanism of these behavioral sex differences is mainly related to the MT+ region. Methods We utilized ultra-high field (UHF) MRI to investigate sex differences in the MT+ brain region. A total of 95 subjects (48 females) participated in two separate studies. Cohort 1, consisting of 33 subjects (16 females), completed task-fMRI (drafting grating stimuli) experiment. Cohort 2, comprising 62 subjects (32 females), engaged in a psychophysical experiment measuring motion perception along different temporal thresholds as well as conducting structural and functional MRI scanning of MT+. Results Our findings show pronounced sex differences in major brain parameters within the left MT+ (but not the right MT+, i.e., laterality). In particular, males demonstrate (i) larger gray matter volume (GMV) and higher brain’s spontaneous activity at the fastest infra-slow frequency band in the left MT+; and (ii) stronger functional connectivity between the left MT+ and the left centromedial amygdala (CM). Meanwhile, both female and male participants exhibited comparable correlations between motion perception ability and the multimodal imaging indexes of the MT+ region, i.e., larger GMV, higher brain’s spontaneous activity, and faster motion discrimination. Conclusions Our findings reveal sex differences of imaging indicators of structure and function in the MT+ region, which also relate to the temporal threshold of motion discrimination. Overall, these results show how behavioral sex differences in visual motion perception are generated, and advocate considering sex as a crucial biological variable in both human brain and behavioral research.

Objective This study aimed to determine the effects of compatibility of Clostridium butyricum and Bacillus subtilis on growth performance, lipid metabolism, antioxidant status and cecal microflora of broilers during the starter phase. Methods A total of 600 1-day-old Ross 308 broilers were randomly divided into two groups with six replicates in each group. Chickens in the control group were fed a basal diet, while chickens in the experimental group were fed a diet supplemented with 2×108 colony forming units (CFU)/kg of C. butyricum and 1×109 CFU/kg of B. subtilis. The experimental period was 21 days. Results Addition of C. butyricum and B. subtilis significantly increased (p

Abstract Bartonella are vector-borne gram-negative facultative intracellular bacteria that can infect a wide spectrum of mammals, and are recognized as emerging human pathogens. This study aimed to investigate the prevalence and molecular characteristics of Bartonella infections in small mammals within the Qinghai Menyuan section of Qilian Mountain National Park, China. Small mammals were captured, and the liver, spleen and kidney were collected for Bartonella detection and identification using a combination of real-time PCR targeting the transfer-mRNA (ssrA) gene and followed by sequencing of the citrate synthase (gltA) gene. A total of 52 rodents were captured, and 36 rodents were positive for Bartonella, with a positivity rate of 69.23% (36/52). Bartonella was detected in Cricetulus longicaudatus, Microtus oeconomus, Mus musculus, and Ochotona cansus. The positivity rate was significantly different in the different habitats. Two Bartonella species were observed, including Bartonella grahamii and Bartonella heixiaziensis, and B. grahamii was the dominant epidemic strain in this area. Phylogenetic analysis showed that B. grahamii mainly clustered into two clusters, which were closely related to the Apodemus isolates from China and Japan and the local plateau pika isolates, respectively. In addition, genetic polymorphism analysis showed that B. grahamii had high genetic diversity, and its haplotype had certain regional differences and host specificity. Overall, high prevalence of Bartonella in small mammals in the Qinghai Menyuan section of Qilian Mountain National Park. B. grahamii is the dominant strain with high genetic diversity and potential pathogenicity to humans, and corresponding control measures should be considered.

Abstract Background Neuroblastoma (NB) is the most common extracranial solid tumor in childhood and is closely related to the early development and differentiation of neuroendocrine (NE) cells. The disease is mainly represented by high-risk NB, which has the characteristics of high mortality and difficult treatment. The survival rate of high-risk NB patients is not ideal. In this article, we not only conducted a comprehensive study of NB through single-cell RNA sequencing (scRNA-seq) but also further analyzed cuproptosis, a new cell death pathway, in order to find clinical treatment targets from a new perspective. Materials and Methods The Seurat software was employed to process the scRNA-seq data. This was followed by the utilization of GO enrichment analysis and GSEA to unveil pertinent enriched pathways. The inferCNV software package was harnessed to investigate chromosomal copy number variations. pseudotime analyses involved the use of Monocle 2, CytoTRACE, and Slingshot software. CellChat was employed to analyze the intercellular communication network for NB. Furthermore, PySCENIC was deployed to review the profile of transcription factors. Result Using scRNA-seq, we studied cells from patients with NB. NE cells exhibited superior specificity in contrast to other cell types. Among NE cells, C1 PCLAF + NE cells showed a close correlation with the genesis and advancement of NB. The key marker genes, cognate receptor pairing, developmental trajectories, metabolic pathways, transcription factors, and enrichment pathways in C1 PCLAF + NE cells, as well as the expression of cuproptosis in C1 PCLAF + NE cells, provided new ideas for exploring new therapeutic targets for NB. Conclusion The results revealed the specificity of malignant NE cells in NB, especially the key subset of C1 PCLAF + NE cells, which enhanced our understanding of the key role of the tumor microenvironment in the complexity of cancer progression. Of course, cell death played an important role in the progression of NB, which also promoted our research on new targets. The scrutiny of these findings proved advantageous in uncovering innovative therapeutic targets, thereby bolstering clinical interventions.

Abstract Hepatocellular carcinoma (HCC) is the primary malignant tumor of the liver. c-Myc is one of the most common oncogenes in clinical settings, and amplified levels of c-Myc are frequently found in HCC. Histone deacetylase inhibitors (HDACi), such as Trichostatin A (TSA), hold enormous promise for the treatment of HCC. However, the potential and mechanism of TSA in the treatment of c-Myc-induced HCC are unclear. In this study, we investigated the effects of TSA treatment on a c-Myc-induced HCC model in mice. TSA treatment delayed the development of HCC, and liver function indicators such as ALT, AST, liver weight ratio, and spleen weight ratio demonstrated the effectiveness of TSA treatment. Oil red staining further demonstrated that TSA attenuated lipid accumulation in the HCC tissues of mice. Through mRNA sequencing, we identified that TSA mainly affected cell cycle and fatty acid degradation genes, with alcohol dehydrogenase 4 (ADH4) potentially being the core molecular downstream target. QPCR, immunohistochemistry, and western blot analysis revealed that ADH4 expression was repressed by c-Myc and restored after TSA treatment both in vitro and in vivo. Furthermore, we observed that the levels of total NAD+ and NADH, NAD+, NAD+/NADH, and ATP concentration increased after c-Myc transfection in liver cells but decreased after TSA intervention. The levels of phosphorylated protein kinase B (p-AKT) and p-mTOR were identified as targets regulated by TSA, and they governed the ADH4 expression and the downstream regulation of total NAD+ and NADH, NAD+, NAD+/NADH, and ATP concentration. Overall, our study suggests that TSA has a therapeutic effect on c-Myc-induced HCC through the AKT-mTOR-ADH4 pathway. These findings provide valuable insights into the potential treatment of HCC using TSA and shed light on the underlying molecular mechanisms involved.

Mung bean, an important economic crop, is considered a crop with relatively high levels of plant protein constituents and is consumed as both a vegetable and a grain. Among various yield-related traits, hundred-seed weight (HSW) is crucial in determining mung bean production. This study employed a recombinant inbred line (RIL) population of 200 lines that were genotyped via whole-genome resequencing to exploit genetic potential in the identification of HSW-associated quantitative trait loci (QTLs) across four environments. We identified 5 QTLs for HSW, each explaining 2.46–26.15% of the phenotypic variance. Among these, qHSW1 was mapped on chromosome 1 in all four environments, explaining 16.65-26.15% of the phenotypic variation. Fine mapping and map-based cloning procedures, along with progeny testing of recombinants, aided in narrowing the candidate interval for qHSW1 to 506 kb. This identification of the qHSW1 genomic interval and closely linked markers to qHSW1 could prove valuable in breeding efforts for improved mung bean cultivars with higher seed weight.

Abstract Multi‐omics studies of breast ductal carcinoma (BRDC) have advanced the understanding of the disease's biology and accelerated targeted therapies. However, the temporal order of a series of biological events in the progression of BRDC is still poorly understood. A comprehensive proteogenomic analysis of 224 samples from 168 patients with malignant and benign breast diseases is carried out. Proteogenomic analysis reveals the characteristics of linear multi‐step progression of BRDC, such as tumor protein P53 (TP53) mutation‐associated estrogen receptor 1 (ESR1) overexpression is involved in the transition from ductal hyperplasia (DH) to ductal carcinoma in situ (DCIS). 6q21 amplification‐associated nuclear receptor subfamily 3 group C member 1 (NR3C1) overexpression helps DCIS_Pure (pure DCIS, no histologic evidence of invasion) cells avoid immune destruction. The T‐cell lymphoma invasion and metastasis 1, androgen receptor, and aldo‐keto reductase family 1 member C1 (TIAM1‐AR‐AKR1C1) axis promotes cell invasion and migration in DCIS_adjIDC (DCIS regions of invasive cancers). In addition, AKR1C1 is identified as a potential therapeutic target and demonstrated the inhibitory effect of aspirin and dydrogesterone as its inhibitors on tumor cells. The integrative multi‐omics analysis helps to understand the progression of BRDC and provides an opportunity to treat BRDC in different stages.

Introduction: Despite receiving alectinib therapy, patients with ALK-positive NSCLC remain at risk of central nervous system (CNS) progression. Our retrospective study aimed to identify baseline clinical and molecular factors associated with the risk of CNS progression in this patient subset. Methods: We analyzed the clinical, molecular, and imaging data of 318 patients with ALK-positive advanced NSCLC who received alectinib as first-line (1L-alectinib) or second-line (2L-alectinib) therapy at baseline (1L, n = 183; 2L, n = 135) and at disease progression (1L, n = 80; 2L, n = 76). Results: The incidence rates of CNS progression were 23.7% after 1L-alectinib treatment and 31.6% after 2L-alectinib treatment. Compared with patients who received 1L-alectinib, CNS progression was similar in patients who received 2L-alectinib (p > 0.05). Oligoprogression was detected in 55.0% (44 of 80) of patients who progressed after first-line alectinib, with the remaining 45.0% (36 of 80) having nonoligoprogression. Univariate and multivariate analyses and stepwise regression analyses consistently identified a higher likelihood of CNS progression among (1) patients who received 2L-alectinib than 1L-alectinib, (2) patients with non-3a/b variant ALK fusion than those with echinoderm microtubule-associated protein-like 4–ALK variant 3a/b, and (3) patients with programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of 50% or higher than PD-L1 TPS of less than 50%. Conclusions: Our study provided real-world evidence that patients who harbored PD-L1 TPS of 50% or higher were more likely to experience CNS progression during alectinib therapy. The association between CNS progression and breakpoint variants warrants further investigation. Our findings suggest that close monitoring and prompt intervention are crucial in prolonging the quality of life of this patient subset.

Background Light-chain proximal tubulopathy (LCPT) is a rare disease characterized by the accumulation of monoclonal light chains within proximal tubular cells. This study aimed to investigate the clinical characteristics of LCPT from a single Chinese nephrology referral center.Methods Patients with kidney biopsy-proven isolated LCPT between 2016 and 2022 at Peking University First Hospital were retrospectively included. Clinical data, kidney pathological type, treatment, and prognosis were analyzed.Results Nineteen patients were enrolled, the mean age at diagnosis was 57 ± 11 and the sex ratio was 6/13 (female/male). Mean proteinuria was 2.44 ± 1.89 g/24 hr and the mean estimated glomerular filtration rate (eGFR) at the point of biopsy was 59.640 ± 27.449 ml/min/1.73 m2. κ-restriction (84%) was dominant among LCPTs. An abnormal free light chain ratio was observed in 86% of the patients. Proximal tubulopathy with cytoplasmic inclusions accounted for the majority (53%), followed by tubulopathy associated with interstitial inflammation reaction (26%), proximal tubulopathy without cytoplasmic inclusions (16%), and proximal tubulopathy with lysosomal indigestion/constipation (5%). One patient presented with acute kidney injury and 16 patients presented with chronic kidney disease. Regarding follow-up, patients received bortezomib-based or R-CHOP chemotherapy or supportive treatment only. The mean follow-up time was 22 ± 16 months, and the mean eGFR was 63.098 ± 27.439 ml/min/1.73 m2 at the end of follow-up. These patients showed improved or stable kidney function.Conclusions This is the first case series report of LCPT in four different pathological types in northern China. Clone-targeted chemotherapy may help preserve the kidney function in these patients.

Objective Lipoprotein glomerulopathy (LPG) is a rare disorder characterized by the development of glomerular lipoprotein thrombosis. LPG exhibits familial aggregation, with mutations in the apolipoprotein E (APOE) gene identified as the leading cause of this disease. This study aimed to investigate APOE gene mutations and the clinicopathological features in eleven LPG patients.Methods Clinicopathological and follow-up data were obtained by extracting DNA, followed by APOE coding region sequencing analysis. This study analyzed clinical and pathological manifestations, gene mutations, treatment and prognosis.Results The mean age of the eleven patients was 33.82 years. Among them, five had a positive family history for LPG, ten presented with proteinuria, four exhibited nephrotic syndrome, and six presented with microscopic hematuria. Dyslipidemia was identified in ten patients. In all renal specimens, there was evident dilation of glomerular capillary lumens containing lipoprotein thrombi, and positive oil red O staining was observed in frozen sections of all samples. APOE gene testing revealed that one patient had no mutations, while the remaining ten patients exhibited mutations in the APOE gene, with three patients presenting with multiple mutations simultaneously. Following the confirmation of LPG diagnosis, treatment with angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) was initiated, and the disease progressed slowly.Conclusion LPG is histologically characterized by lamellated lipoprotein thrombi in glomeruli, and kidney biopsy is essential for diagnosis. Mutations in the APOE gene are the leading cause of LPG. This study revealed clinicopathological characteristics and APOE gene mutations in patients with LPG, which helps us better understand the disease.

Background IgA vasculitis (IgAV), previously known as Henoch-Schönlein purpura, is an IgA-mediated systemic small vessel vasculitis that tends to be more severe in adults than in children. Early diagnosis of IgAV involving the gastrointestinal tract remains difficult, especially in patients who present with gastrointestinal symptoms before purpura. This study aims to systematically analyze the abdominal imaging and endoscopic features of adult patients with abdominal IgAV, providing assistance to clinicians in the early recognition of this condition.Patients and Methods This multicenter retrospective study was conducted in three large tertiary hospitals in China from January 2017 to January 2024. A total of 108 adult patients with abdominal IgAV, who had complete abdominal imaging and/or endoscopy results, were enrolled. The clinical manifestations, abdominal imaging findings, endoscopic characteristics, and serological indicators of the patients were analyzed.Results The median age of the patients was 40 years (IQR: 26–55), with a male-to-female ratio of 2:1. Acute abdominal pain was the most common presenting symptom (100 patients, 92.59%). Bowel wall thickening was the most frequent finding on abdominal imaging (50/86 patients, 58.14%). Gastrointestinal endoscopy showed findings of congestion and erosion (32/67 patients, 47.76%), and erosion with ulcers (21/67 patients, 31.34%). Among patients with both imaging and endoscopic results, the duodenum (28/51 patients, 54.90%) and ileum (28/51 patients, 54.90%) were the most commonly affected sites. Laboratory findings revealed elevated white blood cell count (WBC), neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), D-dimer and fibrinogen levels, along with decreased albumin level. Comparing patients with gastrointestinal symptoms versus purpura as the initial symptom, those with gastrointestinal symptoms had higher levels of WBC (p

During the development of eukaryote, faithful inheritance of chromatin states is central to the maintenance of cell fate. DNA replication poses a significant challenge for chromatin state inheritance because every nucleosome in the genome is disrupted as the replication fork passes. It has been found that many factors including DNA polymerases, histone chaperones, as well as, RNA Pol II and histone modifying enzymes coordinate spatially and temporally to maintain the epigenome during this progress. In this review, we provide a summary of the detailed mechanisms of replication-coupled nucleosome assembly and post-replication chromatin maturation, highlight the inheritance of chromatin states and epigenome during these processes, and discuss the future directions and challenges in this field.

Background: Previous research has elaborated on the role of long non-coding RNA LINC00173 in the pathogenesis of various cancers; however, our knowledge of its clinical consequences and mechanisms in endometrial cancer (EC) is limited. Our current work is aimed at investigating the effect of LINC00173 in combination with its upstream gene HNRNPC on EC progression. Methods: LINC00173 and HNRNPC levels were investigated by qRT-PCR or western blotting in EC tissues. The functional roles of HNRNPC and LINC00173 were assessed using transwell, colony formation and CCK-8 assays. A xenograft was used to verify the phenotype of LINC00173 after its overexpression. The regulatory role between HNRNPC and LINC00173 was investigated using RIP and RNA pull-down analysis. Results: In EC tissues, LINC00173 expression was down-regulated. We observed that increased LINC00173 inhibited EC cell growth and migration. LINC00173 was a downstream target of HNRNPC, and its expression level was elevated by HNRNPC silencing. LINC00173 overexpression shifted part of HNRNPC into the cytoplasm from the nucleus of EC cells. Furthermore, HNRNPC expression was upregulated in EC and its silencing inhibited EC cell malignancy in vitro. Conclusion: LINC00173 can impair the malignancy of EC cell by interacting with HNRNPC. This finding may contribute to the understanding of the tumorigenic effects of HNRNPC and LINC00173 on EC.

The research aims to investigate the effects of proportion and age of maintenance on the strength and economy of filling materials, in order to provide theoretical guidance and technical support for the management of coal mined-out area. Firstly, adjustments are made to the proportioning and maintenance age of the fill materials, and experiments are conducted to explore the strength performance of materials under different proportions. Secondly, GANs is utilized to expand the dataset, and an MLP-LSTM network is constructed to predict the strength of materials experiencing different maintenance ages under various proportions. Finally, integrating practical engineering applications, an economic viability prediction analysis is conducted to examine the cost of fill materials under different proportions and maintenance ages, along with their influencing factors. The results indicate that appropriate adjustments to proportioning can effectively enhance the strength of fill materials, whereas excessively high or low proportions may lead to unstable or surplus strength. Extending the maintenance age can to some extent improve the material’s strength, but it also increases maintenance costs, necessitating a comprehensive balance in terms of economic viability. Consequently, this research offers a theoretical foundation and practical guidelines for optimizing mixture proportions and selecting appropriate curing ages, providing valuable insights for enhancing the efficiency and cost-effectiveness of coal mined-out area filling treatments.

To solve the oxygen dependence problem of photodynamic therapy (PDT), it is critical to explore photosensitizers that do not rely on O2 molecule to generate reactive oxygen species (ROS). Herein, a stable cationic metal‐organic cage [Pd6(RuLoz3)8](BF4)28 (MOC‐88) that possesses high +28 charges is designed. The cage‐confined positive microenvironment enables efficient generation of hydroxyl radicals and improved yield of the singlet oxygen under one‐/two‐photon excitation, showing excellent performance to concurrently enhance Type‐II and O2‐independent‐Type‐I PDT. Moreover, the effective ROS production and robust lipid peroxidation trigger a series of signaling pathways (inflammasome, cyclic guanosine monophosphate–adenosine monophosphate synthase stimulator of interferon genes, and NF‐κB) to evoke PANoptosis and ferroptosis in tumor cells, enabling MOC‐88 to simultaneously cause the loss of cell membrane integrity, release a series of inflammatory cytokines and damage‐associated molecular patterns, stimulate the maturation and antigen presentation ability of dendritic cells, and ultimately activate T‐cell‐dependent adaptive immunity in vivo to inhibit tumor growth.

The prevailing opinion emphasizes fronto-parietal network (FPN) is key in mediating general fluid intelligence (gF). Meanwhile, recent studies show that human MT complex (hMT+), located at the occipito-temporal border and involved in 3D perception processing, also plays a key role in gF. However, the underlying mechanism is not clear, yet. To investigate this issue, our study targets visuo-spatial intelligence, which is considered to have high loading on gF. We use ultra-high field magnetic resonance spectroscopy (MRS) to measure GABA/Glu concentrations in hMT+ combining resting-state fMRI functional connectivity (FC), behavioral examinations including hMT+ perception suppression test and gF subtest in visuo-spatial component. Our findings show that both GABA in hMT+ and frontal-hMT+ functional connectivity significantly correlate with the performance of visuo-spatial intelligence. Further, serial mediation model demonstrates that the effect of hMT+ GABA on visuo-spatial gF is fully mediated by the hMT+ frontal FC. Together our findings highlight the importance in integrating sensory and frontal cortices in mediating the visuo-spatial component of general fluid intelligence.

Summary: Endosomal Toll-like receptors (eTLRs) are essential for the sensing of non-self through RNA and DNA detection. Here, using spatiotemporal analysis of vesicular dynamics, super-resolution microscopy studies, and functional assays, we show that endomembrane defects associated with the deficiency of the small GTPase Rab27a cause delayed eTLR ligand recognition, defective early signaling, and impaired cytokine secretion. Rab27a-deficient neutrophils show retention of eTLRs in amphisomes and impaired ligand internalization. Extracellular signal-regulated kinase (ERK) signaling and β2-integrin upregulation, early responses to TLR7 and TLR9 ligands, are defective in Rab27a deficiency. CpG-stimulated Rab27a-deficient neutrophils present increased tumor necrosis factor alpha (TNF-α) secretion and decreased secretion of a selected group of mediators, including interleukin (IL)-10. In vivo, CpG-challenged Rab27a-null mice show decreased production of type I interferons (IFNs) and IFN-γ, and the IFN-α secretion defect is confirmed in Rab27a-null plasmacytoid dendritic cells. Our findings have significant implications for immunodeficiency, inflammation, and CpG adjuvant vaccination.

Purpose: To investigate the mechanism by which Qingguang'an inhibits scar formation in rabbits administered glaucoma filtering surgery (GFS). Methods: Combined trabeculectomy was performed in 100 rabbits diagnosed with glaucoma, which were assigned to five groups, including the no surgery, surgery only, mitomycin C (MMC; positive control), Qingguang'an (experimental) and PBS (negative control) groups. The animals were followed up at postoperative days 1–28. Ultrastructure was observed under a transmission electron microscope (TEM). Real-Time Polymerase Chain Reaction (RT-PCR), Western blot, Hematoxylin and Eosin (H&E) staining, Masson's trichrome staining and Immuno-histochemistry (IHC) were performed to assess the harvested blocks. Results: In the Qingguang'an group, intraocular pressure (IOP) on postoperative D28 was significantly lower than values in the no surgery, surgery only and PBS groups (P

AIM: To evaluate the predictive value of superficial retinal capillary plexus (SRCP) and radial peripapillary capillary (RPC) for visual field recovery after optic cross decompression and compare them with peripapillary nerve fiber layer (pRNFL) and ganglion cell complex (GCC). METHODS: This prospective longitudinal observational study included patients with chiasmal compression due to sellar region mass scheduled for decompressive surgery. Generalized estimating equations were used to compare retinal vessel density and retinal layer thickness pre- and post-operatively and with healthy controls. Logistic regression models were used to assess the relationship between preoperative GCC, pRNFL, SRCP, and RPC parameters and visual field recovery after surgery. RESULTS: The study included 43 eyes of 24 patients and 48 eyes of 24 healthy controls. Preoperative RPC and SRCP vessel density and pRNFL and GCC thickness were lower than healthy controls and higher than postoperative values. The best predictive GCC and pRNFL models were based on the superior GCC [area under the curve (AUC)=0.866] and the tempo-inferior pRNFL (AUC=0.824), and the best predictive SRCP and RPC models were based on the nasal SRCP (AUC=0.718) and tempo-inferior RPC (AUC=0.825). There was no statistical difference in the predictive value of the superior GCC, tempo-inferior pRNFL, and tempo-inferior RPC (all P>0.05). CONCLUSION: Compression of the optic chiasm by tumors in the saddle area can reduce retinal thickness and blood perfusion. This reduction persists despite the recovery of the visual field after decompression surgery. GCC, pRNFL, and RPC can be used as sensitive predictors of visual field recovery after decompression surgery.

This article investigates the problem of finite-time synchronization of fractional-order complex-valued random multi-layer networks without decomposing them into two real-valued systems. Firstly, by promoting real-valued signum functions, sign functions on the complex-valued domain are introduced. Simultaneously, quantization functions in the complex-valued domain are also introduced, and several related formulas for sign functions and quantization functions in complex-valued domain are established. Under the framework of the given sign function and quantization function, an adaptive quantized control scheme with or without deception attacks is designed. According to the finite-time theorem, Lyapunov function, and graph theory methods, some sufficient criteria for realizing finite-time synchronization in complex-valued fractional-order multi-layer networks have been obtained. Furthermore, the setting time of finite-time synchronization is effectively evaluated. Eventually, the reliability of our results and the practicality of control strategies are verified through numerical examples.

Codonopsis pilosula polysaccharide (CPP) and rare element selenium (Se) have been proved to exert various biological activities, and our previous study demonstrated that selenium nanoparticles modified with CPP (CPP-SeNPs) possessed significantly enhanced tumor cytotoxicity in vitro. This study aimed to investigated the inhibitory effects of CPP-SeNPs complex on H22 solid tumors via immune enhancement. In this study, the H22 tumor-bearing mice model was constructed, and the potential mechanisms of CPP-SeNPs antitumor effects were further explored by evaluating cytokines expression levels, immune cells activities and tumor cells apoptotic indicators in each group. The results demonstrated that CPP-SeNPs effectively exerted dose-dependent protective effects on the immune organs of tumor-bearing mice in vivo, leading to increase in peripheral white blood cell counts and inhibition of solid tumor growth with inhibitory rate of 47.18% in high-dose group (1.5 mg/kg). Furthermore, CPP-SeNPs treatment significantly elevated the levels of TNF-α, IFN-γ, and IL-2 in mice sera, enhanced NK cell cytotoxicity, augmented macrophage phagocytosis capacity, as well as increased both the amounts and proliferation activity of lymphocyte subsets. CPP-SeNPs improved the immune system’s ability to clear tumor cells by up-regulating Bax expression while down-regulating Bcl-2 expression within solid tumors, indicating the potential activation of mitochondrial apoptosis pathway. Therefore, CPP-SeNPs administration can effectively inhibit tumor growth by enhancing immune response in tumor-bearing mice, which might be relevant to the regulation of gut microbiota short-chain fatty acids metabolisms. These findings could provide theoretical support and data foundation for further development of CPP-SeNPs as functional food and drug adjuvants.

This article mainly delves into finite-time passivity and finite-time synchronization of fractional-order spatiotemporal directed networks with multiple weights via boundary control schemes. Firstly, several concepts of finite-time passivity for fractional spatiotemporal models are proposed by virtue of a fractional-order differential inequality. Next, a boundary controller is presented to realize the passivity, which only relies on the information of the state at the spatial boundary. Subsequently, by constructing the Lyapunov function and leveraging some inequality techniques, some sufficient conditions in the form of linear matrix inequalities are established to ensure the finite-time strict passivity, finite-time input strict passivity, and finite-time output strict passivity. As a consequence of the derived result of finite-time output strict passivity, several criteria are obtained for realizing finite-time synchronization of the addressed fractional spatiotemporal networks. A numerical example is eventually presented to verify the developed control protocol and the theoretical criteria.

Abstract Background The current standard of care for locally advanced gastric cancer (GC) involves neoadjuvant chemotherapy followed by radical surgery. Recently, neoadjuvant treatment for this condition has involved the exploration of immunotherapy plus chemotherapy as a potential approach. However, the efficacy remains uncertain. Methods A single‐arm, phase 2 study was conducted to evaluate the efficacy and tolerability of neoadjuvant camrelizumab combined with mFOLFOX6 and identify potential biomarkers of response through multi‐omics analysis in patients with resectable locally advanced GC. The primary endpoint was the pathological complete response (pCR) rate. Secondary endpoints included the R0 rate, near pCR rate, progression‐free survival (PFS), disease‐free survival (DFS), and overall survival (OS). Multi‐omics analysis was assessed by whole‐exome sequencing, transcriptome sequencing, and multiplex immunofluorescence (mIF) using biopsies pre‐ and post‐neoadjuvant therapy. Results This study involved 60 patients, of which 55 underwent gastrectomy. Among these, five (9.1%) attained a pathological complete response (pCR), and 11 (20.0%) reached near pCR. No unexpected treatment‐emergent adverse events or perioperative mortality were observed, and the regimen presented a manageable safety profile. Molecular changes identified through multi‐omics analysis correlated with treatment response, highlighting associations between HER2‐positive and CTNNB1 mutations with treatment sensitivity and a favourable prognosis. This finding was further supported by immune cell infiltration analysis and mIF. Expression data uncovered a risk model with four genes (RALYL, SCGN, CCKBR, NTS) linked to poor response. Additionally, post‐treatment infiltration of CD8+ T lymphocytes positively correlates with pathological response. Conclusion The findings suggest the combination of PD‐1‐inhibitor and mFOLFOX6 showed efficacy and acceptable toxicity for locally advanced GC. Extended follow‐up is required to determine the duration of the response. This study lays essential groundwork for developing precise neoadjuvant regimens.

Fe/N-based biomass porous carbon composite (Fe/N-pCarbon) was prepared by a facile high-temperature carbonization method from biomass, and the effect of Fe/N-pCarbon on the thermal decomposition of energetic molecular perovskite-based material DAP-4 was studied. Biomass porous carbonaceous materials was considered as the micro/nano support layers for in situ deposition of Fe/N precursors. Fe/N-pCarbon was prepared simply by the high-temperature carbonization method. It was found that it showed the inherent catalysis properties for thermal decomposition of DAP-4. The heat release of DAP-4/Fe/N-pCarbon by DSC curves tested had increased slightly, compared from DAP-4/Fe/N-pCarbon-0. The decomposition temperature peak of DAP-4 at the presence of Fe/N-pCarbon had reduced by 79°C from 384.4°C (pure DAP-4) to 305.4°C (DAP-4/Fe/N-pCarbon-3). The apparent activation energy of DAP-4 thermal decomposition also had decreased by 29.1 J/mol. The possible catalytic decomposition mechanism of DAP-4 with Fe/N-pCarbon was proposed.

In order to explore the role of exogenous bacteria in the fermentation process of Pu-erh tea and its impact on tea quality, the present study aimed to explore the differences in metabolite changes during fermentation of Pu-erh tea treated with different bacterial strains. To achieve this, non-targeted metabolomics technology was employed, which was combined with multivariate statistical analysis and differential heat maps. The study analyzed the flavonoids, alkaloids, and terpenoids present in the tea samples. The H group was found to have a fruity and sweet aroma, a bright red soup color, and a strong and sweet taste. The A group had a strong floral and honey aroma, a bright red soup color, and a strong and sweet aftertaste. The R group had a fruity and milky aroma, a bright yellow soup color, and a strong but astringent and bitter taste. These differences in quality were found to be related to the levels of metabolites such as malvidin, genkwanin, catechins, caffeine, and lactucin. The study provided preliminary insights into the differences in metabolite content during the fermentation of Pu-erh tea with different bacterial strains, which can have varying effects on the taste, aroma, and soup color of the tea. The findings of this study could provide theoretical assistance for future Pu-erh tea fermentation.

Abstract Background Prior studies have shown that, when administered as an intravenous bolus to prevent uterine atony, prophylactic phenylephrine infusion increased the dose requirement of oxytocin and second-line uterotonics. For the prevention of uterine atony, oxytocin should be delivered by continuous infusion. Here, we aimed to determine the ED50 and ED90 parameters (the effective doses for 50 and 90% patients without uterine atony) of oxytocin for co-infusion with prophylactic phenylephrine during cesarean delivery. Methods In this prospective randomized double-blinded dose-finding study, one hundred patients were divided into four groups to receive 2.5, 5.0, 7.5, or 10 IU/h oxytocin infusion, after the umbilical cord was clamped during the study period. The uterine tone was evaluated and defined as either adequate or inadequate. Probit regression analysis was applied to calculate the ED50 and ED90 of oxytocin infusion. Uterine tone, the percentage of patients who needed additional oxytocin bolus, second-line uterotonics, side effects, estimated blood loss, and neonatal outcomes were monitored. Results The estimated ED50 and ED90 values of the oxytocin infusion doses for the prevention of uterine atony were 1.9 IU/h (95% CI -4.6-3.8) IU/h and 9.3 IU/h (95% CI 7.3–16.2) IU/h, respectively. Across groups, there was a significant linear trend between the infusion dose and the percentage of patients who required additional oxytocin (p-value = 0.002). No differences were observed in the incidence of side effects and neonatal outcomes. Conclusion Under the conditions of this study, the ED90 of oxytocin infusion for the prevention of uterine atony was 9.3 IU/h, which is higher than the current recommendation. This finding is helpful for clinical practice, because of the routine use of phenylephrine in cesarean delivery. Further studies are needed to determine the appropriate initial bolus of oxytocin after neonatal delivery. Trial registration The study was registered on the Chinese Clinical Trial Register (register no. ChiCTR2200059556 ).

Abstract Background Neural tube defects (NTDs) are one of the most severe congenital abnormalities characterized by failures of the neural tube to close during early embryogenesis. Maternal folate deficiency could impact the occurrence of NTDs, however, the mechanisms involved in the cause of NTDs are poorly defined. Results Here, we report that histone H3 methyltransferase disruptor of telomeric silencing 1-like (DOT1L) expression was significantly downregulated, and low levels of H3K79me2 were found in the corresponding NTDs samples with their maternal serum folate under low levels. Using ChIP-seq assays, we found that a decrease of H3K79me2 downregulates the expression of Shh and Sufu in mouse embryonic stem cells (mESC) under folate deficiency. Interestingly, folate antagonist methotrexate treatment led to attenuation of H3K79me2 due to Dot1l, affecting Shh and Sufu genes regulation. Upon further analysis, we find that the genes Shh and Sufu are both downregulated in the brain tissues of mice and humans with NTDs. There was a positive correlation between the transcription levels of Shh, Sufu and the protein levels of DOT1L by Pearson correlation analysis. Conclusion Our results indicate that abnormal Shh and Sufu genes expression reduced by aberrant Dot1l-mediated H3K79me2 levels could be the cause of NTDs occurrence.

Northeast China (NEC) is one of the vital commercial grain bases in China and it has suffered from soil erosion due to prolonged cultivation and lack of protection. To determine long-term trends of precipitation and rainfall erosivity over NEC during the latest decades, daily precipitation for the entire year during 1961–2020 and hourly precipitation for the warm season (May to September) during 1971–2020 were collected for 192 and 126 stations, respectively. Three seasons, including the cold season (October to April), early warm season (May to June), and late warm season (July to September) were divided according to the combination of precipitation and vegetation. Results demonstrate: (1) Daily precipitation reveals total precipitation and rainfall erosivity in the cold season and early warm season increase significantly at relative rates of 3.1% ∼ 6.1% compared with the average during 1961–2020, and those in the late warm season decrease insignificantly. (2) Hourly precipitation reveals storms occurring in the early and late warm seasons have undergone significant increasing changes, which shift towards longer storm duration, larger amount, peak intensity, kinetic energy, and rainfall erosivity during 1971–2020. Moreover, the frequency of extreme storms increased. (3) Rainfall erosivities estimated from daily precipitation during 1971–2020 increase insignificantly for the early and late warm season, whereas those from hourly precipitation increase significantly (6.1% and 5.5%, respectively), which indicates daily precipitation may not be able to capture the trend fully under the warming background, and precipitation at higher resolutions than the daily scale is necessary to detect trends of rainfall erosivity more accurately.

Abstract Background Research on human pluripotent stem cells (hPSCs) has shown tremendous progress in cell-based regenerative medicine. Corneal endothelial dysfunction is associated with the loss and degeneration of corneal endothelial cells (CECs), rendering cell replacement a promising therapeutic strategy. However, comprehensive preclinical assessments of hPSC-derived CECs for this cell therapy remain a challenge. Results Here we defined an adapted differentiation protocol to generate induced corneal endothelial cells (iCECs) consistently and efficiently from clinical-grade human embryonic stem cells (hESCs) with xeno-free medium and manufactured cryopreserved iCECs. Cells express high levels of typical CECs markers and exhibit transendothelial potential properties in vitro typical of iCECs. After rigorous quality control measures, cells meeting all release criteria were available for in vivo studies. We found that there was no overgrowth or tumorigenicity of grafts in immunodeficient mice. After grafting into rabbit models, the surviving iCECs ameliorated edema and recovered corneal opacity. Conclusions Our work provides an efficient approach for generating iCECs and demonstrates the safety and efficacy of iCECs in disease modeling. Therefore, clinical-grade iCECs are a reliable source for future clinical treatment of corneal endothelial dysfunction.

Abstract Background Platycodon grandiflorus (Jacq.) A. DC is a famous traditional Chinese medicine in China and an authentic medicine in Inner Mongolia. It has been traditionally used as an expectorant in cough and also has anti-inflammatory and other pharmacological effects. As a homologous plant of medicine and food, P. grandiflorus is widely planted in Northeast China. Soil salinity isa limiting factor for its cultivation. In this study, we comprehensively described the physiological characteristics of P. grandiflorus and combined transcriptomics and metabolomics to study the response of roots of P. grandiflorus to salt stress. Results Overall, 8,988 differentially expressed genes were activated and significantly altered the metabolic processes. In total, 428 differentially abundant metabolites were affected by salt stress. After moderate and severe salt stress, most of the differentially abundant metabolites were enriched in the L-phenylalanine metabolic pathway. Through the comprehensive analysis of the interaction between key genes and metabolites, the main pathways such as lignin compound biosynthesis and triterpene saponin biosynthesis were completed. The relative content of compounds related to lignin biosynthesis, such as caffeic acid, coniferin, and syringing, increased under salt stress, and the related genes such as PAL, C4H, and the key enzyme gene UGT72E2 were activated to adapt to the salt stress. Platycodon saponin is one of the major triterpene saponins in P. grandiflorus, and Platycodin D is its most abundant major bioactive component. Under severe salt stress, Platycodin D level increased by nearly 1.77-fold compared with the control group. Most of the genes involved insynthetic pathway of Platycodin D, such as HMGCR, GGPS, SE, and LUP, were upregulated under salt stress. Conclusion Salt stress led to a decrease in the biomass and affected the activities of antioxidant enzymes and contents of osmotic regulators in the plant. These results provided not only novel insights into the underlying mechanisms of response of P. grandiflorus to salt stress but also a foundation for future studies on the function of genes related to salt tolerance in the triterpenoid saponin biosynthesis pathway.

Purpose: To explore the effect of the variation of pupil diameter (PD) and intraocular pressure (IOP) induced by femtosecond laser treatment on the subsequent phacoemulsfication and intraocular lens implantation. And whether the application of 0.1% pranoprofen could significantly reduce the miosis and increased IOP caused by femtosecond laser treatment in femtosecond laser-assisted cataract surgery (FLACS). Methods: In this study, patients were pretreated with (trial group) or without (control group) topical 0.1% pranoprofen. The PD and IOP were measured at different time points within 30 ​min after the completion of the femtosecond laser treatment. Results: The comparisons of the two groups showed the PD of patients pretreated with 0.1% pranoprofen was significantly larger than that of the control only at 15 ​min after FLACS (P ​= ​0.046), and there was no significant difference in IOP at any time point (P ​> ​0.05). Neither the ratio of significant miosis (PD ​≤ ​5 ​mm) nor intraocular hypertension (IOP ≥30 ​mmHg) was significantly different between the control group (1.72%, 6.67%) and the trial group (1%, 4.17%) (P ​> ​0.05). Conclusions: The PD and IOP of patients undergoing FLACS showed fluctuations within a small range. The rates of significant miosis and intraocular hypertension are very low, it is safe for surgeons to complete the follow-up procedures within 30 ​min after femtosecond laser treatment. Pretreatment with 0.1% pranoprofen exerted a slight, albeit significant prophylactic effect preventing pupil miosis. However, it provided only a limited benefit in patients undergoing FLACS without other complications.