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Abstract The most common treatment method for patients with acute ischemic stroke with large vessel occlusion is mechanical thrombectomy. However, complications such as cerebral edema and hemorrhage transformation after MT can affect patient prognoses, while decompression craniectomy considerably improves patient prognoses. The aim of this study was to identify clinical indicators, such as the neutrophil/high-density lipoprotein cholesterol ratio, to predict DC. A retrospective analysis was conducted in AIS-LVO patients who received MT at Huizhou Central People’s Hospital and the Affiliated Hospital of Guilin Medical University. The patients were randomly divided into training, internal validation group and external validation group sets to generate and validate a nomogram model. Multivariate binary logistic analyses indicated that SBP > 178.5 mmHg, WBC > 12.05*109/L, PT > 14.54 s, and NHR > 8.874*109/mmol were independent risk factors for DC after MT in patients with AIS-LVO. In the training set, the area under the curve indicated good accuracy. Calibration curve results showed the average error in the training set was 0.038, and 0.036 in the validation set, showing good model fit. NHR was an independent risk factor for DC treatment after MT in AIS-LVO patients. A nomogram based on NHR accurately predicted if DC treatment was required after MT in patients with AIS-LVO.

Abstract Objective A ureteric stone is a type of urinary tract stone that is found within the ureter. While most cases can be managed with conservative treatment or minimally invasive surgery, these methods often cause significant pain for the patient. Interestingly, a new type of ureteroscope has shown considerable promise in treating patients with ureteric stones, and this study aims to explore its clinical application. Methods A total of 120 patients with ureteric stones were recruited from our hospitals between January 1, 2023, and December 31, 2023. These patients were randomly assigned to either the control group, which received the traditional straight ureteroscope, or the experimental group, which was treated with the new type of ureteroscope. Both groups provided general data and blood samples for further analysis. A logistic regression analysis was conducted to examine the factors influencing infection following surgery in patients with ureteric stones, including preoperative CRP greater than 8 mg/L, postoperative CRP greater than 8 mg/L, preoperative white blood cell count (> 109/L), postoperative white blood cell count (> 109/L), preoperative urinalysis count greater than 28 (/ul), postoperative urinalysis count greater than 28 (/ul), and urine routine leukocyte count. Results The findings indicated no significant differences between the observation group and the control group regarding preoperative demographic, participants general data (P > 0.05). Postoperative CRP > 8 mg/L, white blood cell count > 10 × 109/L, urinalysis count > 28/µL, and urine leukocyte count significantly decreased in the experimental group compared to the control group (P 8 mg/L (OR = 7.03), white blood cell count > 109/L (OR = 3.86), urinalysis count > 28/µL (OR = 2.83), and urine leukocyte count (OR = 1.004) were predictive factors for ureteric stones. Preoperative values showed no significant difference (P > 0.05). Conclusions The binary logistic regression analysis identified Postoperative CRP > 8 mg/L, white blood cell count > 10 × 109/L, urinalysis count > 28/µL, and urine leukocyte count as significant predictors of postoperative infections. Our research findings indicate that the new ureteroscope has significant advantages over traditional ureteroscopes in terms of ease of entry into the ureteral lumen, stone fragmentation angle during surgery, surgical field of view, surgical operability, and reducing the risk of postoperative potential infections. These characteristics demonstrate that the new ureteroscope has significant potential in clinical applications, warranting further promotion and use.

Abstract Background: Mesenchymal stem cells (MSCs) derived from gestational tissues offer a promising avenue for prenatal intervention in congenital malformations although their application is hampered by concerns related to cellular plasticity and the need for invasive, high-risk surgical procedures. Here, we present naturally occurring exosomes (EXOs) isolated from amniotic fluid-derived MSCs (AF-MSCs) and their mimetic analogs (MIMs) as viable, reproducible, and stable alternatives. These nanovesicles present a minimally invasive therapeutic option, addressing the limitations of MSC-based treatments while retaining therapeutic efficacy. Methods: MIMs were generated from AF-MSCs by combining sequential filtration steps through filter membranes with different porosity and size exclusion chromatography columns. A physicochemical, structural, and molecular comparison was conducted with exosomes (EXOs) released from the same batch of cells. Additionally, their distribution patterns in female mice were evaluated following in vivo administration, along with an assessment of their safety profile throughout gestation in a mouse strain predisposed to neural tube defects (NTDs). The possibility to exploit both formulations as mRNA-therapeutics was explored by evaluating cell uptake in two different cell types(fibroblasts, and macrophages) and mRNA functionality overtime in an in vitro experimental setting as well as in an ex vivo, whole embryo culture using pregnant C57BL6 dams. Results: Molecular and physiochemical characterization showed no differences between EXOs and MIMs, with MIMs determining a threefold greater yield. Biodistribution patterns following intraperitoneal administration were comparable between the two particle types, with the uterus being among targeted organs. No toxic effects were observed in the dams during gestation, nor were there any malformations or significant differences in the number of viable versus dead fetuses detected. MIMs delivered a more intense and prolonged expression of mRNA encoding for green fluorescent protein in macrophages and fibroblasts. An ex-vivo whole embryo culture demonstrated that MIMs mainly accumulate at the level of the yolk sac, while EXOs reach the embryo. Conclusions: The present data confirms the potential application of EXOs and MIMs as suitable tools for prevention and treatment of NTDs and proposes MIMs as prospective vehicles to prevent congenital malformations caused by in utero exposure to drugs.

Objective To screen the prognostic influencing factors of patients with endovascular treatment for acute basilar artery occlusion (ABAO⁃EVT). Methods The baseline, clinical and follow⁃up data of 215 patients with ABAO⁃EVT from October 2017 to August 2022 in The First Affiliated Hospital of University of Science and Technology of China, Linyi People's Hospital of Shandong and Maoming People's Hospital of Guangdong were retrospectively collected, including sex, age, stroke or transient ischemic attack (TIA), hypertension, diabetes, coronary heart disease, atrial fibrillation, smoking and drinking history, National Institutes of Health Stroke Scale (NIHSS) score, intravenous thrombolysis, first pass effect, times of embolectomy, extended Thrombolysis in Cerebral Infarction (eTICI), and modified Rankin Scale (mRS) score 90 d after operation. According to the 90 d mRS score, the patients were divided into 2 groups: good prognosis group (mRS score 0-3, n = 93) and poor prognosis group (mRS score 4-6, n = 122). Univariate and multivariate stepwise Logistic regression analyses were used to screen the neurological prognostic influencing factors of ABAO ⁃ EVT patients 90 d after operation. Results Logistic regression analysis showed that the baseline NIHSS score increased was a risk factor for poor prognosis of ABAO⁃EVT patients (aOR = 0.936, 95%CI: 0.907-0.965, P = 0.000; aOR = 0.940, 95%CI: 0.910-0.970, P = 0.000), with the first pass effect (aOR = 5.752, 95%CI: 2.875-11.508; P = 0.000), eTICI grade 2c-3 (aOR = 7.113, 95%CI: 3.665-13.805; P = 0.000) were protective factors for good prognosis. Conclusions Low baseline NIHSS score, first pass effect and reperfusion level of eTICI 2c-3 are all protective factors for good neurological prognosis of ABAO⁃EVT patients.

Abstract Background CNSLBP accounts for 85% of all LBP cases and impairs physical health, quality of life, and work productivity, posing a significant health and economic burden. Baduanjin (BDJ) exercises are traditional Chinese Qi Gong mind-body exercises that have been practiced for over 1,000 years. However, the standard BDJ protocol established by the State Sports General Administration does not stimulate core muscles, limiting the effectiveness of low back pain rehabilitation. Therefore, it is necessary to improve the original BDJ protocol. Methods This 24-week single-center, single-blind, parallel-group randomized control superiority trial will allocate 100 patients into two groups (control and intervention) at a 1:1 ratio. The patients in the control group will perform the standard BDJ protocol established by the State Sports General Administration. The patients in the patients in the control group will perform the standard BDJ protocol established by the State Sports General Administration. The intervention group will perform intervention. The primary outcomes will be Quebec back pain disability scale. Secondary outcomes will include visual analog scale pain scores, Surface electromyography. The assessments of the tests will be performed at four time points. Adverse events will be recorded faithfully during the study. Discussion This randomized control trial is the first to compare a standard BDJ protocol and an optimized protocol in patients with CNSLBP. This study can help guide rehabilitation programs. Trial registration Chinese Clinical Trial Registry, ChiCTR2200065618, Registered on 10 Nov. 2022. This protocol is the first version 1, which was approved on 26 Aug 2022.

Abstract Background Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiomyopathy characterized with progressive cardiac fibrosis and heart failure. However, the exact mechanism driving the progression of cardiac fibrosis and heart failure in ACM remains elusive. This study aims to investigate the underlying mechanisms of progressive cardiac fibrosis in ACM caused by newly identified Desmoglein-2 (DSG2) variation. Methods We identified homozygous DSG2 F531C variant in a family with 8 ACM patients using whole-exome sequencing and generated Dsg2 F536C knock-in mice. Neonatal and adult mouse ventricular myocytes isolated from Dsg2 F536C knock-in mice were used. We performed functional, transcriptomic and mass spectrometry analyses to evaluate the mechanisms of ACM caused by DSG2 F531C variant. Results All eight patients with ACM were homozygous for DSG2 F531C variant. Dsg2 F536C/F536C mice displayed cardiac enlargement, dysfunction, and progressive cardiac fibrosis in both ventricles. Mechanistic investigations revealed that the variant DSG2-F536C protein underwent misfolding, leading to its recognition by BiP within the endoplasmic reticulum, which triggered endoplasmic reticulum stress, activated the PERK-ATF4 signaling pathway and increased ATF4 levels in cardiomyocytes. Increased ATF4 facilitated the expression of TGF-β1 in cardiomyocytes, thereby activating cardiac fibroblasts through paracrine signaling and ultimately promoting cardiac fibrosis in Dsg2 F536C/F536C mice. Notably, inhibition of the PERK-ATF4 signaling attenuated progressive cardiac fibrosis and cardiac systolic dysfunction in Dsg2 F536C/F536C mice. Conclusions Hyperactivation of the ATF4/TGF-β1 signaling in cardiomyocytes emerges as a novel mechanism underlying progressive cardiac fibrosis in ACM. Targeting the ATF4/TGF-β1 signaling may be a novel therapeutic target for managing ACM.

Abstract Background Glaesserella parasuis (G. parasuis) is the causative agent of Glässer’s disease, which causes significant economic losses in the swine industry. However, research on the pathogenesis of G. parasuis has been hampered by the lack of a simple and efficient marker-free knockout system. Results In this study, a marker-free knockout system was developed for G. parasuis using a temperature-sensitive vector. By alternating the incubation of transformants at 30°C and 37°C, we optimized the screening process for this system. The system was successfully applied to knockout the Kan R cassette from JS0135ΔnanH::Kan R , achieving a knockout efficiency of 90% in the final round of screening. To confirm that temperature variation was a key factor, we proceeded with knocking out the nanH and apd genes in the CF7066 strain. The knockout efficiency reached up to 100%, with the shortest screening time being only four days. The knockout of the nanH gene resulted in a significant reduction in the growth vitality of the strains, while the knockout of the apd gene led to an approximate 56% improvement in the adhesion rate. Additionally, we observed that the expression of recombinant genes in transformants was higher at 30℃ than at 37℃, with the recC gene being upregulated approximately 7-fold. In contrast, there was almost no difference in the expression of recombinant genes between 30℃ and 37℃ in the wild-type strains. This discrepancy was likely due to an elevated copy number of target plasmids at 30℃, which may have resulted in the enhanced expression of recombinant genes. Conclusions In conclusion, this newly developed gene knockout system for G. parasuis presents a valuable tool for advancing research on this organism.

Abstract Alterations in the reward and cognitive control systems are commonly observed among adolescents with internet dependence (ID), and this impairment is often accompanied by social dysfunctions, such as academic burnout. However, the intercorrelations among ID, reward, cognitive control processing, and learning burnout remain unclear. We recruited 1074 Chinese adolescents to investigate the complex interrelationships among these variables using network analysis. The resulting network revealed patterns that connected ID to the behavioral inhibition/activation system (BIS/BAS), self-control, and learning burnout; these results exhibited reasonable stability and test–retest consistency. Throughout the network, the node of BAS-drive was the critical influencing factor, and the node of self-control was the protection factor. In addition, several symptoms of learning burnout and ID were positively associated with sensitivity to punishment. As revealed by the network comparison test, the network constructed among internet dependent (ID) group differed from the network constructed among internet nondependent (IND) group not only in the edges between BIS and learning burnout but also in terms of the edges associated with learning burnout. In conclusion, this study provides insights into the complex mechanisms underlying ID among adolescents from the perspective of the network relationships between core influencing factors and negative consequences. It validates the dual-system model of risky behavior among adolescents and offers a foundation for early warning and interventions for ID in this context.

Abstract Schizophrenia (SCZ) is a complex psychiatric disorder presenting challenges for characterization. The current study aimed to identify and evaluate disease‐responsive essential genes (DREGs) to enhance the molecular characterization of SCZ. RNA‐sequencing data from PsychENCODE (536 SCZ patients, 832 controls) and peripheral blood transcriptome data from 144 recruited subjects (59 SCZ patients, 6 non‐SCZ psychiatric patients, 79 controls) are analyzed. Shared differential expression genes are obtained using three algorithms. Support vector machine (SVM)‐based recursive feature elimination is employed to identify DREGs. The biological relevance of these DREGs is examined through protein–protein interaction network, pathway enrichment, polygenic scoring, and brain tissue expression. Key DREGs are validated in SCZ animal models. A DREGs‐based machine‐learning model for SCZ characterization is developed and its performance is assessed using multiple datasets. The analysis identified 184 DREGs forming an interconnected network involved in synaptic plasticity, inflammation, neuronal development, and neurotransmission. DREGs exhibited distinct expression in SCZ‐related brain regions and animal models. Their genetic contributions are comparable to genome‐wide polygenic risk scores. The DREG‐based SVM model demonstrated high performance (AUC 85% for SCZ characterization, 79% for specificity). These findings provide new insights into the molecular mechanisms underlying SCZ and emphasize the potential of DREGs in improving SCZ characterization.

Social equity consists of opportunity equity and outcome equity, where outcome equity refers to the equitable distribution of resource, while opportunity equity refers to equivalent sets of opportunities to obtain a satisfactory outcome, ensuring equality in expected payoffs rather than the actual payoffs. Previous studies showed the existence of inequity aversion for opportunity inequality and identified some differences between opportunity equity and outcome equity in the behavior pattern of evaluation and reaction processes. However, the commonalities and distinctions in brain activity during the fairness decision-making of opportunity equity and outcome equity remain unclear. Our study used a modified version of the ultimatum game (UG) and the classic UG, and recorded electroencephalogram (EEG) data to investigate underlying neural mechanisms of fairness decision-making of opportunity equity and outcome equity. The EEG results revealed that both shared the same components of the P300 and delta bands associated with reward processing. Compared to outcome equity, opportunity equity did not identify conflict-related medial frontal negativity (MFN) and theta bands, but showed differences in the P2 and beta bands. Moreover, we used a computational modeling approach to estimate the utility for each trial, and found that larger P2 amplitudes were associated with lower utility in opportunity distribution, while larger P300 amplitudes were associated with higher utility in outcome distribution. Our findings provide electrophysiological evidence for the existence of opportunity equity and shed light on the cognitive processing disparities between opportunity equity and outcome equity. These results not only validate and expand the theory of inequality aversion but also empirically support the targeted resolution of social inequalities in various contexts.

Human immunodeficiency Virus (HIV) and Mycobacterium tuberculosis (Mtb) co-infection presents a significant public health challenge worldwide. Comprehensive assessment of the immune response in HIV/Mtb co-infection is complex and challenging. CD8+T cells play a pivotal role in the adaptive immune response to both HIV and Mtb. The differentiation of CD8+T cells follow a hierarchical pattern, with varying degrees of exhaustion throughout the process. Memory stem T cells (TSCM cells) is at the apex of the memory T lymphocyte system, which has recently emerged as a promising target in immunotherapy. In this context, we discuss the alterations of CD8+TSCM cells in HIV/Mtb mono- and co-infection, their implications and clinical significance, and potential for improving immunotherapy.

Objective To evaluate the outcomes of radiofrequency ablation (RFA) for papillary thyroid microcarcinoma (PTMC) adjacent to the trachea and compare them with those of PTMC distant from the trachea.Methods Patients who received RFA for solitary low-risk PTMC between June 2014 and July 2020 were reviewed and classified into adjacent and distant groups. To balance between-group confounders, the propensity score matching approach was employed. Volume, volume reduction ratio (VRR), tumor disappearance, complications, and disease progression were assessed and compared between the groups. Furthermore, factors affecting disease progression were evaluated.Results A total of 122 and 470 patients were included in the adjacent and distant groups, respectively. Overall VRR was 99.5% ± 3.1 and cumulative tumor disappearance rate was 99.4% after a mean follow-up time of 40.1 months ± 16.2. Overall disease progression and complications incidence were 3.7% and 1.0%, respectively. No substantial differences were observed between the two groups in the latest volume (0.8 mm3 ± 4.1 vs. 0.9 mm3 ± 4.2, p = .77), VRR (99.7% ± 1.6 vs. 99.5% ± 2.7, p = .75), cumulative tumor disappearance rate (92.6% vs. 94.2%, p = .58), and incidence of disease progression (4.1% vs. 4.5%, p = .70) and complication (1.7% vs. 0.8%, p = .86) after 1:2 matching. Additionally, tracheal adjacency exhibited no association with disease progression in multivariate Cox regression analysis (p = .73).Conclusion For eligible patients with PTMC located adjacent to or distant from the trachea, RFA may offer a safe and effective alternative treatment method.

BackgroundDevelopment of anti-drug antibodies (ADAs) and neutralizing antibodies (NAbs) to monoclonal antibodies may adversely impact pharmacokinetics, efficacy, and/or safety.ObjectiveTo describe incidence, titer, and persistence of dupilumab ADAs and NAbs, and their effects on pharmacokinetics, efficacy, and safety in patients with atopic dermatitis (AD).MethodsThis analysis included seven phase 3 randomized, placebo-controlled (N=2,992) and two long-term open-label extension (N=2,287) trials of subcutaneous dupilumab in adults and pediatric patients with moderate-to-severe AD. ADA, NAb, and dupilumab concentration in serum were assessed using validated immunoassays. ADA impacts on efficacy (EASI) and safety were assessed.ResultsTreatment-emergent ADAs were observed in up to 8.6% (aged ≥18 years), 16.0% (12-17 years), 5.3% (6-11 years), and 2.0% (6 months to 5 years) dupilumab-treated patients. Among dupilumab-treated patients, ≤3.7% had persistent responses,

Abstract Background Leukocyte Ig-like receptor B family 4 (LILRB4) as an immune checkpoint on myeloid cells is a potential target for tumor therapy. Extensive osteolytic bone lesion is the most characteristic feature of multiple myeloma. It is unclear whether ectopic LILRB4 on multiple myeloma regulates bone lesion. Methods The conditioned medium (CM) from LILRB4-WT and -KO cells was used to analyze the effects of LILRB4 on osteoclasts and osteoblasts. Xenograft, syngeneic and patient derived xenograft models were constructed, and micro-CT, H&E staining were used to observe the bone lesion. RNA-seq, cytokine array, qPCR, the activity of luciferase, Co-IP and western blotting were used to clarify the mechanism by which LILRB4 mediated bone damage in multiple myeloma. Results We comprehensively analyzed the expression of LILRB4 in various tumor tissue arrays, and found that LILRB4 was highly expressed in multiple myeloma samples. The patient’s imaging data showed that the higher the expression level of LILRB4, the more serious the bone lesion in patients with multiple myeloma. The conditioned medium from LILRB4-WT not -KO cells could significantly promote the differentiation and maturation of osteoclasts. Xenograft, syngeneic and patient derived xenograft models furtherly confirmed that LILRB4 could mediate bone lesion of multiple myeloma. Next, cytokine array was performed to identify the differentially expressed cytokines, and RELT was identified and regulated by LILRB4. The overexpression or exogenous RELT could regenerate the bone damage in LILRB4-KO cells in vitro and in vivo. The deletion of LILRB4, anti-LILRB4 alone or in combination with bortezomib could significantly delay the progression of bone lesion of multiple myeloma. Conclusions Our findings indicated that LILRB4 promoted the bone lesion by promoting the differentiation and mature of osteoclasts through secreting RELT, and blocking LILRB4 singling pathway could inhibit the bone lesion.

Abstract Background Microtubule polymerization is usually considered as the upstream of apoptotic cell death induced by taxanes, but recently published studies provide more insights into the mechanisms responsible for the antineoplastic effect of taxanes. In this study, we figure out the role of the stress-related PERK/eIF2α axis in tumor cell death upon taxane treatment along with paclitaxel resistance. Methods Utilizing immunoblot assay, the activation status of PERK-eIF2α signaling was detected in a panel of cancer cell lines after the treatment of taxanes. The causal role of PERK-eIF2α signaling in the cancer cell apoptosis induced by taxanes was examined via pharmacological and genetic inhibitions of PERK. The relationship between microtubule polymerization and PERK-eIF2α activation was explored by immunofluorescent and immunoblotting assays. Eventaually, the combined therapeutic effect of paclitaxel (PTX) and CCT020312, a PERK agonist, was investigated in PTX-resistant breast cancer cells in vitro and in vivo. Results PERK-eIF2α axis was dramatically activated by taxanes in several cancer cell types. Pharmacological or genetic inhibition of PERK efficiently impaired taxane-induced apoptotic cell death, independent of the cellular microtubule polymerization status. Moreover, PTX was able to activate the PERK/eIF2α axis in a very low concentration without triggering microtubule polymerization. In PTX-resistant breast cancer cells, the PERK/eIF2α axis was attenuated in comparison with the PTX-sensitive counterparts. Reactivation of the PERK/eIF2α axis in the PTX-resistant breast cancer cells with PERK agonist sensitized them to PTX in vitro. Combination treatment of the xenografted PTX-resistant breast tumors with PERK agonist and PTX validated the synergic effect of PTX and PERK activation in vivo. Conclusion Activation of the PERK/eIF2α axis is a pivotal prerequisite of taxanes to initiate cancer cell apoptosis, which is independent of the well-known microtubule polymerization-dependent manner. Simultaneous activation of PERK-eIF2α signaling would be a promising therapeutic strategy to overcome PTX resistance in breast cancer or other cancers.

To enhance image clarity and address the difficulties in feature extraction and incomplete haze removal in traditional image dehazing processes, a multi-feature fusion based generative adversarial dehazing network is proposed.The network adopts a generative adversarial approach and consists of a generator and a discriminator.The generator utilizes an encoderdecoder structure, and extracts haze-related feature maps from multiple receptive fields by a multi-feature extraction fusion (MFEF) block.The discriminator uses a series of convolutional calculations to analyze the feature differences between the generated images and the clear images, guiding the generator to output move realistic dehazing images.The experimental images show that the proposed method can effectively eliminate haze interference while preserving the original color tone of the image to the greatest extent possible.The experimental results demonstrate that the dehazed images produced by our algorithm have improved peak signal-to-noise ratio and structural similarity with an average of 2.588 dB and 2.66% respectively, compared with existing methods.

Abstract Non-small cell lung cancer (NSCLC)-originating cancer-associated fibroblasts (CAFs) expressing CD248 regulate interaction with immune cells to accelerate cancer progression. Epithelial–mesenchymal transition (EMT) is a key feature of metastatic cells. In our pervious study, we found that CD248+CAFs activated M2-polarized macrophages, enhancing the progression of NSCLC. However, it is yet unclear how CD248+CAFs inducing M2-polarized macrophages induce EMT program in NSCLC cells. Herein, we examined CD248 expression from CAFs derived from NSCLC patient tumour tissues. Furthermore, we determined the influence of CD248 knock down CAFs on macrophages polarization. Next, we explored the influences of CD248-harboring CAFs-mediated M2 macrophage polarization to promote NSCLC cells EMT in vitro. We constructed fibroblasts specific CD248 gene knock out mice to examine the significance of CD248-harboring CAFs-induced M2-polarized macrophages to promote NSCLC cells EMT in vivo. Based on our analysis, CD248 is ubiquitously expressed within NSCLC-originating CAFs. CD248+CAFs mediated macrophages polarized to M2 type macrophages. CD248+CAFs induced M2 macrophage polarization to enhance NSCLC cells EMT both in vivo and in vitro. Our findings indicate that CD248-harboring CAFs promote NSCLC cells EMT by regulating M2-polarized macrophages.

Abstract Single cell RNA sequencing (scRNA-seq), a powerful tool for studying the tumor microenvironment (TME), does not preserve/provide spatial information on tissue morphology and cellular interactions. To understand the crosstalk between diverse cellular components in proximity in the TME, we performed scRNA-seq coupled with spatial transcriptomic (ST) assay to profile 41,700 cells from three colorectal cancer (CRC) tumor-normal-blood pairs. Standalone scRNA-seq analyses revealed eight major cell populations, including B cells, T cells, Monocytes, NK cells, Epithelial cells, Fibroblasts, Mast cells, Endothelial cells. After the identification of malignant cells from epithelial cells, we observed seven subtypes of malignant cells that reflect heterogeneous status in tumor, including tumor_CAV1, tumor_ATF3_JUN | FOS, tumor_ZEB2, tumor_VIM, tumor_WSB1, tumor_LXN, and tumor_PGM1. By transferring the cellular annotations obtained by scRNA-seq to ST spots, we annotated four regions in a cryosection from CRC patients, including tumor, stroma, immune infiltration, and colon epithelium regions. Furthermore, we observed intensive intercellular interactions between stroma and tumor regions which were extremely proximal in the cryosection. In particular, one pair of ligands and receptors (C5AR1 and RPS19) was inferred to play key roles in the crosstalk of stroma and tumor regions. For the tumor region, a typical feature of TMSB4X-high expression was identified, which could be a potential marker of CRC. The stroma region was found to be characterized by VIM-high expression, suggesting it fostered a stromal niche in the TME. Collectively, single cell and spatial analysis in our study reveal the tumor heterogeneity and molecular interactions in CRC TME, which provides insights into the mechanisms underlying CRC progression and may contribute to the development of anticancer therapies targeting on non-tumor components, such as the extracellular matrix (ECM) in CRC. The typical genes we identified may facilitate to new molecular subtypes of CRC.

Objective In the central Yunnan region, the geological structure is complex and karst formations are prevalent. Sudden water gushing and attenuation of spring flow are among the most difficult problems in tunnel construction. The Mengkuanggou karst water system exhibits a high degree of karst conduitization, with significant differences between karst fissures and karst conduits. Methods This study employs the MODFLOW-CFPv2 dual medium numerical model to simulate the karst water system of Mengkuanggou, providing a detailed description of karst pipeline and diversion tunnel to understand the influence of tunnel construction on groundwater flow and spring flow. Results The results show that (1) The MODFLOW-CFPv2 model can describe the complex geological structure of karst areas, and simulate the dynamic characteristics of the groundwater level and the response characteristics of karst spring flow in the study area. (2) Under the condition of strong discharge, the water inflow per unit length of the tunnel is 164 m3/d·m, with a stable water inflow of 69 m3/d·m, while the Mengkuanggou karst spring flow shows a significant downwards trend. During the simulation period, the average spring flow decreased from 1 578 L/s under natural conditions to 1 098 L/s, an overall decrease of 30.4%, and the peak flow rate decreased from 2 133 L/s to 1 375 L/s, a decrease of 35.5%. The construction of strong discharge conditions will have a significant impact on tunnel construction and the groundwater environment. Under the condition of limited discharge, the maximum water inflow of the tunnel is 39 m3/d·m, and the stable water inflow is 24 m3/d·m. The water inflow of the tunnel is significantly reduced, and the downwards trend of the karst spring flow in Mengkuanggou is also improved to a certain extent. During the simulation period, the average spring flow is reduced to 1 284 L/s, a reduction of 18.6%, and the peak flow is reduced to 1 617 L/s, a decrease of 22.1%. Conclusion The MODFLOW-CFPv2 dual-medium model used in this study accurately describes highly heterogeneous karst water systems with pipelines, karst caves and fissures in karst areas. It can be used to quantitatively evaluate the karst water of Mengkuanggou during Xianglushan Tunnel construction.

Voice conversion is a research topic in the fields of speech and artificial intelligence.The goal of voice conversion is to change the timbre of speech while preserving the content of the source speech, making it sounds like spoken by the target speaker.It is essential to ensure both the quality and naturalness of the converted speech.Voice conversion based on nonparallel data gains much attention currently, where models are trained using non-parallel multilingual speaker datasets, enabling many-to-many and any-to-any voice conversions.This paper provides a comprehensive summary and analysis of recent developments in non-parallel voice conversion.Firstly, we outline the early voice conversion techniques based on parallel corpus and their limitations.Then, we introduce and compare various approaches to voice conversion based on nonparallel data, providing a thorough analysis.Finally, a summary and outlook on voice conversion technology is provided.

A gas pressure meter-based portable/miniaturized analytical kit was established for rapid and on-site detection of oxalate. Potassium permanganate (KMnO4) and oxalate solution were mixed together in bottle-in-bottle reaction device, a simple oxidation reaction process occurred within 6 min and carbon dioxide (CO2) was generated, inducing the pressure of the sealed bottle changed, which was measured by a portable gas pressure meter. A detectable range of 0.1–6 μmol mL−1 and a detection limit of 0.064 μmol mL−1 were achieved. The proposed analytical method was further used for the analysis of several real samples (spinach, beverages and water samples), with the recoveries of 89–111%. Considering the interferences from the complicated matrix, calcium chloride (CaCl2) was served as a precipitant, oxalate (C2O42−) was precipitated with Ca2+ to form precipitation (CaC2O4), CaC2O4 was then separated from the matrix by centrifuge/filter, eliminating the interferences. It is a rapid, easy-used and interference-free analytical system/device for oxalate on-site and real time analysis.

ABSTRACT The widespread prevalence of saline environments poses a significant global environmental challenge. Salt stress, induced by saline soils, disrupts soil microecology and affects the plant-microbe-soil cycling process. Utilizing microbial fungicides stands as a primary strategy to mitigate salt stress-induced damage to plants and soils. This study investigated the influence of Bacillus subtilis (Bs) inoculation on the microbial community, assembly processes, and functional changes in bacteria and fungi in Glycyrrhiza uralensis Fisch. (licorice) seedlings under varying salt stress levels, primarily employing microbiomics techniques. Soil enzyme activities displayed a declining trend with increasing salt stress, which was mitigated by Bs inoculation. Microbiome analysis revealed a significant increase in bacterial and fungal operational taxonomic units, particularly in Ascomycetes and Nitrogen-fixing Bacteria, thereby enhancing soil denitrification. The abundance of Proteobacteria, Actinobacteriota, Bacteroidota, and Firmicutes in bacteria, as well as Ascomycota in fungi, increased with higher salt stress levels, a process facilitated by Bs inoculation. However, functional predictions indicated a reduction in the relative abundance of Dung Saprotrophs with Bs inoculation. Salt stress disrupted soil assembly processes, showcasing a continuous decline in diffusion limitation with increased salt concentration, where Bs inoculation reached a peak under moderate stress. In summary, this research elucidates the communication mechanism of Bs in enhancing salt tolerance in licorice from a microbiome perspective, contributing to a comprehensive understanding of abiotic and biotic factors.IMPORTANCELicorice is a herb that grows in deserts or saline soils. Enhancing the salt tolerance of licorice is necessary to maintain the quality of cultivated licorice and to ensure the supply of medicinal herbs. In the past, we have demonstrated the effectiveness of inoculation with Bacillus subtilis (Bs) to enhance the salt tolerance of licorice and revealed the key metabolic pathways for the development of salt tolerance through multi-omics. In this study, we used the microbiomics approach to reveal the plant-microbe-soil interactions at the level of inoculation of Bs affecting the dynamics of soil microbial communities from bacterial and fungal perspectives, thus bridging the interactions between biotic and abiotic factors.

Objective Pregnant women with COVID-19 are at elevated risk for severe outcomes, but clinical data on management of these patients are limited. Monoclonal antibodies, such as casirivimab plus imdevimab (CAS+IMD), have proven effective in treating non-pregnant adults with COVID-19, prompting further evaluation in pregnant women.Methods A phase 3 portion of an adaptive, multicentre, randomised, double-blind, placebo-controlled trial evaluated the safety, clinical outcomes, pharmacokinetics and immunogenicity of CAS+IMD (1200 mg or 2400 mg) in the treatment of pregnant outpatients with COVID-19 (NCT04425629). Participants were enrolled between December 2020 and November 2021, prior to the emergence of Omicron-lineage variants against which CAS+IMD is not active. Safety was evaluated in randomised participants who received study drug (n=80); clinical outcomes were evaluated in all randomised participants (n=82). Only two pregnant participants received placebo, limiting conclusions regarding treatment effect. Infants born to pregnant participants were followed for developmental outcomes ≤1 year of age.Results In pregnant participants, CAS+IMD was well tolerated, with no grade ≥2 hypersensitivity or infusion-related reactions reported. There were no participant deaths, and only one COVID-19–related medically attended visit. Although two pregnancies (3%) reported issues in the fetus/neonate, they were confounded by maternal history or considered to be due to an alternate aetiology. No adverse developmental outcomes in infants ≤1 year of age were considered related to in utero exposure to the study drug. CAS+IMD 1200 mg and 2400 mg rapidly and similarly reduced viral loads, with a dose-proportional increase in concentrations of CAS+IMD in serum. Pharmacokinetics were consistent with that reported in the general population. Immunogenicity incidence was low.Conclusion CAS+IMD treatment of pregnant outpatients with COVID-19 showed similar safety, clinical outcomes and pharmacokinetic profiles to that observed in non-pregnant adults. There was no evidence of an impact on developmental outcomes in infants ≤1 year of age.Trial registration number NCT04425629.

In patients with rheumatoid arthritis (RA), intestinal flora imbalance and butyrate metabolism disorders precede clinical arthritis and are associated with the pathogenesis of RA. This imbalance can alter the immunology and intestinal permeability of the intestinal mucosa, leading to damage to the intestinal barrier. In this context, bacteria and their metabolites can enter the bloodstream and reach the distant target tissues of the host, resulting in local inflammation and aggravating arthritis. Additionally, arthritis is also exacerbated by bone destruction and immune tolerance due to disturbed differentiation of osteoclasts and adaptive immune cells. Of note, butyrate is a metabolite of intestinal flora, which not only locally inhibits intestinal immunity and targets zonulin and tight junction proteins to alleviate intestinal barrier-mediated arthritis but also inhibits osteoclasts and autoantibodies and balances the immune responses of T and B lymphocytes throughout the body to repress bone erosion and inflammation. Therefore, butyrate is a key intermediate linking intestinal flora to the host. As a result, restoring the butyrate-producing capacity of intestinal flora and using exogenous butyrate are potential therapeutic strategies for RA in the future.

WRKY is one of the largest transcription factor families in higher plants, playing a crucial role in plant growth, development, and responses to environmental stresses by binding to the W-box motif in the target gene promoters. Glycyrrhiza uralensis Fish. (G. uralensis), known for its extensive medicinal value and adaptation to saline-alkali environments, has garnered attention. However, information regarding the members and functions of the G. uralensis WRKY gene family is relatively limited. In this study, we identified 52 GuWRKY genes from the G. uralensis genome and comprehensively investigated their characteristics through phylogenetic analysis, examination of gene duplication events, analysis of gene structures, and conservation of protein motifs. The GuWRKY family was classified into seven groups based on phylogenetic analysis, and collinearity analysis revealed that many GuWRKY genes originated from segmental duplications, demonstrating a highly conserved domain. Promoter cis-element analysis indicated the presence of elements related to hormones, stress, and growth and development in GuWRKYs. Transcriptomic analysis revealed distinct expression patterns of GuWRKYs under salt stress, with GuWRKY31 identified as a potential key regulator in salt stress responses. Subcellular localization experiments validated some of the predicted results. The provided biological information lays a crucial foundation for further exploration of the functions of GuWRKY genes.

IntroductionAcquired vulvar lymphangioma (AVL), a rare disease caused by the dilation of superficial lymphatic vessels secondary to deep lymphatic vessel injury, is characterized by a wide range of morphological diversity and massive exudate. This morphological heterogeneity has often led to misdiagnosis or non-diagnosis. The management of AVL presents a therapeutic challenge due to the absence of a standardized treatment protocol.Case presentationA 53-year-old female patient, previously received surgical treatments for stage IIb cervical squamous cell carcinoma, presented with vulvar enlargement and copious amount of yellow exudate seven years post-treatment. Clinically, the patient exhibited chronic vulvar swelling, with easily-exudated nodules. The vulvar biopsy revealed lymphatic vessel dilation with lymphocyte infiltration, consistent with AVL. Due to the extensive lesions and severe exudate, staged excisions of bilateral vulvar lesions were performed at one-month intervals. Follow-up examinations of this patient for one-year post-surgery showed no evidence of recurrence.ConclusionIn this instance, AVL manifest secondary to cervical cancer surgery, as a result of damage to the deep lymphatic vessels of the vulva, with characteristic symptoms of copious amounts of exudate and vulvar lesions with diverse morphologies, which provides a cautionary note for physicians. Besides, the staged resection strategy in this case may offer insights into surgical treatment protocol for extensive AVL.

BackgroundThis study aimed to identify the predictive factors for prolonged length of stay (LOS) in elderly type 2 diabetes mellitus (T2DM) patients suffering from cerebral infarction (CI) and construct a predictive model to effectively utilize hospital resources.MethodsClinical data were retrospectively collected from T2DM patients suffering from CI aged ≥65 years who were admitted to five tertiary hospitals in Southwest China. The least absolute shrinkage and selection operator (LASSO) regression model and multivariable logistic regression analysis were conducted to identify the independent predictors of prolonged LOS. A nomogram was constructed to visualize the model. The discrimination, calibration, and clinical practicality of the model were evaluated according to the area under the receiver operating characteristic curve (AUROC), calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC).ResultsA total of 13,361 patients were included, comprising 6,023, 2,582, and 4,756 patients in the training, internal validation, and external validation sets, respectively. The results revealed that the ACCI score, OP, PI, analgesics use, antibiotics use, psychotropic drug use, insurance type, and ALB were independent predictors for prolonged LOS. The eight-predictor LASSO logistic regression displayed high prediction ability, with an AUROC of 0.725 (95% confidence interval [CI]: 0.710–0.739), a sensitivity of 0.662 (95% CI: 0.639–0.686), and a specificity of 0.675 (95% CI: 0.661–0.689). The calibration curve (bootstraps = 1,000) showed good calibration. In addition, the DCA and CIC also indicated good clinical practicality. An operation interface on a web page (https://xxmyyz.shinyapps.io/prolonged_los1/) was also established to facilitate clinical use.ConclusionThe developed model can predict the risk of prolonged LOS in elderly T2DM patients diagnosed with CI, enabling clinicians to optimize bed management.

Under resource distribution context, individuals have a strong aversion to unfair treatment not only toward themselves but also toward others. However, there is no clear consensus regarding the commonality and distinction between these two types of unfairness. Moreover, many neuroimaging studies have investigated how people evaluate and respond to unfairness in the abovementioned two contexts, but the consistency of the results remains to be investigated. To resolve these two issues, we sought to summarize existing findings regarding unfairness to self and others and to further elucidate the neural underpinnings related to distinguishing evaluation and response processes through meta-analyses of previous neuroimaging studies. Our results indicated that both types of unfairness consistently activate the affective and conflict-related anterior insula (AI) and dorsal anterior cingulate cortex/supplementary motor area (dACC/SMA), but the activations related to unfairness to self appeared stronger than those related to others, suggesting that individuals had negative reactions to both unfairness and a greater aversive response toward unfairness to self. During the evaluation process, unfairness to self activated the bilateral AI, dACC, and right dorsolateral prefrontal cortex (DLPFC), regions associated with unfairness aversion, conflict, and cognitive control, indicating reactive, emotional and automatic responses. In contrast, unfairness to others activated areas associated with theory of mind, the inferior parietal lobule and temporoparietal junction (IPL-TPJ), suggesting that making rational judgments from the perspective of others was needed. During the response, unfairness to self activated the affective-related left AI and striatum, whereas unfairness to others activated cognitive control areas, the left DLPFC and the thalamus. This indicated that the former maintained the traits of automaticity and emotionality, whereas the latter necessitated cognitive control. These findings provide a fine-grained description of the common and distinct neurocognitive mechanisms underlying unfairness to self and unfairness to others. Overall, this study not only validates the inequity aversion model but also provides direct evidence of neural mechanisms for neurobiological models of fairness.

Rheumatoid arthritis (RA) is a chronic autoimmune disease with a complex etiology. Neutrophil extracellular traps (NETs are NETwork protein structures activated by neutrophils to induce the cleavage and release of DNA-protein complexes). Current studies have shown the critical involvement of NETs in the progression of autoimmune diseases, Neutrophils mostly gather in the inflammatory sites of patients and participate in the pathogenesis of autoimmune diseases in various ways. NETs, as the activated state of neutrophils, have attracted much attention in immune diseases. Many molecules released in NETs are targeted autoantigens in autoimmune diseases, such as histones, citrulline peptides, and myeloperoxidase. All of these suggest that NETs have a direct causal relationship between the production of autoantigens and autoimmune diseases. For RA in particular, as a disorder of the innate and adaptive immune response, the pathogenesis of RA is inseparable from the generation of RA. In this article, we investigate the emerging role of NETs in the pathogenesis of RA and suggest that NETs may be an important target for the treatment of inflammatory autoimmune diseases.

Abstract In this paper, we present a novel Secure Clustering Routing Method based on Blockchain and Swarm Intelligence (BS-SCRM) for Wireless Sensor Networks (WSNs), which serves as a cornerstone in the Internet of Things (IoT) infrastructure. Recognizing the limitations of existing clustering routing methods in addressing security threats, our approach integrates blockchain technology to fortify WSNs against vulnerabilities such as man-in-the-middle attacks. The proposed BS-SCRM method is structured in two phases: (1) an enhanced cluster head (CH) election utilizing an elite strategy-enhanced Whale Optimization Algorithm (WOA) that considers node energy and proximity to the base station, and (2) a secure data on-chain phase where blockchain comes into play, encrypting and validating cluster data to safeguard integrity and prevent tampering. We further tackle the challenge of implementing blockchain in resource-constrained WSNs by assigning distinct roles to devices, i.e., ordinary nodes with data viewing permissions and accounting nodes entrusted with both data viewing and consensus algorithm execution. Extensive simulations confirm that BS-SCRM not only improves clustering quality but also provides a more secure and energy-efficient routing solution compared to contemporary methods. More specifically, simulation results in different scenarios demonstrate that BS-SCRM enhances network lifetime by 24–73% compared to other clustering methods when facing attacks.

Based on varieties, area and distribution of wheat in China, 1 377 newly harvested wheat samples from 12 provinces were collected in 2022. The physio-chemical quality as well as end-use quality evolutions were carried out, and the current quality status of wheat were analyzed. The results showed that the average crude protein content and gluten content of wheat were 13.1% and 29.6%, respectively, and the mean gluten index was 69. Among the rheological parameters of dough, the water absorption of flour was 63.2 mL, and the average stability time was 6.7 min. The mean tensile curve area, elongation and maximum tensile resistance were 75 cm2, 140 mm and 398 EU, respectively. All samples were evaluated for the processing quality of noodles and steamed bread, and samples with strong gluten wheat varieties and wet gluten content ≤25% were evaluated for the processing quality of bread and cake, respectively. The average scores of noodles, steamed bread, bread and cake were 79, 75, 73 and 69 points, respectively. Only 1.7% of the samples met the requirements of “High quality wheat-Strong gluten wheat” (GB/T 17892—1999), while 1.3% of the samples met the requirements of “High quality wheat-Weak gluten wheat” (GB/T 17893—1999). In addition, 44.9%, 31.4% and 2.8% of the samples met the requirements of quality classification, high-quality wheat and high-quality strong gluten wheat in “Quality classification of wheat varieties” (GB/T 17320—2013), respectively, and 56.0% and 3.0% of the samples met the requirements of quality classification and strong gluten hard wheat in “The Grain & Oil Products of China-Wheat” (LS/T 3109—2017), respectively. The results showed that the processing quality of wheat in China was general, and the food quality of steamed food was higher than that of baked food. A few varieties with excellent food processing quality bred were also planted.

Abstract The objective of this study is to investigate the expression and influence of adenosine triphosphate-sensitive potassium channel (KATP) in human umbilical arterial smooth muscle cells (HUASMCs) of patients with hypertensive disorders of pregnancy (HDP). Western blotting was used to detect the protein expression levels of KATP inwardly rectifying potassium channel (Kir)6.1 and sulphonylurea receptor (SUR)2B subunits in HUASMCs from patients with normal parturients (NP), gestational hypertension (GH), chronic hypertension (CH), preeclampsia (PE) and chronic hypertension with superimposed preeclampsia (CHSP), respectively. There was no significant difference in the protein expression of Kir6.1 subunit in NP group, GH group, CH group, PE group and CHSP group (P > 0.05). The protein expression of SUR2B subunit was gradually decreased in NP group, GH group, CH group, PE group and CHSP group, with statistically significant difference among the groups (P

Objective To prepare liposomes encapsulate hemoglobin and paclitaxel(LEHP)to improve tumor hypoxia resistance. Methods LEHP were prepared by thin-film method, and the particle size, Zeta potential and polydispersity were investigated by nanoparticle size analyzer, and encapsulation efficiency was investigated by high performance liquid chromatography, and the interaction between the liposomes and tumor cells was evaluated by in vitro cell experiments. Results The optimal preparation conditions of LEHP was as follows: total phospholipid 36 mM, DPPC∶Dope∶cholesterol molar ratio 7∶2∶1, paclitaxel 3 mg, hydrated with 3 mg·mL-1 Hb-PBS for 30 min at room temperature; The average particle size was (189.17±8.22) nm, polydispersity was 0.14±0.023, paclitaxel encapsulation efficiency was (58.27±2.55)%, hemoglobin content was (0.63±0.05) mg·mL-1. In vitro cell experiments, the killing effect of LEHP was about 1.5 times that of LEP, about 1.2 times that of LEP, and ROS production was about 1.8 times that of LEP. Conclusion The preparation conditions of LEHP was optimized, and cell experiments showed that LEHP can promote tumor cell apoptosis by improving hypoxia and increasing ROS production, which is expected to provide a safe and effective new method for drug resistance caused by tumor hypoxia.

Abstract Renal biopsy remains the gold standard for diagnosing membranous nephropathy (MN). Recent studies have suggested that renal biopsy can be replaced with the serum phospholipase A2 receptor (PLA2R) antibody test for MN diagnosis in patients with nephrotic syndrome. However, this test has not been validated in the Chinese population. In this study, we investigated whether renal biopsy provides additional diagnostic information on patients with proteinuria who are seropositive for PLA2R antibodies (SAb +). We retrospectively reviewed the clinicopathological characteristics of SAb + adult patients (aged ≥ 18 years) with proteinuria (≥ 0.5 g/24 h) assessed at the Department of Nephrology, the First Affiliated Hospital of Zhengzhou University, from June 2021 to March 2022. Among a total of 801 SAb + patients who received renal biopsy, those with incomplete pathological data, diabetes or any potential cause of secondary MN were excluded. Among the 491 remaining patients, 474 had primary MN (PMN), 16 had atypical MN (AMN, 9 patients with “full house” and 2 patients with HBsAg + /HBcAg + immunofluorescence results), and 1 had focal segmental glomerulosclerosis. In patients with an eGFR of ≥ 60 mL/min/1.73 m2 (n = 451), 436 had PMN, and 71 (16.3%) exhibited additional biopsy findings, with obesity-related glomerulopathy being the most common. In patients with an impaired eGFR (n = 40), 38 had PMN, and 31 (81.6%) showed additional findings, with acute tubular injury being the most common. In conclusion, anti-PLA2R antibody positivity is highly predictive of PMN in Chinese adults but often coexists with other pathological diagnoses. The advantages of renal biopsy for detecting other pathologies should be weighed against the potential risks of the biopsy procedure.

Abstract Background Pathway mutations have been calculated to predict the poor prognosis and immunotherapy resistance in head and neck squamous cell carcinoma (HNSCC). To uncover the unique markers predicting prognosis and immune therapy response, the accurate quantification of pathway mutations are required to evaluate epithelial-mesenchymal transition (EMT) and immune escape. Yet, there is a lack of score to accurately quantify pathway mutations. Material and methods Firstly, we proposed Individualized Weighted Hallmark Gene Set Mutation Burden (IWHMB, https://github.com/YuHongHuang-lab/IWHMB ) which integrated pathway structure information and eliminated the interference of global Tumor Mutation Burden to accurately quantify pathway mutations. Subsequently, to further elucidate the association of IWHMB with EMT and immune escape, support vector machine regression model was used to identify IWHMB-related transcriptomic features (IRG), while Adversarially Regularized Graph Autoencoder (ARVGA) was used to further resolve IRG network features. Finally, Random walk with restart algorithm was used to identify biomarkers for predicting ICI response. Results We quantified the HNSCC pathway mutation signatures and identified pathway mutation subtypes using IWHMB. The IWHMB-related transcriptomic features (IRG) identified by support vector machine regression were divided into 5 communities by ARVGA, among which the Community 1 enriching malignant mesenchymal components promoted EMT dynamically and regulated immune patterns associated with ICI responses. Bridge Hub Gene (BHG) identified by random walk with restart was key to IWHMB in EMT and immune escape, thus, more predictive for ICI response than other 70 public signatures. Conclusion In summary, the novel pathway mutation scoring-IWHMB suggested that the elevated malignancy mediated by pathway mutations is a major cause of poor prognosis and immunotherapy failure in HNSCC, and is capable of identifying novel biomarkers to predict immunotherapy response.

A method for simultaneous determination of Theanine and γ-aminobutyric acid (GABA), as the novel food of amino acids, which was established using pre-column derivatization and high-performance liquid chromatography (HPLC). 4-Dimethylaminoazobe nzene-4′-sulfonyl chloride (DABS-Cl) is employed as the derivatization reagent with chromophore linked to Theanine and GABA, which lacks chromophore for DAD analysis in its pristine structure. After the detection wavelength was confirmed, the chromatographic and derivatization conditions were also optimized, including the chromatographic column, mobile phases and their gradient, derivatization temperature and time, the additive amount of buffer solution and derivatization reagent. Methodological verification showed that the derivant of Theanine (DABS-Theanine) and derivant of GABA (DABS-GABA) have good linearity in the range of 1–100 μg/mL, with correlation coefficients of 0.9996 and 0.9995, respectively. The recoveries for both amino acids were between 93.95% and 103.90%, with RSDs ranging from 0.99% to 3.93%. The limit of detection (LOD) was 0.6 mg/kg for Theanine and 0.2 mg/kg for GABA. The limit of quantification (LOQ) was 1.7 mg/kg for Theanine and 0.6 mg/kg for GABA. Furthermore, five commercial products containing Theanine or GABA in two matrices (candy and beverage) were analyzed by the proposed method for validation. The average contents of Theanine and GABA were in the range of 307.49–1312.13 mg/kg and 22.98–6744.55 mg/kg, respectively. The developed method features easy sample pretreatment, a simple derivatization system, good separation specificity, good repeatability, accuracy and reliability, and can meet the large-scale determination Theanine and GABA in various food substrates.

Accurate crop density estimation is critical for effective agricultural resource management, yet existing methods face challenges due to data acquisition difficulties and low model usability caused by inconsistencies between optical and radar imagery. This study presents a novel approach to maize density estimation by integrating optical and radar data, addressing these challenges with a unique mapping strategy. The strategy combines available data selection, key feature extraction, and optimization to improve accuracy across diverse growth stages. By identifying critical features for maize density and incorporating machine learning to explore optimal feature combinations, we developed a multi-temporal model that enhances estimation accuracy, particularly during leaf development, stem elongation, and tasseling stages (R2 = 0.602, RMSE = 0.094). Our approach improves performance over single-temporal models, and successful maize density maps were generated for the three typical demonstration counties. This work represents an advancement in large-scale crop density estimation, with the potential to expand to other regions and support precision agriculture efforts, offering a foundation for future research on optimizing agricultural resource management.

It is a great challenge to prepare efficient and stable electrocatalysts for hydrogen evolution (HER) using non-precious metals. In this study, a series of PtCo/Ti3C2Tx-Y (Y: 16, 32, and 320, Y indicates the quality of Co(NO3)2) catalysts were synthesized by loading PtCo alloy on Ti3C2Tx. The PtCo/Ti3C2Tx-32 catalyst showed the best HER performance, reaching a current density of 10 mA cm−2 with low overpotential (36 and 101 mV) and small Tafel slopes (66.37 and 105.17 mV dec−1) in 0.5 mol L−1 H2SO4 and 1 mol L−1 KOH solution. The excellent HER activity of PtCo/Ti3C2Tx-32 can be attributed as follows: Ti3C2Tx has a unique two-dimensional structure, which can provide a large number of attachment sites for the PtCo alloy, hence exposing more active sites; on the other hand, it can also provide a fast and efficient conductive network for electron transport during electrocatalytic processes, thus enhancing the connectivity between electrolyte and catalyst. PtCo alloy makes the PtCo/Ti3C2Tx catalyst more hydrophilic, accelerating the release rate of bubbles. The DFT calculation results showed that the energy barrier of HER is reduced because the charge around Pt is redistributed by Co after alloying Pt and Co, so that the PtCo/Ti3C2Tx catalyst has a suitable ΔGH* value. This study can be expected to provide some references for the design and synthesis of Ti3C2Tx-supported alloy electrocatalysts with high activity and stability for HER.

Background: Emerging studies demonstrate that exposure to brominated flame retardants (BFRs) can have harmful effects on human health. Our study focused on the relationship between exposure to various BFRs and markers of liver function. Methods: To further explore the association between BFR exposure and liver function impairment, we used data from the National Health and Nutrition Examination Surveys (NHANES) for three cycles from 2009 to 2014, leaving 4206 participants (≥20 years of age) after screening. Nine BFRs and eight liver function tests (LFTs) were measured in the participants’ serum to represent BFRs and liver function impairment in vivo. To investigate whether there is a relationship between BFRs and health outcome, statistical research methods such as the weighted linear regression model, restricted cubic spline (RCS), weighted quantile sum (WQS), quantile-based g computing (QGC), and the Bayesian Kernel Machine Regression (BKMR) were used to evaluate the correlation between serum BFRs and LFTs. Results: The studies reveals that exposure to BFRs is associated with liver function biomarkers. In a weighted linear regression model, we found that PBB153, PBDE99, PBDE154, PBDE209, PBDE85 exposure was positively correlated with AST, ALT, GGT, ALP, TP, and SL risk. In RCS model, the nonlinear relationships between PBB153 and AST, ALT, and GGT and PBDE209 and ALT and TP are the most significant. The exposure to combined BFRs was positively correlated with AST, ALT, and GGT in WQS and QGC models. BKMR analysis showed that BFR exposure was positively correlated with AST, ALT, ALP, and GGT. Conclusions: Exposure to BFRs is associated with liver function impairment, suggesting that BFR exposure is potentially toxic to the human liver, but more in-depth studies are needed to explore this correlation.

Background: Qingdu Fang (QDF) is a traditional Chinese herbal formula with remarkable clinical effect in the treatment of HR-HPV, but its mechanism remains unclear. In this study, UPLC-QTOF-MS was used to detect its components, network pharmacology was used to explore the traditional Chinese medicine monomers and their related targets for the treatment of HR-HPV in QDF. Molecular docking and in vitro experiments were performed to verify the results.Methods: QDF constituents and active compounds were identified using UPLC-QTOF-MS analysis. TCMSP and GeneCard databases were used to identify active components, targets, and potential therapeutic targets in HR-HPV. PPI network was constructed using the String database to analyze protein-protein interactions. Cytoscape3.7.2 was used to construct PPI networks, while GO enrichment and KEGG pathway analyses with R. The effect of QDF on H8 cell proliferation was measured using the CCK-8 method, and apoptosis and cell cycle was assessed with flow cytometry. The effects of QDF on PI3K/AKT pathway were detected by Western blotting.Results: A total of 27 compounds were identified on QDF by UPLC-QTOF-MS. Base on Network pharmacology,a total of 254 target genes are involved in the action of QDF on cervical HR-HPV. PPI analysis suggested that TP53, JUN, AKT1, STAT3, TNF and IL6 were potential targets for QDF treatment of HR-HPV. Molecular docking shows that two compounds have strong binding activity with AKT1. CCK-8 and morphological observation have shown that QDF inhibits H8 cell proliferation in a dose-dependent manner. Flow cytometry experiments suggest that QDF induces apoptosis and cell cycle arrest in H8 cells. Western blotting experiments reveal that QDF inhibits the PI3K/AKT signaling pathway.Conclusion: QDF has a multi-faceted therapeutic approach for HR-HPV, targeting inflammation, oxidation, and apoptosis. It induces apoptosis in H8 cells by inhibiting the PI3K/AKT pathway.

BackgroundSputum immunoglobulin G (Sp-IgG) has been discovered to induce cytolytic extracellular trap cell death in eosinophils, suggesting a potential autoimmune mechanism contributing to asthma. This study aimed to explore the potential origin of Sp-IgG and identify clinically relevant subtypes of Sp-IgG that may indicate autoimmune events in asthma.MethodsThis study included 165 asthmatic patients and 38 healthy volunteers. We measured Sp-IgG and its five subtypes against eosinophil inflammatory proteins (Sp-IgGEPs), including eosinophil peroxidase, eosinophil major basic protein, eosinophil-derived neurotoxin, eosinophil cationic protein, and Charcot-Leyden Crystal protein in varying asthma severity. Clinical and Mendelian randomization (MR) analyses were conducted. A positive Sp-IgGEPs signature (Sp-IgGEPs+) was defined when any of the five Sp-IgGEPs values exceeded the predefined cutoff thresholds, calculated as the mean values of healthy controls plus twice the standard deviation.ResultsThe levels of Sp-IgG and Sp-IgGEPs were significantly elevated in moderate/severe asthma than those in mild asthma/healthy groups (all p < 0.05). Sp-IgG levels were positively correlated with airway eosinophil and Sp-IgGEPs. MR analysis showed causality between eosinophil and IgG (OR = 1.02, 95%CI = 1.00-1.04, p = 0.020), and elevated IgG was a risk factor for asthma (OR = 2.05, 95%CI = 1.00-4.17, p = 0.049). Subjects with Sp-IgGEPs+ exhibited worse disease severity and served as an independent risk factor contributing to severe asthma (adjusted-OR = 5.818, adjusted-95% CI = 2.193-15.431, adjusted-p < 0.001). Receiver operating characteristic curve analysis demonstrated that the combination of Sp-IgGEPs+ with non-allergic status, an ACT score < 15, and age ≥ 45 years, effectively predicted severe asthma (AUC = 0.84, sensitivity = 86.20%, specificity = 67.80%).ConclusionThis study identifies a significant association between airway eosinophilic inflammation, Sp-IgG, and asthma severity. The Sp-IgGEPs panel potentially serves as the specific biomarker reflecting airway autoimmune events in asthma.

There are lasting concerns on calvarial development because cranium not only accommodates the growing brain, but also safeguards it from exogenous strikes. In the past decades, most studies attributed the dynamic expansion and remodeling of cranium to the proliferation of osteoprecursors in cranial primordium, and the proliferation of osteoprogenitors at the osteogenic front of cranial suture mesenchyme. Further investigations identified series genes expressed in suture mesenchymal cells as the markers of the progenitors, precursors and postnatal stem cells in cranium. However, similar to many other organs, it is suggested that the reciprocal interactions among different tissues also play essential roles in calvarial development. Actually, there are increasing evidence indicating that dura mater (DM) is indispensable for the calvarial morphogenesis and osteogenesis by secreting multiple growth factors, cytokines and extracellular matrix (ECM). Thus, in this review, we first briefly introduce the development of cranium, suture and DM, and then, comprehensively summarize the latest studies exploring the involvement of ECM in DM and cranium development. Eventually, we discussed the reciprocal interactions between calvarium and DM in calvarial development. Actually, our review provides a novel perspective for cranium development by integrating previous classical researches with a spotlight on the mutual interplay between the developing DM and cranium.

Accurate estimation of evapotranspiration (ET) at high spatial resolution is crucial for drought monitoring and water resources management, but currently available remote sensing ET products generally have coarse spatial resolution (≥1000 m). To estimate ET at a high spatial resolution, Landsat images, Global Land Surface Satellite (GLASS), Moderate Resolution Imaging Spectroradiometer (MODIS), and meteorological forcing data were integrated, and the surface energy balance (SEBS) model was employed to calculate the 16-day average ET at 30 m resolution for China’s Tarim River Basin, spanning from 2009 to 2018. The results indicated that the average 16-day ET estimates correlated well with ground observations for land and water surfaces (root mean square error (RMSE) for land = 0.92 mm day−1, RMSE for water = 1.63 mm day−1, mean bias for land = 0.3 mm day−1, mean bias for water = 0.52 mm day−1). Cross validation with GLASS, ETMonitor, and Penman-Monteith-Leuning (PML_V2) ET datasets revealed an overall increasing trend for all four products (PML_V2 = 6.277 mm year−1, GLASS = 2.185 mm year−1, ETMonitor = 3.258 mm year−1, SEBS = 1.441 mm year−1), demonstrating good spatial consistency. The consistent increasing pixels were primarily distributed in the northern, southwestern, and southeastern mountainous regions, accounting for 22.8%, while 0.29% of the consistent decreasing pixels were mainly concentrated in the central desert and mountain-front oasis areas. Inconsistent pixels accounted for 76.9%, with 2.34% of the inconsistent decreasing pixels exhibiting a scattered distribution, while 37.28% of the inconsistent increasing pixels were mainly found in the central desert and some oasis areas. Furthermore, SEBS ET trend analysis indicated that the oasis area experienced more pronounced changes than the mountainous and desert areas during the 2009–2018 period. The SEBS ET estimated in this study can provide high-precision data support and a reference for future research on the water resources management.

ABSTRACT: Chicken egg chalaza (CLZ) is a natural colloidal structure in eggs that exists as an egg yolk stabilizer and is similar in composition to egg white. In this study, the proteome, phosphoproteome, and N-glycoproteome of CLZ were characterized in depth. We hydrolyzed the CLZ proteins and enriched the phosphopeptides and glycopeptides. We identified 45 phosphoproteins and 80 N-glycoproteins, containing 59 phosphosites and 203 N-glycosylation sites, respectively. Typically, the ovalbumin in CLZ was both phosphorylated and N-glycosylated, with 4 phosphosites and 4 N-glycosylation sites. Moreover, we identified 2 N-glycosylated subunits of ovomucin, mucin-5B and mucin-6, with 32 and nine N- glycosylation sites, respectively. Analysis of the phosphorylation and N-glycosylation status of CLZ proteins could provide novel insights into the structural and functional characteristics of CLZ.

Abstract Biochar application is widely studied to mitigate the threats of soil degradation to food security and climate change. However, there are big variations in the effects of biochar application on crops, soils, and the atmosphere during crop production. This study provides a global dataset of biochar application effects on crop yield, soil properties, and greenhouse emissions. The dataset is extracted and integrated from 367 peer-reviewed studies with 891 independent field, laboratory, and incubation experiments across 37 countries. This dataset includes 21 variables before and after biochar application (including soil properties, crop yield, greenhouse gas emissions, etc.) of 2438 items, focusing on two main biochar application types: biochar application alone and combined with fertilizers. Background information on climate conditions, initial soil properties, management practices, and characteristics of biochar sources and production is also contained in the dataset. This dataset facilitates a comprehensive understanding of the impact of biochar application, supports the utilization of agricultural wastes for biochar production, and assists researchers in refining experimental protocols for further studies.

Abstract Background The altered respiratory patterns have a significant impact on our health. However, the links between respiration patterns during spontaneous breathing and physical fitness remain unknown. Therefore, we sought to examine how the respiratory pattern during spontaneous breathing interacts with physical fitness. Methods A total of 610 participants (aged 20-59 years) were enrolled; 163 men (age = 41 ± 11) and 401 women (age = 42 ± 9) were included for analysis. The parameters of the respiration pattern were respiration rate (RR) and inhalation/exhalation (I/E) ratio. The physical fitness components were body size, visuomotor reaction time, balance, flexibility, hand grip strength, back extension strength, vertical jump height, number of push-ups, number of sit-ups, and the maximum rate of oxygen consumption. The data were analyzed separately for two gender groups. Participants within each gender group were further divided into two age categories (young: 20−39 years, middle-aged: 40−59 years) for the analysis, and both correlational and comparative tests were used to solidify the results. Results Neither RRs nor the I/E ratios were substantially correlated with physical fitness in women. In addition, the I/E ratios showed no significant correlation with physical fitness in young men, while the results from correlational and comparative tests were inconsistent in middle-aged men. Consistently, men with lower RRs exhibited significantly shorter visuomotor reaction times in two age groups, and demonstrated significantly higher vertical jump heights in the middle-aged group. Conclusions In women, respiratory patterns were not correlated with physical fitness. The relationship between middle-aged men’s I/E ratios and their physical fitness warrants further investigation. Men with lower RRs may have better visual-motor coordination and/or sustained attention, while middle-aged men with lower RRs may also have greater leg explosive power and neuromuscular coordination, which should be considered for physical assessment and health improvement.

Luojia 3-01 is the world's first intelligent remote sensing satellite, equipped with various imaging modes including video, frame-pushing, and scan-pushing. It boasts submeter level multimode optical imaging capabilities, on-orbit intelligent processing, and real-time intra-satellite and satellite-to-ground data transmission. Throughout the satellite's design and development, we have established the real-time intelligent information service architecture for Luojia 3-01, marking a new paradigm in on-orbit processing and real-time services for intelligent remote sensing satellites. We have proposed the on-orbit real-time processing architecture of Luojia 3-01, addressing the challenges of limited computational and storage resources, particularly in on-orbit processing of vast volumes of remote sensing data, including core algorithmic bottlenecks in “correction-extraction-compression.” A novel intelligent remote sensing satellite system has been developed, featuring multimode imaging, an open platform, intelligent processing, and satellite-to-ground interconnectivity, which significantly reduces the response time of remote sensing services to less than 8 min, thereby shortening the cycle from data acquisition to intelligent information service. This innovation spearheads a technological leap in remote sensing satellite services from data to information, from post-event to real-time, and from professional to widespread public applications, laying a solid foundation for the popularization and commercialization of China's intelligent remote sensing satellites.

In China, the process of emasculation of seed maize usually occurs in August. To prevent self-pollination by removing the tassels from every few rows of maize and to ensure the production of high-quality hybrid maize seeds, resulting in the formation of distinctive stripe-like textural features that show up in high-resolution satellite images. These features can be used as distinctive features to differentiate seed maize fields from common maize fields. In this study, Beijing-3A1 satellite image data with a resolution of 0.5 m were used to identify seed maize fields in Zhangye City, Gansu Province. First, the extraction of maize plots in remote sensing images is performed using a modified U2-net with a new field boundary loss function. Second, a new feature named “histogram of stripe slopes (HoSS)” was developed for seed maize field classification. We compare the classification accuracy obtained using HoSS features with different classifiers using other conventional features. The results show that HoSS features exhibit superiority for both single-feature classification and feature set classification. The feature set including entropy and HoSS with the K-nearest neighbor classification model as the method chosen in this study achieved 93.7% accuracy in identifying seed maize fields.

Federated learning uses data from multiple participants to collaboratively train global models and has played an increasingly important role in recent years in facilitating inter-firm data collaboration.On the other hand, the federal learning training paradigm often faces the dilemma of insufficient data, so it is important to provide assurance of fairness to motivate more participants to contribute their valuable resources.This paper illustrates the issue of fairness in federated learning.Firstly, three classifications of fairness based on different equity goals, from model performance balance, contribution assessment equity, and elimination of group discrimination are proposed, and then we provide indepth introduction and comparison of existing fairness promotion methods, aiming to help researchers develop new fairness promotion methods.Finally, by dissecting the needs in the process of federal learning implementation, five directions for future federated learning fairness research are proposed.