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Abstract Background Low-dose IL-2 (Ld-IL2) has shown favorable therapeutic effects in systemic lupus erythematosus (SLE) therapy. However, previous clinical trials reported an SLE Responder Index-4 (SRI-4) response rate of 65.52%-68%, with approximately half failing to achieve the primary endpoint by week 24. Our study aims to determine the real-world use of Ld-IL2 and to identify determinants of its effectiveness in SLE. Methods We pooled data from 342 SLE patients undergoing sequential Ld-IL2 treatment, with 314 persisting for over 3 months were included in effectiveness and prediction analyses. All patients were categorized into responder (n = 136) and non-responder group (n = 178) according to SRI-4. Lupus Low Disease Activity State (LLDAS) was also analyzed to validate our results. Results Rash, lower complement 3 (C3), and renal involvement including urine protein, urine occult blood and urine casts emerged as prominent predictors of achieving SRI-4. Adjusting for baseline values using the ratio of change to baseline revealed significant differences in CD4 + T cell immune profiles between responders and non-responders. ROC analysis confirmed a satisfactory performance of rash, renal involvement, percentage change of CD4 + T cells, and C3 in predicting SRI-4, yielding an AUC of 0.933. LLDAS analysis showed that hematological involvements and lower CLA + Treg were potent predictive markers in LLDAS attainment. Conversely, renal involvement failed to have significant association in achieving LLDAS. The analysis of background therapy in SLE patients showed that MMF was more likely to reach the SRI-4 response with the combination of Ld-IL2. Conclusions These findings uncovered the predictors of Ld-IL2 treatment efficacy in SLE patients and provided guidance to physicians for rational utilization.

Abstract The task of UAV-based maritime rescue object detection faces two significant challenges: accuracy and real-time performance. The YOLO series models, known for their streamlined and fast performance, offer promising solutions for this task. However, existing YOLO-based UAV maritime rescue object detection methods tend to prioritize high accuracy, often at the expense of real-time performance and ease of implementation and expansion. This study proposes a modular plug-and-play optimization approach based on the YOLOv8 framework, aiming to enhance real-time performance while maintaining high accuracy for UAV maritime rescue object detection. The proposed optimization modules are flexible, easy to implement, and extendable. In experiments on the large-scale publicly available SeaDronesSee dataset, our method achieved a 13.53% improvement in accuracy over YOLOv8x while reducing computational cost by 85.63%. Additionally, it surpassed the detection speed of the SeaDronesSee official code’s two-stage detector by over 20 times, while maintaining comparable accuracy. Furthermore, our analysis of the experimental results highlights differences in detection difficulty among various objects and potential biases within the dataset.

Abstract In federated learning, secret sharing is a key technology to maintain the privacy of participants’ local models. Moreover, with the rapid development of quantum computers, existing federated learning privacy protection schemes based on secret sharing will no longer be able to guarantee the data security of participants in the post-quantum era. In addition, existing privacy protection methods have the problem of high communication and computational overhead. Although the multi-stage secret sharing scheme proposed by Pilaram et al. is one of the effective solutions to the above problems, existing studies have proven the privacy leakage risk of this scheme. This paper firstly designs a new lattice-based multi-stage secret sharing scheme Improved-Pilaram to solve the security problem, which allows participants to use public vectors to reconstruct different secret values without changing the secret sharing. Based on Improved-Pilaram, this article proposes a post-quantum secure federated learning scheme PQSF. PQSF uses double masking technology to encrypt model parameters and achieves mask reconstruction through secret sharing. Since Improved-Pilaram is multi-stage, participants do not need to update their local secret shares frequently during training. Analysis and experimental results show that the PQSF proposed in this paper reduces the communication complexity between participants and reduces the computational overhead by about 20% compared with existing solutions.

Abstract Background Neoadjuvant chemoradiotherapy followed by total mesorectal excision is a standard treatment for locally advanced rectal cancer. Mismatch repair-deficient locally advanced rectal cancer (LARC) was highly sensitive to PD-1 blockade. However, most rectal cancers are microsatellite stable (MSS) or mismatch repair-proficient (pMMR) subtypes for which PD-1 blockade is ineffective. Radiation can trigger the activation of CD8 + T cells, further enhancing the responses of MSS/pMMR rectal cancer to PD-1 blockade. Radioimmunotherapy offers a promising therapeutic modality for rectal cancer. Progenitor T exhausted cells are abundant in tumour-draining lymph nodes and play an important role in immunotherapy. Conventional irradiation fields include the mesorectum and regional lymph nodes, which might cause considerable damage to T lymphocytes and radiation-induced fibrosis, ultimately leading to a poor response to immunotherapy and rectal fibrosis. This study investigated whether node-sparing modified short-course irradiation combined with chemotherapy and PD-1 blockade could be effective in patients with MSS/ pMMR LARC. Methods This was a open-label, single-arm, multicentre, prospective phase II trial. 32 LARC patients with MSS/pMMR will receive node-sparing modified short-course radiotherapy (the irradiated planned target volume only included the primary tumour bed but not the tumour-draining lymph nodes, 25 Gy/5f, 5 Gy/f) followed by CAPOX and tislelizumab. CAPOX and tislelizumab will be started two days after the completion of radiotherapy: oxaliplatin 130 mg/m2 intravenous infusion, day 1; capecitabine 1000 mg/m2 oral administration, days 1–14; and tislelizumab 200 mg, intravenous infusion, day 1. There will be four 21-day cycles. TME will be performed at weeks 14–15. We will collect blood, tumour, and lymphoid specimens; perform flow cytometry and in situ multiplexed immunofluorescence detection; and analyse the changes in various lymphocyte subsets. The primary endpoint is the rate of pathological complete response. The organ preservation rate, tumour regression grade, local recurrence rate, disease-free survival, overall survival, adverse effects, and quality of life will also be analysed. Discussion In our research, node-sparing modified radiotherapy combined with immunotherapy probably increased the responsiveness of immunotherapy for MSS/pMMR rectal cancer patients, reduced the occurrence of postoperative rectal fibrosis, and improved survival and quality of life. This is the first clinical trial to utilize a node-sparing radiation strategy combined with chemotherapy and PD-1 blockade in the neoadjuvant treatment of rectal cancer, which may result in a breakthrough in the treatment of MSS/pMMR rectal cancer. Trial registration This study was registered at www.clinicaltrials.gov . Trial registration number: NCT05972655. Date of registration: 31 July 2023.

Abstract Mitochondrial dysfunction is a significant contributor to podocyte injury in diabetic kidney disease (DKD). While previous studies have shown that PVT1 might play a vital role in DKD, the precise molecular mechanisms are largely unknown. By analyzing the plasma and kidney tissues of DKD patients, we observed a significant upregulation of PVT1 expression, which exhibited a positive correlation with albumin/creatinine ratios and serum creatinine levels. Then, we generated mice with podocyte-specific deletion of PVT1 (Nphs2-Cre/Pvt1 flox/flox ) and confirmed that the deletion of PVT1 suppressed podocyte mitochondrial dysfunction and inflammation in addition to ameliorating diabetes-induced podocyte injury, glomerulopathy, and proteinuria. Subsequently, we cultured podocytes in vitro and observed that PVT1 expression was upregulated under hyperglycemic conditions. Mechanistically, we demonstrated that PVT1 was involved in mitochondrial dysfunction by interacting with TRIM56 post-transcriptionally to modulate the ubiquitination of AMPKα, leading to aberrant mitochondrial biogenesis and fission. Additionally, the release of mtDNA and mtROS from damaged mitochondria triggered inflammation in podocytes. Subsequently, we verified the important role of TRIM56 in vivo by constructing Nphs2-Cre/Trim56flox/flox mice, consistently with the results of Nphs2-Cre/Pvt1 flox/flox mice. Together, our results revealed that upregulation of PVT1 could promote mitochondrial dysfunction and inflammation of podocyte by modulating TRIM56, highlighting a potential novel therapeutic target for DKD.

Abstract Small molecular RNAs, including microRNA (miRNA) and small interfering RNA (siRNA), participate in the regulation of gene expression. As powerful regulators, miRNAs, take part in posttranscriptional regulation of gene expression and play important roles in the diagnosis and treatment of cancer. Meanwhile, siRNA can induce sequence-specific gene silencing, thus being able to inhibit tumorigenesis by suppressing the expression of their targeted proto-oncogenes. Small RNAs (including naked miRNAs and siRNAs) are easily degraded by circulating RNAase, which can be retarded through the package of nanoparticles. Therefore, nanoparticles help tumor therapy by regulating targeted genes of small RNAs. Here, we reviewed the effects of small RNAs on gene expression; the advantages, disadvantages, and targeted modification of nanoparticles as carriers transporting small RNAs; and the application of nanocarriers delivering small RNA for cancer-targeted therapy.

Abstract Background Esophageal squamous cell carcinoma (ESCC) is often diagnosed at advanced stages due to the inherent limitations of current screening methodologies. Central to evaluating tumor invasion and prognostic assessment in ESCC is the integrity of the basement membrane (BM). However, current research on the implications of BM-related genes (BMRGs) in diagnosing ESCC remains sparse. Methods We performed a comprehensive analysis using single-cell RNA-sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database, alongside gene expression profiles acquired from GEO and The Cancer Genome Atlas (TCGA) databases. This identified differentially expressed BMRGs in ESCC. Employing LASSO, RF, and SVM-RFE, we selected potential BM biomarkers and crafted a diagnostic nomogram for ESCC, validated by ROC curves and AUC values. We also explored immune infiltration and biological mechanisms through consensus clustering and GSVA, and utilized single cell trajectory analysis and GSCALite to study gene distributions and pathways. In vitro experiments further elucidated the role of these genes in ESCC carcinogenesis. Results Here, we discovered that ESCC cell types exhibited markedly elevated BM-related scores. Our analysis pinpointed seven BM genes upregulated and linked to immune infiltration, showcasing unique gene expression profiles and varying immune cell densities across the BM-related subtypes. Furthermore, a robust positive correlation was observed between these genes expression and EMT activity. The knockdown of BGN significantly suppressed cell proliferation, migration, invasion, while also augmenting cell viability following chemotherapy drug treatment. Conclusion Our study identified seven key BMRGs (BGN, LAMB3, SPARC, MMP1, LUM, COL4A1, and NELL2) and established a diagnostic nomogram for ESCC. Of noteworthy significance is the discovery of BGN as a promising drug target, indicating a novel strategy for future clinical combination therapies in ESCC.

ABSTRACT: We investigated the short- and long-term effects of different forage types supplemented in preweaning dairy calves on growth performance, blood metabolites, rumen fermentation, bacterial community, and milk production during first lactation. A total of 60 healthy 30-d-old female Holstein calves were blocked by birth date and body weight and randomly assigned to 1 of 3 groups (n = 20): normal milk and pelleted starter feeding (CON), supplemented with chopped oat hay (OAH; 75.0 g/d per calf [DM basis]), or alfalfa hay (ALF; 75.0 g/d per calf [DM basis]). The forage supplementation started when calves were 30 d old (d 1 of the experimental period) and ended when they were 73 d old (d 44 of the experimental period, when calves were weaned). Milk and feed intakes and fecal consistency scores were recorded daily. Growth performance, rumen fluid, and blood samples were collected biweekly. After weaning, all the calves were integrated with the same barn and diets. After calving, the milk production was recorded daily. During the experimental period, the OAH group had greater solid feed and total DM intakes and greater rumen pH than the CON group (P ≤ 0.04), but had lower forage intake and CP digestibility than the ALF group (P ≤ 0.04). The ALF group had higher rumen pH and blood BHB concentration (P ≤ 0.04), lower fecal score (P = 0.02), and greater ether extract digestibility (P = 0.02) than the CON group. The ALF and OAH groups had lower concentrations of ruminal total VFA (P = 0.01). Still, the ALF group had a greater proportion of acetate and a relative abundance of cellulose degradation-related bacteria (Lachnoclostridium_1 and Oribacterium) and a lower relative abundance of inflammation-related bacteria (Erysipelotrichaceae_UCG-009) in the rumen compared with CON. Interestingly, the average milk production from 6 to 200 DIM was greater in the ALF group (P < 0.01), even though no significant effects were found on the rumen fermentation parameters and blood metabolites at 200 DIM. Generally, alfalfa hay supplementation in preweaning dairy calves had positive effects in the short- and long-term for rumen development, health status, and future milk production.

Optimizing blasting parameters is of paramount importance in minimizing overbreak during tunneling. Hence, this paper proposed an intelligent approach, which integrates separate parameter optimization based on varying rock mass qualities, with the objective of reducing overbreak. This novel intelligent method constructs a comprehensive model with three distinct functions, which can provide precise overbreak prediction, analyze the mechanisms by which input parameters influence overbreak, and integrate feature importance into the blasting parameters optimization process. First, the hyperparameters of seven tree-based algorithms were optimized using the Sparrow Search Algorithm (SSA), and the best predictive model was selected by comparing various performance metrics. Then, the importance and influencing mechanisms of input features on overbreak were revealed through the utilization of the Shapley Additive Explanation. Subsequently, interactions among crucial parameters were investigated, and their design values were recommended. Finally, a novel parameter optimization method was employed to reduce overbreak, which combines the conclusions drawn from the importance analysis of input features with SSA through three key steps: modification of the initial position, expanding the search scope, and neighborhood perturbation. Compared to the unimproved methods, the proposed approach can significantly reduce post-blast overbreak areas in different sections of the tunnel by 12.8 % and 16.4 %, respectively.

In non-small cell lung cancer (NSCLC), as an improtant oncogenic driver gene, epidermal growth factor receptor exon 20 insertion (EGFR ex20ins) has a unique protein structure and is primarily drug-resistant to traditional EGFR-tyrosine kinase inhibitors (EGFR-TKIs). In recent years, exploration of targeted therapy for EGFR ex20ins has never stopped. Firstly Mobocertinib and Amivantamab obtained approval from U.S. Food and Drug Administration (FDA) for EGFR ex20ins mutant NSCLC patients, then other drugs, such as Sunvozertinib, made breakthroughs and combination therapies also obtained gains. Multi-pronged measures are hopeful to overcome EGFR ex20ins drug resistance. As mentioned above, it’s definitely important to gain deeper understanding of molecular mechanism of EGFR ex20ins and assess effect and difference between novel drugs. This review is devoted to make a summary about newest achievement so to provide valuable reference about precise therapy for patients with EGFR ex20ins.

Abstract RNase H1 has been acknowledged as an endoribonuclease specializing in the internal degradation of the RNA moiety within RNA–DNA hybrids, and its ribonuclease activity is indispensable in multifaceted aspects of nucleic acid metabolism. However, the molecular mechanism underlying RNase H1-mediated hybrid cleavage remains inadequately elucidated. Herein, using single-molecule approaches, we probe the dynamics of the hybrid cleavage by Saccharomyces cerevisiae RNase H1. Remarkably, a single RNase H1 enzyme displays 3′-to-5′ exoribonuclease activity. The directional RNA degradation proceeds processively and yet discretely, wherein unwinding approximately 6-bp hybrids as a prerequisite for two consecutive 3-nt RNA excisions limits the overall rate within each catalytic cycle. Moreover, Replication Protein A (RPA) reinforces RNase H1’s 3′-to-5′ nucleolytic rate and processivity and stimulates its 5′-to-3′ exoribonuclease activity. This stimulation is primarily realized through the pre-separation of the hybrids and consequently transfers RNase H1 to a bidirectional exoribonuclease, further potentiating its cleavage efficiency. These findings unveil unprecedented characteristics of an RNase and provide a dynamic view of RPA-enhanced processive hybrid cleavage by RNase H1.

Abstract Background Tumor recurrence and mortality rates remain challenging in cancer patients despite comprehensive treatment. Neoadjuvant chemotherapy and immunotherapy aim to eliminate residual tumor cells, reducing the risk of recurrence. However, drug resistance during neoadjuvant therapy is a significant hurdle. Recent studies suggest a correlation between RNA methylation regulators (RMRs) and response to neoadjuvant therapy. Methods Using a multi-center approach, we integrated advanced techniques such as single-cell transcriptomics, whole-genome sequencing, RNA sequencing, proteomics, machine learning, and in vivo/in vitro experiments. Analyzing pan-cancer cohorts, the association between neoadjuvant chemotherapy/immunotherapy effectiveness and RNA methylation using single-cell sequencing was investigated. Multi-omics analysis and machine learning algorithms identified genomic variations, transcriptional dysregulation, and prognostic relevance of RMRs, revealing distinct molecular subtypes guiding pan-cancer neoadjuvant therapy stratification. Results Our analysis unveiled a strong link between neoadjuvant therapy efficacy and RNA methylation dynamics, supported by pan-cancer single-cell sequencing data. Integration of omics data and machine learning algorithms identified RMR genomic variations, transcriptional dysregulation, and prognostic implications in pan-cancer. High-RMR-expressing tumors displayed increased genomic alterations, an immunosuppressive microenvironment, poorer prognosis, and resistance to neoadjuvant therapy. Molecular investigations and in vivo/in vitro experiments have substantiated that the JAK inhibitor TG-101,209 exerts notable effects on the immune microenvironment of tumors, rendering high-RMR-expressing pan-cancer tumors, particularly in pancreatic cancer, more susceptible to chemotherapy and immunotherapy. Conclusions This study emphasizes the pivotal role of RMRs in pan-cancer neoadjuvant therapy, serving as predictive biomarkers for monitoring the tumor microenvironment, patient prognosis, and therapeutic response. Distinct molecular subtypes of RMRs aid individualized stratification in neoadjuvant therapy. Combining TG-101,209 adjuvant therapy presents a promising strategy to enhance the sensitivity of high-RMR-expressing tumors to chemotherapy and immunotherapy. However, further validation studies are necessary to fully understand the clinical utility of RNA methylation regulators and their impact on patient outcomes.

Objective: To investigate the effect and mechanism of Hippophae rhamnoides flavone (HRF) on polycystic ovarian syndrome (PCOS) in rats, and to provide new ideas for the prevention and treatment of PCOS. Methods: A PCOS rat model was duplicated by giving rats a high-fat diet combined with the intragastric administration of letrozole, and the model rats were randomly divided into model group, low-dose HRF group (200 mg/kg HRF), high-dose HRF group (400 mg/kg HRF) and metformin group (100 mg/kg). Changes in the related indicators were detected on the 21 d after the rats were administered with the different agents by gavage. Results: Compared with that in the model group, the ovarian index, the percentage of interestrus temporal image, the fasting blood glucose (FBG) level, the fasting insulin (FINS) content, the insulin resistance index (HOMA-IR), the activities of serum luteinizing hormone (LH) and testosterone (T), the levels of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and C reactive protein (CRP) of rats in low- and high-dose HRF groups were respectively decreased significantly (P

Abstract Astragaloside IV, a prime active component of Astragalus membranaceus, has potential as a neuroprotectant. We aimed to identify the active ingredients in A. membranaceus and assess if Astragaloside IV can improve cerebral ischemia-reperfusion injury (CIRI) cell apoptosis by reducing P-Src and P-GRK2 via ryanodine receptor (RyR) expression inhibition. We used bioinformatics analysis to examine the effects of A. membranaceus on ischemic stroke. We studied brain samples from middle cerebral artery occlusion (MCAO) mice treated with normal saline, Astragaloside IV, and sham mice for pathology and Western blot tests. We also tested PC12 cells in vitro with or without Astragaloside IV or GSK180736A using Western blotting and fluorescence assays. Our bioinformatics analysis suggested a possible association between A. membranaceus, calcium ion pathways, and apoptosis pathways. Western blot data indicated Astragaloside IV significantly decreased RyR, p-Src, and downstream phosphorylated GRK2, PLC, CaMKII, and IP3R levels in MCAO mice brains. Astragaloside IV also considerably inhibited pro-apoptotic and oxidative stress-associated proteins’ expression while boosting anti-apoptotic protein expression. The results suggest Astragaloside IV can inhibit RyR expression, subsequently reducing brain cell apoptosis.

Abstract Background Addressing presbyopia in the aging population, particularly in non-cataractous patients, remains a challenge. This study evaluates the outcomes of refractive lens exchange (RLE) with AT LISA tri 839MP trifocal intraocular lens (IOL) implantation in a Chinese presbyopic population without cataracts. Methods The study included 164 eyes from 82 patients undergoing bilateral RLE at Peking Union Medical College Hospital. Comprehensive evaluations encompassed visual acuities, refraction, ocular aberrometry, and subjective outcomes via the VF-14 questionnaire. The focus was on postoperative visual performance, refractive outcomes, safety, objective optical quality, and patient satisfaction. Results 100%, 90.2%, and 89.0% of patients achieved binocular UDVA, UNVA, and UIVA of logMAR 0.1 or better at 6 months postoperatively. 97.6% of eyes were within ± 1.00 D of emmetropia postoperatively. Optical quality assessments showed increases in modulation transfer function and Strehl ratios (p

Abstract The outcomes of patients with sepsis are influenced by the contractile function of the right ventricle (RV), but the impact of cardiopulmonary interaction in ICU-mortality of sepsis patients remains unclear. This study aims to investigate the ICU-mortality impact of right ventricular-pulmonary artery (RV-PA) coupling in patients with sepsis. We employed echocardiography to assess patients with sepsis within the initial 24 h of their admission to the ICU. RV-PA coupling was evaluated using the tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP) ratio. A total of 92 subjects were enrolled, with 55 survivors and 37 non-survivors. TAPSE/PASP ratio assessed mortality with an area under the curve (AUC) of 0.766 (95% CI 0.670–0.862) and the optimal cutoff value was 0.495 mm/mmHg. We constructed a nomogram depicting the TAPSE/PASP in conjunction with IL-6 and Lac for the joint prediction of sepsis prognosis, and demonstrated the highest predictive capability (AUC = 0.878, 95% CI 0.809–0.948). In conclusion, the TAPSE/PASP ratio demonstrated prognostic value for ICU mortality in sepsis patients. The nomogram, which combines the TAPSE/PASP, IL-6, and LAC, demonstrated enhanced predictive efficacy for the prognosis of sepsis patients.

Gynostemma pentaphyllum (Thunb.) Makino (GP), a plant with homology of medicine and food, as a traditional Chinese medicine, possesses promising biological activities in the prevention and treatment of type 2 diabetes mellitus (T2DM). However, the material basis and the mechanism of action of GP in the treatment of T2DM have not been fully elucidated. This study aimed to clarify the active components, potential targets and signaling pathways of GP in treating T2DM. The chemical ingredients of GP were collected by combining UPLC-HRMS analysis and literature research. Network pharmacology revealed that GP had 32 components and 326 potential targets in treating T2DM. The results showed that GP affected T2DM by mediating the insulin resistance signaling pathway, PI3K/Akt signaling pathway and FoxO1 signaling pathway, which had a close relationship with T2DM. Molecular docking results showed that STAT3, PIK3CA, AKT1, EGFR, VEGFA and INSR had high affinity with the active compounds of GP. In vitro, GP extracts obviously increased the glucose uptake and glucose consumption in IR-HepG2 cells. GP extracts increased the levels of PI3K, p-AKT, p-GSK3β and p-FoxO1 and decreased the expression of p-IRS1, p-GS, PEPCK and G6Pase, which indicated that GP could promote glycogen synthesis and inhibit gluconeogenesis by regulating the IRS1/PI3K/Akt signaling pathway. The results demonstrated that GP could improve insulin resistance by promoting glucose uptake and glycogen synthesis and inhibiting gluconeogenesis through regulating the IRS1/PI3K/Akt signaling pathway, which might be a potential alternative therapy for T2DM.

Abstract The term “geographical synthetic thinking” is taken from the latest Chinese version of the “Geography Curriculum Standards” (General High School 2017 edition, Compulsory Education 2022 edition) and is one of the four core competencies prioritized in the teaching of geography at the secondary-school level. This study proposes that using geographic subject mind maps improves students’ geographical synthetic thinking and develops a set of geographic subject mind map (GSMM) drawing standards for teachers and matching standards and suggestions for teaching applications. Seven geography teachers and their students from eight class sections in seven provinces and cities in China were recruited to participate in the study. The teachers taught students how to use geographic subject mind maps designed to develop students’ geographical synthetic thinking in the geography classroom. After 4–5 experimental lessons, the geographical synthetic thinking level of the 267 valid student participants showed a significant improvement, with a statistically significant difference between pretest and posttest scores. The teachers’ level of application of geographic subject mind maps in teaching was significantly and positively correlated with the students’ improvements in geographical synthetic thinking, demonstrating that the standardized use of geographic subject mind maps in accordance with teaching application standards can effectively improve students’ geographical synthetic thinking levels.

Salt stress could lead to plant growth barriers and crop yield reduction. Strawberries are sensitive to salt stress, and improving salt tolerance is important for strawberry production. This study aimed to explore the potential of hydrogen-rich water (HRW) to enhance salt tolerance in strawberries. Through pot experiments, we investigated how HRW affects plant growth, ion absorption, osmotic stress, oxidative stress, antioxidant enzyme levels, hormone levels, and root endophytic bacteria in strawberry seedlings under salt stress. The results showed that under 100 mM NaCl treatment, 50% and 100% HRW treatments significantly increased strawberry biomass by 0.29 g and 0.54g, respectively, wherein, 100% HRW significantly increased the shoot and root length by 15.34% and 24.49%, respectively. In addition, under salt stress the absorption of K+ by strawberry seedlings was increased with the HRW supplement, while the absorption of Na+ was reduced. Meanwhile, HRW treatment reduced the transfer of Na+ from root to shoot. Furthermore, under salt stress, HRW treatment increased the relative water content (RWC) by 12.35%, decreased the electrolyte leakage rate (EL) by 7.56%. HRW modulated phytohormone levels in strawberry seedlings, thereby alleviating the salt stress on strawberries. Moreover, HRW was found to promote plant growth by altering the diversity of bacteria in strawberry roots and recruiting specific microorganisms, such as Tistella. Our findings indicate that HRW could help restore the microecological homeostasis of strawberry seedlings, thus further mitigating salt stress. This study provides a novel perspective on the mechanisms by which HRW alleviates salt stress, thereby enriching the scientific understanding of hydrogen’s applications in agriculture.

Abstract Few predictive biomarkers exist for identifying patients who may benefit from neoadjuvant therapy (NAT). The intratumoral microbial composition is comprehensively profiled to predict the efficacy and prognosis of patients with esophageal squamous cell carcinoma (ESCC) who underwent NAT and curative esophagectomy. Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis is conducted to screen for the most closely related microbiota and develop a microbiota‐based risk prediction (MRP) model on the genera of TM7x, Sphingobacterium, and Prevotella. The predictive accuracy and prognostic value of the MRP model across multiple centers are validated. The MRP model demonstrates good predictive accuracy for therapeutic responses in the training, validation, and independent validation sets. The MRP model also predicts disease‐free survival (p = 0.00074 in the internal validation set and p = 0.0017 in the independent validation set) and overall survival (p = 0.00023 in the internal validation set and p = 0.11 in the independent validation set) of patients. The MRP‐plus model basing on MRP, tumor stage, and tumor size can also predict the patients who can benefit from NAT. In conclusion, the developed MRP and MRP‐plus models may function as promising biomarkers and prognostic indicators accessible at the time of diagnosis.

Psoralea corylifolia polysaccharide (PPs) was the bioactive ingredient that conferred health benefits. In this study, simulated digestion and anaerobic fermentation models were employed to explore the digestion and fermentation characteristics of PPs and its effect on the intestinal microbiota. The results revealed that while the total and reducing sugar contents of PPs increased after simulated digestion, their molecular weight, monosaccharide composition, and overall structure remained unchanged, indicating that PPs was not degraded during digestion. On the other hand, during anaerobic fermentation, PPs was metabolized by intestinal microbiota, leading to the production of acetic acid and propionic acid, which subsequently reduced the pH of the fecal culture solution. Additionally, PPs modulated the composition of the intestinal flora, significantly decreasing the relative abundance of Proteobacteria while increasing the relative abundance of Bacteroidota and Firmicutes to varying degrees. This study highlighted the potential of PPs for development as functional foods and therapeutic agents.

Effective management of corn straw and stubble is critical in conservation tillage, as it impacts soil health and productivity. However, accurate classification of different types of straw cover has been hindered by their similar spectral and spatial characteristics and the low spatial resolution of hyperspectral satellite imagery. Moreover, traditional convolution neural network (CNN)-based methods, which rely on first-order statistics for feature extraction, often struggle to extract distinguishable features of highly similar objects effectively, thereby reducing classification accuracy. In this study, a second-order statistical-feature extraction algorithm based on CNN that uses fused multispectral and hyperspectral data was tested for its ability to classify types of straw cover. In the first step, coupled non-negative matrix factorization (CNMF) was used to fuse hyperspectral and multispectral images effectively, thereby enhancing the spatial resolution of the hyperspectral data. In this study, we integrated pointwise convolution (PWC), depthwise convolution (DWC), and a distance covariance matrix (DCM) to form a mixed convolution and DCM (MCDCM) network; we used this to extract and integrate deep spectral–spatial features of the hyperspectral images. Our experimental results show that the MCDCM network significantly improved classification accuracy compared to traditional methods, with accuracy rates for the different straw-cover types exceeding 90% and overall accuracy reaching 98.26%. The fused image also exhibited better preservation of feature edges and contours. The accurate identification of corn-straw-cover types achieved with the proposed MCDCM method is a major step in optimizing conservation-farming practices, improving soil fertility and farm productivity, and supporting sustainable ecological development.

Introduction Critically ill patients are at a heightened risk for post-traumatic stress disorder (PTSD). While the intensive care unit (ICU) diary has been shown to improve the mental health and quality of life of ICU patients, the handwritten version still has some limitations such as a lack of support for multimedia content and writing by remote family members, as well as being time-consuming and labour-intensive. We hypothesise that constructing an ICU electronic diary platform based on a co-design approach and verifying its applicability could alleviate these limitations, making the ICU diary more convenient for users.Methods and analysis This sequential exploratory mixed-methods study will consist of four consecutive phases: understanding the ICU diary research content and implementation, developing an ICU electronic diary platform after conducting qualitative interviews with stakeholders, verifying the applicability of the platform and verifying its effectiveness.Ethics and dissemination Ethics approval was obtained from the Biomedical Research Ethics Committee of the Affiliated Hospital of Zunyi Medical University (approval number: KLL-2023–602). The results of this study will be distributed through peer-reviewed journals.Trial registration number Chinese Clinical Trial Register (ChiCTR2400079903).

ABSTRACT Pulmonary cryptococcosis is a common complication in immunocompromised patients. In a mouse model of pulmonary cryptococcosis, Cryptococcus neoformans induces a type 2 immune response that is detrimental to host protection. Long non-coding RNAs (lncRNAs) have emerged as key players in the pathogenesis of infectious diseases. However, the roles and mechanisms of lncRNAs in fungal infection are largely elusive. In the present study, we aimed to explore the roles of LincR-PPP2R5C in pulmonary cryptococcosis. We observed an increase in the level of LincR-PPP2R5C in the lung tissues of C57BL/6J mice after tracheal infection with C. neoformans. Subsequently, we intratracheally infected LincR-PPP2R5C knockout (KO) mice and wild-type mice with C. neoformans. LincR-PPP2R5C deficiency mitigates C. neoformans infection, which can be demonstrated by extending survival time and decreasing fungal burden in the lung. In the lung tissues of infected LincR-PPP2R5C KO mice, there was a notable increase in the levels of type 2 cytokines [interleukin (IL)-4 and IL-5] and an increase in the number of neutrophils in both the lung tissue and bronchoalveolar lavage fluid. Mechanistically, the lack of LincR-PPP2R5C results in increased protein phosphatase 2A phosphorylation, thereby enhancing the fungicidal activity of neutrophils against Cryptococcus neoformans, with IL-4 playing a synergistic role in this process. Overall, LincR-PPP2R5C deficiency mitigated pulmonary cryptococcosis by increasing the fungicidal activity of neutrophils, which was associated with increased IL-4 levels. Our study presented specific evidence of the role of host-derived lncRNAs in the regulation of C. neoformans infection.IMPORTANCEPulmonary cryptococcosis is a human fungal disease caused by Cryptococcus neoformans, which is common not only in immunocompromised individuals but also in patients with normal immune function. Therefore, studying the control mechanisms of pulmonary cryptococcosis is highly important. Here, we demonstrated that the deletion of LincR-PPP2R5C leads to increased killing of C. neoformans by neutrophils, thereby reducing pulmonary cryptococcal infection. These findings will greatly enhance our understanding of the mechanisms by which lncRNAs regulate the pathogenesis of C. neoformans, facilitating the use of lncRNAs in pulmonary cryptococcosis therapy.

Abstract Acute kidney injury (AKI) is the sudden decrease in renal function that can be attributed to dysregulated reactive oxygen species (ROS) production and impaired mitochondrial function. Irisin, a type I membrane protein secreted by skeletal muscles in response to physical activity, has been reported to alleviate kidney damage through regulation of mitochondrial biogenesis and oxidative metabolism. In this study, a macrophage membrane‐coated metal‐organic framework (MCM@MOF) is developed as a nanocarrier for encapsulating irisin to overcome the inherent characteristics of irisin, including a short circulation time, limited kidney‐targeting ability, and low membrane permeability. The engineered irisin‐mediated biomimetic nanotherapeutics have extended circulation time and enhanced targeting capability toward injured kidneys due to the preservation of macrophage membrane proteins. The irisin‐encapsulated biomimetic nanotherapeutics effectively mitigate acute ischemia‐reperfusion injury by protecting mitochondrial function and modulating SOD2 levels in renal tubular epithelial cells. The present study provides novel insights to advance the development of irisin as a potential therapeutic approach for AKI.

A major challenge for second language learners on academic programmes is how they develop their writing abilities. This study uses the framework of process writing (Flower & Hayes, 1981; Hayes, 2012) and an autoethnographic research design data construction (Starfield, 2020; Yazan et al., 2020) to explore how one-second language learner changed how they planned their assignments and responded to feedback from their tutors on a one-year MA programme. Working with a critical friend, the author-researcher draws on six data sets: assignment briefs, guidance provided by lecturers, the author/researcher’s outlines/plans for the assignments with comments from lecturers, notes on journal articles and textbooks, feedback from lecturers and personal reflections on the writing process. The author/researcher’s development became more sophisticated in locating/ using sources and structuring her writing with language feedback impacting writing strategies rather than language knowledge. Her writing development was influenced by contextual features, particularly non-academic factors that limited the time she had for writing, and the structure of the assessment on her programme scaffolded her writing in terms of increasing the length of assignments and the use of the author/researcher’s own experience.

Abstract Objective This study aims to assess the tricuspid annular plane systolic excursion (TAPSE)/PASP ratio as a potential indicator for predicting the probability of developing pulmonary arterial hypertension (PAH) in hyperthyroidism patients. A nomogram model will be developed based on our findings, as well as the receiver operating characteristic (ROC) curve. Methods The study involved 166 hyperthyroid patients treated at Yijishan Hospital, and the period covered August 2021 to August 2022. Patients were divided into two groups according to pulmonary artery systolic pressure ≥35 mmHg. Univariate and multivariate logistic analyses were performed on the two groups' demographic and laboratory data to identify potential diagnostic markers. These parameters were evaluated using ROC curves to determine their precision in forecasting PAH. The findings were validated by plotting a calibration curve based on a line chart model. Results In the study, eventually, 80 patients were enrolled: 30 in the PAH group and 50 in the No PAH group. Multipleistic regression analysis predicted the occurrence risk of developing PAH. When paired with other conventional echocardiographic parameters (such as TAPSE, MPI, and SV) and serological markers (such as FT3 and FT4), the developed model demonstrated outstanding predictive performance with an area under the ROC curve of 0.985, a Youden index of 0.971, a sensitivity of 100%, and a specificity of 97.1%. Conclusions The nomogram model constructed by combining the TAPSE/PASP ratio with FT3 and FT4 serum markers, as well as conventional ultrasound parameters SV and MPI in hyperthyroidism patients, demonstrates robust discriminatory ability and consistency.

IntroductionThe relationship between serum uric acid (SUA) and cervical cancer is inconclusive. This study aims to investigate the causal relationship between SUA levels and cervical cancer incidence, and to evaluate the potential role of nutritional interventions in cervical cancer prevention.MethodsWe conducted a two-sample bidirectional Mendelian randomization (MR) analysis using genetic instruments from publicly available genome-wide association studies (GWASs) of individuals of predominantly European ancestry. Methods such as inversevariance weighted, weighted-median, weighted model, and MR-Egger were applied. Sensitivity tests, including leave-one-out, MR-PRESSO, and Cochran’s Q test, assessed heterogeneity and pleiotropy.ResultsOur findings revealed that a high SUA concentration significantly increased the risk of malignant cervical cancer: a 1 mg/mL increase in SUA was associated with a 71% higher risk (OR = 1.71, 95% CI = 1.10–2.67; p = 0.018). Stratification by histological type showed a significant causal effect on cervical adenocarcinoma risk (OR = 2.56, 95% CI = 1.14–5.73; p = 0.023). However, no clear evidence was found for a causal effect of cervical cancer on SUA levels.ConclusionThis study identified a causal relationship between elevated SUA levels and the risk of malignant cervical cancer, particularly cervical adenocarcinoma. These findings provide novel insights into the mechanisms of cervical carcinogenesis and suggest that managing SUA levels could be a potential strategy for cervical cancer prevention through dietary management.

Summary: The strategy of lowering cholesterol levels by promoting cholesterol excretion is still lacking, and few molecular targets act on multiple cholesterol metabolic processes. In this study, we find that Nogo-B deficiency/inhibition simultaneously promotes hepatic uptake of cholesterol and cholesterol excretion. Nogo-B deficiency decreases cholesterol levels by activating ATP-binding cassette transporters (ABCs), apolipoprotein E (ApoE), and low-density lipoprotein receptor (LDLR) expression. We discover that Nogo-B interacts with liver X receptor α (LXRα), and Nogo-B deficiency inhibits ubiquitination degradation of LXRα, thereby enhancing its function on cholesterol excretion. Decreased cellular cholesterol levels further activate SREBP2 and LDLR expression, thereby promoting hepatic uptake of cholesterol. Nogo-B inhibition decreases atherosclerotic plaques and cholesterol levels in mice, and Nogo-B levels are correlated to cholesterol levels in human plasma. In this study, Nogo-B deficiency/inhibition not only promotes hepatic uptake of blood cholesterol but also facilitates cholesterol excretion. This study reports a strategy to lower cholesterol levels by inhibiting Nogo-B expression to promote hepatic cholesterol uptake and cholesterol excretion.

Fibroblast activation and extracellular matrix (ECM) deposition play an important role in the tracheal abnormal repair process and fibrosis. As a transcription factor, SOX9 is involved in fibroblast activation and ECM deposition. However, the mechanism of how SOX9 regulates fibrosis after tracheal injury remains unclear. We investigated the role of SOX9 in TGF-β1-induced fibroblast activation and ECM deposition in rat tracheal fibroblast (RTF) cells. SOX9 overexpression adenovirus (Ad-SOX9) and siRNA were transfected into RTF cells. We found that SOX9 expression was up-regulated in RTF cells treated with TGF-β1. SOX9 overexpression activated fibroblasts and promoted ECM deposition. Silencing SOX9 inhibited cell proliferation, migration, and ECM deposition, induced G2 arrest, and increased apoptosis in RTF cells. RNA-seq and chromatin immunoprecipitation sequencing (ChIP-seq) assays identified MMP10, a matrix metalloproteinase involved in ECM deposition, as a direct target of SOX9, which promotes ECM degradation by increasing MMP10 expression through the Wnt/β-catenin signaling pathway. Furthermore, in vivo, SOX9 knockdown ameliorated granulation proliferation and tracheal fibrosis, as manifested by reduced tracheal stenosis. In conclusion, our findings indicate that SOX9 can drive fibroblast activation, cell proliferation, and apoptosis resistance in tracheal fibrosis via the Wnt/β-catenin signaling pathway. The SOX9–MMP10–ECM biosynthesis axis plays an important role in tracheal injury and repair. Targeting SOX9 and its downstream target MMP10 may represent a promising therapeutic approach for tracheal fibrosis.

Abstract Introduction This study aimed to analyze the risk factors associated with isoniazid-resistant and rifampicin-susceptible tuberculosis (Hr-TB) in adults. Method The clinical data of 1,844 adult inpatients diagnosed with culture-positive pulmonary tuberculosis (PTB) in Nanjing Second Hospital from January 2019 and December 2021 were collected. All culture positive strain from the patient specimens underwent drug susceptibility testing (DST). Among them, 166 patients with Hr-TB were categorized as the Hr-TB group, while the remaining 1,678 patients were classified as having drug-susceptible tuberculosis (DS-TB). Hierarchical logistic regression was employed for multivariate analysis to identify variables associated with Hr-TB. Results: Multivariate logistic regression analysis revealed that individuals with diabetes mellitus (DM) (OR 1.472, 95% CI 1.037–2.088, p = 0.030) and a history of previous tuberculosis treatment (OR 2.913, 95% CI 1.971–4.306, p = 0.000) were at higher risk of developing adult Hr-TB, with this risk being more pronounced in male patients. Within the cohort, 1,640 patients were newly treated, and among them, DM (OR 1.662, 95% CI 1.123–2.461, p = 0.011) was identified as risk factors for Hr-TB. Conclusions: Diabetes mellitus is a risk factor for Hr-TB in adults, and the contribution of diabetes as a risk factor was more pronounced in the newly treatment or male subgroup. And previous TB treatment history is also a risk factor for Hr-TB in adults.

Abstract Background To find the relationship between the changes of retinal and choriodal structure/ vascular densities (VD) and the myopia progress. Methods 126 eyes of 126 age-matched young participants were divided into three groups: Emmetropia and Low Myopia (EaLM) (33 eyes), Moderate Myopia (MM) (39 eyes), and High Myopia (HM) (54 eyes). Fundus images measuring 12 × 12 mm were captured using ultra-widefield swept-source optical coherence tomography angiography (SS-OCTA). Each image was uniformly divided into nine regions: supra-temporal (ST), temporal (T), infra-temporal (IT), superior (S), central macular area (C), inferior (I), supra-nasal (SN), nasal (N), and infra-nasal (IN). Various structural parameters, including inner retina thickness (IRT), outer retina thickness (ORT), and choroid thickness (CT), were assessed, and the VD of the superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaries (CC), and choroid vessels (ChdV) were quantified. Results CT in upper fundus exhibited a significant reduction from EaLM to MM. Additionally, ORT (ST, S. SN, C, N, IT, I, IN), CT (ST, S, SN, T, C, N, IT, I, IN) and VDs of SCP (ST, S, C, I, IN), DCP (ST, S, T, C, I) and ChdV (T, N, I, IN) were statistically diminished in EaLM compared to HM. Furthermore, IRT (N), ORT (N, IN), CT (S, SN, T, C, IT, I) and VDs of SCP (I, IN) and DCP (I) exhibited significant decreases as MM progressed towards HM. Intriguingly, there was a notable increase in the VD of CC (ST, S, T, C, N) as myopia progressed from MM to HM. Conclusion Significant changes in retinal and choroid structure and vascular density occur as moderate myopia advances to high myopia. Efforts to curb myopia progression to this stage are essential, as the failure to do so may lead to the development of corresponding retinopathy.

Abstract Background This study aimed to investigate the impact of nursing interventions on the rehabilitation outcomes of patients after lumbar spine surgery and to provide effective references for future postoperative care for patients undergoing lumbar spine surgery. Methods The study included two groups: a control group receiving routine care and an observation group receiving additional comprehensive nursing care. The comprehensive care encompassed postoperative rehabilitation, pain, psychological, dietary management, and discharge planning. The Visual Analogue Scale (VAS), Oswestry Disability Index (ODI), Short-Form 36 (SF-36) Health Survey, self-rating depression scale (SDS) and self-rating anxiety scale(SAS) were used to assess physiological and psychological recovery. Blood albumin, haemoglobin, neutrophil counts, white blood cell counts, red blood cell counts, inflammatory markers (IL-6, IL-10, and IFN-γ) were measured, and the incidence of postoperative adverse reactions was also recorded. Results Patients in the observation group exhibited significantly improved VAS, ODI, SF-36, SDS and SAS scores assessments post-intervention compared to the control group (P 0.05), suggesting that the comprehensive nursing interventions did not increase the risk of adverse effects. Conclusion Comprehensive nursing interventions have a significant impact on the postoperative recovery outcomes of patients with LSS, alleviating pain, reducing inflammation levels, and improving the overall quality of patient recovery without increasing the patient burden. Therefore, in clinical practice, it is important to focus on comprehensive nursing interventions for patients with LSS to improve their recovery outcomes and quality of life.

Abstract Background Developing and enriching genetic resources plays important role in the crop improvement. The flag leaf affects plant architecture and contributes to the grain yield of wheat (Triticum aestivum L.). The genetic improvement of flag leaf traits faces problems such as a limited genetic basis. Among the various genetic resources of wheat, Thinopyrum intermedium has been utilized as a valuable resource in genetic improvement due to its disease resistance, large spikes, large leaves, and multiple flowers. In this study, a recombinant inbred line (RIL) population was derived from common wheat Yannong15 and wheat-Th. intermedium introgression line SN304 was used to identify the quantitative trait loci (QTL) for flag leaf-related traits. Results QTL mapping was performed for flag leaf length (FLL), flag leaf width (FLW) and flag leaf area (FLA). A total of 77 QTLs were detected, and among these, 51 QTLs with positive alleles were contributed by SN304. Fourteen major QTLs for flag leaf traits were detected on chromosomes 2B, 3B, 4B, and 2D. Additionally, 28 QTLs and 8 QTLs for flag leaf-related traits were detected in low-phosphorus and drought environments, respectively. Based on major QTLs of positive alleles from SN304, we identified a pair of double-ended anchor primers mapped on chromosome 2B and amplified a specific band of Th. intermedium in SN304. Moreover, there was a major colocated QTL on chromosome 2B, called QFll/Flw/Fla-2B, which was delimited to a physical interval of approximately 2.9 Mb and contained 20 candidate genes. Through gene sequence and expression analysis, four candidate genes associated with flag leaf formation and growth in the QTL interval were identified. Conclusion These results promote the fine mapping of QFll/Flw/Fla-2B, which have pleiotropic effects, and will facilitate the identification of candidate genes for flag leaf-related traits. Additionally, this work provides a theoretical basis for the application of Th. intermedium in wheat breeding.

Objectives Acute myeloid leukemia (AML) with ETV6::CHIC2 and basophilia is rare in hematologic malignancies with poor prognosis. Due to the small number of clinical cases, it is misdiagnosed and missed frequently, and it is necessary to explore laboratory detection for accurate diagnosis.Methods We report a case of AML with ETV6::CHIC2 and basophilia by morphological screening, immunotyping with precise gating, interpretation of FISH results, and RNA transcriptome sequencing, thus laying the accurate diagnosis for clinical treatment.Results We confirmed a rare case of AML with ETV6::CHIC2 rather than FIP1L1::PDGFRA by morphological analysis, correct immunophenotyping via precise gating, rejecting one-sided view of FISH positive result and targeted RNA sequencing. Precise analysis and more advanced means avoid misdiagnosis and missed frequently. After accurate diagnosis, venetoclax and decitabine therapy were given instead of imatinib; eventually, the patient achieved a relatively good effect.Discussion Immunophenotype analysis is necessary to detect the expression of CD7 when encountering pseudo-lymphocytes with multilineage dysplasia and basophilia. FISH and RT–PCR are still indispensable means of diagnosis of fusion genes in hematologic malignancies but can only detect a limited number of known partner genes and fusion genes with known break points. NGS can achieve sequence analysis indiscriminately and detect all fusion transcripts theoretically, greatly improving the detection range. NGS sequencing is required for t(4;12)(q11;p13) in AML that are not accompanied by eosinophilia.

To observe the antitumour efficacy of programmed death 1 (PD-1) inhibitors in the real world and explore the relationship between NRS2002 score or other clinical characteristics and immunotherapy efficacy, we retrospectively analyzed 341 tumor patients who received immune checkpoint inhibitor (ICI) treatment at one center. A total of 341 solid tumor patients treated with ICIs from June 2018 to December 2021 were retrospectively included in this study. Patient characteristics, ICI responses, and survival status were documented, and the relationships between clinical factors and survival were analyzed. Among all patients, the median progression-free survival (PFS) was 5.8 months, and the median overall survival (OS) was 12.5 months. The Performance Status (PS), NRS2002 score, The Naples Prognostic Score (NPS), Lymphocyte and C-reactive protein ratio (LCR), line of therapy, and nutritional support were significantly related to PFS or OS according to univariate analysis. The median PFS and OS were significantly better in the group without nutritional risk (NRS2002 0–2) than those with nutritional risk (NRS2002 ≥ 3) (PFS: HR = 1.82, 95% CI 1.30–2.54, p value

BackgroundCytokine network disturbances in primary Sjögren’s syndrome (pSS) have been reported in many studies. However, their functions in patients with primary Sjögren’s syndrome and interstitial lung disease (pSS-ILD) is controversial. In this study, we aim to investigate the associations of immunological characteristics and cytokine profiles with pSS-ILD pathogenesis and explore their predictive values for pSS progression.MethodsA total of 256 patients initially diagnosed with pSS at Henan Provincial People’s Hospital were enrolled. After excluding the patients previously diagnosed with various serious acute and chronic respiratory system diseases and cases with other connective tissue diseases or congenital heart diseases, 94 pSS patients were included for further analysis, including 40 patients with ILD (pSS-ILD) and 54 patients without ILD (pSS-N-ILD). For comparison, 41 age- and sex-matched healthy individuals were included as normal controls. Their clinical symptoms and serological data including cyclic citrullinated peptide (CCP) antibody (anti-CCP), antinuclear antibody (ANA), anti-Ro52, anti-SSA, anti-SSB, C-reactive protein, IgG, IgM, IgA, C3, C4, and 10 cytokines and chemokines were obtained. Wilcoxon test, chi-square test, Spearman correlation analysis, and logistics regression analysis were performed.ResultsHigher positive rates of anti-SSB and higher incidence of dry cough, dyspnea, and arthrosis symptoms were shown in pSS-ILD patients than in the pSS-N-ILD cases. Anti-CCP antibodies and cytokines (IL-1β, TNFα, IL-6, IL-5, IL-12p70, and IL-17) were higher, while C3 was lower in pSS-ILD patients than in pSS-N-ILD cases. Significant negative correlations of IgG with C3 and C4 and positive correlations of IL-12p70 and IL-17 with IL-6 were only shown in pSS-ILD patients. The anti-CCP antibody was positively correlated with IL-5 in pSS-ILD patients, but not in pSS-N-ILD cases. Multi-variable logistics regression analysis revealed the combination of anti-CCP, IL-17, IL-12p70, and IL-5 was effective in predicting the status of pSS-ILD in the pSS cases.ConclusionThere were significant differences in serum marker levels between pSS-ILD and pSS-N-ILD cases. The combination of anti-CCP, IL-17, IL-12p70, and IL-5 might be a potential risk predictor for pSS-ILD occurrence. The cytokines might be involved in the development and progression of pSS-ILD. These results would provide new therapeutic targets for pSS-ILD treatment.

Objective: Several circulating microRNAs, including microRNA-126-3p, have been identified as diagnostic and prognostic biomarker of cardiovascular disease. However, whether microRNA-126-3p is an independent risk predictor for coronary artery calcification is unclear. Methods: In this prospective single-center study, we collected blood samples from coronary artery atherosclerosis patients ( n = 54), patients with coronary artery calcification ( n = 33) and controls ( n = 56). Total RNA was extracted from plasma and blood cells with TRIzol reagents. The microRNA-126-3p level was determined via quantitative real-time polymerase chain reaction (RT-PCR). Results: MicroRNA-126-3p levels were significantly increased in patients with coronary artery calcification than in coronary artery atherosclerosis patients or controls. The highest expression of microRNA-126-3p was observed in patients with moderate calcification who were diagnosed with Grade 2 calcification by coronary angiography. Age, microRNA-126-3p expression in veins, hypertension and diabetes significantly influence the occurrence of coronary artery calcification, among which diabetes and venous microRNA-126-3p expression were found to be independent risk factors for coronary artery calcification. Conclusions: Taken together, the data in this study suggest that circulating microRNA-126-3p may be a novel noninvasive biomarker for coronary artery calcification. Regulating microRNA-126-3p expression may be an effective and promising strategy for the diagnosis and treatment of cardiovascular diseases, especially coronary artery calcification.

Cannabinoids and the endocannabinoid system (ECS) have been intensively studied for their neuroregulatory roles in the central nervous system (CNS), especially in regulating learning and memory. However, many experimental and clinical studies obtained conflicting results indicating a complex network of interaction underlying the regulation of learning and memory by different cannabinoids and the ECS. The ECS influences neuronal synaptic communications, and therefore may exert different regulation via their different impact on other neurotransmitters. The monoaminergic system includes a variety of neurotransmitters, such as dopamine, norepinephrine, and serotonin, which play important roles in regulating mood, cognition, and reward. The interaction among cannabinoids, ECS and the monoaminergic system has drawn particular attention, especially their contributions to learning and memory. In this review, we summarized the current understanding of how cannabinoids, ECS and the monoaminergic system contribute to the process of learning and memory, and discussed the influences of monoaminergic neurotransmission by cannabinoids and ECS during this process.

ObjectivesTo construct deep learning-assisted diagnosis models based on automatic segmentation of ultrasound images to facilitate radiologists in differentiating benign and malignant parotid tumors.MethodsA total of 582 patients histopathologically diagnosed with PGTs were retrospectively recruited from 4 centers, and their data were collected for analysis. The radiomics features of six deep learning models (ResNet18, Inception_v3 etc) were analyzed based on the ultrasound images that were obtained under the best automatic segmentation model (Deeplabv3, UNet++, and UNet). The performance of three physicians was compared when the optimal model was used and not. The Net Reclassification Index (NRI) and Integrated Discrimination Improvement (IDI) were utilized to evaluate the clinical benefit of the optimal model.ResultsThe Deeplabv3 model performed optimally in terms of automatic segmentation. The ResNet18 deep learning model had the best prediction performance, with an area under the receiver-operating characteristic curve of 0.808 (0.694−0.923), 0.809 (0.712−0.906), and 0.812 (0.680−0.944) in the internal test set and external test sets 1 and 2, respectively. Meanwhile, the optimal model-assisted clinical and overall benefits were markedly enhanced for two out of three radiologists (in internal validation set, NRI: 0.259 and 0.213 [p = 0.002 and 0.017], IDI: 0.284 and 0.201 [p = 0.005 and 0.043], respectively; in external test set 1, NRI: 0.183 and 0.161 [p = 0.019 and 0.008], IDI: 0.205 and 0.184 [p = 0.031 and 0.045], respectively; in external test set 2, NRI: 0.297 and 0.297 [p = 0.038 and 0.047], IDI: 0.332 and 0.294 [p = 0.031 and 0.041], respectively).ConclusionsThe deep learning model constructed for automatic segmentation of ultrasound images can improve the diagnostic performance of radiologists for PGTs.

Medium-deep U-shaped butted well (MUBW) is one of the most potential geothermal-heating way. However, the thermal interference may happen during long-term geothermal extraction period, which results in a heating performance attenuation. In this work, the heat transfer performance and surrounding rock-soil temperature distribution characteristics of MUBW in whole life cycle were investigated. The three-dimension full-size heat transfer model for long-term thermal extraction was proposed and the different structure sizes were considered. The results showed that the thermal interference is more likely to happen in a high heating load condition for the conventional structure size. By increasing horizontal length from 200 m to 600 m, the average specific heating load could increase by 26.1 %. When vertical depth increases to 3000 m, the heating load increases by 47.0 % at least. It is noted that the annual average inlet and outlet temperatures decrease by 5.1 °C in the whole life cycle, which should be considered in design on system operation. Additionally, the horizontal length of 600 m is large enough to avoid thermal interference in whole life cycle for MUBW with depth of 2000∼3000 m. This study has a practical meaning for ensuring a sustainable thermal extraction of MUBW.

IntroductionFermented jujube powder (FJP) promotes a balance between the intestinal microflora and immune factors in animals. In this study, we aimed to investigate the effects of FJP on the production performance, nutrient digestion, rumen fermentation, and antioxidant properties of bulls.MethodsForty Simmental bulls were randomly divided into four groups based on body weight and fed a basal diet with [5, 7.5, or 10% dry matter (DM)] or without FJP. The experimental period was 20 d for adaptation and 60 d for the feeding trial.ResultsDietary FJP supplementation did not affect DM intake (P > 0.05) but increased the average daily gain quadratically (P = 0.049) and decreased the feed conversion ratio linearly (P = 0.042). FJP quadratically enhanced DM and crude protein digestibility (P = 0.026 and P = 0.041, respectively) and linearly enhanced acid detergent fiber digestibility (P = 0.048). It also increased the total volatile fatty acid concentration quadratically (P = 0.037), acetate molar percentage, and acetate-to-propionate ratio linearly (P = 0.002 and 0.001), and reduced the ammonia nitrogen concentration linearly (P = 0.003). Additionally, xylanase and protease activities and Ruminococcus flavefaciens abundance increased linearly (P = 0.006, 0.018, and 0.009, respectively), and total bacteria, Ruminococcus albus, and Ruminobacter amylophilus abundance increased quadratically (P = 0.047, 0.011, and 0.021, respectively). FJP linearly increased serum total protein concentration and antioxidant capacity (P = 0.003 and 0.018, respectively) and decreased malonaldehyde content (P = 0.006).DiscussionFJP supplementation (7.5%) enhanced production performance, nutrient digestion, rumen fermentation, and serum antioxidant capacity in bulls. The improved nutrient digestion may be due to an increase in ruminal microorganisms and total volatile fatty acids from the FJP. High blood antioxidant levels indicate that FJP may preserve proteins, thereby boosting the production performance of bulls.

Abstract Microvesicles (MVs) containing proteins, nucleic acid or organelles are shed from the plasma membrane. Although the mechanisms of MV budding are well elucidated, the connection between endosomal trafficking and MV formation remains poorly understood. In this report, RAB22A is revealed to be crucial for EGFR‐containing MVs formation by the RAB GTPase family screening. RAB22A recruits TBC1D2B, a GTPase‐activating protein (GAP) of RAB7A, to inactivate RAB7A, thus preventing EGFR from being transported to late endosomes and lysosomes. RAB22A also engages SH3BP5L, a guanine‐nucleotide exchange factor (GEF) of RAB11A, to activate RAB11A on early endosomes. Consequently, EGFR is recycled to the cell surface and packaged into MVs. Furthermore, EGFR can phosphorylate RAB22A at Tyr136, which in turn promotes EGFR‐containing MVs formation. Our findings illustrate that RAB22A acts as a sorter on early endosomes to sort EGFR to recycling endosomes for MV shedding by both activating RAB11A and inactivating RAB7A.

This review examines recent advancements in interventional treatments and nursing care for lower extremity deep vein thrombosis (DVT), highlighting significant innovations and their clinical applications. It discusses the transition to novel anticoagulants such as Direct Oral Anticoagulants, which offer a safer profile and simplified management compared to traditional therapies. Mechanical interventions, including balloon angioplasty and venous stenting, are detailed for their roles in improving immediate and long-term vascular function in acute DVT cases. Furthermore, the use of image-guided techniques is presented as essential for enhancing the accuracy and safety of DVT interventions. Additionally, this study outlines advances in nursing care strategies, emphasizing comprehensive preoperative and postoperative evaluations to optimize patient outcomes. These evaluations facilitate tailored treatment plans, crucial for managing the complex needs of DVT patients. Long-term care strategies are also discussed, with a focus on patient education to ensure adherence to treatment protocols and to prevent recurrence. The synthesis aims to inform healthcare professionals about cutting-edge practices in DVT management, promoting a deeper understanding of how these advancements can be integrated into clinical practice. It also underscores the necessity for ongoing research to address challenges such as cost-effectiveness and patient compliance, ensuring that future treatments are both accessible and effective.

The pharmacological effects of flavonoids in Oroxylum indicum (L.) Kurz against inflammation, bacterial, and oxidation have been well-documented. Additionally, it is commonly consumed as tea. However, the in vivo mechanism of its main compounds has not been well elucidated. In this study, a highly selective and sensitive UHPLC-Q-TOF-MS method combined with Mass Spectrum-based Orthogonal Projection (MSOP) theory and four-step analytical strategy was established and validated to identify metabolites in rats following oral administration Oroxylum indicum (L.) Kurz extract. Furthermore, a sensitive LC-MS/MS method was developed and validated for the first time to analyze the pharmacokinetics of ten main flavonoids in rats. Notably, a total of 47 metabolites were identified in blood, bile, urine, and feces samples. The maximum plasma concentration (Cmax) values for oroxin A, oroxin B, baicalin, chrysin, baicalein, scutellarein, apigenin, quercetin oroxylin A and isorhamnetin were 2945.1 ± 11.23 ng/mL, 3123.9 ± 16.37 ng/mL, 130.40 ± 27.52 ng/mL, 117.20 ± 28.54 ng/mL, 64.12 ± 19.33 ng/mL, 97.22 ± 24.27 ng/mL, 145.22 ± 29.92 ng/mL, 45.19 ± 18.84 ng/mL, 67.32 ± 15.78 ng/mL and 128.44 ± 26.42 ng/mL. A double peak was observed in the drug-time curve of apigenin, due to enterohepatic recirculation. This study demonstrated that MSOP method provided more technical support for the identification of flavonoid metabolites in complex system than traditional methods.

Abstract How brain functions in the distorted ischemic state before and after reperfusion is unclear. It is also uncertain whether there are any indicators within ischemic brain that could predict surgical outcomes. To alleviate these issues, we applied individual brain connectome in chronic steno‐occlusive vasculopathy (CSOV) to map both ischemic symptoms and their postbypass changes. A total of 499 bypasses in 455 CSOV patients were collected and followed up for 47.8 ± 20.5 months. Using multimodal parcellation with connectivity‐based and pathological distortion‐independent approach, areal MR features of brain connectome were generated with three measurements of functional connectivity (FC), structural connectivity, and PageRank centrality at the single‐subject level. Thirty‐three machine‐learning models were then trained with clinical and areal MR features to obtain acceptable classifiers for both ischemic symptoms and their postbypass changes, among which, 11 were deemed acceptable (AUC > 0.7). Notably, the FC feature‐based model for long‐term neurological outcomes performed very well (AUC > 0.8). Finally, a Shapley additive explanations plot was adopted to extract important individual features in acceptable models to generate “fingerprints” of brain connectome. This study not only establishes brain connectomic fingerprint databases for brain ischemia with distortion, but also provides informative insights for how brain functions before and after reperfusion.

Summary: Emerging evidence highlights the regulatory role of paired-like (PRD-like) homeobox transcription factors (TFs) in embryonic genome activation (EGA). However, the majority of PRD-like genes are lost in rodents, thus prompting an investigation into PRD-like TFs in other mammals. Here, we showed that PRD-like TFs were transiently expressed during EGA in human, monkey, and porcine fertilized embryos, yet they exhibited inadequate expression in their cloned embryos. This study, using pig as the research model, identified LEUTX as a key PRD-like activator of porcine EGA through genomic profiling and found that LEUTX overexpression restored EGA failure and improved preimplantation development and cloning efficiency in porcine cloned embryos. Mechanistically, LEUTX opened EGA-related genomic regions and established histone acetylation via recruiting acetyltransferases p300 and KAT2A. These findings reveal the regulatory mechanism of LEUTX to govern EGA in pigs, which may provide valuable insights into the study of early embryo development for other non-rodent mammals.

BackgroundCD46 has been revealed to be a key factor in malignant transformation and cancer treatment. However, the clinical significance of CD46 in cervical cancer remains unclear, and this study aimed to evaluate its role in cervical cancer diagnosis and prognosis evaluation.MethodsA total of 180 patients with an initial diagnosis of cervical cancer were enrolled at Taizhou Hospital of Zhejiang Province, China. The plasma levels of soluble CD46 (sCD46) and the expression of membrane-bound CD46 (mCD46) were detected by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC), respectively.ResultsCD46 was found to be significantly upregulated in cervical cancer tissues vs. normal tissues, while no CD46 staining was detected in paired adjacent noncancerous tissues. CD46 staining was more pronounced in cancer cells than in stromal cells in situ (in tissues). Moreover, the plasma levels of sCD46 were able to some extent discriminate between cancer patients and healthy women (AUC=0.6847, 95% CI:0.6152–0.7541). Analysis of Kaplan–Meier survival curves revealed that patients with low CD46 expression had slightly longer overall survival (OS) than patients with high CD46 expression in the tumor microenvironment, but no significant difference. Univariate Cox regression analysis revealed that CD46 (P=0.034) is an independent risk factor for OS in cervical cancer patients.ConclusionThe present study demonstrated that cervical cancer patients exhibit aberrant expression of CD46, which is closely associated with a poor prognosis, suggesting that CD46 plays a key role in promoting cervical carcinogenesis and that CD46 could serve as a promising potential target for precision therapy for cervical cancer.