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Studies that focus on brazing high-nitrogen steel (HNS) to high-entropy alloys (HEAs) are currently limited. In this study, the HEA Al0·3CoCrFeNi was successfully brazed to HNS using a commercial BNi-2 filler at 1080–1140 °C. The microstructure and shear strength of the Al0·3CoCrFeNi/HNS brazed joints were observed and evaluated. The typical microstructure of the brazed joint was HNS/infiltration layer/reaction layer/Ni(s,s) (containing NiAl3)/reaction layer/infiltration layer/Al0·3CoCrFeNi. The higher brazing temperature and longer holding time promoted the diffusion of B as a brazing seam with homogeneous Ni(s,s), and more intergranular Cr-rich borides formed in the base materials. The optimized shear strength attained 549.2 MPa after the joint brazed at 1120 °C for 15 min, and ductile fracture occurred in the reaction zone. The insufficient and excessive diffusion of B resulted in residual Cr–B compounds in the brazing seam and excess borides in the HNS, respectively, which negatively affected shear strength. All the joints showed poor corrosion resistance following immersion in a 3.5 wt% NaCl solution because the excess Cr-rich compounds resulted in decreased Cr content in the surrounding matrix. Therefore, Ni-based fillers without B were more suitable for obtaining Al0·3CoCrFeNi/HNS joints with a favorable corrosion resistance.

Abstract This study aimed to develop a pan-genotypic and multifunctional small interfering RNA (siRNA) against hepatitis B virus (HBV) with an efficient delivery system for treating chronic hepatitis B (CHB), and explore combined RNA interference (RNAi) and immune modulatory modalities for better viral control. Twenty synthetic siRNAs targeting consensus motifs distributed across the whole HBV genome were designed and evaluated. The lipid nanoparticle (LNP) formulation was optimized by adopting HO-PEG2000-DMG lipid and modifying the molar ratio of traditional polyethylene glycol (PEG) lipid in LNP prescriptions. The efficacy and safety of this formulation in delivering siHBV (tLNP/siHBV) along with the mouse IL-2 (mIL-2) mRNA (tLNP/siHBVIL2) were evaluated in the rAAV-HBV1.3 mouse model. A siRNA combination (terms “siHBV”) with a genotypic coverage of 98.55% was selected, chemically modified, and encapsulated within an optimized LNP (tLNP) of high efficacy and security to fabricate a therapeutic formulation for CHB. The results revealed that tLNP/siHBV significantly reduced the expression of viral antigens and DNA (up to 3log10 reduction; vs PBS) in dose- and time-dependent manners at single-dose or multi-dose frequencies, with satisfactory safety profiles. Further studies showed that tLNP/siHBVIL2 enables additive antigenic and immune control of the virus, via introducing potent HBsAg clearance through RNAi and triggering strong HBV-specific CD4+ and CD8+ T cell responses by expressed mIL-2 protein. By adopting tLNP as nucleic acid nanocarriers, the co-delivery of siHBV and mIL-2 mRNA enables synergistic antigenic and immune control of HBV, thus offering a promising translational therapeutic strategy for treating CHB.

Bassia scoparia, an annual potherb belonging to the family Amaranthaceae, has been widely used in traditional Chinese and Japanese medicine for over 2000 years. Herein, we presented its complete chloroplast. The chloroplast genome sequence was 151,278 bp in length with a 36.6% content of GC. The genome showed the typical quadripartite structure, comprising a pair of inverted repeat (IR) regions (24,353 bp) separated by a large single-copy (LSC) region (84,067 bp) and a small single-copy (SSC) region (18,505 bp). This chloroplast genome harbored 133 predicted genes, including 88 protein-coding genes, 37 transfer RNA (tRNA) genes, and eight ribosomal RNA (rRNA) genes. The phylogenetic analysis indicated that B. scoparia was closely related to B. littorea. This newly sequenced chloroplast genome not only enhances our understanding of the genome of Bassia but also provides valuable insights for the evolutionary study of the family Amaranthaceae.

Abstract Background Berberine (BBR), an isoquinoline alkaloid from Coptidis rhizoma, has been found to have powerful activities against various human malignancies, including breast cancer. However, the underlying antitumor mechanisms of BBR in breast cancer remain poorly understood. Methods Breast cancer cells were cultured and treated with different doses (0, 20, 40, and 60 μM) of BBR for 48 h. Cell viability, proliferation, apoptosis, invasion, and migration were assessed using 3‐(4, 5‐dimethyl‐2‐thiazolyl)‐2, 5‐diphenyl‐2H‐tetrazolium bromide (MTT), 5‐ethynyl‐2′‐deoxyuridine (EdU), flow cytometry, transwell, and wound healing assays. Fibroblast growth factor 7 (FGF7), methyltransferase‐like 3 (METTL3), and insulin‐like growth factor‐2 mRNA‐binding protein 3 (IGF2BP3) mRNA levels and protein levels were measured using real‐time quantitative polymerase chain reaction (RT‐qPCR) and western blot. Interaction between METTL3 and FGF7 m6A was assessed using methylated RNA immunoprecipitation (MeRIP)‐qPCR and RNA immunoprecipitation (RIP) assay. Binding ability between IGF2BP3 and FGF7 mRNA was analyzed using RIP assay. Results BBR treatment hindered breast cancer cell proliferation, invasion, migration, and induced apoptosis. FGF7 expression was upregulated in breast cancer tissues, while its level was reduced in BBR‐treated tumor cells. FGF7 upregulation relieved the repression of BBR on breast cancer cell malignant behaviors. In mechanism, METTL3 stabilized FGF7 mRNA through the m6A‐IGF2BP3‐dependent mechanism and naturally improved FGF7 expression. BBR treatment inhibited breast cancer growth in vivo. Conclusion BBR treatment blocked breast cancer cell growth and metastasis partly by regulating METTL3‐mediated m6A modification of FGF7 mRNA, providing a promising therapeutic target for breast cancer treatment.

Abstract Background Hepatitis B virus (HBV) infection can cause liver failure, while individuals with Acquired Immunodeficiency Virus Disease (AIDS) are highly susceptible to various opportunistic infections, which can occur concurrently. The treatment process is further complicated by the potential occurrence of immune reconstitution inflammatory syndrome (IRIS), which presents significant challenges and contributes to elevated mortality rates. Case presentation The 50-year-old male with a history of chronic hepatitis B and untreated human immunodeficiency virus (HIV) infection presented to the hospital with a mild cough and expectoration, revealing multi-drug resistant pulmonary tuberculosis (MDR-PTB), which was confirmed by XpertMTB/RIF PCR testing and tuberculosis culture of bronchoalveolar lavage fluid (BALF). The patient was treated with a regimen consisting of linezolid, moxifloxacin, cycloserine, pyrazinamide, and ethambutol for tuberculosis, as well as a combination of bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) for HBV and HIV viral suppression. After three months of treatment, the patient discontinued all medications, leading to hepatitis B virus reactivation and subsequent liver failure. During the subsequent treatment for AIDS, HBV, and drug-resistant tuberculosis, the patient developed disseminated cryptococcal disease. The patient’s condition worsened during treatment with liposomal amphotericin B and fluconazole, which was ultimately attributed to IRIS. Fortunately, the patient achieved successful recovery after appropriate management. Conclusion Enhancing medical compliance is crucial for AIDS patients, particularly those co-infected with HBV, to prevent HBV reactivation and subsequent liver failure. Furthermore, conducting a comprehensive assessment of potential infections in patients before resuming antiviral therapy is essential to prevent the occurrence of IRIS. Early intervention plays a pivotal role in improving survival rates.

Calystegia hederacea Wall. in Roxb. 1824 is a perennial herbaceous vine in the family Convolvulaceae and has several biological effects. Herein, we reported the first complete chloroplast genome of C. hederacea. The chloroplast genome sequence was 152,057 bp in length, comparing a large single-copy (LSC) region of 87,891 bp, a small single-copy (SSC) region of 19,866 bp, and a pair of inverted repeat (IR) regions of 22,150 bp. This sequenced chloroplast genome contained 126 predicted genes, including 81 protein-coding genes, 37 tRNA genes, and eight rRNA genes, and the total GC content of the chloroplast genome was 37.79%. Phylogenetic analysis revealed that C. hederacea was closely related to C. soldanella. The chloroplast genome presented in this study will enrich the genome information of the genus Calystegia and provide deeper insights into the evolution study of the family Convolvulaceae.

Hydrocotyle vulgaris is a perennial wetland clonal plant in the Araliaceae family, which was introduced to China as an ornamental plant in the 1990s. Although H. vulgaris is now considered a potential invasiveness species in China, it also plays a significant role in the remediation of water pollution. Here, we reported its complete chloroplast genome and analyzed the basic characteristics. The chloroplast genome was 153,165 bp in length, including a pair of inverted repeat (IR) regions of 25,072 bp separated by a large single-copy (LSC) region of 84,291 bp and a small single-copy (SSC) region of 18,730 bp. The H. vulgaris chloroplast genome contained 132 predicted genes, and its overall GC content was 37.60%. Phylogenetic analysis revealed that H. vulgaris was closely related to H. verticillata. The H. vulgaris chloroplast genome presented in this study will lay a foundation for further genetic and genomic studies of the genus Hydrocotyle.

Abstract Background Postoperative delirium (POD) is a common complication after major surgery and can cause a variety of adverse effects. However, no large-scale national database was used to assess the occurrence and factors associated with postoperative delirium (POD) following hepatic resection. Methods Patients who underwent hepatic resection from 2015 to 2019 were screened using the International Classification of Diseases (ICD) 10th edition clinical modification code from the National Inpatient Sample (NIS) Database. Peri-operative factors associated with delirium were screened and underwent statistical analysis to identify independent predictors for delirium following hepatic resection. Results A total of 80,070 patients underwent hepatic resection over a five-year period from 2015 to 2019. The overall occurrence of POD after hepatic resection was 1.46% (1039 cases), with a slight upward trend every year. The incidence of elective admission was 6.66% lower (88.60% vs. 81.94%) than that of patients without POD after hepatic resection and 2.34% (45.53% vs. 43.19%) higher than that of patients without POD in teaching hospitals (P

Abstract Background The genetic diversity of yak, a key domestic animal on the Qinghai-Tibetan Plateau (QTP), is a vital resource for domestication and breeding efforts. This study presents the first yak pangenome obtained through the de novo assembly of 16 yak genomes. Results We discovered 290 Mb of nonreference sequences and 504 new genes. Our pangenome-wide presence and absence variation (PAV) analysis revealed 5,120 PAV-related genes, highlighting a wide range of variety-specific genes and genes with varying frequencies across yak populations. Principal component analysis (PCA) based on binary gene PAV data classified yaks into three new groups: wild, domestic, and Jinchuan. Moreover, we proposed a ‘two-haplotype genomic hybridization model’ for understanding the hybridization patterns among breeds by integrating gene frequency, heterozygosity, and gene PAV data. A gene PAV-GWAS identified a novel gene (BosGru3G009179) that may be associated with the multirib trait in Jinchuan yaks. Furthermore, an integrated transcriptome and pangenome analysis highlighted the significant differences in the expression of core genes and the mutational burden of differentially expressed genes between yaks from high and low altitudes. Transcriptome analysis across multiple species revealed that yaks have the most unique differentially expressed mRNAs and lncRNAs (between high- and low-altitude regions), especially in the heart and lungs, when comparing high- and low-altitude adaptations. Conclusions The yak pangenome offers a comprehensive resource and new insights for functional genomic studies, supporting future biological research and breeding strategies.

Societal Impact Statement Advancements in science and technology enable us to address the challenges of the times: hunger, malnutrition, climate change, and dwindling natural resources. One of the most significant innovations in food and agriculture is the advent of genetic engineering, which may help us address the aforementioned challenges. Millions of people could benefit from the application of genetically engineered crops in agriculture and food. However, it is vital that biosafety assessments of unintended effects are carried out to identify any potential risks to humans, the environment, or society. Summary The study compared the extent of siRNA, transcriptomic and metabolomic changes in the leaves of four RNAi‐based genetically engineered rice lines to evaluate whether RNAi‐based genetically engineered rice that is resistant to black‐streaked dwarf virus experiences changes not seen in the non‐genetically engineered counterpart. siRNA, transcriptome, and metabolome profiling were conducted. siRNAs with different lengths and abundance were highly enriched in the transcript of rice; however, relative expression analysis of eight potential off‐target genes revealed that there was no decrease in gene expression in the RNAi‐based genetically engineered lines, meaning that no off‐target phenomena were caused as a result of siRNA derived from invert repeat sequences of rice black‐streaked dwarf virus in this study. This study identified some differentially expressed genes and differentially accumulated metabolites in the RNAi‐based genetically engineered lines; however, they were not enriched in pathways detrimental for humans, animals and the environment. Only 30 differentially expressed genes were significantly enriched in the plant hormone signal transduction pathway via a combined analysis using two‐way orthogonal partial least squares model. These genes belonging to salicylic acid, jasmonic acid, cytokinin, abscisic acid, and brassinosteroid pathway involved in pathways related to virus resistance or infection response were significantly changed. Taken together, there was no off‐target in RNAi‐based genetically engineered rice lines and may have a positive effect on virus resistance overall in this study.

Abstract Background Prostate cancer (PCa) is becoming the most common malignancy in men worldwide. We investigated the effect of astragaloside IV combined with PESV on the gut microbiota and metabolite of PCa mice and the process of treating PCa. Methods Nude mice were genetically modified to develop tumors characteristic of PCa. The treatment of PCa mice involved the administration of a combination of astragaloside IV and peptides derived from scorpion venom (PESV). Feces were collected for both 16 S rDNA and metabolic analysis. Fecal supernatant was extracted and used for fecal transplantation in PCa mice. Tumor development was observed in both PCa mice and nude mice. Tumor histopathology was examined, and the expression of inflammatory factors and the AGE-RAGE axis in PCa tissues were analyzed. Results PCa mice treated with Astragaloside IV in combination with PESV showed a significant reduction in tumor volume and weight, and stabilization of gut microbiota and metabolites. At the Genus level, significant differences were observed in Porphyromonas, Corynebacterium, Arthromitus and Blautia, and the differential metabolites were PA16_016_0, Astragaloside+, Vitamin A acid, Nardosinone, a-Nortestoster, D-Pantethine, Hypoxanthine, Pregnenolone, cinnamic acid, Pyridoxa, Cirtruline and Xanthurenate. There was a correlation between gut microbiota and metabolites. After the fecal transplantation, tumor growth was effectively suppressed in the PCa mice. Notably, both the mRNA and protein levels of the receptor for advanced glycation end products (RAGE) were significantly decreased. Furthermore, the expression of inflammatory factors, namely NF-κB, TNF-α, and IL-6, in the tumor tissues was significantly attenuated. Conversely, upregulation of RAGE led to increased inflammation and reversed tumor growth in the mice. Conclusion Astragaloside IV combined with PESV could treat PCa by intervening in gut microbiota composition and metabolite by targeting RAGE.

Abstract Background Knee osteoarthritis (KOA) is a prevalent and debilitating condition that markedly affects the sit-to-stand (STS) activity of patients, a prerequisite for daily activities. Biomechanical recognition of movements in patients with mild KOA is currently attracting attention. However, limited studies have been conducted solely on the observed differences in sagittal plane movement and muscle activation. Aim This study aimed to identify three-dimensional biomechanical and muscle activation characteristics of the STS activity in patients with mild KOA. Methods A cross-sectional study was conducted to observe the differences between patients with mild KOA and a control group (CG). It was conducted to observe the differences in muscle activation, including root mean square (RMS%) and integrated electromyography (items), kinematic parameters like range of motion (ROM) and maximum angular velocity, as well as dynamic parameters such as joint moment and vertical ground reaction force (vGRF). Results Patients with mild KOA had a higher body mass index and longer task duration. In the sagittal plane, patients with KOA showed an increased ROM of the pelvic region, reduced ROM of the hip–knee–ankle joint, and diminished maximum angular velocity of the knee–ankle joint. Furthermore, patients with KOA displayed increased knee–ankle joint ROM in the coronal plane and decreased ankle joint ROM in the horizontal plane. Integrated vGRF was higher in both lower limbs, whereas the vGRF of the affected side was lower. Furthermore, patients showed a decreased peak adduction moment (PADM) and increased peak external rotation moment in the knee joint and smaller PADM and peak internal rotation moment in the ankle joint. The affected side exhibited decreased RMS% and iEMG values of the gluteus medius, vastus medialis, and vastus lateralis muscles, as well as a decreased RMS% of the rectus femoris muscle. Conversely, RMS% and iEMG values of the biceps femoris, lateral gastrocnemius, and medial gastrocnemius muscles were higher. Conclusion The unbalanced activation characteristics of the anterior and posterior muscle groups, combined with changes in joint moment in the three-dimensional plane of the affected joint, may pose a potential risk of injury to the irritated articular cartilage.

Background and objective: After vestibular schwannoma (VS) surgery, some patients exhibit different degrees of peripheral facial paralysis, which can seriously affect their quality of life. The recovery of facial nerve function after surgery typically takes a considerable amount of time; therefore, the recovery of facial nerve function depends mainly on the rehabilitation treatment and nursing after discharge. In the past, we implemented conventional paralysis rehabilitation nursing program for patients with facial paralysis due to VS surgery. However, several patients with facial paralysis have bad compliance and do not achieve ideal facial nerve function recovery. Therefore, this study aimed to investigate whether modified facial paralysis rehabilitation nursing improves the effectiveness of rehabilitation of facial paralysis after VS surgery by analysing the clinical data of patients. Methods: We screened the patients with facial paralysis after VS surgery from December 2019 to May 2023. The patients were divided into the conventional and modified groups based on the different nursing programs (conventional vs. modified facial paralysis rehabilitation nursing program) to compare the differences in facial nerve function, quality of life of patients, and compliance of rehabilitation between the two groups. Results: We analysed 128 patients with facial paralysis after VS surgery who met the inclusion and exclusion criteria; 65 and 63 patients in the conventional and modified group, respectively. The number of patients in the modified group with House–Brackmann grade changes >0 in facial nerve function was significantly higher than that in the conventional group 3 months after surgery (82.5 % vs 63.1 %, p = 0.01). Except for the lacrimal control score, the mean scores of the Chinese version of the FaCE scale were significantly higher in the modified group than those in the conventional group at 1 and 3 months postoperatively. Conclusions: The modified facial paralysis rehabilitation nursing, i.e., integrated use of facial expressive muscle exercises and facial massage with video-assisted education, substantially improved the facial nerve function, quality of life, and compliance of rehabilitation nursing of patients with facial paralysis after VS surgery.

Abstract Minimal hepatic encephalopathy (MHE) has a substantial impact on the clinical outcomes and quality of life (QOL) of patients with cirrhosis. However, timely diagnosis and intervention are challenging due to sophisticated diagnostic methods. In this study, 673 healthy controls and 905 patients with cirrhosis were screened, and 660 healthy controls and 757 patients with cirrhosis, divided into the test (292 patients) and validation (465 patients) cohort, were analyzed after screening. A diagnostic model of the Stroop test (Stroop‐CN) was constructed by multivariate linear regression based on the results of healthy controls. The prevalence of MHE and the comparison results with psychometric hepatic encephalopathy score through the Stroop‐CN model were stable in the test and validation cohorts. Moreover, the prevalence of MHE remained significantly higher in patients with worse disease conditions marked as high Child–Pugh grades and the Model for End‐stage Liver Disease and Sodium (MELD‐Na) scores in the test and validation cohort. The EuroQol 5‐D questionnaire revealed that patients with MHE had a worse QOL than those without MHE both in the test and validation cohort. In conclusion, an easy and practical Stroop‐CN model for MHE diagnosis based on the EncephalApp is established. It is found that a considerable number of Chinese patients with cirrhosis experience MHE, which significantly impacts their QOL.

Abstract The diverse morphologies of 2D transition metal dichalcogenides (2D TMDs) motivate their broad potential applications in the next generation of electronic, optical, and catalytic technologies. It is advantageous to develop controllable growth techniques that afford versatility through direct manipulation of the growth parameters. A fundamental understanding of the physical mechanisms driving various growth modes is crucial for achieving the process precision necessary for obtaining reproducible morphologies in 2D TMDs. Thermodynamic and kinetic considerations are two key physical strategies. Thermodynamic strategies mainly involve the manipulation of parameters like temperature and the chemical potential of precursors to ensure the thermostability of various morphologies. Conversely, kinetic strategies, focusing on the factors, like precursor diffusion, adsorption, and desorption during the growth, also enable atomic‐level kinetics control of the resulting morphologies. Often, an interplay of both mechanisms drives the growth of a particular morphology. This review aims to provide an updated guidance for exploiting these physical strategies in the versatile technique of chemical vapor deposition. The opportunities for further exploring the control of these physical mechanisms are discussed through recent examples with an eye on unlocking the untapped potential of 2D TMDs in areas such as phase engineering and shape control for advanced applications.

Abstract Objective Capillary leak syndrome (CLS) is characterized by severe systemic edema without specific treatment, resulting in a high mortality rate. This study investigated whether there is organ edema in neonatal CLS patients and specific treatment strategies to improve patient prognosis. Methods Thirty-seven newborns diagnosed with CLS were included in this study. (1) Routine point-of-care ultrasound (POCUS) was used to identify whether the patients had visceral edema or fluid collection. (2) All patients were treated with 3% NaCl intravenously, and the clinical manifestations, laboratory indices and outcomes were compared before and after treatment. Results (1) Diffuse severe edema was found in 92.0% of the patients. (2) The POCUS examination revealed that CLS patients exhibited significant visceral edema in addition to diffuse severe edema, which included pulmonary edema in 67.6%, cerebral edema in 37.8%, severe intestinal edema in 24.3%, severe myocardial edema in 8.1%, pericardial effusion in 5.4%, pleural effusion in 29.7% and peritoneal effusion in 18.9%. Two patients (5.45%) had only myocardial edema without other manifestations. (3) Before and after the intravenous injection of 3% NaCl, there were no significant differences in the serum sodium or potassium levels of CLS patients, while the hemoglobin and hematocrit levels were significantly lower after treatment (p

Here, we present a high ductility of the Be–Al alloy manufactured by investment casting. It was superior to most Be–Al based alloys reported so far, exhibiting high yield strength of 53∼58 MPa, ultimate tensile strength of 111∼117 MPa, and high tensile strain of 14.1–18.8 %. The many < c + a> dislocations in the Be phase were primarily responsible for the exceptionally high mechanical characteristics. A high Schmid factor for pyramidal slip led to slip transfer between the Be grains and Al grains, which may contribute to relieving stress concentration and delaying early fracture.The profuse activated pyramidal < c + a> dislocations could render the unusual high tensile strain. The high strength was attributed to both the good interfacial strength and the constraint of hard Be phase, which makes the soft Al phase strong like the hard Be phase. It demonstrates the strong texture microstructure design of the Be phase had a synergistic improvement in the strength-ductility balance, suggesting that this could be a useful tactic for enhancing the mechanical characteristics of Be–Al alloys.

Identified as the pathogenic genes of Alzheimer's disease (AD), APP, PSEN1, and PSEN2 mainly lead to early-onset AD, whose course is more aggressive, and atypical symptoms are more common than sporadic AD. Here, a novel missense mutation, APP E674Q (also named “Shanghai APP”), was detected in a Chinese index patient with typical late-onset AD (LOAD) who developed memory decline in his mid-70s. The results from neuroimaging were consistent with AD, where widespread amyloid β deposition was demonstrated in 18F-florbetapir Positron Emission Tomography (PET). APP E674Q is close to the β-secretase cleavage site and the well-studied Swedish APP mutation (KM670/671NL), which was predicted to be pathogenic in silico. Molecular dynamics simulation indicated that the E674Q mutation resulted in a rearrangement of the interaction mode between APP and BACE1 and that the E674Q mutation was more prone to cleavage by BACE1. The in vitro results suggested that the E674Q mutation was pathogenic by facilitating the BACE1-mediated processing of APP and the production of Aβ. Furthermore, we applied an adeno-associated virus (AAV)-mediated transfer of the human E674Q mutant APP gene to the hippocampi of two-month-old C57Bl/6 J mice. AAV-E674Q-injected mice exhibited impaired learning behavior and increased pathological burden in the brain, implying that the E674Q mutation had a pathogenicity that bore a comparison with the classical Swedish mutation. Collectively, we report a strong amyloidogenic effect of the E674Q substitution in AD. To our knowledge, E674Q is the only pathogenic mutation within the amyloid processing sequence causing LOAD.

This is an article in the field of earth sciences. Xidamingshan polymetallic ore concentration area is critical mineral prospecting district in Guangxi. With the promotion of the large-scale mineral breakthrough work, the Xidamingshan mineral exploration, the Nongtun large-scale Pb-Zn deposit has been newly discovered. However, the understanding of the metallogenic characteristics of the deposit, especially the genesis of the deposit, is still at the superficial stage. Based on detailed field geological investigations and previous work, this paper systematically summarizes the regional metallogenic geological background, mining area and geological characteristics, and analyzes the genesis of the Nongtun lead-zinc deposit to find out the metallogenic mechanism. The study shows the Nongtun Pb-Zn deposit is related-magmatic hydrothermal deposit, the ore-forming fluids originated from magmatic, and later mixed with meteoric water. The fluids extracted Pb and Zn ore-forming elements from the strata during long-distance transport, and combined with S of magmatic fluids to synthesize [HS]-ligand that converged in the fracture zone and transported to the shallow part, thus forming Pb-Zn ore vein. The above research results have established the metallogenic model of the Nongtun Pb-Zn deposit, which provides a good guidance for prospecting prediction and exploration.

Abstract False data injection (FDI) attacks are serious threats to a cyber‐physical power system (CPPS), which may be launched by a malicious software or virus accessing only the measurements from one substation. This study proposes a novel attack method named the temporal FDI (TFDI) attack. Namely, the virus makes decisions based on temporal observations of the CPPS, and the attack is driven by a deep Q network (DQN) algorithm. As DQN takes vectors of continuous variables as input states, the proposed method is free of the state space explosion problem, which helps the virus to learn the optimal attack strategy efficiently. Moreover, for adopting time‐series measurements as quasi‐dynamic observations, long short‐term memory cells are employed as a layer of the Q network. The TFDI attack enables the virus to discern trends of load variations and enhance the attack’s effectiveness. Meanwhile, a countermeasure is also presented to detect the proposed FDI attack. Binary classifiers are trained for each bus to detect suspicious local measurements according to their deviations from system‐state manifolds. When suspicious measurements are spotted frequently, the corresponding bus is believed to be under FDI attacks. Test cases validate the efficacy of the proposed FDI attack method as well as its countermeasure.

Banana phenotypic parameters are one of the important elements in the study of banana growth and development. Through the measurement of banana phenotypic parameters, we can obtain information about the growth status, nutritional status and quality indexes of banana plants, and pseudo-stem parameters are significant indicators in banana phenotypic parameters. This research proposes a two-stage approach combining morphological features and deep learning point cloud segmentation to extract banana pseudo-stem parameters. Specifically, in the first step, seed points are extracted using the DBSCAN clustering algorithm, and banana individual plant segmentation is accomplished using the region growing algorithm based on seed points. Its precision, recall and F1-score were 97.73%, 97.36% and 97.54%, respectively. This indicates that the DBSCAN clustering algorithm and the seed point based region growing algorithm can effectively realize the plant count of banana plants and initially realize the individual plant segmentation of banana. The second step is to use PointNet++, PointNet, and DGCNN for pseudo-stem and canopy segmentation of individual banana plants. All three models perform well in segmentation, with PointNet++ performing the best. Its precision, recall, F1-score, Matthews correlation coefficient and Dice coefficient reached 0.9956, 0.9709, 0.9831, 0.9670 and 0.9831. This shows that deep learning has a better applicability in segmenting banana plants. In the results of segmentation, we measure the banana pseudo-stem circumference and pseudo-stem height. The correlation between the extracted pseudo-stem height and pseudo-stem circumference compared to the measured values was 96.70% and 82.32%, respectively. The above two-stage method of extracting banana pseudo-stem parameters overcomes the difficulties of point cloud individual plant segmentation associated with intensive banana cultivation. It makes the management of individual banana plants possible and provides accurate phenotypic parameter information for banana plantation management. It lays the foundation for further assessment of banana growth and nutritional status.

Abstract Switch defective/sucrose non-fermentable (SWI/SNF) chromatin remodeling complexes are multi-subunit machineries that establish and maintain chromatin accessibility and gene expression by regulating chromatin structure. However, how the remodeling activities of SWI/SNF complexes are regulated in eukaryotes remains elusive. B-cell lymphoma/leukemia protein 7 A/B/C (BCL7A/B/C) have been reported as subunits of SWI/SNF complexes for decades in animals and recently in plants; however, the role of BCL7 subunits in SWI/SNF function remains undefined. Here, we identify a unique role for plant BCL7A and BCL7B homologous subunits in potentiating the genome-wide chromatin remodeling activities of SWI/SNF complexes in plants. BCL7A/B require the catalytic ATPase BRAHMA (BRM) to assemble with the signature subunits of the BRM-Associated SWI/SNF complexes (BAS) and for genomic binding at a subset of target genes. Loss of BCL7A and BCL7B diminishes BAS-mediated genome-wide chromatin accessibility without changing the stability and genomic targeting of the BAS complex, highlighting the specialized role of BCL7A/B in regulating remodeling activity. We further show that BCL7A/B fine-tune the remodeling activity of BAS complexes to generate accessible chromatin at the juvenility resetting region (JRR) of the microRNAs MIR156A/C for plant juvenile identity maintenance. In summary, our work uncovers the function of previously elusive SWI/SNF subunits in multicellular eukaryotes and provides insights into the mechanisms whereby plants memorize the juvenile identity through SWI/SNF-mediated control of chromatin accessibility.

Practical Byzantine Fault Tolerance (PBFT), a classic consensus algorithm in blockchain technology, is extensively used in consortium blockchain networks. However, it is challenged by issues such as low consensus efficiency, poor scalability, inability to guarantee throughput with large-scale node access, and complex communication processes. To solve these problems, this paper proposes an improved PBFT consensus mechanism based on credit scoring and aggregated signatures, i.e., the CA-PBFT algorithm. First, the algorithm designs the node credit scoring mechanism, adds the coordination node in the original algorithm model, stipulates the node state and functional limitations, and realizes the dynamic joining and exiting of the nodes, to solve the low efficiency of the PBFT algorithm during the consensus process and the problem of not supporting the dynamic joining and exiting of the nodes; at the same time, the signature scheme based on the BLS aggregated signature is designed, which reduces the length of the signature and simplifies the signing process, to solve the problem of the node’s signature taking up too much space during the consensus process, which affects the efficiency of the signature validation as well as the efficiency of the signature construction. Experimental results show that this consensus mechanism enables an efficient, secure, and scalable consensus process with low resource and computational costs.

Apoptosis-inducing factor mitochondrion-associated 2 (AIFM2) has been identified as a gene with anti-ferroptosis properties. To explore whether AIFM2 exerts anti-ferroptosis role in yaks (Bos grunniens), we cloned yak AIFM2 gene and analyzed its biological characteristics. The coding region of AIFM2 had 1122 bp and encoded 373 amino acids, which was conserved in mammals. Next, RT-qPCR results showed an extensive expression of AIMF2 in yak tissues. Furthermore, we isolated yak skin fibroblasts (YSFs) and established a bisphenol A (BPA)-induced ferroptosis model to further investigate the role of AIFM2. BPA elevated oxidative stress (reactive oxygen species, ROS) and lipid peroxidation (malondialdehyde, MDA and BODIPY), and reduced cell viability and antioxidant capacity (glutathione, GSH), with the severity depending on the dosage. Of note, a supplement of Ferrostatin-1 (Fer), an inhibitor of ferroptosis, restored the previously mentioned indicators. Subsequently, we constructed an AIFM2 overexpression vector and designed AIFM2 specific interfering siRNAs, which were transfected into YSFs. The results showed that overexpressing AIFM2 alleviated ferroptosis, characterizing by significant changes of cell viability, ROS, BODIPY, MDA and GSH. Meanwhile, interfering AIFM2 aggravated ferroptosis, demonstrating the critical anti-ferroptosis role of the yak AIFM2 gene. This study shed light on further exploring the molecular mechanism of AIFM2 in plateau adaptability.

RationaleSepsis is a life-threatening organ dysfunction and lack of effective measures in the current. Exosomes from mesenchymal stem cells (MSCs) reported to alleviate inflammation during sepsis, and the preconditioning of MSCs could enhance their paracrine potential. Therefore, this study investigated whether exosomes secreted by lipopolysaccharide (LPS)-pretreated MSCs exert superior antiseptic effects, and explored the underlying molecular mechanisms.MethodsExosomes were isolated and characterized from the supernatants of MSCs. The therapeutic efficacy of normal exosomes (Exo) and LPS-pretreated exosomes (LPS-Exo) were evaluated in terms of survival rates, inflammatory response, and organ damage in an LPS-induced sepsis model. Macrophages were stimulated with LPS and treated with Exo or LPS-Exo to confirm the results of the in vivo studies, and to explain the potential mechanisms.ResultsLPS-Exo were shown to inhibit aberrant pro-inflammatory cytokines, prevent organ damages, and improve survival rates of the septic mice to a greater extent than Exo. In vitro, LPS-Exo significantly promoted the M2 polarization of macrophages exposed to inflammation. miRNA sequencing and qRT-PCR analysis identified the remarkable expression of miR-150–5p in LPS-Exo compared to that in Exo, and exosomal miR-150–5p was transferred into recipient macrophages and mediated macrophage polarization. Further investigation demonstrated that miR-150–5p targets Irs1 in recipient macrophages and subsequently modulates macrophage plasticity by down-regulating the PI3K/Akt/mTOR pathway.ConclusionThe current findings highly suggest that exosomes derived from LPS pre-conditioned MSCs represent a promising cell-free therapeutic method and highlight miR-150–5p as a novel molecular target for regulating immune hyperactivation during sepsis.

ObjectivesThe objective of this study was to develop a predictive nomogram for intermediate-risk differentiated thyroid cancer (DTC) patients after fixed 3.7GBq (100mCi) radioiodine remnant ablation (RRA).MethodsData from 265 patients who underwent total thyroidectomy with central lymph node dissection (CND) and received RRA treatment at a single institution between January 2018 and March 2023 were analyzed. Patients with certain exclusion criteria were excluded. Univariate and multivariate logistic regression analyses were performed to identify risk factors for a non-excellent response (non-ER) to RRA. A nomogram was developed based on the risk factors, and its performance was validated using the Bootstrap method with 1,000 resamplings. A web-based dynamic calculator was developed for convenient application of the nomogram.ResultsThe study included 265 patients with intermediate-risk DTC. Significant differences were found between the ER group and the non-ER group in terms of CLNM>5, Hashimoto’s thyroiditis, sTg level, TgAb level (P < 0.05). CLNM>5 and sTg level were identified as independent risk factors for non-ER in multivariate analysis. The nomogram showed high accuracy, with an area under the curve (AUC) of 0.833 (95% CI = 0.770–0.895). The nomogram’s predicted probabilities aligned closely with actual clinical outcomes.ConclusionsThis study developed a predictive nomogram for intermediate-risk DTC patients after fixed 3.7GBq (100mCi) RRA. The nomogram incorporates CLNM>5 and sTg levels as risk factors for a non-ER response to RRA. The nomogram and web-based calculator can assist in treatment decision-making and improve the precision of prognosis information. Further research and validation are needed.

Background: The induction of intestinal inflammation as a result of abdominal surgery is an essential factor in postoperative ileus (POI) development. Electroacupuncture (EA) at ST36 has been demonstrated to relieve intestinal inflammation and restore gastrointestinal dysmotility in POI. This study aims to elucidate the neuroimmune pathway involved in the anti-inflammatory properties of EA in POI. Methods: After intestinal manipulation (IM) was performed to induce POI, intestinal inflammation and motility were assessed 24 h post-IM, by evaluating gastrointestinal transit (GIT), cytokines expression, and leukocyte infiltration. Experimental surgery, pharmacological intervention, and genetic knockout mice were used to elucidate the neuroimmune mechanisms of EA. Results: EA at ST36 significantly improved GIT and reduced the expression of pro-inflammatory cytokines and leukocyte infiltration in the intestinal muscularis following IM in mice. The anti-inflammatory effectiveness of EA treatment was abolished by sub-diaphragmatic vagotomy, whereas splenectomy did not hinder the anti-inflammatory benefits of EA treatment. The hexamethonium chloride (HEX) administration contributes to a notable reduction in the EA capacity to suppress inflammation and enhance motility dysfunction, and EA is ineffective in α7 nicotinic acetylcholine receptor (α7nAChR) knockout mice. Conclusions: EA at ST36 prevents intestinal inflammation and dysmotility through a neural circuit that requires vagal innervation but is independent of the spleen. Further findings revealed that the process involves enteric neurons mediating the vagal signal and requires the presence of α7nAChR. These findings suggest that utilizing EA at ST36 may represent a possible therapeutic approach for POI and other immune-related gastrointestinal diseases.

Abstract Purpose This study aimed to assess the biodistribution, detection rate, and uptake of the [18F]FAPI-42 at two distinct time intervals. Methods This prospective study enrolled 60 consecutive patients (median age 59; range 35–74) referred to [18F]FAPI-42 PET/CT. [18F]FAPI-42 PET/CT was performed early and late timepoint after tracer injection for staging or restaging. Positive lesions specified for anatomic locations (primary or recurrent tumor, LN metastasis and other metastasis) by visual analysis at both timepoints. Semiquantitative analysis of the tracer activity in lesions as well as normal tissues at both time points were measured and compared. In a subgroup analysis, eleven patients underwent 2-[18F]FDG PET/CT within 1 week, the detection rate and uptake of lesion were compared between early [18F]FAPI-42 and 2-[18F]FDG. Results Uptake of [18F]FAPI-42 in the late timepoint was significantly lower than the early timepoint in most organs (all p

Objective: To explore the effects and underlying mechanisms of Guilu Erxian glue (GLEXG) on oxidative damage in a mouse GC-1 spermatogonial (MGS) cell model. Methods: A cellular model for oxidative damage was created using MGS cells exposed to hydrogen peroxide (H2O2). Cell viability was assessed using the cell counting kit-8 assay, while reactive oxygen species (ROS) and malondialdehyde (MDA) levels were measured via flow cytometry and enzyme-linked immunosorbent assay, respectively. Western blotting and immunofluorescence techniques were employed to quantify the relative expression levels of sequestosome-1 (p62), nuclear factor erythroid 2-related factor 2 (Nrf2), microtubule-associated protein light chain 3β (LC3B), and Kelch-like ECH-associated protein 1 (Keap1). Quantitative real-time PCR was used to evaluate Keap1 mRNA expression. Transmission electron microscopy (TEM) was conducted to observe structural changes in autophagy-related vesicles. Results: The cellular model of oxidative damage induced by H2O2 showed reduced cell viability along with elevated levels of ROS and MDA. Treatment with 10% GLEXG-enriched serum significantly enhanced cell viability (P = .0002) while decreasing ROS and MDA levels (P = .0105 and P = .0033, respectively). In rapamycin-treated MGS cells, GLEXG treatment substantially upregulated the relative protein expression of p-mTOR, Nrf2, and p62 (all P

Abstract Background Caspase 6 is an essential regulator in innate immunity, inflammasome activation and host defense. We aimed to characterize the causal mechanism of Caspase 6 in liver sterile inflammatory injury. Methods Human liver tissues were harvested from patients undergoing ischemia-related hepatectomy to evaluate Caspase 6 expression. Subsequently, we created Caspase 6-knockout (Caspase 6KO) mice to analyze roles and molecular mechanisms of macrophage Caspase 6 in murine models of liver ischemia/reperfusion (IR) injury. Results In human liver biopsies, Caspase 6 expression was positively correlated with more severe histopathological injury and higher serum ALT/AST level at one day postoperatively. Moreover, Caspase 6 was mainly elevated in macrophages but not hepatocytes in ischemic livers. Unlike in controls, the Caspase 6-deficient livers were protected against IR injury, as evidenced by inhibition of inflammation, oxidative stress and iron overload. Disruption of macrophage NF-κB essential modulator (NEMO) in Caspase 6-deficient livers deteriorated liver inflammation and ferroptosis. Mechanistically, Caspase 6 deficiency spurred NEMO-mediated IκBα phosphorylation in macrophage. Then phosphorylated-inhibitor of NF-κBα (p-IκBα) co-localized with receptor-interacting serine/ threonine-protein kinase 1 (RIPK1) in the cytoplasm to degradate RIPK1 under inflammatory conditions. The disruption of RIPK1-IκBα interaction preserved RIPK1 degradation, triggering downstream apoptosis signal-regulating kinase 1 (ASK1) phosphorylation and inciting NIMA-related kinase 7/NOD-like receptor family pyrin domain containing 3 (NEK7/NLRP3) activation in macrophages. Moreover, ablation of macrophage RIPK1 or ASK1 diminished NEK7/NLRP3-driven inflammatory response and dampened hepatocyte ferroptosis by reducing HMGB1 release from macrophages. Conclusions Our findings underscore a novel mechanism of Caspase 6 mediated RIPK1-IκBα interaction in regulating macrophage NEK7/NLRP3 function and hepatocytes ferroptosis, which provides therapeutic targets for clinical liver IR injury. Graphical Abstract Video Abstract

Introduction: There is no standard treatment strategy for rectosigmoid cancer because of the diverse definitions of the proximal rectal origin. This study aimed to evaluate sigmoid take-off compared with other landmarks of the rectosigmoid junction in guiding oncological therapy and outcomes. Materials and methods: This retrospective, comparative cohort study included patients diagnosed with rectosigmoid carcinoma at our centre between January 2010 and December 2018. The patients were classified into the neoadjuvant treatment group and upfront surgery group. The oncological outcomes were compared between the two groups in relation to the tumor position. Results: A total of 656 patients (median age 64 years) were included. After propensity score matching, the 3- and 5-year overall survival and disease-free survival in patients in both the groups were comparable. However, when only patients with rectal cancer as defined by the sigmoid take-off point were included, the disease-free survival rate in the upfront surgery group was significantly lower than that in the neoadjuvant treatment group (p = 0.03 in patients who underwent computed tomography, p = 0.03 in patients who underwent magnetic resonance imaging). The turning point of the beneficial hazard ratio of neoadjuvant therapy was compared according to the different definitions of the rectosigmoid junction and the sigmoid take-off was found to be the most effective. Conclusion: The sigmoid take-off point is a suitable landmark for identifying the rectosigmoid junction and is an important defining criterion for assessing the benefit of neoadjuvant therapy. The application of this definition in clinical practice and future trials is warranted.

Despite improvements in the early intervention of myocardial infarction (MI) in recent decades, left ventricular aneurysms (LVA) remain a major health concern, particularly in developing nations. The progression of MI can lead to the thinning of the myocardial wall and the formation of a ventricular wall bulge, characteristic of an LVA. Furthermore, cardiac magnetic resonance (CMR) has emerged as the gold standard for LVA diagnosis due to its superior imaging capabilities. Notably, surgical ventricular reconstruction (SVR) is an effective treatment for LVA, aiming to restore the normal volume and structure of the left ventricle, thereby improving cardiac function. However, the criteria for selecting patients for SVR treatment remains a subject of debate. This review focuses on the current understanding of surgical indications, procedures, and prognostic risk factors that influence outcomes in left ventricular reconstruction, highlighting the need for precise patient selection to optimize surgical benefits.

Biomass serves as a crucial indicator of plant productivity, and the development of biomass models has become an efficient way for estimating tree biomass production rapidly and accurately. This study aimed to develop a rapid and accurate model to estimate the individual aboveground biomass of Salix suchowensis. Growth parameters, including plant height (PH), ground diameter (GD), number of first branches (NFB), number of second branches (NSB) and aboveground fresh biomass weight (FW), were measured from 892 destructive sample trees. Correlation analysis indicated that GD had higher positive correlations with FW than PH, NFB and NSB. According to the biological features and field observations of S. suchowensis, the samples were classified into three categories: single-stemmed type, first-branched type and second-branched type. Based on the field measurement data, regression models were constructed separately between FW and each growth trait (PH, GD, NFB and NSB) using linear and nonlinear regression functions (linear, exponential and power). Then, multiple power regression and multiple linear regression were conducted to estimate the fresh biomass of three types of S. suchowensis. For the single-stemmed plant type, model M1 with GD as the single parameter had the highest adj R2, outperforming the other models. Among the 16 constructed biomass-estimating equations for the first-branched plant type, model M32 FW = 0.010371 × PH1.15862 × GD1.250581 × NFB0.190707 was found to have the best fit, with the highest coefficient of determination (adj R2 = 0.6627) and lowest Akaike Information Criterion (AIC = 5997.3081). When it comes to the second-branched plant type, the best-fitting equation was proved to be the multiple power model M43 with PH, GD, NFB and NSB as parameters, which had the highest adj R2 value and best-fitting effect. The stability and reliability of the models were confirmed by the F-test, repeated k-fold cross-validation and paired-sample t-tests. The models developed in this study could provide efficient tools for accurately estimating the total aboveground biomass for S. suchowensis at individual tree levels. The results of this study could also be useful for optimizing the economic productivity of shrub willow plantations.

Fumonisin B1 (FB1), a mycotoxin produced by Fusarium species, is prevalent in crops and animal feed, posing significant health risks to livestock and humans. FB1 induces oxidative stress in Sertoli cells, destroys testicular structure, and affects spermatogenesis. However, methods to mitigate the reproductive toxicity of FB1 in testes remain unknown. Quercetin, a natural flavonoid antioxidant, may offer protective benefits. This study investigated the protective effects and mechanisms of quercetin against FB1-induced reproductive toxicity in TM4 cells (a Sertoli cell line). The results indicated that 40 μM quercetin improved cell viability, reduced apoptosis, and preserved cell functions. Quercetin also decreased reactive oxygen species (ROS) levels in TM4 cells exposed to FB1, enhanced the expression of antioxidant genes, and improved mitochondrial membrane potential. Compared with FB1 alone, the combination of quercetin and FB1 increased ATP levels, as well as pyruvate and lactic acid, the key glycolysis products. Furthermore, this combination elevated the mRNA and protein expression of glycolysis-related genes, including glucose-6-phosphate isomerase 1 (Gpi1), hexokinase 2 (Hk2), aldolase (Aldoa), pyruvate kinase, muscle (Pkm), lactate dehydrogenase A (Ldha) and phosphofructokinase, liver, B-type (Pfkl). Quercetin also boosted the activity of PKM and LDHA, two crucial glycolytic enzymes. In summary, quercetin mitigates FB1-induced toxicity in TM4 cells by reducing ROS levels and enhancing glycolysis. This study offers new insights into preventing and treating FB1-induced toxic damage to the male reproductive system and highlights the potential application of quercetin.

BackgroundThis study aims to investigate the clinical outcome between high-flow nasal cannula (HFNC) and non-invasive ventilation (NIV) therapy in mild to moderate hypoxemic patients on the first ICU day and to develop a predictive model of 48-h intubation.MethodsThe study included adult patients from the MIMIC III and IV databases who first initiated HFNC or NIV therapy due to mild to moderate hypoxemia (100

Abstract Skin wound healing often leads to scar formation, presenting physical and psychological challenges for patients. Advancements in messenger RNA (mRNA) modifications offer a potential solution for pulsatile cytokine delivery to create a favorable wound‐healing microenvironment, thereby preventing cutaneous fibrosis. This study aimed to investigate the effectiveness of human adipose‐derived stem cells (hADSCs) enriched with N1‐methylpseudouridine (m1ψ) modified transforming growth factor‐β3 (TGF‐β3) and interleukin‐10 (IL‐10) mRNA in promoting scar‐free healing in preclinical models. The results demonstrated that the modified mRNA (modRNA)‐loaded hADSCs efficiently and temporarily secreted TGF‐β3 and IL‐10 proteins. In a dorsal injury model, hADSCs loaded with modRNA TGF‐β3 and IL‐10 exhibited multidimensional therapeutic effects, including improved collagen deposition, extracellular matrix organization, and neovascularization. In vitro experiments confirmed the ability of these cells to markedly inhibit the proliferation and migration of keloid fibroblasts, and reverse the myofibroblast phenotype. Finally, collagen degradation mediated by matrix metalloproteinase upregulation was observed in an ex vivo keloid explant culture model. In conclusion, the synergistic effects of the modRNA TGF‐β3, IL‐10, and hADSCs hold promise for establishing a scar‐free wound‐healing microenvironment, representing a robust foundation for the management of wounds in populations susceptible to scar formation.

BackgroundThe molecular mechanisms underlying window of implantation (WOI) displacement in patients with recurrent implantation failure (RIF) remain unclear. This study aims to explore the transcriptomic signatures of endometrium with normal and displaced WOIs and to identify the causes of endometrial receptivity (ER) abnormalities and WOI displacement in RIF patients.MethodsIn this study, 40 RIF patients were recruited and underwent personalized embryo transfer (pET) guided by the predicted results of endometrial receptivity diagnosis (ERD) model. Transcriptome analysis of endometrium from patients with clinical pregnancies after pET was performed to identify differentially expressed genes (DEGs) associated with WOI displacement. Gene expression data from HRT and natural cycle endometrium were compared to identify specific gene expression patterns of ER-related genes during WOI.ResultsThe ERD results indicated that 67.5% of RIF patients (27/40) were non-receptive in the conventional WOI (P+5) of the HRT cycle. The clinical pregnancy rate in RIF patients improved to 65% (26/40) after ERD-guided pET, indicating the effectiveness of transcriptome-based WOI prediction. Among the 26 patients with clinical pregnancy, the gene expression profiles of P+5 endometrium from advanced (n=6), normal (n=10) and delayed (n=10) WOI groups were significantly different from each other. Furthermore, 10 DEGs identified among P+5 endometrium of 3 groups were involved in immunomodulation, transmembrane transport and tissue regeneration, which could accurately classify the endometrium with different WOIs. Additionally, a large number of ER-related genes showed significant correlation and similar gene expression patterns in P+3, P+5, and P+7 endometrium from HRT cycles and LH+5, LH+7, and LH+9 endometrium from natural cycles.ConclusionOur study shows that ER-related genes share similar gene expression patterns during WOI in both natural and HRT cycles, and their aberrant expression is associated with WOI displacements. The improvement of pregnancy outcomes in RIF patients by adjusting ET timing according to ERD results demonstrates the importance of transcriptome-based endometrial receptivity assessment and the clinical efficiency of ERD model.

Abstract Background Previous studies have reported SIRT1 was inversely modulated by miR‐34a, However, mechanism of metformin (MFN)'s renal podocyte protection under high glucose (HG) conditions and the connection between miR‐34a and SIRT1 expression in diabetic nephropathy (DN) remain unclear. Method We aimed to further elucidate the role of miR‐34a in HG‐treated podocytes in DN. A conditionally immortalized human podocyte cell line was cultivated in d‐glucose (30 mM). Results Microarray and RT‐qPCR revealed that miR‐34a was downregulated in HG‐treated podocytes. Additionally, miR‐34a levels increased in MFN‐treated HG‐induced podocytes. CCK‐8 assay, colony formation assay, flow cytometry, and Western blot detection showed that HG treatment reduced cell viability and promoted via HG treatment, and MFN treatment reversed this phenotypic change. MiR‐34a upregulation caused restored cell viability and suppressed cell apoptosis in HG‐treated podocytes, and miR‐34a downregulation led to damaged cell survival and induced apoptosis in MFN‐administered and HG‐treated podocytes. The dual luciferase reporter assay showed that SIRT1 3′‐UTR was a direct miR‐34a target. Further studies demonstrated an elevation in SIRT1 levels in HG‐exposed podocytes, whereas MFN treatment decreased SIRT1 levels. In addition, miR‐34a upregulation led to reduced SIRT1 expression, whereas miR‐34a inhibition increased SIRT1 levels in cells. MFN‐induced miR‐34a suppresses podocyte apoptosis under HG conditions by acting on SIRT1. Conclusion This study proposes a promising approach to interpret the mechanisms of action of the MFN‐miR‐34a axis involved in DN.

Summary: Background: Pathogenic variants in the centrosome protein (CEP) family have been implicated in primary microcephaly, Seckel syndrome, and classical ciliopathies. However, most CEP genes remain unlinked to specific Mendelian genetic diseases in humans. We sought to explore the roles of CEP295 in human pathology. Methods: Whole-exome sequencing was performed to screen for pathogenic variants in patients with severe microcephaly. Patient-derived fibroblasts and CEP295-depleted U2OS and RPE1 cells were used to clarify the underlying pathomechanisms, including centriole/centrosome development, cell cycle and proliferation changes, and ciliogenesis. Complementary experiments using CEP295 mRNA were performed to determine the pathogenicity of the identified missense variant. Findings: Here, we report bi-allelic variants of CEP295 in four children from two unrelated families, characterized by severe primary microcephaly, short stature, developmental delay, intellectual disability, facial deformities, and abnormalities of fingers and toes, suggesting a Seckel-like syndrome. Mechanistically, depletion of CEP295 resulted in a decrease in the numbers of centrioles and centrosomes and triggered p53-dependent G1 cell cycle arrest. Moreover, loss of CEP295 causes extensive primary ciliary defects in both patient-derived fibroblasts and RPE1 cells. The results from complementary experiments revealed that the wild-type CEP295, but not the mutant protein, can correct the developmental defects of the centrosome/centriole and cilia in the patient-derived skin fibroblasts. Interpretation: This study reports CEP295 as a causative gene of the syndromic microcephaly phenotype in humans. Our study also demonstrates that defects in CEP295 result in primary ciliary defects. Funding: A full list of funding bodies that contributed to this study can be found under “Acknowledgments.”

Enhancing corrosion resistance of Mg-Zn alloys with high strength and low cost was critical for broadening their large-scale practical applications. Here we prepared solutionized, peak- and over-aged ZK60 alloys with and without microalloying Ca (0.26 wt.%) to explore the effects of nanoscale precipitates on their corrosion behavior in detail via experimental analyses and theoretical calculations. The results suggested the peak-aged ZK60 alloy with Ca addition showed improved corrosion resistance in comparison with the alloys without Ca, owing to the contribution of Ca on the refinement of precipitates and increase in their number density. Although the precipitates and Mg matrix formed micro-galvanic couples leading to dissolution, the fine and dense precipitates could generate “in-situ pinning” effect on the corrosion products, forming a spider-web-like structure and improving the corrosion inhibition ability accordingly. The pinning effect was closely related to the size and number density of precipitates. This study provided important insight into the design and development of advanced corrosion resistant Mg alloys.

Abstract Background The role of prophylactic antibiotics in preventing ventilator-associated pneumonia (VAP) in patients undergoing invasive mechanical ventilation (IMV) remains unclear. This network meta-analysis compared the efficacy and safety of antibiotic prophylaxis in preventing VAP in an IMV population in intensive-care units (ICUs). Methods We searched the PubMed, Web of Science, Embase, and Cochrane Library databases from inception to December 2021, to identify relevant studies assessing the impact of prophylactic antibiotics on the incidence of VAP, the mortality, and the duration of ICU stays and hospitalization to perform a meta-analysis. Results Thirteen studies (2144 patients) were included, 12 of which were selected for the primary analysis, which revealed that treatment with prophylactic antibiotics resulted in a lower VAP rate compared with control groups [risk ratio (RR) = 0.62]. Bayesian network meta-analysis indicated that aerosolized tobramycin and intravenous ampicillin–sulbactam presented the greatest likelihood being the most efficient regimen for reducing VAP. Conclusions Antibiotic prophylaxis may reduce the incidence of VAP, but not the mortality, for adult patients undergoing IMV in ICUs. Tobramycin via nebulization and ampicillin–sulbactam via intravenous administration presented the greatest likelihood of being the most efficient regimen for preventing VAP. However, well-designed randomized studies are warranted before definite recommendations can be made.

Abstract An accurate estimation of earth pressure on retaining walls is imperative to achieving its design. This paper presents an analytical method framework that considers the effect of plant transpiration relative to the traditional calculation approaches. Specifically, a closed-form solution for one-dimensional steady unsaturated flow considering plant transpiration is incorporated into a representation of effective stress to obtain the changes in matric suction, and effective stress. The representations are used to extend Hooke’s law and Rankine’s earth pressure theory to determine at-rest, active, and passive earth pressures. Subsequently, the analytical method is used in a series of analysis case studies on the influence of root architecture types, transpiration rates, and soil types on earth pressure, to reveal that it can rapidly obtain the earth pressure. Notably, the effect of plant transpiration on earth pressure is significant. Furthermore, it is found that soil types and transpiration rates have a larger influence than root architecture types. Collectively, the research not only reveals the effect of plant on earth pressure for retaining wall, but also provides a theoretical basis for further exploration of the contribution of plants to the stability of retaining wall.

Abstract Paracrine signals play pivotal roles in organ homeostasis. Mesenchymal stromal cells (MSCs) play a key role in regulating epithelium homeostasis in the intestine while their paracrine effects are poorly characterized. Here, we identified prostaglandin E2 (PGE2) secreted by cyclooxygenase (COX)-expressing MSCs as a vital factor to maintain the intestinal mucosal barrier. We found that MSCs-induced organoid swelling through paracrine effect in vitro, a process due to enhanced water adsorption and is mediated by the COX-PGE2-EP4 axis. To further explore the regulatory effect of this axis on the intestinal epithelial barrier in vivo, we established the conditional knockout mouse model to specifically delete COX in MSCs and found that PGE2 reduction downregulated the gene Muc2 and induced a gastric metaplasia-like phenotype. Moreover, PGE2 defects increased the susceptibility of intestinal epithelium to colitis. Our study uncovers the paracrine signaling of COX-expressing MSCs in intestinal mucosal barrier maintenance, providing a basis for understanding the role of mesenchymal cells in the pathophysiological function of the intestine.

Online quantitative analysis of the reaction gas or tail gas of industrial production process can help to adjust the production process and improve product quality in time, which is of great significance to the transformation and upgrading of the relevant industries. However, due to the influence of industrial production cost, the application of expensive high-resolution mass spectrometer in industrial online quantitative analysis is relatively limited, while low-resolution mass spectrometer may detect the mass spectra with overlapping peaks, causing difficulties in the accurate quantification of reaction or tail gases. Although the current online quantitative analysis methods are relatively mature, there are still some spaces for optimization in terms of quantitative accuracy, method applicability and equipment complexity. For more accurate and more efficient online quantitative analysis, an online process mass spectrometer was proposed to detect the reaction gas or tail gas and separate the overlapping spectral peaks. At first, the component gases and their corresponding contents of the reaction gas or tail gas under measurement were accurately predicted according to industrial production scenarios, obtaining a prediction matrix and formulating a calibration standard gas. Secondly, all the overlapping spectral peaks of the calibration standard gas were obtained through finding the standard mass spectra of each component gas, and the simplest ratio matrix was constructed according to its relationship with the main peaks of each component gas, which was corrected by formulating the ratio standard gases with the same content as the relevant component gases. Then, the calibration matrix was obtained through detecting and calculating the calibration standard gas with the mass spectrometer, together with the prediction matrix and the ratio matrix, the calibration mathematical model was constructed to obtain the relative sensitivity matrix. Finally, a quantitative mathematical model was constructed with the calculated relative sensitivity matrix, the corrected ratio matrix and the detection matrix obtained after detecting and calculating the reaction gas or tail gas under measurement, and the content matrix of each component gas was obtained to monitor and control the industrial production process in real time. The online quantitative analysis of representative yeast fermenter tail gas showed that the method has high accuracy and strong applicability. After several rounds of online quantitative analysis experiments, the maximum quantitative error could be controlled within 0.4%, and the maximum quantitative relative standard deviation could be limited within 2%.

Abstract Metastasis is a leading cause of mortality in patients with lung adenocarcinoma. Histone deacetylases have emerged as promising targets for anti-tumor drugs, with histone deacetylase inhibitors (HDACi) being an active area of research. However, the precise mechanisms by which HDACi inhibits lung cancer metastasis remain incompletely understood. In this study, we employed a range of techniques, including qPCR, immunoblotting, co-immunoprecipitation, chromatin-immunoprecipitation, and cell migration assays, in conjunction with online database analysis, to investigate the role of HDACi and HDAC2/YY1 in the process of lung adenocarcinoma migration. The present study has demonstrated that both trichostatin A (TSA) and sodium butyrate (NaBu) significantly inhibit the invasion and migration of lung cancer cells via Histone deacetylase 2 (HDAC2). Overexpression of HDAC2 promotes lung cancer cell migration, whereas shHDAC2 effectively inhibits it. Further investigation revealed that HDAC2 interacts with YY1 and deacetylates Lysine 27 and Lysine9 of Histone 3, thereby inhibiting Cdh1 transcriptional activity and promoting cell migration. These findings have shed light on a novel functional mechanism of HDAC2/YY1 in lung adenocarcinoma cell migration.

Rocky desertification is a devastating process in Karst areas of Southwest China and induces serious fragmentation in ecosystems. Therefore, vegetation restoration and the scientific evaluation of soil quality are key restorative strategies in these areas. In this study, a natural closed forest and a disturbed forest with three restoration models, including an evergreen broad-leaved forest, mixed forest, and deciduous forest, were investigated in Huanjiang County. More than nineteen soil properties (including physical, chemical, and biotic properties) were analyzed across treatments, and principal component analyses (PCA) were combined with a minimum data set (MDS) applied to evaluate the soil quality. Our study sought to identify a vegetation restoration model to improve the soil quality in this area. We demonstrated that soil physical and chemical properties, microbial biomass, and enzyme activities significantly differed across all of the models. Soil water content, capillary porosity, total porosity, organic carbon, total phosphorus, available phosphorus, and urease activity were high in the mixed forest, leading to better physical soil properties. Also, relatively high soil total nitrogen, total potassium, available nitrogen, available potassium, microbial biomass C and N, catalase, sucrose, and alkaline phosphatase levels were observed in the deciduous broad-leaved forest, resulting in improved soil chemical properties. Based on the minimum data set (MDS) method, six indicators, including non-capillary porosity, organic carbon, total phosphorus, pH, microbial biomass nitrogen, and urease activity, were selected to evaluate the soil quality across the models. Our data showed that, among the five models, the deciduous broad-leaved forest had the highest soil quality index (0.618), followed by the mixed forest (0.593). Stepwise regression analysis showed that soil organic carbon explained 79.9% of the variations in the soil quality indices, suggesting it was a major factor affecting the soil quality. Thus, vegetation restoration models mainly comprised of native tree species effectively improved the soil quality in Karst rocky desertification areas, with deciduous broad-leaved forests displaying the best effects, followed by mixed forests.

The study aimed to explore the relationship and interaction between humans and nature in specific areas. Latent Dirichlet allocation topic recognition and SnowNLP sentiment analysis were used to extract the topics and analyze the sentiments from visitors’ online reviews of Wuyishan National Park. The conclusions were as follows: (1) The tourists mainly expressed positive emotions toward Wuyishan National Park, and the tourists acknowledged its ecological environment and natural and cultural heritage value. (2) The tourists’ comments focused on four themes: tourism activities and facilities, natural and cultural heritage value, characteristic tourism products, and tourism management and services. Natural experience was the main tourism activity in Wuyishan National Park, while cultural activities were related to the tea culture. (3) The tourist facilities, ticket and reservation mechanism, and management and services of Wuyishan National Park were the main concerns of the tourists. The study suggested that Wuyishan National Park could be transformed from a tourist destination into a comprehensive national park that provides recreational experiences and environmental education. This should be conducted by (1) developing detailed natural and cultural education and experience products and (2) improving public service functions and enhancing the public welfare of the national park.

Excessive consumption of sugary foods increases the likelihood of obesity, as well as the preventable risk of lifestyle illnesses such as diabetes and cardiovascular diseases. Frequent intake of sweet snacks is considered to increase the risk of overweight/obesity in industrial nations. However, we cannot stop snacking against our better judgment. Therefore, in this study, we sought to develop high-protein, low-carb “mock snacks” to satisfy snack lovers’ appetites and nutrition. Soy protein-based, ball-shaped food products with 57.7% (w/w) protein and 3.6% sugar have been developed. The addition of canola oil made them melty in the mouth without sacrificing their crispiness. Moreover, evaluation of the surface topography of the “soy balls” by 3D laser scanning demonstrated their high degree of sphericity. Conclusively, the snacks developed here may be one of the healthy alternatives for the current sugary ones.

In this study, a simple two-step heat treatment is proposed to design a TRIP metastable β-Zr alloy with good strength-ductility synergy by introducing heterogeneous α precipitates. The heterogeneous α precipitates mainly consist of necklace-like α at β grain boundaries and a small amount of randomly distributed intragranular α. Compared with the sample consisting of single β phase with yield strength of 683 MPa and ductility of 14.6%, yield strength of the designed two samples with heterogeneous α precipitates increases to 781 MPa and 842 MPa respectively, while the ductility increases to 15.3% and decreases to 13.6% respectively. The microstructure analysis shows that the dominant deformation mechanisms of the sample containing single β phase are β to α′ martensitic transformation and domaination of α′ martensite, accompanied by kinking band, and {101¯1}α′ twinning. For samples with heterogeneous α precipitates, the precipitation of α will increase the triggering stress of the kinking band, resulting in an increase in the yield strength at early stage of deformation. More importantly, the unique heterogeneous α structure brings a gently cutting effect of the necklace-like α on β grains and a traversability of the intragranular α to the growing α′ martensite, making the β to α′ martensitic transformation and domaination of α′ martensite slightly inhibited, together with the absorption and transfer of plastic deformation energy by α precipitates endow the alloy with high ductility. The present work can provide inspiration for improving the strength-ductility synergy of metastable β-Zr or β-Ti alloy through heterogeneous precipitate structure design.

The poor age-hardening response of Mg alloys limited their development and applications. In this study, the age-hardening response of Mg–7Sn alloy has been improved significantly by a 40 MPa compressive stress aging at 220 °C. Phase transition from metastable βˈ (Mg3Sn) phase to β (Mg2Sn) phase occurs during the stress aging. The βˈ with L12 structure has an orientation relationship with the Mg matrix of (11¯0)β＇//(112¯0)α and [1¯1¯0]β＇//⌈0001¯⌉α. The precipitated sequence in the stress-aged alloy is S.S.S. (supersaturated solid solution)→GP→βˈ(Mg3Sn)→β(Mg2Sn). The stress-aged alloy exhibits a high peak-aged hardness (∼71 HV) and short time to reach the peak hardness (12 h) as compared with the aged alloy without the stress. Interestingly, a long-time aging platform with 71 HV for 96 h is observed during stress aging. The formation of the platform is related to a balance of hardening and softening arisen from microstructure evolution during stress aging. The stress aging provides a promising heat treatment way to improve aging hardening response of Mg alloys.