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Abstract There is limited data on the prognostic implications of residual mild coarctation (RMC) in patients with repaired native coarctation of the aorta (CoA). To explore the association of RMC with mid‐term comorbidities in post‐interventional patients, and the predictive value of the residual pressure gradient. The authors retrospectively analyzed 79 native CoA patients who received successful intervention at our hospital between October 2010 and June 2023. The outcomes of the study were late arterial hypertension (either raised blood pressure or commencement of hypotensive medications) only in normotensive patients at early follow‐up and the composite mid‐term comorbidities including new‐onset aortic injury, re‐stenosis, and re‐intervention. At a median follow‐up of 60 months, late hypertension and mid‐term comorbidities occurred in 16 (28.1%) and nine (11.4%) patients, respectively. Multivariate Cox proportional hazard regression analysis identified invasive peak systolic CoA pressure gradient (PSPG) as the best independent predictor of both outcomes. The maximally selected rank statistics indicated 10 mm Hg as the best PSPG cut‐off value for predicting late hypertension. Compared to patients with PSPG

IntroductionSpecialty agricultural farmers have widely adopted digital technologies in all aspects of their specialty agricultural operations. However, the effect of digital technology application (DTA) on specialty agricultural farmers’ income has not been fully evaluated. Moreover, it remains unclear whether DTA enhances farmers’ income (FI) by improving their varied capabilities. To fill this gap, we analyzed the intrinsic relationship and mechanism between DTA, farmers’ capability (FC), and specialty agricultural farmers’ income.MethodsUsing field survey data from 635 litchi farmers in China, we employed OLS regression models and mediation effect models to empirically investigate DTA’s direct and indirect impacts on litchi farmers’ income. Additionally, we examined the group heterogeneity and regional heterogeneity.Results and discussionThe empirical results show that DTA can promote specialty agricultural farmers’ income by enhancing their production capacity (PC) and transaction capacity (TC). Heterogeneity analysis showed that the empowering effect of DTA is especially significant for disadvantaged farmers, and farmers who are in specialty agricultural resources-rich regions.ConclusionThis study contributes to the body of research on the empowerment of specialty agricultural farmers by examining the effect of DTA from a capability perspective. Consequently, to better play the empowering effect of DTA for specialty agricultural farmers, policymakers should account for regional disparities in promoting digital agriculture, and enhance heterogeneous farmers’ DTA capability.

Metal tolerance protein (MTP) is a cation transporter that plays an important role in tolerance to heavy metal stress. However, thus far, there has been no genome-wide investigation of the MTP gene family in Quercus plants. Quercus dentata is one of the main constructive species of forest in northern China. It has strong tolerance to a variety of heavy metal stresses. In this study, 25 MTPs were identified from the Q. dentata genome and classified into three subfamilies and seven groups according to their sequence characteristics and phylogenetic relationships. Both tandem and segmental duplication events contributed to the expansion of the QdMTP gene family. Interestingly, all 10 tandem duplication events contributed to the expansion of the Mn-CDF subfamily. The expression of Mn-CDF subfamily members in different organs and tissues of Q. dentata was different, and they responded differently to manganese, iron, zinc and cadmium stress treatments. QdMTP10.7, a member of the Mn-CDF subfamily, enhanced yeast growth under manganese, zinc and iron stresses. The subcellular localization in tobacco leaf epidermis cells showed that QdMTP10.7 was located in vacuoles. These data generated from this study provide an important foundation to elucidate the biological roles of QdMTP genes related to heavy metal tolerance in Q. dentata.

Organizational commitment is key to sustainable development and the success of farmer cooperatives. The relationship and effectiveness of contractual and relational governance as important means of managing partnerships remain debatable, and their impact on organizational commitment is unclear, particularly in the context of farmer cooperatives. Based on transaction cost theory and social exchange theory, we investigate how contractual and relational governance affect members’ organizational commitment (MOC) under different market uncertainties. Using survey data of 239 farmer cooperatives in China, we examined the conceptual model utilizing hierarchical regression and bootstrapping techniques. The results showed that both contractual and relational governance have significant positive impacts on members’ continuance and affective commitment, but relational governance exerts more positive effects. Contractual governance can significantly promote relational governance; the two have complementary rather than substitute relationships. Moreover, relational governance mediates the link between contractual governance and members’ continuance/affective commitment, and this mediating role strengthens as market uncertainty increases. This study expands the literature on MOC from the perspective of alliance governance, and has important implications for cooperative governance mechanisms and partnership management.

Improving farmer cooperatives' operating performance is essential for their economic sustainability and for promoting sustainable agricultural development. Despite the prominent role of benefit distribution and asset specificity in cooperation organizations, their impact on performance remains controversial, and the relationship between the three is unclear. This study focuses on cooperative benefit distribution in terms of their rebates (first and second rebates) and investigates the relationship between asset specificity, cooperative rebate and operating performance. The results show that both the first and second rebates have a positive impact on operating performance and play substitutive roles in increasing operating performance. Physical asset specificity (PAS) impacts first rebates positively, whereas human asset specificity (HAS) impacts first rebates negatively. PAS has a positive effect on operating performance whereas HAS has no significant influence on operating performance. Furthermore, the first rebate mediates the relationship between PAS and operating performance and suppresses the relationship between HAS and operating performance. These findings provide support for developing relevant policies to improve cooperative performance and sustainability.

Lily (Lilium spp.) is one of the most famous ornamental flowers globally. Lily basal rot (also known as root rot or stem rot) and lily gray mold have seriously affected the yield and quality of lily, resulting in huge economic losses. In this study, bacterial strain E was isolated from a continuous lily cropping field. Strain E displayed high control efficiency against lily basal rot and gray mold, caused by Fusarium oxysporum and Botrytis cinerea respectively, and promoted the occurrence of scale bulblets. Strain E displayed strong inhibitory effects against several other plant pathogenic fungi and two pathogenic bacteria in dual culture and disc diffusion assays, respectively. Whole genome sequencing revealed that strain E contained a 3,929,247 bp circular chromosome with 4,056 protein-coding genes and an average GC content of 47.32%. Strain E was classified as Bacillus velezensis using genome-based phylogenetic analysis and average nucleotide identity and digital DNA–DNA hybridization analyses. A total of 86 genes and 13 secondary metabolite biosynthetic gene clusters involved in antifungal and antibacterial activity, plant growth promotion, colonization, nutrient uptake and availability were identified in the genome of strain E. In vitro biochemical assays showed that strain E produced siderophores, proteases, cellulases, biofilms, antifungal and antibacterial substances, and exhibited organic phosphate solubilization and swimming and swarming motility, which were consistent with the results of the genome analysis. Colonization analysis showed that strain E could colonize the root of the lily, but not the leaf. Overall, these results demonstrate that B. velezensis strain E can be used as a potential biofertilizer and biocontrol agent for lily production.

Background: There have been marked advances in devices such as Amplatzer Duct Occluder II (ADO-II) or vascular plug through 5Fr delivery sheath for closure of patent ductus arteriosus (PDA) in the past five decades, making it possible for cardiologists to deliver occluders via different approaches. However, comparisons of these different approaches have not been reported. Therefore, the aim of this study was to summarize and compare the advantages of different approaches for PDA closure, and to guide clinical strategies.Methods: This retrospective study included all patients undergoing transcatheter closure of PDA from 2019 to 2020. Patients were matched by 1:1 propensity score matching (PSM). The retrograde femoral artery approach (FAA) and simple vein approach (SVA) groups were compared with the conventional arteriovenous approach (CAA).Results: The average age of the 476 patients was 21.05 ± 21.15 years. Their average weight was 38.23 ± 24.1 kg and average height was 130.14 ± 34.45 cm. The mean diameter of the PDA was 4.29 ± 2.25 mm. There were 127 men and 349 women, comprising 205 adults and 271 children. Among them, 197 patients underwent CAA, 223 underwent SVA, and 56 underwent retrograde FAA. The diameter in the FAA group was smaller than that in the other two groups, but was similar in adults and children. In the PSM comparison of CAA and SVA, 136 patients with CAA and 136 patients with SVA were recruited. Simple vein approach was associated with markedly reduced length of hospital stay, length of operation, and contrast medium usage as compared with CAA (all P < 0.05). In the PSM comparison of FAA and CAA, 30 patients with CAA and 30 patients with FAA were recruited. The operation duration was longer in the CAA than in the FAA group. There were no significant differences in postoperative complications among groups.Conclusion: Patent ductus arteriosus closure by using the SVA and FAA is safe and effective, and has certain advantages in some respects as compared with CAA.

Cardiovascular disease (CVD) is the leading cause of the death worldwide. An increasing number of studies have found that autophagy is involved in the progression or prevention of CVD. However, the precise mechanism of autophagy in CVD, especially the myocardial ischaemia-reperfusion injury (MI/R injury), is unclear and controversial. Here, we show that the cardiomyocyte-specific disruption of autophagy by conditional knockout of Atg7 leads to severe contractile dysfunction, myofibrillar disarray and vacuolar cardiomyocytes. A negative cytoskeleton organization regulator, CLP36, was found to be accumulated in Atg7-deficient cardiomyocytes. The cardiomyocyte-specific knockout of Atg7 aggravates the MI/R injury with cardiac hypertrophy, contractile dysfunction, myofibrillar disarray and severe cardiac fibrosis, most probably due to CLP36 accumulation in cardiomyocytes. Altogether, this work reveals autophagy may protect cardiomyocytes from the MI/R injury through the clearance of CLP36, and these findings define a novel relationship between autophagy and the regulation of stress fibre in heart.

Abstract Background Balance dysfunction affects 70% of stroke patients. Emerging neurophysiological approaches, such as virtual reality therapy (VRT) and repetitive transcranial magnetic stimulation (rTMS), have been proven by clinical studies that the balance function of stroke patients can be improved when applied alone, but there are relatively few studies on the combined treatment of balance dysfunction after stroke. This study aimed to evaluate the impact of a 4-week intensive intervention combining VRT and rTMS on both balance function and brain plasticity among stroke patients. Methods This single-blind, randomized controlled trial was conducted at the Rehabilitation Medical Center of the Rehabilitation General Hospital of Ningxia Medical University. A cohort of 136 stroke patients, with durations of 2 to 24 weeks post-stroke, were enrolled in the study. Participants were randomly allocated in a 1:1:1:1 ratio to four groups: the VR group (n = 34), the rTMS group (n = 34), the combined treatment group receiving both VR and rTMS (n = 34), and the control group undergoing traditional balance training (n = 34). All patients underwent a standardized inpatient rehabilitation program over 4 weeks. The VR group received daily 30-min sessions of VR therapy for 20 days. The rTMS group underwent daily sessions of rTMS stimulation for 20 min, targeting the motor imagery region in the affected hemisphere. The combination group received VR therapy after completing their rTMS treatment. The control group received conventional balance training, with each session lasting 30 min. Additionally, all patients received an extra 60 min of standard rehabilitation therapy twice daily. Assessments were conducted at baseline, 2 weeks, and 4 weeks post-treatment, using the Berg Balance Scale (BBS) as the primary measure, and secondary measures including the Timed Up-and-Go Test (TUGT), Fugl-Meyer Assessment-Lower Extremity (FMA-LE), and 6-m walking test (6MWT), as well as assessments for brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VGEF), tyrosine receptor kinase (TrκB), motor-evoked potential latency (PL), central motor conduction time (CMCT), and amplitude. Discussion The widespread application of VR technology and rTMS in clinical settings is well-established. However, the potential synergistic effects of combining these modalities on balance function and neuroplasticity in stroke patients remain uncertain. Our hypothesis suggests that the integration of VR with rTMS may result in more pronounced improvements in both balance function and neuroplasticity among stroke patients, surpassing the outcomes achievable with VR alone, rTMS alone, or traditional therapy. The possible mechanism is that VR-based training combined with rTMS plays a superimposed effect, promoting better repair of damaged neurons and ultimately improving balance function in stroke patients. The positive results anticipated from this trial could provide objective evidence advocating for the concurrent use of VR and rTMS in clinical interventions. Trial registration The study protocol underwent review and approval by the Medical Research Ethics Committee of the General Hospital of Ningxia Medical University on January 26, 2024 (No. KYLL-2024–0162). Subsequently, it was registered in the Chinese Clinical Trial Registry on March 11, 2024 (registration number: ChiCTR2400081775). Currently, the study is still ongoing.

Abstract On-chip metasurface for guided wave radiation works as an upgrade of conventional grating couplers, enriching the interconnection between guided wave and free-space optical field. However, the number of controllable parameters in equivalent Jones matrix of on-chip metasurface is limited that restricts the channels for multiplexing. Here, a supercell design based on detour phase and geometric phase has been proposed to reach full-parametric modulation of Jones matrix. As proof of concept, four independent sets of amplitude-phase channels have been experimentally demonstrated through a single on-chip metasurface. Moreover, through joint modulation of three phase mechanisms including detour phase, geometric phase and propagation phase, the Jones matrix could be decoupled from forward- and backward-propagating guided waves for direction multiplexing. This work paves the way for guided wave radiation towards high-capacity multiplexing and may further extend its application in optical communications, optical displays and augmented/virtual reality.

This study aimed to assess the level of knowledge regarding influenza viruses and vaccines among different professional groups to investigate the reasons for vaccine hesitancy. We collected 2190 questionnaires regarding influenza vaccines in China in 2022. The respondents were categorized into the general population (GP), foreign affairs workforce population (FAWP), and veterinary workforce population (VWP) according to their job positions. Linear regression was used to assess the association between multiple factors and influenza vaccination rates. The association between work and influenza vaccination rates was also assessed by grouping different workforce populations. The vaccination rate of the GP was higher than that of the VWP (odds ratio: 1.342, 95% confidence interval: 1.025–1.853), surpassing the rates reported in previous studies. This may be attributed to heightened concerns about infectious diseases influenced by the ongoing coronavirus disease 2019 pandemic. Despite the VWP’s more in-depth knowledge of the VWP on zoonotic diseases and their recognition of their importance, there was no significant difference in influenza knowledge among the three populations. This discrepancy contrasts with the observed differences in vaccination rates. Further investigation revealed that, compared with FAWP, the price of vaccines emerged as a primary influencing factor for vaccination rates (odds ratio:0.398, 95%CI; 0.280–0.564). General concerns regarding the protective effects and side effects of vaccines were also noted.

Gastrointestinal (GI) cancer stands as one of the most prevalent forms of cancer globally, presenting a substantial medical and economic burden on cancer treatment. Despite advancements in therapies, it continues to exhibit the second highest mortality rate, primarily attributed to drug resistance and post-treatment side effects. There is an urgent need for novel therapeutic approaches to tackle this persistent challenge. Scutellaria baicalensis , widely used in Traditional Chinese Medicine (TCM), holds a profound pharmaceutical legacy. Modern pharmacological studies have unveiled its anticancer, antioxidant, and immune-enhancing properties. S. baicalensis contains hundreds of active ingredients, with flavonoids, polysaccharides, phenylethanoid glycosides, terpenoids, and sterols being the principal components. These constituents contribute to the treatment of GI cancer by inducing apoptosis in tumor cells, arresting the cell cycle, inhibiting tumor proliferation and metastasis, regulating the tumor microenvironment, modulating epigenetics, and reversing drug resistance. Furthermore, the utilization of modern drug delivery technologies can enhance the bioavailability and therapeutic efficacy of TCM. The treatment of GI cancer with S. baicalensis is characterized by its multi-component, multi-target, and multi-pathway advantages, and S. baicalensis has a broad prospect of becoming a clinical adjuvant or even the main therapy for GI cancer.

BackgroundBreast cancer (BC) is the prevailing malignant tumor, with its prevalence and death rate steadily rising over time. BC often does not show obvious symptoms in its early stages and is difficult to distinguish from benign breast disease. We aimed to find a distinct group of miRNAs utilizing serum as a non-invasive biomarker for early BC diagnosis.MethodsHerein, we mainly include the screening stage, testing stage, and verification stage. In the screening stage, 8 miRNAs associated with BC were selected and analyzed via literature reading, and the expression of the above miRNAs in BC was further verified by bioinformatics and included in the research analysis. In the testing phase, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was deployed to select the five miRNAs with the most significant expression differences in 15 BC patients and 15 benign breast controls to proceed to the next stage. In a subsequent validation phase, the five miRNAs obtained from serum samples from an additional 75 BC patients and 50 benign control patients were evaluated using RT-qPCR. The diagnostic capacity, specificity, and sensitivity of candidate miRNAs were estimated with the receiver operating characteristic (ROC) curve and area under the curve (AUC). Finally, the optimal diagnostic combination model with high sensitivity and strong specificity was constructed by using the above 5 miRNAs.ResultsThe BC patients reported a significant decline in mir-10b-5p, mir-133a-3p, mir-195-5p, and mir-155-3p levels in serum levels contrasted with those in benign controls. Additionally, BC patients experienced elevated mir-195-3p levels than in benign controls. We implemented ROC analysis to evaluate its diagnostic capacity for BC. We demonstrated that all five miRNAs had robust diagnostic capability, with an AUC above 0.8. We developed a conclusive diagnostic combination model consisting of these 5 miRNAs in order to enhance the diagnosis accuracy. This model demonstrated a high diagnostic value, as shown by an AUC of 0.948.ConclusionThe serum biomarker panels composed of five miRNAs identified in this study (mir-10b-5p, mir-133a-3p, mir-195-5p, mir-195-3p, and mir-155-3p) provide hope for early, non-invasive, and accurate diagnosis of BC.

Abstract Through applying a 4‐MHz linear frequency modulation waveform, which has high range resolution and signal intensity, we successfully detected for the first time the ionospheric 150‐km echo enhancement at 430–450 MHz of the Ultra‐High‐Frequency (UHF) band using the newly built Sanya Incoherent Scatter Radar (SYISR). The obtained low signal enhancement (less than 0.5 dB) explains why previous UHF experiments did not detect them. We also found that our measured fine structure shows a much wider forbidden region than previous results and covers a much larger altitudinal and local time region. In comparison with recent upper‐hybrid instability theory and simulation, our results confirmed the predicted higher altitude occurrence, wider gaps between enhancements, the turn corner feature around sunrise, and perhaps the weak enhancement, which provide an independent evaluation of the newly proposed mechanism in UHF band. Future UHF experiments could further improve the physical understanding of 150‐km echo phenomenon.

Sensory analysis is an interdisciplinary field that combines multiple disciplines to analyze food qualitatively and quantitatively. At present, this analysis method has been widely used in product development, quality control, marketing, flavor analysis, safety supervision and inspection of alcoholic beverages. Due to the changing needs of analysis, new and more optimized methods are still emerging. Thereinto, intelligent and biometric technologies with growing attention have also been applied to sensory analysis. This work summarized the sensory analysis methods from three aspects, including traditional artificial sensory analysis, intelligent sensory technology, and innovative technologies. Meanwhile, the application sensory analysis in alcoholic beverages and its industrial production was scientifically emphasized. Moreover, the future tendency of sensory analysis in the alcoholic beverage industry is also highlights.

Abstract To deal with the highly nonlinear and time-varying characteristics of Batch Process, a model named adaptive stacking approximate kernel based broad learning system is proposed in this paper. This model innovatively introduces the approximate kernel based broad learning system (AKBLS) algorithm and the Adaptive Stacking framework, giving it strong nonlinear fitting ability, excellent generalization ability, and adaptive ability. The Broad Learning System (BLS) is known for its shorter training time for effective nonlinear processing, but the uncertainty brought by its double random mapping results in poor resistance to noisy data and unpredictable impact on performance. To address this issue, this paper proposes an AKBLS algorithm that reduces uncertainty, eliminates redundant features, and improves prediction accuracy by projecting feature nodes into the kernel space. It also significantly reduces the computation time of the kernel matrix by searching for approximate kernels to enhance its ability in industrial online applications. Extensive comparative experiments on various public datasets of different sizes validate this. The Adaptive Stacking framework utilizes the Stacking ensemble learning method, which integrates predictions from multiple AKBLS models using a meta-learner to improve generalization. Additionally, by employing the moving window method—where a fixed-length window slides through the database over time—the model gains adaptive ability, allowing it to better respond to gradual changes in industrial Batch Process. Experiments on a substantial dataset of penicillin simulations demonstrate that the proposed model significantly improves predictive accuracy compared to other common algorithms.

Guizhou Province is located in Southwest of China, with many mountains and hills, and is a typical karst topography and geomorphology area with frequent geological disasters such as collapses and landslides. The existing dangerous rock mass in the Xiaotunyan collapse zone in Sinan County has large range and volume, and fissures, concave cavities, and solution caves have developed. Objective In order to study the failure probability of passive protection nets for rockfalls in typical karst areas. Methods A three-dimensional model of the collapse zone through high-precision realistic modeling technology was constructed, by which the movement process of collapsed falling rocks was simulated. According to the results of the field investigation, aerial photography of the unmanned aerial vehicle and numerical simulation, an appropriate rockfall location layout for the passive protection net was selected. And based on the identification of the rockfall particle size, the different rockfall particle sizes were selected to simulate the interception effect of the passive protection net, then the failure probability of the passive protective net can be calculated. Results The results show that the rockfall breakthrough rates of 13 particle sizes vary: the interception effect of small to medium sized falling rocks with particle sizes ranging from 0.25 m to 2.25 m is effective, but the interception rate of passive protection net cannot reach 100%. When the particle size is larger than 2.25 m, the passive protection net fails, that is the upper limit of the design of the passive protection net under the Xiaotunyan collapse zone is the 2.25 m particle size of rockfall. According to the calculation, the failure probability of all rockfall particle sizes intercepted by the passive protection net is less than 5%, which is within the acceptable scope. Conclusion The research results provide a reference for rockfall protection measures in the Xiaotunyan collapse zone and are of great significance for the protection of life and property safety for people in karst mountainous areas.

Abstract Optical encryption plays an increasingly important role in the field of information security owing to its parallel processing capability and low power consumption. Employing the ultrathin metasurfaces in optical encryption has promoted the miniaturization and multifunctionality of encryption systems. Nevertheless, with the few number of degrees of freedom (DoFs) multiplexed by single metasurface, both key space and encoding space are limited. To address this issue, we propose a high-security and large-capacity optical encryption scheme based on perfect high-dimensional Poincaré beams with expanded DoFs. By cascading two arrayed metasurfaces, more beam properties can be independently engineered, which gives rise to the extensively expanded key and encoding spaces. Our work provides a promising strategy for optical encryption with high security level and large information capacity and might facilitate the applications of Poincaré beams in optical communications and quantum information.

Abstract Angelman syndrome (AS) is a neurodevelopmental disorder caused by abnormal expression of the maternal ubiquitin protein ligase E3A gene (UBE3A). As one of the most challenging symptoms and important focuses of new treatment, sleep disturbance is reported to occur in 70–80% of patients with AS and has a serious impact on the lives of patients and their families. Although clinical studies and animal model studies have provided some clues, recent research into sleep disorders in the context of AS is still very limited. It is generally accepted that there is an interaction between neurodevelopment and sleep; however, there is no recognized mechanism for sleep disorders in AS patients. Accordingly, there are no aetiologically specific clinical treatments for AS-related sleep disorders. The most common approaches involve ameliorating symptoms through methods such as behavioural therapy and symptomatic pharmacotherapy. In recent years, preclinical and clinical studies on the targeted treatment of AS have emerged. Although precision therapy for restoring the UBE3A level and the function of its signalling pathways is inevitably hindered by many remaining obstacles, this approach has the potential to address AS-related sleep disturbance.

Gamma/delta T (γδ T)cells possess a unique mechanism for killing tumors, making them highly promising and distinguished among various cell therapies for tumor treatment. This review focuses on the major histocompatibility complex (MHC)-independent recognition of antigens and the interaction between γδ T cells and solid tumor cells. A comprehensive review is provided regarding the classification of human gamma-delta T cell subtypes, the characteristics and mechanisms underlying their functions, as well as their r545egulatory effects on tumor cells. The involvement of γδ T cells in tumorigenesis and migration was also investigated, encompassing potential therapeutic targets such as apoptosis-related molecules, the TNF receptor superfamily member 6(FAS)/FAS Ligand (FASL) pathways, butyrophilin 3A-butyrophilin 2A1 (BTN3A-BTN2A1) complexes, and interactions with CD4, CD8, and natural killer (NK) cells. Additionally, immune checkpoint inhibitors such as programmed cell death protein 1/Programmed cell death 1 ligand 1 (PD-1/PD-L1) have the potential to augment the cytotoxicity of γδ T cells. Moreover, a review on gamma-delta T cell therapy products and their corresponding clinical trials reveals that chimeric antigen receptor (CAR) gamma-delta T therapy holds promise as an approach with encouraging preclinical outcomes. However, practical issues pertaining to manufacturing and clinical aspects need resolution, and further research is required to investigate the long-term clinical side effects of CAR T cells. In conclusion, more comprehensive studies are necessary to establish standardized treatment protocols aimed at enhancing the quality of life and survival rates among tumor patients utilizing γδ T cell immunotherapy.

Understanding the impact-induced ignition properties and energy release behavior of polymer-bonded explosives (PBXs) is critical for the safety of explosive systems. In this study, a new impact test component was designed using a light gas gun to quantify the ignition mechanism and chemical reaction of micro-damaged PBXs under different inertial loading conditions. A constitutive model was developed to describe the mechanical-thermal-chemical response of the PBXs. This model was employed to further investigate the correlation between microcracks, debonding, hot spots, and chemical reactions. The results show that the stress state of the material is not uniformly distributed due to the micro-inhomogeneities and structural defects of PBXs. The shear friction of the microcracks contributes to localized hot spots, thereby inducing ignition. The critical loading condition for ignition is the length of the steel pillar is 32 mm. The damage and hotspot temperatures of the anterior lateral and posterior lateral regions are greater than those of other locations. The ignition response is accentuated with longer steel pillars, resulting in a more violent release of energy.

Abstract Background Exposure to PM2.5 has been implicated in a range of detrimental health effects, particularly affecting the respiratory system. However, the precise underlying mechanisms remain elusive. Methods To address this objective, we collected ambient PM2.5 and administered intranasal challenges to mice, followed by single-cell RNA sequencing (scRNA-seq) to unravel the heterogeneity of neutrophils and unveil their gene expression profiles. Flow cytometry and immunofluorescence staining were subsequently conducted to validate the obtained results. Furthermore, we assessed the phagocytic potential of neutrophils upon PM2.5 exposure using gene analysis of phagocytosis signatures and bacterial uptake assays. Additionally, we utilized a mouse pneumonia model to evaluate the susceptibility of PM2.5-exposed mice to Pseudomonas aeruginosa infection. Results Our study revealed a significant increase in neutrophil recruitment within the lungs of PM2.5-exposed mice, with subclustering of neutrophils uncovering subsets with distinct gene expression profiles. Notably, exposure to PM2.5 was associated with an expansion of PD-L1high neutrophils, which exhibited impaired phagocytic function dependent upon PD-L1 expression. Furthermore, PM2.5 exposure was found to increase the susceptibility of mice to Pseudomonas aeruginosa, due in part to increased PD-L1 expression on neutrophils. Importantly, monoclonal antibody targeting of PD-L1 significantly reduced bacterial burden, dissemination, and lung inflammation in PM2.5-exposed mice upon Pseudomonas aeruginosa infection. Conclusions Our study suggests that PM2.5 exposure promotes expansion of PD-L1high neutrophils with impaired phagocytic function in mouse lungs, contributing to increased vulnerability to bacterial infection, and therefore targeting PD-L1 may be a therapeutic strategy for reducing the harmful effects of PM2.5 exposure on the immune system.

Abstract Liver metastasis is the major reason for most of colorectal cancer (CRC) related deaths. Accumulating evidence indicates that CRC patients with non-alcoholic fatty liver disease (NAFLD) are at a greater risk of developing liver metastasis. With the growing prevalence of NAFLD, a better understanding of the molecular mechanism in NAFLD-driven CRC liver metastasis is needed. In this study, we demonstrated that NAFLD facilitated CRC liver metastasis as a metabolic disorder and promoted the stemness of metastatic CRC cells for their colonization and outgrowth in hepatic niches. Metabolically, the lipid-rich microenvironment in NAFLD activated de novo palmitate biosynthesis in metastatic CRC cells via upregulating fatty acid synthase (FASN). Moreover, increased intracellular palmitate bioavailability promoted EGFR palmitoylation to enhance its protein stability and plasma membrane localization. Furthermore, we demonstrated that the FDA-approved FASN inhibitor orlistat could reduce NAFLD-activated endogenous palmitate production, thus inhibiting palmitoylation of EGFR to suppress CRC cell stemness and restrict liver metastasis in synergy with conventional chemotherapy. These findings reveal that the NAFLD metabolic microenvironment boosts endogenous palmitate biosynthesis in metastatic CRC cells and promotes cell stemness via EGFR palmitoylation, and FASN inhibitor orlistat could be a candidate adjuvant drug to suppress liver metastasis in CRC patients with NAFLD.

Abstract Background This study aimed to screen and validate noise-induced hearing loss (NIHL) associated single nucleotide polymorphisms (SNPs), construct genetic risk prediction models, and evaluate higher-order gene-gene, gene-environment interactions for NIHL in Chinese population. Methods First, 83 cases and 83 controls were recruited and 60 candidate SNPs were genotyped. Then SNPs with promising results were validated in another case-control study (153 cases and 252 controls). NIHL-associated SNPs were identified by logistic regression analysis, and a genetic risk model was constructed based on the genetic risk score (GRS), and classification and regression tree (CART) analysis was used to evaluate interactions among gene-gene and gene-environment. Results Six SNPs in five genes were significantly associated with NIHL risk (p

Throughout the past several decades, the manufacturing industry has been confronted with rapidly evolving market demands. The Reconfigurable Assembly Line (RAL) changes the quantity and variety of products produced through reconfiguration at different stages. The reconfiguration stages of RAL include the reallocation of operations and resources. However, existing research has neglected the resources. In the paper, a mixed integer linear program for the Reconfigurable Assembly Line Reconfiguring Problem is first formulated. Subsequently, an efficient data structure is developed to model the process precedence constraint and alternative resources. And an improved Variable Neighborhood Search which includes new problem-specific neighborhood structures and local search for resource selection is proposed to solve the problem. Computational results demonstrate the contribution of the proposed data structure and the improved procedure. Furthermore, the experiments verify the superiority and stability of the proposed method compared with other heuristic algorithms.

Fine particulate matter (PM2.5) has been extensively implicated in the pathogenesis of neurodevelopmental disorders, but the underlying mechanism remains unclear. Recent studies have revealed that PM2.5 plays a role in regulating iron metabolism and redox homeostasis in the brain, which is closely associated with ferroptosis. In this study, the role and underlying mechanism of ferroptosis in PM2.5-induced neurotoxicity were investigated in mice, primary hippocampal neurons, and HT22 cells. Our findings demonstrated that exposure to PM2.5 could induce abnormal behaviors, neuroinflammation, and neuronal loss in the hippocampus of mice. These effects may be attributed to ferroptosis induced by PM2.5 exposure in hippocampal neurons. RNA-seq analysis revealed that the upregulation of iron metabolism-related protein Heme Oxygenase 1 (HO-1) and the activation of mitophagy might play key roles in PM2.5-induced ferroptosis in HT22 cells. Subsequent in vitro experiments showed that PM2.5 exposure significantly upregulated HO-1 in primary hippocampal neurons and HT22 cells. Moreover, PM2.5 exposure activated mitophagy in HT22 cells, leading to the loss of mitochondrial membrane potential, alterations in the expression of autophagy-related proteins LC3, P62, and mTOR, as well as an increase in mitophagy-related protein PINK1 and PARKIN. As a heme-degradation enzyme, the upregulation of HO-1 promotes the release of excess iron, genetically inhibiting the upregulation of HO-1 in HT22 cells could prevent both PM2.5-induced mitophagy and ferroptosis. Furthermore, pharmacological inhibition of mitophagy in HT22 cells reduced levels of ferrous ions and lipid peroxides, thereby preventing ferroptosis. Collectively, this study demonstrates that HO-1 mediates PM2.5-induced mitophagy-dependent ferroptosis in hippocampal neurons, and inhibiting mitophagy or ferroptosis may be a key therapeutic target to ameliorate neurotoxicity following PM2.5 exposure.

BackgroundLower respiratory tract infections represent prevalent ailments. Nonetheless, current comprehension of the microbial ecosystems within the lower respiratory tract remains incomplete and necessitates further comprehensive assessment. Leveraging the advancements in metagenomic next-generation sequencing (mNGS) technology alongside the emergence of machine learning, it is now viable to compare the attributes of lower respiratory tract microbial communities among patients across diverse age groups, diseases, and infection types.MethodWe collected bronchoalveolar lavage fluid samples from 138 patients diagnosed with lower respiratory tract infections and conducted mNGS to characterize the lung microbiota. Employing various machine learning algorithms, we investigated the correlation of key bacteria in patients with concurrent bronchiectasis and developed a predictive model for hospitalization duration based on these identified key bacteria.ResultWe observed variations in microbial communities across different age groups, diseases, and infection types. In the elderly group, Pseudomonas aeruginosa exhibited the highest relative abundance, followed by Corynebacterium striatum and Acinetobacter baumannii. Methylobacterium and Prevotella emerged as the dominant genera at the genus level in the younger group, while Mycobacterium tuberculosis and Haemophilus influenzae were prevalent species. Within the bronchiectasis group, dominant bacteria included Pseudomonas aeruginosa, Haemophilus influenzae, and Klebsiella pneumoniae. Significant differences in the presence of Pseudomonas phage JBD93 were noted between the bronchiectasis group and the control group. In the group with concomitant fungal infections, the most abundant genera were Acinetobacter and Pseudomonas, with Acinetobacter baumannii and Pseudomonas aeruginosa as the predominant species. Notable differences were observed in the presence of Human gammaherpesvirus 4, Human betaherpesvirus 5, Candida albicans, Aspergillus oryzae, and Aspergillus fumigatus between the group with concomitant fungal infections and the bacterial group. Machine learning algorithms were utilized to select bacteria and clinical indicators associated with hospitalization duration, confirming the excellent performance of bacteria in predicting hospitalization time.ConclusionOur study provided a comprehensive description of the microbial characteristics among patients with lower respiratory tract infections, offering insights from various perspectives. Additionally, we investigated the advanced predictive capability of microbial community features in determining the hospitalization duration of these patients.

BackgroundThe efficacy of Chinese herbal medicine (CHM) in managing irritable bowel syndrome with diarrhea (IBS-D) accompanied by anxiety and depression remains uncertain. Thus, a systematic review was carried out employing meta-analysis and network pharmacology to ascertain the efficacy and underlying mechanisms of CHM therapy.MethodsBy conducting a systematic review, including literature search, screening, and data extraction, we identified 25 randomized controlled trials to assess CHM’s effectiveness in treating irritable bowel syndrome alongside anxiety and depression. Network pharmacology was utilized to scrutinize the metabolite utility of CHM in addressing this condition. Potential primary mechanisms were synthesized using information sourced from the PubMed database.ResultsTwenty-five studies, including 2055 patients, were analyzed, revealing significant treatment efficacy for IBS-D in the trial group compared to controls [OR = 4.01, 95% CI (2.99, 5.36), I2 = 0%] Additionally, treatment for depression [SMD = −1.08, 95% CI (-1.30, −0.86), p < 0.00001, I2 = 68%; SDS: SMD = -1.69, 95% CI (-2.48, −0.90), p < 0.0001, I2 = 96%] and anxiety [HAMA: SMD = -1.29, 95% CI (-1.68, −0.91), p < 0.00001, I2 = 89%; SAS: SMD = -1.75, 95% CI (-2.55, −0.95), p < 0.00001, I2 = 96%] significantly improved in the trial group. Furthermore, the trial group exhibited a significantly lower disease relapse rate [OR = 0.30, 95% CI (0.20, 0.44), p < 0.00001, I2 = 0%]. CHM treatment consistently improved IBS severity (IBS-SSS) and symptom scores. Network pharmacology analysis identified key chemical metabolites in traditional Chinese medicine formulations, including Beta-sitosterol, Stigmasterol, Quercetin, Naringenin, Luteolin, Kaempferol, Nobiletin, Wogonin, Formononetin, and Isorhamnetin. Utilizing the STRING database and Cytoscape v3.9.0 software, a protein-protein interaction (PPI) network revealed the top eight key targets: IL-6, TNF, PPARG, PTGS2, ESR1, NOS3, MAPK8, and AKT1, implicated in anti-inflammatory responses, antioxidant stress modulation, and neurotransmitter homeostasis maintenance.ConclusionChinese Herbal Medicine (CHM) offers a promising and safe treatment approach for patients dealing with Diarrheal Irritable Bowel Syndrome (IBS-D) accompanied by anxiety and depression; thus, indicating its potential for practical implementation. The most active metabolites of CHM could simultaneously act on the pathological targets of IBS-D, anxiety, and depression.The diverse scope of CHM’s therapeutic role includes various aspects and objectives, underscoring its potential for broad utilization.

In aquaculture, good germplasm resources are nearly decisive for its development. The hard clam (Mercenaria mercenaria), a significant marine aquaculture bivalve in China, has flourished quickly since being introduced from North America in 1997. However, for numerous reasons, it has suffered from germplasm deterioration and uncertain origins. To address these issues, seven microsatellite DNA loci (SSRs) and mtCOI were employed to evaluate germplasm and trace the origins of various Chinese populations. The results of these two molecular genetic markers revealed weak genetic differentiation among all Chinese populations, with high genetic diversity observed across most individuals, except for a few outliers. This suggests an alarming situation regarding germplasm resources in China. Based on results of traceability analysis, the most likely areas of origin for the Chinese populations are Chesapeake Bay and the southern region of Cape Hatteras. This study provides a crucial theoretical foundation for the cultivation, conservation, and subsequent introduction of hard clam populations in China, thereby ensuring the sustainable growth of the hard clam breeding sector.

ObjectiveTo explore the relationship between abdominal obesity index and hypertension among the elderly in Zhongshan city for the prevention and control of hypertension. MethodsThe data of the analysis were from 8 318 residents aged ≥ 65 years and participating in free physical examination project during June – September 2020 in a town and a district of Zhongshan city, Guangdong province. Multivariate logistic regression model was used to analyze the relationship between abdominal obesity indexes and hypertension among the residents; the abdominal obesity indexes included neck circumference (NC), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), lipid accumulation product (LAP), and China visceral obesity index (CVAI). The dose-response correlation between NC and the risk of hypertension was analyzed with restricted cubic splines. ResultsThe observed prevalence rate of hypertension among the elderly physical examinees was 45.5% (44.4% in the males and 46.3% in the females). Compared to those in the male and female non-hypertensives, significantly higher mean values of NC (37.29 ± 2.83 cm vs. 36.41 ± 2.82 cm and 33.91 ± 2.67 cm vs. 33.04 ± 2.55 cm), WC (87.90 ± 9.51 cm vs. 84.40 ± 9.59 cm and 86.52 ± 9.48 cm vs. 83.24 ± 9.50 cm), WHR (0.93 ± 0.07 vs. 91 ± 0.07 and 0.91 ± 0.07 vs. 0.90 ± 0.07), WHtR (0.54 ± 0.06 vs. 0.52 ± 0.06 and 0.57 ± 0.06 vs. 0.55 ± 0.06), LAP (43.00 ± 38.70 vs. 32.54 ± 31.22 and 46.98 ± 39.47 vs. 58.08 ± 46.96), and CVAI (116.19 ± 42.01 vs. 98.42 ± 42.94 and 133.18 ± 30.78 vs. 119.80 ± 30.25) were measured in the hypertensives (all P < 0.001). After adjusting for age, education, marital status, monthly household income per capita, smoking, alcohol drinking, exercise, salted vegetable consumption habits, body mass index (BMI), fasting blood glucose (FPG), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C), multivariate logistic regression analysis showed that the risk of hypertension increased in the male elderly with higher NC compared to that in those with the NC of the lowest quartile (third quartile: odds ratio [OR] = 1.314, 95% confidence interval [CI]: 1.029 – 1.676; the highest quartile: OR = 1.512, 95%CI: 1.131 – 2.022) and in the female elderly with higher WHtR compared to that in those with the WHtR of the lowest quartile (second quartile: OR = 1.214, 95%CI: 1.009 – 1.463; third quartile: OR = 1.289, 95%CI: 1.084 – 1.532; the highest quartile: OR = 1.503, 95%CI: 1.223 – 1.846); the analysis also demonstrated that the risk of hypertension decreased in the male elderly with higher WHtR (the second quartile vs. the lowest quartile: OR = 0.636, 95%CI: 0.469 – 0.863). After adjusting for confounding factors mentioned above, the results of restricted cubic spline analysis revealed a linear dose-response relationship between NC and hypertension risk in both the male and the female elderly (χ2 = 94.62 and 128.22, both P < 0.001). ConclusionThere is a positive linear correlation between NC and the risk of hypertension among the elderly in Zhongshan City.

Abstract Background Myocardial ischemia (MI) can cause angina, myocardial infarction, and even death. Angiogenesis is beneficial for ensuring oxygen and blood supply to ischemic tissue, promoting tissue repair, and reducing cell damage. In this study, we evaluated the effects of Salvianolic acid B (Sal B) against myocardial ischemia and explored its underlying mechanism on autophagy. Methods The anti-apoptosis effect of Sal B was conducted by staining Annexin V-FITC/PI and Hoechst as well as evaluating apoptosis bio-markers at protein level in H9c2 cells at glucose deprivation condition. HUVECs were co-cultured with H9c2, and the tube formation assay was used to monitor Sal B’s impact on angiogenesis. The MI model of mice was induced by intraperitoneal injection of isoproterenol (ISO). The effect of Sal B on MI mice was evaluated by HE, Masson, immunohistochemistry, WB and kits. In addition, Atg5 siRNA was applied to verify whether the protective effect of Sal B was regulated to autophagy. Results In H9c2, Sal B reduced the levels of lactate dehydrogenase (LDH), malondialdehyde (MDA) and reactive oxygen species (ROS), improved the levels of superoxide dismutase (SOD) and mitochondrial membrane potential, downregulated the expressions of Bax and cleaved-Caspase3, upregulated the expression of Bcl-2. Therefore, Sal B could significantly inhibit the damage of H9c2 caused by glucose deprivation. In the co-culture system of H9c2 and HUVECs, vascular endothelial growth factor (VEGF) level in the supernatant was dramatically raised by Sal B. Sal B upregulated the expressions of VEGF, platelet derived growth factor (PDGF) and endothelial marker CD31. It implied that Sal B exerted a significant pro-angiogenic effect. Moreover, Sal B increased the expression of LC3, Atg5, and Beclin1, while reducing the level of P62. When the expression of Atg5 was inhibited, the protective effects of Sal B on apoptosis and angiogenesis was reversed. Conclusions Sal B inhibited cardiomyocyte apoptosis and promoted angiogenesis by regulating autophagy, thereby improving MI.

In this study, we used the Sanya Incoherent Scatter Radar (SYISR) to observe the altitude profiles of traveling ionospheric disturbances (TIDs) during a moderate magnetic storm from 13 to 15 March 2022. Three TIDs were recorded, including two large-scale TIDs (LSTIDs) and one medium-scale TID (MSTID). These LSTIDs occurred during the storm recovery phase, characterized by periods of ~110–155 min, downward phase velocities of 22–60 m/s, and a relative amplitude of 17–25%. A nearly vertical front was noted at ~350–550 km, differing from AGW theory predictions. This structure is more attributed to the combined effects of sunrise-induced electron density changes and pre-sunrise uplift. Moreover, GNSS observations linked this LSTID to high-latitude origins, indicating a connection to polar magnetic storm excitation. However, the second LSTID was observed at lower altitudes (150–360 km) with a higher elevation angle (~17°). This LSTID, observed by the SYISR, was absent in the GNSS data from mainland China and Japan, suggesting a potential local source. The MSTID exhibited a larger relative amplitude of 29–36% at lower altitudes (130–210 km) with severe upward attenuation. The MSTID may be related to atmospheric gravity waves from the lower atmosphere. AGWs are considered to be the perturbation source for this MSTID event.

As a significant global issue, aging is prompting people’s interest in the potential anti-aging properties of Anoectochilus roxburghii (A. roxburghii), a plant traditionally utilized in various Asian countries for its purported benefits in treating diabetes and combating aging. However, the specific anti-aging components and mechanisms of A. roxburghii remain unclear. This study aims to investigate the anti-aging effects and mechanisms of A. roxburghii extract E (ARE). Caenorhabditis elegans (C. elegans) were exposed to media containing different concentrations of ARE whose superior in vitro radical scavenging capacity was thus identified. Lifespan assays, stress resistance tests, and RT-qPCR analyses were conducted to evaluate anti-aging efficacy, reactive oxygen species (ROS) levels, antioxidant enzyme activity, and daf-16, sod-3, and gst-4 levels. Additionally, transcriptomic and metabolomic analyses were performed to elucidate the potential anti-aging mechanisms of ARE. Fluorescence protein assays and gene knockout experiments were employed to validate the impacts of ARE on anti-aging mechanisms. Our results revealed that ARE not only prolonged the lifespan of C. elegans but also mitigated ROS and lipofuscin accumulation, and boosted resistance to UV and heat stress. Furthermore, ARE modulated the expression of pivotal anti-aging genes including daf-16, sod-3, and gst-4, facilitating the nuclear translocation of DAF-16. Significantly, ARE failed to extend the lifespan of daf-16-deficient C. elegans (CF1038), indicating its dependency on the daf-16/FoxO signaling pathway. These results underscored the effectiveness of ARE as a natural agent for enhancing longevity and stress resilience to C. elegans, potentially to human.

Hematite (α-Fe2O3) is widely used in sensor sensitization due to its excellent optical properties. In this study, we present a sensitivity-enhanced surface plasmon resonance alcohol sensor based on Fe2O3/Au. We describe the fabrication process of the sensor and characterize its structure. We conduct performance testing on sensors coated multiple times and use solutions with the same gradient of refractive indices as the sensing medium. Within the refractive index range of 1.3335–1.3635, the sensor that was coated twice achieved the highest sensitivity, reaching 2933.2 nm/RIU. This represents a 30.26% enhancement in sensitivity compared to a sensor with a pure gold monolayer film structure. Additionally, we demonstrated the application of this sensor in alcohol concentration detection by testing the alcohol content of common beverages, showing excellent agreement with theoretical values and highlighting the sensor’s potential in food testing.

Background and objective Idiopathic pulmonary fibrosis (IPF) is an idiopathic chronic, progressive interstitial lung disease with a diagnosed median survival of 3-5 years. IPF is associated with an increased risk of lung cancer. Therefore, exploring the shared pathogenic genes and molecular pathways between IPF and lung adenocarcinoma (LUAD) holds significant importance for the development of novel therapeutic approaches and personalized precision treatment strategies for IPF combined with lung cancer. Methods Bioinformatics analysis was conducted using publicly available gene expression datasets of IPF and LUAD from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis was employed to identify common genes involved in the progression of both diseases, followed by functional enrichment analysis. Subsequently, additional datasets were used to pinpoint the core shared genes between the two diseases. The relationship between core shared genes and prognosis, as well as their expression patterns, clinical relevance, genetic characteristics, and immune-related functions in LUAD, were analyzed using The Cancer Genome Atlas (TCGA) database and single-cell RNA sequencing datasets. Finally, potential therapeutic drugs related to the identified genes were screened through drug databases. Results A total of 529 shared genes between IPF and LUAD were identified. Among them, SULF1 emerged as a core shared gene associated with poor prognosis. It exhibited significantly elevated expression levels in LUAD tissues, concomitant with high mutation rates, genomic heterogeneity, and an immunosuppressive microenvironment. Subsequent single-cell RNA-seq analysis revealed that the high expression of SULF1 primarily originated from tumor-associated fibroblasts. This study further demonstrated an association between SULF1 expression and tumor drug sensitivity, and it identified potential small-molecule drugs targeting SULF1 highly expressed fibroblasts. Conclusions This study identified a set of shared molecular pathways and core genes between IPF and LUAD. Notably, SULF1 may serve as a potential immune-related biomarker and therapeutic target for both diseases.

Hydrogen embrittlement is a serious phenomenon resulting in severe ductility deterioration of engineering materials due to the presence of hydrogen atoms. The low concentration of dissolved oxygen in deep-sea provide the condition for hydrogen production. Herein, the hydrogen permeation behavior in X70 pipeline steel in acid/alkaline environment under different hydrostatic pressure were investigated via electrochemical hydrogen permeation parameters. The results revealed the different trends of i∞ with increasing hydrostatic pressure. The phenomenon was described from the perspectives of hydrogen generation, absorption/desorption and permeation process by potentiodynamic polarization, linear sweep voltammetry (LSV) and EIS tests. The experimental permeation data were fitted with surface effect model and leads to the conclusion that the hydrostatic pressure greatly enhanced the adsorption rate and restricts the desorption rate of absorbed hydrogen atoms on the metal surface, thereby the process of atomic hydrogen compounding into hydrogen molecules is inhibited, leading to an increase in sub-surface hydrogen concentration (C0).

The effect of La3+ on the hydrogen permeation behavior of 27CrMo44S/1 steel in acidic environments containing H2S is investigated through the measurement of steady-state permeation current density (i∞), hydrogen diffusivity (D), and subsurface hydrogen concentration (C0). Results indicate that the addition of La3+ can remarkably reduce i∞. The corrosion products with La3+ involved in the film formation process in the H2S-free environment have a good hydrogen barrier effect, but the addition of La3+ hardly influence the D value of 27CrMo44S/1 steel in the H2S-containing environment. However, the presence of La3+ substantially reduces the C0 on metal surface regardless of the presence of H2S in the solution. Static immersion and tensile experiments illustrate that the addition of La3+ can improve the corrosion resistence and plasticity loss of the material in the H2S environment.

In order to comprehend the underlying mechanisms contributing to the development and exacerbation of asthma resulting from exposure to fine particulate matter (PM2.5), we established an asthmatic model in fat mass and obesity-associated gene knockdown mice subjected to PM2.5 exposure. Histological analyses using hematoxylin-eosin (HE) and Periodic Acid-Schiff (PAS) staining revealed that the down-regulation of the fat mass and obesity-associated gene (Fto) expression significantly ameliorated the pathophysiological alterations observed in asthmatic mice exposed to PM2.5. Furthermore, the down-regulation of Fto gene expression effectively attenuated damage to the airway epithelial barrier. Additionally, employing in vivo and in vitro models, we elucidated that PM2.5 modulated FTO expression by inducing oxidative stress. Asthmatic mice exposed to PM2.5 exhibited elevated Fto expression, which correlated with increased levels of reactive oxygen species. Similarly, when cells were exposed to PM2.5, FTO expression was up-regulated in a ROS-dependent manner. Notably, the administration of N-acetyl cysteine successfully reversed the PM2.5-induced elevation in FTO expression. Concurrently, we performed transcriptome-wide Methylated RNA immunoprecipitation Sequencing (MeRIP-seq) analysis subsequent to PM2.5 exposure. Through the implementation of Gene Set Enrichment Analysis and m6A-IP-qPCR, we successfully identified inhibitor of nuclear factor kappa B kinase subunit beta (IKBKB) as a target gene regulated by FTO. Interestingly, exposure to PM2.5 led to increased expression of IKBKB, while m6A modification on IKBKB mRNA was reduced. Furthermore, our investigation revealed that PM2.5 also regulated IKBKB through oxidative stress. Significantly, the down-regulation of IKBKB effectively mitigated epithelial barrier damage in cells exposed to PM2.5 by modulating nuclear factor-kappa B (NF-κB) signaling. Importantly, we discovered that decreased m6A modification on IKBKB mRNA facilitated by FTO enhanced its stability, consequently resulting in up-regulation of IKBKB expression. Collectively, our findings propose a novel role for FTO in the regulation of IKBKB through m6A-dependent mRNA stability in the context of PM2.5-induced oxidative stress. Therefore, it is conceivable that the utilization of antioxidants or inhibition of FTO could represent potential therapeutic strategies for the management of asthma exacerbated by PM2.5 exposure.

Hakka rice wine is produced from grains by co-fermentation with abundant microbes in an open fermentation environment. Indigenous microbiota and enzymes convert the nutrients in grains into flavor compounds through enzymatic biochemical reactions and microbial metabolism. High-throughput sequencing technology revealed that non-Saccharomyces yeasts dominated the traditional fermentation process, with genera such as Kodamaea ohmeri, Candida orthopsilosis, and Trichosporon asteroides forming a dynamic community that highly correlated with the evolution of 80 volatile compounds in Hakka rice wine. Among the 104 volatile compounds detected by GC–MS, 22 aroma-active compounds with relative odor activity values (ROAV) > 1 were quantified, 11 of which made significant contributions (P

Introduction Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA) are prevalent respiratory diseases in China and impose significant burdens on the healthcare system. Moreover, the co-occurrence of COPD and OSA exacerbates clinical outcomes significantly. However, comprehensive epidemiological investigations in China remain scarce, and the defining characteristics of the population affected by COPD and OSA, alongside their intrinsic relationship, remain ambiguous.Methods and analysis We present a protocol for a prospective, multicentre, observational cohort study based on a digital health management platform across three different healthcare tiers in five sites among Chinese patients with COPD. The study aims to establish predicative models to identify OSA among patients with COPD and to predict the prognosis of overlap syndrome (OS) and acute exacerbations of COPD through the Internet of Things (IoT). Moreover, it aims to evaluate the feasibility, effectiveness and cost-effectiveness of IoT in managing chronic diseases within clinical settings. Participants will undergo baseline assessment, physical examination and nocturnal oxygen saturation measuring. Specific questionnaires screening for OSA will also be administered. Diagnostic lung function tests and polysomnography will be performed to confirm COPD and OSA, respectively. All patients will undergo scheduled follow-ups for 12 months to record the changes in symptoms, lung functions and quality of life. Primary outcomes include the prevalence and characteristics of OS, while secondary outcomes encompass OS prognosis and the feasibility of the management model in clinical contexts. A total of 682 patients with COPD will be recruited over 12–24 months.Ethics and dissemination The study has been approved by Peking University Third Hospital, and all study participants will provide written informed consent. Study results will be published in an appropriate journal and presented at national and international conferences, as well as relevant social media and various stakeholder engagement activities.Trial registration number NCT04833725.

ObjectiveThis study aimed to explore the phenolic compounds (PCs) present in three Chinese olive (Canarium album L.) cultivars and the contribution of these PCs to the anti-inflammatory activities of the cultivars.MethodsUltra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap/mass spectrometry (UPLC-Q-Exactive/MS) was used to identify and quantify the PCs present in three Chinese olive cultivars, “Na zhong,” “Tan xiang,” and “Xiang zhong”. 2,2-diphenyl-1-picrylhydrazyl (DPPH); 2,2′-azinobis (3-ethylbenzothiazoline 6-sulfonate) (ABTS); and oxygen radical absorption capacity (ORAC) assays were used to assess the antioxidant activities of the PCs. Furthermore, we analyzed the anti-inflammatory action of these PCs using lipopolysaccharide (LPS)-induced RAW264.7 cells.ResultsA total of 44 PCs were identified in the three cultivars. Of these, 17 PCs were previously unidentified in Chinese olive. Among the cultivars, the free phenolics (FPs) of “Tan xiang” showed the strongest antioxidant activity. All cultivars have shown significant inhibition of TNF-α and IL-6 production. Clustering correlation analysis showed galloyl-bis-HHDP-glucose and paeonol have significant anti-inflammatory ability in FPs. Quininic, galloylquinic acid, 4-hydroxycinnamic acid and gallic acid hexoside have shown significant inhibition of IL-6 production in BPs. Furthermore, gallic acid, catechin, syringic acid, and nobiletin exhibit negative correlation in FPs and positive correlation in BPs of cytokine production, while corilagin and methyl ellagic acid pentoside exhibited opposite correlation.ConclusionIn summary, this study contributed to the literature on PCs in Chinese olives and the potential health benefits of FPs and BPs.

Fibrotic hypersensitivity pneumonitis (FHP) is a fatal interstitial pulmonary disease with limited treatment options. Lung macrophages are a heterogeneous cell population that exhibit distinct subsets with divergent functions, playing pivotal roles in the progression of pulmonary fibrosis. However, the specific macrophage subpopulations and underlying mechanisms involved in the disease remain largely unexplored. In this study, a decision tree model showed that matrix metalloproteinase-14 (MMP14) had higher scores for important features in the up-regulated genes in macrophages from mice exposed to the Saccharopolyspora rectivirgula antigen (SR-Ag). Using single-cell RNA sequencing (scRNA-seq) analysis of hypersensitivity pneumonitis (HP) mice profiles, we identified MMP14high macrophage subcluster with a predominant M2 phenotype that exhibited higher activity in promoting fibroblast-to myofibroblast transition (FMT). We demonstrated that suppressing toll-like receptor 2 (TLR2) and nuclear factor kappa-B (NF-κB) could attenuate MMP14 expression and exosome secretion in macrophages stimulation with SR-Ag. The exosomes derived from MMP14-overexpressing macrophages were found to be more effective in regulating the transition of fibroblasts through exosomal MMP14. Importantly, it was observed that the transfer of MMP14-overexpressing macrophages into mice promoted lung inflammation and fibrosis induced by SR-Ag. NSC-405020 binding to the hemopexin domain (PEX) of MMP-14 ameliorated lung inflammation and fibrosis induced by SR-Ag in mice. Thus, MMP14-overexpressing macrophages may be an important mechanism contributing to the exacerbation of allergic reactions. Our results indicated that MMP14 in macrophages has the potential to be a therapeutic target for HP.

The design of non-eddy-resolving numerical models requires a good understanding and an appropriate representation of the eddy-mean flow feedback. To understand this feedback, we propose a diagnostic framework that links eddy geometry with the eddy-mean energy exchange terms in the Lorenz energy diagram. This framework provides explicit mathematical formulas that link eddy-mean energy exchange rates with both the mean state structure and the properties of eddy momentum ellipses and eddy buoyancy ellipses. Considering that the mean flow contains both along- and cross-stream variations, we decompose the eddy-mean kinetic energy exchange term into 3 components: one associated with the cross-stream variation in mean flow (MC), one associated with the along-stream variation in mean flow (MA), and one associated with the variation in mean flow (MR). We also state the corresponding geometric formulas. The geometric interpretation of MC is consistent with barotropic instability theories and the literature on eddy geometry. As for MA, the weakening (strengthening) of mean flow in the along-stream direction corresponds to eddy kinetic energy generation (decay) through MA. MA and a portion of MR are related under the quasi-geostrophic assumption. From a global integral perspective, both the along-stream and cross-stream variations in the mean flow contribute considerably to eddy-mean kinetic energy exchange. At the Kuroshio Extension, both the mean state energy level and eddy energy level are key to shaping the spatial pattern of eddy-mean energy exchange. This framework offers a tool for geometrically interpreting eddy-mean energy exchange, which may offer guidance for eddy parameterizations.

In the biotechnological industry, multicopy gene integration represents an effective strategy to maintain a high-level production of recombinant proteins and to assemble multigene biochemical pathways. In this study, we developed copper-induced in vivo gene amplification in budding yeast for multicopy gene expressions. To make copper as an effective selection pressure, we first constructed a copper-sensitive yeast strain by deleting the CUP1 gene encoding a small metallothionein-like protein for copper resistance. Subsequently, the reporter gene fused with a proline–glutamate–serine–threonine-destabilized CUP1 was integrated at the δ sites of retrotransposon (Ty) elements to counter the copper toxicity at 100 μM Cu2+. We further demonstrated the feasibility of modulating chromosomal rearrangements for increased protein expression under higher copper concentrations. In addition, we also demonstrated a simplified design of integrating the expression cassette at the CUP1 locus to achieve tandem duplication under high concentrations of copper. Taken together, we envision that this method of copper-induced in vivo gene amplification would serve as a robust and useful method for protein overproduction and metabolic engineering applications in budding yeast.

ObjectiveThis study aimed to evaluate the effectiveness and safety of carbon nanoparticles-guided lymph node dissection during thyroidectomy in patients with papillary thyroid cancer(PTC).MethodsClinical trials consisted of two subgroups: unilateral lobectomy (UL; n=283) and total thyroidectomy (TT; n=286). From each subgroup, the patients were randomly assigned to two groups: the carbon nanoparticle group and control group. Primary endpoints included parathyroid hormone (PTH) levels, number of lymph nodes (LNs) detected, number of tiny lymph nodes detected, and recognition and retention of the parathyroid glands. Secondary endpoint was recognition and protection of the recurrent laryngeal nerve.ResultsA total of 569 patients with PTC were recruited. There were no statistically significant differences in demographics between the carbon nanoparticles and control groups (P > 0.05). In the UL subgroup, there were no significant differences in PTH levels between the two groups at preoperative, intraoperative, and postoperative day one, and postoperative month one (P>0.05). There was no significant difference in the serum Ca2+ levels between the two groups preoperatively and at postoperative month one (P>0.05). The number of lymph nodes dissected in the carbon nanoparticles group was significantly higher than that in the control group (P0.05). However, the mean PTH level in the carbon nanoparticles group was significantly higher than that of the control group at postoperative month one (P=0.0368). There was no significant difference in the serum Ca2+ levels between the two groups preoperatively and at postoperative month one (P>0.05). There were no significant differences between the two groups in the number of dissected LNs (P>0.05) or the detection rate of tiny lymph nodes (P>0.05). No drug-related AE and complications due to the injection of carbon nanoparticles were recorded in this study. There were no significant differences between the two groups in terms of parathyroid preserved in situ and recurrent laryngeal nerve injury in the UL and TT subgroups.ConclusionsCarbon nanoparticles demonstrated efficacy and safety in thyroidectomy. The application of carbon nanoparticles could significantly facilitate the identification and clearance of LNs and the optimum preservation of parathyroid function.Clinical trial registrationhttps://www.chictr.org.cn/, identifier ChiCTR2300068502.

Chronic noise exposure is correlated with gut microbiota dysbiosis and glucose and lipid metabolism disorders. However, evidence on the mechanisms underlying of gut microbiota alterations in chronic noise induced glucose and lipid metabolism disorders is limited, and the potential aftereffects of chronic noise exposure on metabolic disorders remain unclear. In present study, we established chronic daytime and nighttime noise exposure mice models to explore the effects and underlying mechanism of gut microbiota on chronic noise-induced glucose and lipid metabolism disorders. The results showed that exposure to chronic daytime or nighttime noise significantly increased the fasting blood glucose, serum and liver TG levels, impaired glucose tolerance, and decreased serum HDL-C levels and liver TC levels in mice. However, after 4 weeks of recovery, only serum TG of mice in nighttime noise recovery group remained elevated. Besides, exposure to chronic noise reduced the intestinal tight junction protein levels and increased intestinal permeability, while this effect did not completely dissipate even after the recovery period. Moreover, chronic noise exposure changed the gut microbiota and significantly regulated metabolites and metabolic pathways, and further activate hepatic gluconeogenesis CRTC2/CREB-PCK1 signaling pathway and lipid synthesis SREBP1/SCD signaling pathway through intestinal hepatic axis. Together, our findings demonstrated that chronic daytime and nighttime noise exposure could cause the glucose and lipid metabolism disorder by modulating the gut microbiota and serum metabolites, and activating hepatic gluconeogenic CREB/CRTC2-PCK1 signaling and lipid synthesis SREBP1/SCD signaling pathway. The potential aftereffects of noise exposure during wakefulness on metabolic disorders are more significant than that of noise exposure during sleep.