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Abstract Stomach adenocarcinoma (STAD) is known for its high prevalence and poor prognosis, which underscores the need for novel therapeutic targets. Peroxidasin (PXDN), an enzyme with peroxidase activity, has been linked to cancer development in previous studies. However, its specific role in STAD is not well understood. In our study, we used public databases and clinical specimens to determine that PXDN expression is significantly elevated in STAD tissues and serves as an independent prognostic marker for patient outcomes. Our in vitro assays demonstrated that silencing PXDN significantly reduced STAD cell proliferation, invasion, and migration. Mechanistically, we found that PXDN promotes epithelial‒mesenchymal transition and angiogenesis in STAD cells and may be regulated by the PI3K/AKT pathway. Further analysis revealed that PXDN levels affect the sensitivity of STAD cells to various chemotherapeutic and small molecule drugs. Additionally, we observed a significant association between PXDN levels and the abundances of various immune cell types in patients with STAD. Our study highlighted a strong link between PXDN levels and the tumor immune microenvironment (TIM), suggesting that PXDN is a useful metric for evaluating the response to immune checkpoint inhibitors. Moreover, we found that PXDN is significantly associated with multiple immune checkpoints. In summary, our findings indicate that PXDN plays a critical role in STAD and that its level could serve as a potential prognostic biomarker. Thus, targeting PXDN may represent an effective treatment strategy for STAD.

Sesame is a widely cultivated crop in China, which contains a large amount of fat and protein, as well as dietary fiber, sesame lignans,γ- Aminobutyric acid(GABA) and other active nutrients. In recent years, many studies have pointed out that GABA and sesamol from sesamin could possess anxiolytic and anti-inflammatory properties, but their specific roles and mechanisms during foodborne pathogenic bacterial infections remain unexplored. We analyzed the extract obtained from ethanol-soaked germinated sesame and found that the contents of sesamol and GABA were 6 times and 4 times higher, respectively, compared to non-germinated sesame. Constructing an animal model by infecting mice with Salmonella typhimurium SL1344, and exploring the effects of germinating sesame extract, sesamol, and GABA on Salmonella typhimurium infection in mice. It was found that germinating sesame extract could reduce weight loss in Salmonella infected mice, and improve anxiety behavior in Salmonella infected mice. Germinating sesame extract also reduced Salmonella infection in mouse spleen, and increased colon villus length and mucin content in Salmonella infected mice, which could inhibit colitis factors, and increase acetic acid and propionic acid content in feces. Germinated sesame extract alleviated anxiety and protected the gut in mice infected with Salmonella. This study was aimed to provide a theoretical reference for dietary intervention to alleviate anxiety and protect the gut.

Fe-4.5 wt% Si electrical steel is an exceptional soft magnetic material whose outstanding magnetic characteristics are significantly influenced by its texture. This work utilized ND type columnar grains (columnar grains is parallel to the normal direction), as the initial material to fabricate non-oriented 4.5 wt%Si electrical steel exhibiting superior magnetic characteristics. The EBSD technique was utilized to investigate the structural and textural evolution during hot rolling, normalizing, warm rolling, and annealing. Concentrate on the deformation and recrystallization characteristics of cube-oriented grains. The empirical data clearly indicated that ND type columnar grains display considerable initial organization and texture dependence during deformation and recrystallization processes. The robust cube-oriented grains that develop post-annealing originate from the retention of the original strong cube texture and the directional nucleation within the {100} shear band. With an increase in annealing temperature, cube-oriented grains demonstrate aberrant development due to the augmented mobility of high-energy grain boundaries. The experimental steel has optimum magnetic characteristics during annealing at 1000 °C, due to its homogeneous organization, increased grain size, and robust λ(∥ND) texture. The findings of this experiment can furnish a data foundation and theoretical backing for the fabrication of high-performance 4.5 wt% Si non-oriented electrical steel.

Abstract Immune checkpoint blockade therapy has revolutionized cancer treatment, but resistance remains prevalent, often due to dysfunctional tumor-infiltrating lymphocytes. A key contributor to this dysfunction is mitochondrial dysfunction, characterized by defective oxidative phosphorylation, impaired adaptation, and depolarization, which promotes T cell exhaustion and severely compromises antitumor efficacy. This review summarizes recent advances in restoring the function of exhausted T cells through mitochondria-targeted strategies, such as metabolic remodeling, enhanced biogenesis, and regulation of antioxidant and reactive oxygen species, with the aim of reversing the state of T cell exhaustion and improving the response to immunotherapy. A deeper understanding of the role of mitochondria in T cell exhaustion lays the foundation for the development of novel mitochondria-targeted therapies and opens a new chapter in cancer immunotherapy.

Abstract Background Echinocandin B (ECB) is a key precursor of the antifungal drug anidulafungin and its biosynthesis occurs via ani gene cluster in Aspergillus nidulans NRRL8112. Strain improvement for industrial ECB production has mainly relied on mutation breeding due to the lack of genetic tools. Results Here, a CRISPR-base-editing tool was developed in A. nidulans NRRL8112 for simultaneous inactivation of the nkuA gene and two marker genes, pryoA and riboB, which enabled efficient genetic manipulation. Then, in-vivo plasmid assembly was harnessed for ani gene expression screening, identifying the rate-limiting enzyme AniA and a pathway-specific transcription factor AniJ. Stepwise titer enhancement was achieved by overexpressing aniA and/or aniJ, and ECB production reached 1.5 g/L during 5-L fed-batch fermentation, an increase of ~ 30-fold compared with the parent strain. Conclusion This study, for the first time, revealed the regulatory mechanism of ECB biosynthesis and harnessed genetic engineering for the development of an efficient ECB-producing strain.

Abstract Suppression of energy disorders in the vertical direction of a photovoltaic device, along which charge carriers are forced to travel, has been extensively studied to reduce unproductive charge recombination and thus achieve high-efficiency perovskite solar cells. In contrast, energy disorders in the lateral direction of the junction for large-area modules are largely overlooked. Herein, we show that the micro-inhomogeneity characteristics in the surface lateral energetics of formamidinium (FA)-based perovskite films also significantly influence the device performance, particularly with accounting for the stability and scale-up aspects of the devices. By using organic amidinium passivators, instead of the most commonly used organic ammonium ones, the micro-inhomogeneity in the lateral energy landscapes can be suppressed, greatly improving device stability and efficiency of FA-based single-junction perovskite solar cells.

Abstract Purpose Retraction of the hepatic left lateral segment (HLLS) is a crucial maneuver for surgical field exposure during laparoscopic gastrectomy with systematic lymphadenectomy. Though various methods of retraction are available, there is no perfect solution. Here, we report the results of our initial 42 cases with HLLS inversion method and discuss the feasibility, safety, effectiveness and technical aspects of this method. Methods The intraoperative and postoperative short-term outcomes of 42 patients who underwent HLLS inversion during laparoscopic total gastrectomy and proximal gastrectomy in our department September, 2023 to January, 2024 were reviewed. HLLS inversion was performed by mobilizing the HLLS and inverting it to the right supra-hepatic space through an incision at the falciform ligament. Results 42 patients underwent HLLS inversion successfully with an average time of 13.9 min. 7 patients needed re-inversion due to slipping back of the HLLS during operation. Optimal exposure of the surgical field was achieved in all patients. No intra-operative complications occurred, except for 1 patient presented with mild intraoperative hepatic hemorrhage requiring electrocoagulation for hemostasis. Alanine aminotransferase and glutamine aminotransferase elevated in some patients on postoperative day 1(POD1), but declined to preoperative levels on the 7th postoperative day. There were no Clavien-Dindo II grade or higher digestive complications after surgery. In 5 patients with preservation the hepatic branch of the vagus nerve, the contractile function of the gall bladder was intact or slightly impaired 2 weeks after operation. Conclusion For laparoscopic proximal gastrectomy (LPG) and laparoscopic total gastrectomy (LTG), HLLS inversion is a feasible method for optimizing visualization of the surgical field with preservation of the function of the hepatic branch of the vagus nerve. It is safe and acceptable as to the manipulation time. Re-inversion is easy and effective even in case of failure of inversion. HLLS inversion seems to be a promising technique for retraction of the liver during laparoscopic gastrectomy.

Abstract This study explored the factors influencing serum 25(OH)D3 levels and the effects of Vitamin D deficiency (VDD) and VD supplementation on 25(OH)D3 levels and neuropsychobehavioral development in premature infants, to provide a theoretical basis for improving their prognosis. Physical examination, neuropsychobehavioral development and serum 25(OH)D3 levels were assessed regularly in 158 preterm infants supplemented with VD formulation. 25(OH)D3 levels were analyzed at 3, 6, 9, 12, and 18 months after birth. The Gesell neuropsychological development test was conducted at 6, 9, 12, and 18 months after birth to obtain the developmental quotient (DQ). Based on the serum 25(OH)D3 levels at 42 days of age, the infants were divided into VDD and non-VDD groups. Preterm infants in the VDD group were supplemented with more VD until their 25(OH)D3 levels were normal, and were divided into sustained VDD (SVDD) and corrected VDD (CVDD) groups according to serum 25(OH)D3 levels at 3 months of age. Appropriate statistical methods were chosen to compare differences in 25(OH)D3 and DQ between or among different groups, screen for the factors influencing 25(OH)D3 levels in preterm infants at 42 days of age, and analyze the relationship between 25(OH)D3 and DQ. The 25(OH)D3 levels of preterm infants at 42 days of age were positively correlated with VD supplementation during pregnancy, and before 42 days after birth (P

Abstract Background Balance and mobility deficits are major concerns in stroke rehabilitation. Virtual reality (VR) training and Swiss-ball training are commonly used approaches to improve balance and mobility. However, no study has compared the efficacy of VR training, Swiss-ball training, and their combination in improving balance and mobility function or investigated cortical activation and connectivity in individuals with stroke. Methods A prospective, single-blinded, parallel-armed, multi-center randomized controlled trial with factorial design will be conducted. Seventy-six participants aged 30–80 years with stroke will be recruited. Participants will be allocated to one of the four groups: (A) the VR training + Swiss-ball training + conventional physical therapy group; (B) the Swiss-ball training + conventional physical therapy group; (C) the VR training + conventional physical therapy group; or (D) the conventional physical therapy group. All participants will receive 50 min of training per day, 5 times per week, for a total of 4 weeks. The primary outcomes will be balance and mobility measures. Secondary outcomes will include the 10-min walk test, dynamic gait index, and cortical activation. Outcomes will be measured on three occasions: at baseline, after the training, and at the 4-week follow-up. Discussion This trial will provide evidence to determine whether there are differences in clinical outcomes and cortical activation following two different types of exercise programs and their combination, and to elucidate the recovery mechanisms of balance and mobility function in individuals with stroke. Trial registration Chinese Clinical Trial Registry reference: www.chictr.org.cn (No. ChiCTR2400082135). Registered on May 24, 2024.

Abstract Tuberculous meningitis (TBM) is a fatal tuberculosis caused by a large number of Mycobacterium tuberculosis (M. tuberculosis) spread by blood flow, with a case fatality rate of more than 50%. It is one of the most serious complications of miliary tuberculosis (MT), whose incidence is closely related to MT. If doctors can provide early diagnosis and active treatment for TBM, the case fatality rate will be significantly reduced. At present, there is a lack of methods to predict the progression of MT to TBM in clinic. To explore whether MT cases will experience TBM, we propose an early screening model of miliary tuberculosis with tuberculous meningitis (MT-TBM) based on few-shot learning with multiple windows and feature granularities (MWFG). This model aims to screen potential TBM cases through chest computerized tomography (CT) images of MT cases. Chest CT is a routine examination for MT cases. The MWFG module can extract more comprehensive features from a set of CT images of each MT case. The softmax classifier with adaptive regularization is trained on the cooperation of support set and query set, which can effectively prevent overfitting. Experiments on a dataset of 40 MT cases with chest CT images established by the medical records demonstrate that our proposed model achieves state-of-the-art performance in the early screening of MT-TBM. It can establish the connection between MT and MT-TBM through chest CT images of MT cases. The early screening model of MT-TBM based on few-shot learning with MWFG fills the research gap in computer-aided predicting TBM and has certain clinical effects. This research can provide some reference for clinicians in early diagnosis of MT-TBM and help clinicians in the early prevention and treatment of TBM for MT patients.

Abstract Background This study explored the significance of consolidation maintenance chemotherapy after concurrent chemoradiotherapy with different regimens in patients with esophageal squamous cell carcinoma. Method A prospective randomized controlled phase III clinical trial was designed and registered in the China Clinical Trials Registry (Registration number: ChiCTR‐TRC‐12002719). Survival data were analyzed in terms of intention‐to‐treat (ITT) and per‐protocol (PP) sets for patients undergoing cisplatin and 5‐fluorouracil (PF) (group A), or cisplatin and paclitaxel (TP) (group B). Results The incidence risk of grade III–IV leukopenia in group B was higher than in group A (49.2% vs. 25.5%, p = 0.012). The survival rates at 1, 2, 3, and 5 years were 83.8%, 62.6%, 53.1%, and 41.3%, respectively. Consolidation chemotherapy after concurrent chemoradiation therapy had no benefit on median progression‐free survival (PFS) (p = 0.95) and overall survival (OS) (p = 0.809). According to the ITT analysis, the median PFS in group A and group B was 28.6 months and 30.3 months (X2 = 0.242, p = 0.623), while the median OS was 31.0 months and 50.3 months (X2 = 1.25，p = 0.263). For the PP analysis, the median PFS in group A and group B were 28.6 months and 30.3 months (p = 0.584), while the median OS was 31.0 months and 50.3 months (p = 0.259), respectively. Patients receiving consolidation chemotherapy did not show significant OS benefits (46.9 months vs. 38.3 months; X2 = 0.059, p = 0.866). Conclusion Similar PFS and OS were found between PF and TP regimens with concurrent chemoradiotherapy. Consolidation chemotherapy did not show any significant OS benefits.

A reliable suspension-based platform for scaling engineered cardiac tissue (ECT) production from human induced pluripotent stem cells (hiPSCs) is crucial for regenerative therapies. Here, we compared the production and functionality of ECTs formed using our scaffold-based, engineered tissue microsphere differentiation approach with those formed using the prevalent scaffold-free aggregate platform. We utilized a microfluidic system for the rapid (1 million cells/min), high density (30, 40, 60 million cells/ml) encapsulation of hiPSCs within PEG-fibrinogen hydrogel microspheres. HiPSC-laden microspheres and aggregates underwent suspension-based cardiac differentiation in chemically defined media. In comparison to aggregates, microspheres maintained consistent size and shape initially, over time, and within and between batches. Initial size and shape coefficients of variation for microspheres were eight and three times lower, respectively, compared to aggregates. On day 10, microsphere cardiomyocyte (CM) content was 27 % higher and the number of CMs per initial hiPSC was 250 % higher than in aggregates. Contraction and relaxation velocities of microspheres were four and nine times higher than those of aggregates, respectively. Microsphere contractile functionality also improved with culture time, whereas aggregate functionality remained unchanged. Additionally, microspheres displayed improved β-adrenergic signaling responsiveness and uniform calcium transient propagation. Transcriptomic analysis revealed that while both microspheres and aggregates demonstrated similar gene regulation patterns associated with cardiomyocyte differentiation, heart development, cardiac muscle contraction, and sarcomere organization, the microspheres exhibited more pronounced transcriptional changes over time. Taken together, these results highlight the capability of the microsphere platform for scaling up biomanufacturing of ECTs in a suspension-based culture platform.

Abstract Immune-mediated liver injury is a common characteristic of various liver diseases, including autoimmune and viral hepatitis. Here, we investigated the role of DEAD-box helicase 3, X-linked (DDX3X) in immune-mediated liver injury. Liver injury was induced in C57BL/6J mice via concanavalin A (Con A). DDX3X hepatocyte-specific knockout (DDX3XΔHep) mice and control (DDX3Xfl/fl) mice were utilized to investigate the role of DDX3X in liver injury. Primary hepatocytes were treated with tunicamycin (TM) to induce ER stress in vitro. The expression of DDX3X in patients with various liver diseases was evaluated. Hepatic DDX3X expression increased, and DDX3X translocated from the cytoplasm to the nucleus during Con A-induced liver injury. DDX3X deficiency ameliorated mouse liver injury and reduced ER stress in liver tissue. The inhibition of ER stress with 4-PBA significantly attenuated liver injury while decreasing DDX3X levels in liver tissue. However, the upregulation of hepatic DDX3X expression reversed Con A-induced liver injury and negated the protective effect of 4-PBA. Mechanistically, the nuclear translocation of DDX3X promoted ER stress-induced apoptosis through the transcriptional induction of CHOP. Moreover, DDX3X was elevated and translocated into the nucleus in patients with HBV-LF and AIH. Additionally, serum DDX3X levels markedly increased in patients with HBV-LF, and a consistent decrease in DDX3X was associated with a good prognosis. The cytoplasmic-to-nuclear translocation of DDX3X promotes ER stress-induced apoptosis, which is an obligatory step that drives hepatic necrosis and tissue damage. Notably, DDX3X is a potential therapeutic target for immune-mediated liver injury.

Abstract Currently, even the most effective anti-cancer therapies are often limited by the development of drug resistance and tumor relapse, which is a major challenge facing current cancer research. A deep understanding of the molecular and biochemical bases of drug efficacy that can help predict the clinical drug resistance, coupled with the evolution of systematic genomic and proteomic technologies, have facilitated studies identifying and elucidating the underlying mechanisms. In this review, we focus on several important issues on cancer drug resistance and provide a framework for understanding the common ways by which cancers develop resistance to therapeutic agents. With the increasing arsenal of novel anticancer agents and techniques, there are now unprecedented opportunities to understand and overcome drug resistance. The proteolysis targeting chimera (PROTAC) technology, immunotherapy, nanomedicine, and real-time monitoring of drug response all provide effective approaches for combating drug resistance. In addition to the advancement of therapeutic technologies, the revolution of treatment concept is also of great importance. We can take advantage of the interplay between drug sensitive and resistant subclones for combating cancer. However, there remains a long way to go in the protracted war against cancer drug resistance.

Abstract Background N6-Methyladenosine (m6A) methylation, a common form of RNA modification, play an important role in the pathogenesis of various diseases and in the ontogeny of organisms. Nevertheless, the precise function of m6A methylation in photoaging remains unknown. Objectives This study aims to investigate the biological role and underlying mechanism of m6A methylation in photoaging. Methods m6A dot blot, Real-time quantitative PCR (RT-qPCR), western blot and immunohistochemical (IHC) assays were employed to detect the m6A level and specific m6A methylase in ultraviolet ray (UVR)-induced photoaging tissue. The profile of m6A-tagged mRNA was identified by methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq analysis. Finally, we investigated the regulatory mechanism of KIAA1429 by MeRIP-qPCR, RNA knockdown and immunofluorescence assay. Results m6A levels were increased in photoaging and were closely associated with the upregulation of KIAA1429 expression. 1331 differentially m6A methylated genes were identified in the UVR group compared with the control group, of which 1192 (90%) were hypermethylated. Gene ontology analysis showed that genes with m6A hypermethylation and mRNA downregulation were mainly involved in extracellular matrix metabolism and collagen metabolism-related processes. Furthermore, KIAA1429 knockdown abolished the downregulation of TGF-bRII and upregulation of MMP1 in UVR-irradiated human dermal fibroblasts (HDFs). Mechanically, we identified MFAP4 as a target of KIAA1429-mediated m6A modification and KIAA1429 might suppress collagen synthesis through an m6A-MFAP4-mediated process. Conclusions The increased expression of KIAA1429 hinders collagen synthesis during UVR-induced photoaging, suggesting that KIAA1429 represents a potential candidate for targeted therapy to mitigate UVR-driven photoaging.

Abstract Abscisic acid (ABA) is the primary preventing factor of seed germination, which is crucial to plant survival and propagation. ABA-induced seed germination inhibition is mainly mediated by the dimeric PYR/PYL/RCAR (PYLs) family members. However, little is known about the relevance between dimeric stability of PYLs and seed germination. Here, we reveal that stabilization of PYL dimer can relieve ABA-induced inhibition of seed germination using chemical genetic approaches. Di-nitrobensulfamide (DBSA), a computationally designed chemical probe, yields around ten-fold improvement in receptor affinity relative to ABA. DBSA reverses ABA-induced inhibition of seed germination mainly through dimeric receptors and recovers the expression of ABA-responsive genes. DBSA maintains PYR1 in dimeric state during protein oligomeric state experiment. X-ray crystallography shows that DBSA targets a pocket in PYL dimer interface and may stabilize PYL dimer by forming hydrogen networks. Our results illustrate the potential of PYL dimer stabilization in preventing ABA-induced seed germination inhibition.

Integrated pest management is a pest control strategy that combines biological and chemical methods to reduce environmental pollution and protect biodiversity. Recent research indicated that the fear caused by predators had a significant effect on the growth, development, and reproductive processes of prey. Therefore, we have proposed a pest-natrual enemy system, which is a nonlinear state-dependent feedback control model that incorporated the fear effect in the predator-prey relationship. We discussed impulsive sets and phase sets of the model and derived an expression for the Poincaré map. Furthermore, we analyzed the existence and stability of order-$ 1 $ periodic solutions and explored the existence of order-$ k $ $ (k\ge2) $ periodic solutions. Finally, numerical simulations were conducted to validate our theoretical results and reveal their biological implications.

Abstract Background The prognosis nutritional index (PNI) and the systemic inflammatory immunological index (SII) are characteristic indicators of the nutritional state and the systemic inflammatory response, respectively. However, there is an unknown combined effect of these indicators in the clinic. Therefore, the practicality of using the SII-PNI score to predict prognosis and tumor response of locally advanced gastric cancer (LAGC) following chemotherapy was the main focus of this investigation. Methods We retrospectively analyzed 181 patients with LAGC who underwent curative resection after neoadjuvant chemotherapy in a prospective study (NCT01516944). We divided these patients into tumour regression grade(TRG) 3 and non-TRG3 groups based on tumor response (AJCC/CAP guidelines). The SII and PNI were assessed and confirmed the cut-off values before treatment. The SII-PNI values varied from 0 to 2, with 2 being the high SII (≥ 471.5) as well as low PNI (≤ 48.6), a high SII or low PNI is represented by a 1 and neither is represented by a 0, respectively. Results 51 and 130 samples had TRG3 and non-TRG3 tumor responses respectively. Patients with TRG3 had substantially higher SII-PNI scores than those without TRG3 (p

Abstract Background In cardiac surgical procedures, patients carrying high-risk profiles are prone to encompass complicated cardiopulmonary bypass (CPB) separation. Intraoperative transesophageal echocardiography (TEE), a readily available tool, is utilized to detect cardiac structural and functional pathologies as well as to facilitate clinical management of CPB separation, especially in the episodes of hemodynamic compromise. However, the conventional TEE examination, always performed in a liberal fashion without any restriction of view acquisition, is relatively time-consuming; there appear its flaws in the context of critically severe status. We therefore developed the perioperative rescue transesophageal echocardiography (PReTEE), a simplified three-view TEE protocol consisting of midesophageal four chamber, midesophageal left ventricular long axis, and transgastric short axis. Methods This is a single-center and randomized controlled trial which will be implemented in Peking Union Medical College Hospital, Beijing, China. A total of 46 TEE scans are schemed to be performed by 6 operators participating in and randomly assigned to either the PReTEE or the conventional TEE group. This study is purposed to investigate whether the efficiency of discriminating leading causes of difficult CPB wean-off can be significantly improved via an abbreviated sequence of TEE views. The primary outcome of interest is the difference between the groups of PReTEE and the conventional TEE in the successful discrimination of etiologies in specified 120 s. Cox proportional hazards model will be further employed to calculate the outcome difference. Discussion The estimated results of this trial are oriented at verifying whether a simplified TEE exam sequence can improve the efficiency of etiologies discrimination during CPB separation in cardiac surgery. Trial registration ClinicalTrials.gov NCT05960552. Registered on 6 July 2023.

Abstract In August 2023, Xiaomi unveiled the Redmi K60 Ultra, the first multi-frequency smartphone integrated with BeiDou-3 Navigation Satellite System Precise Point Positioning (PPP-B2b) services and employing PPP technology as the primary positioning method. The positioning enhancement service is provided by the Assisted Global Navigation Satellite System (A-GNSS) location platform developed by the China Academy of Information and Communications Technology. The signaling interaction between the server and the users strictly adheres to the Third Generation of Mobile Communications Technology Partnership Project Long-Term Evolution Positioning Protocol and the Open Mobile Alliance Secure User Plane Location framework. To comprehensively evaluate the Redmi K60 Ultra’s capabilities, this study designed six distinct experimental scenarios and conducted comprehensive research on multi-frequency and multi-GNSS observation noise, Time to First Fix (TTFF), as well as the performance of both GNSS-based and network-based positioning. Experimental results indicate that the GNSS chipset within the Redmi K60 Ultra has achieved a leading position in the consumer market concerning supported satellite constellations, frequencies, and observation accuracy, and is comparable to some low-cost GNSS receivers. A-GNSS positioning can reduce the TTFF from 30 to under 5 s, representing an improvement of over 85% in the cold start speed compared to a standalone GNSS mode. The positioning results show that the A-GNSS PPP-B2b service can achieve positioning performance with RMS errors of less than 1.5 m, 2.5 m, and 4 m in open-sky, realistic, and challenging urban environments. Compared to GNSS-based positioning, cellular network-based Observed Time Difference of Arrival (OTDOA) positioning achieves an accuracy ranging from tens to hundreds of meters in various experimental scenarios and currently functions primarily as coarse location determination. Additionally, this study explores the potential of the Three-Dimensional Mapping-Aided (3DMA) GNSS algorithm in detecting Non-Line-of-Sight signals and enhancing positioning performance. The results indicate that 3DMA PPP, as compared to conventional PPP, can significantly accelerate PPP convergence and improve positioning accuracy by over 30%. Consequently, 3D city models can be utilized as future assistance data for the A-GNSS location platform.

Abstract Alternative splicing is a crucial process in multicellular eukaryote, facilitated by the assembly of spliceosomal complexes comprising numerous small ribonucleoproteins. At an early stage, U1C is thought to be required for 5′ splice site recognition and base pairing. However, a systematic analysis of the U1C gene family in response to developmental cues and stress conditions has not yet been conducted in plants. This study identified 114 U1C genes in 72 plant species using basic bioinformatics analyses. Phylogenetic analysis was used to compare gene and protein structures, promoter motifs, and tissue- and stress-specific expression levels, revealing their functional commonalities or diversity in response to developmental cues, such as embryonic expression, or stress treatments, including drought and heat. Fluorescence quantitative expression analysis showed that U1C gene expression changed under salt, low temperature, drought, and Cd stress in rice seedlings. However, gene expression in shoots and roots was not consistent under different stress conditions, suggesting a complex regulatory mechanism. This research provides foundational insights into the U1C gene family's role in plant development and stress responses, highlighting potential targets for future studies.

Codonopsis pilosula (known as dangshen) is experiencing a serious replant disease caused by continuous monoculture in its main and endemic cultivation region in Dingxi, China. In this study, changes in physicochemical properties, fungal microbiomes, and isolated strains were investigated in the rhizosphere soil of 1-, 2-, 3-, and 5-year continuous monoculture natural fields. It was observed that wilted seedlings and a variety of root rot diseases occurred after the third year of continuous monoculture in the field. The soil-available potassium content and the pH value decreased significantly in the 3- and 5-year fields. Using Illumina sequencing, it was demonstrated that the 3- and 5-year fields had a higher diversity of fungal communities compared with the 1- and 2-year fields. At the genus level, abundance of some potentially pathogenic fungal taxa also increased. A total of 33 isolated strains belonging to the Fusarium species complexes Plectosphaerella cucumerina, Paraphoma ledniceana, Alternaria alstroemeriae, Mucor hiemalis, and Clonostachys rosea were obtained from the roots in 3- and 5-year fields. The correlation analysis revealed that the abundance of the fungal community at the genus level was positively correlated with the available phosphorus, total nitrogen, and soil organic matter. The results revealed that continuous monoculture has a negative impact on the fungal community and enriches potential pathogenic fungi in the rhizosphere of C. pilosula.

Abstract Background Higher mammographic density (MD), a radiological measure of the proportion of fibroglandular tissue in the breast, and lower terminal duct lobular unit (TDLU) involution, a histological measure of the amount of epithelial tissue in the breast, are independent breast cancer risk factors. Previous studies among predominantly white women have associated reduced TDLU involution with higher MD. Methods In this cohort of 611 invasive breast cancer patients (ages 23–91 years [58.4% ≥ 50 years]) from China, where breast cancer incidence rates are lower and the prevalence of dense breasts is higher compared with Western countries, we examined the associations between TDLU involution assessed in tumor-adjacent normal breast tissue and quantitative MD assessed in the contralateral breast obtained from the VolparaDensity software. Associations were estimated using generalized linear models with MD measures as the outcome variables (log-transformed), TDLU measures as explanatory variables (categorized into quartiles or tertiles), and adjusted for age, body mass index, parity, age at menarche and breast cancer subtype. Results We found that, among all women, percent dense volume (PDV) was positively associated with TDLU count (highest tertile vs. zero: Expbeta = 1.28, 95% confidence interval [CI] 1.08–1.51, ptrend =

Abstract Background Diabetes mellitus (DM)-induced testicular damage is associated with sexual dysfunction and male infertility in DM patients. However, the pathogenesis of DM-induced testicular damage remains largely undefined. Methods A streptozotocin (STZ)-induced diabetic model and high glucose (HG)-treated in vitro diabetic model were established. The histological changes of testes were assessed by H&E staining. Serum testosterone, iron, MDA and GSH levels were detected using commercial kits. Cell viability and lipid peroxidation was monitored by MTT assay and BODIPY 581/591 C11 staining, respectively. qRT-PCR, immunohistochemistry (IHC) or Western blotting were employed to detect the levels of BRD7, Clusterin, EZH2 and AMPK signaling molecules. The associations among BRD7, EZH2 and DNMT3a were detected by co-IP, and the transcriptional regulation of Clusterin was monitored by methylation-specific PCR (MSP) and ChIP assay. Results Ferroptosis was associated with DM-induced testicular damage in STZ mice and HG-treated GC-1spg cells, and this was accompanied with the upregulation of BRD7. Knockdown of BRD7 suppressed HG-induced ferroptosis, as well as HG-induced Clusterin promoter methylation and HG-inactivated AMPK signaling in GC-1spg cells. Mechanistical studies revealed that BRD7 directly bound to EZH2 and regulated Clusterin promoter methylation via recruiting DNMT3a. Knockdown of Clusterin or inactivation of AMPK signaling reverses BRD7 silencing-suppressed ferroptosis in GC-1spg cells. In vivo findings showed that lack of BRD7 protected against diabetes-induced testicular damage and ferroptosis via increasing Clusterin expression and activating AMPK signaling. Conclusion BRD7 suppressed Clusterin expression via modulating Clusterin promoter hypermethylation in an EZH2 dependent manner, thereby suppressing AMPK signaling to facilitate ferroptosis and induce diabetes-associated testicular damage.

Abstract Background Irinotecan (CPT-11) is a first-line treatment for advanced colorectal cancer (CRC). Four components (baicalin, baicalein, wogonin, and glycyrrhizic acid) derived from Huangqin Decoction (HQD) have been proven to enhance the anticancer activity of CPT-11 in our previous study. Objective This study aimed to determine the optimal combination of the four components for sensitizing CPT-11 as well as to explore the underlying mechanism. Methods The orthogonal design method was applied to obtain candidate combinations (Cmb1-9) of the four components. The influence of different combinations on the anticancer effect of CPT-11 was first evaluated in vitro by cell viability, wound healing ability, cloning formation, apoptosis, and cell cycle arrest. Then, a CRC xenograft mice model was constructed to evaluate the anticancer effect of the optimal combination in vivo. Potential mechanisms of the optimal combination exerting a sensitization effect combined with CPT-11 against CRC were analyzed by targeted metabolomics. Results In vitro experiments determined that Cmb8 comprised of baicalin, baicalein, wogonin, and glycyrrhizic acid at the concentrations of 17 μM, 47 μM, 46.5 μM and 9.8 μM respectively was the most effective combination. Importantly, the cell viability assay showed that Cmb8 exhibited synergistic anticancer activity in combination with CPT-11. In in vivo experiments, this combination (15 mg/kg of baicalin, 24 mg/kg of baicalein, 24 mg/kg of wogonin, and 15 mg/kg of glycyrrhizic acid) also showed a synergistic anticancer effect. Meanwhile, inflammatory factors and pathological examination of the colon showed that Cmb8 could alleviate the gastrointestinal damage induced by CPT-11. Metabolic profiling of the tumors suggested that the synergistic anticancer effect of Cmb8 might be related to the regulation of fatty acid metabolism. Conclusion The optimal combination of four components derived from HQD for the synergistic sensitization of CPT-11 against CRC was identified.

Asthma, is a common, significant and diverse condition marked by persistent airway inflammation, with a major impact on human health worldwide. The predisposing factors for asthma are complex and widespread. The beneficial effects of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) in asthma have increasingly attracted attention recently. In asthma therapy, n-3 PUFAs may reduce asthma risk by controlling on levels of inflammatory cytokines and regulating recruitment of inflammatory cells in asthma. The specialized pro-resolving mediators (SPMs) derived from n-3 PUFAs, including the E- and D-series resolvins, protectins, and maresins, were discovered in inflammatory exudates and their biosynthesis by lipoxygenase mediated pathways elucidated., SPMs alleviated T-helper (Th)1/Th17 and type 2 cytokine immune imbalance, and regulated macrophage polarization and recruitment of inflammatory cells in asthma via specific receptors such as formyl peptide receptor 2 (ALX/FPR2) and G protein-coupled receptor 32. In conclusion, the further study of n-3 PUFAs and their derived SPMs may lead to novel anti-inflammatory asthma treatments.

Global developmental delay (GDD) is a common neurodevelopmental disorder in children under 5 years of age. This study assessed the potential of functional Near-Infrared Spectroscopy (fNIRS) technology aiding diagnosis of GDD in premature infants and explored brain pathogenesis of GDD. This prospective cohort study was conducted between December 2020 and June 2023 among preterm infants in five hospitals in China. The primary outcome was the diagnosis of GDD. A 5-min fNIRS brain scan was performed in preterm infants at 4-, 8-, and 12-month corrected age in two hospitals. A diagnostic model based on fNIRS brain network and an integrated diagnostic model built on fNIRS data as well as birth head circumference was developed. Diagnostic models were assessed using the area under the curve (AUC) from receiver operating characteristic curves. Brain network analysis revealed significantly worse left-sided functional connectivity in GDD preterm infants. The fNIRS technique had satisfactory diagnostic value for GDD in all age groups. The diagnostic accuracy of the combined diagnostic model significantly improved. This study suggested that fNIRS could be considered for early screening and late auxiliary diagnosis of GDD in preterm infants. Furthermore, it can also be used to explore GDD brain pathogenesis.

Abstract Accurate identification and isolation of target cells are crucial for precision diagnosis and treatment. DNA aptamer‐based logic devices provide a distinct advantage in this context, as they can logically analyze multiple cell surface markers with high efficiency. However, the susceptibility of natural DNA (D‐DNA) to degradation can compromise the sensitivity and specificity of these devices, potentially leading to false‐positive and false‐negative results, particularly in complex biological environments. To address this issue, dual‐ and triple‐aptamer‐based cell‐surface logic devices are designed and developed using mirror‐image L‐DNA, a chiral molecule of D‐DNA with high biostability. These devices allow for simultaneous analysis of multiple cell surface proteins, achieving greater specificity in cell identification and isolation than D‐DNA‐based logic devices. The L‐DNA probes realized 98.7% and 70.5% sensitivities in FBS buffer with dual‐ and triple‐aptamer‐based logic devices for target cell identification, while D‐DNA probes only showed 27.9% and 0.1%. It is believed that the high stability of L‐DNA and the high efficiency of the devices for labeling cell subpopulations will have broad applications in the life sciences, biomedical engineering, and personalized medicine.

Objectives Necrotizing enterocolitis (NEC) is a common and sometimes fatal disease affecting premature infants. Elevated formate has been found in the stool of patients with NEC. Sodium formate (NaF) is used to explore the role of formate in the intestinal epithelial injury.Methods In this study, 150 mM NaF solution was intraluminally injected in 14-day-old and 28-day-old mice. Mice were sacrificed after 24 h of feces collection, and the blood and small intestinal tissues were collected to detect the pathological damage of intestinal tissue, intestinal permeability, oxidative stress indicators including SOD, HO-1, MDA, and 4-HNE, inflammatory cytokines including IL-1β, TNF-α and IL-6, mitochondrial function such as ATP and PGC-1α in mice intestinal tissue, indicators of the cell death modes including necroptosis-related protein RIPK1 and p-MLKL, and apoptosis- related protein cleaved-caspase-3 and p-AKT (S473).Results NaF treatment significantly damaged intestinal epithelial tissue and barrier function, caused mitochondrial dysfunction, manifesting as decreased ATP and PGC-1α levels, increased lipid peroxidation products MDA and 4-HNE, depleted antioxidant enzyme SOD, and upregulated the expression of HO-1. Furthermore, NaF treatment induced inflammatory responses by promoting the release of IL-1β, IL-6 and TNF-α in a development-dependent manner, eventually inducing necroptosis and apoptosis.Conclusions Formate may be a source of metabolic intestinal injury contributing to the pathogenesis of NEC in human newborns.

Summary: We aim to investigate muscle ARNT-like protein 1 (BMAL1) regulation of syntaxin17 (STX17) in mouse hippocampal neurons, focusing on autophagy and amyloid-β (Aβ) deposition. Autophagosome-lysosome fusion in APP/PS1 hippocampal tissues was observed using transmission electron microscopy, while mRNA levels of LC3II and P62 were measured via reverse-transcription PCR (RT-PCR) after Amyloid precursor protein (APP) overexpression. STX17, linked to autophagy and differentially expressed in Alzheimer’s disease (AD) brains, was knocked down or overexpressed to assess its effects. The results showed that reduced STX17 impairs autophagosome-lysosome fusion, leading to abnormal Aβ deposition. Coimmunoprecipitation (Co-IP) and immunofluorescence confirmed STX17 interaction with SNAP29 and VAMP8 to form SNARE complexes. Furthermore, BMAL1 binding to STX17 was examined using luciferase assays. Circadian rhythm disturbances and decreased BMAL1 expression in APP/PS1 mice were noted, while BMAL1 overexpression upregulated STX17 expression and promoted autophagy to reduce Aβ deposition. Thus, the BMAL1 protein can promote STX17 transcription to induce STX17-SNAP29-VAMP8 complex formation to clear intracellular Aβ through autophagy.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, characterized by the loss or low expression of estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2) and progesterone receptor (PR). Due to the lack of clear therapeutic targets, paclitaxel (PTX) is often used as a first-line standard chemotherapy drug for the treatment of high-risk and locally advanced TNBC. PTX is a diterpenoid alkaloid extracted and purified from Taxus plants, functioning as an anticancer agent by inducing and promoting tubulin polymerization, inhibiting spindle formation in cancer cells, and preventing mitosis. However, its clinical application is limited by low solubility and high toxicity. Nanodrug delivery system (NDDS) is one of the feasible methods to improve the water solubility of PTX and reduce side effects. In this review, we summarize the latest advancements in PTX-targeted NDDS, as well as its combination with other codelivery therapies for TNBC treatment. NDDS includes passive targeting, active targeting, stimuli-responsive, codelivery, and multimode strategies. These systems have good prospects in improving the bioavailability of PTX, enhancing tumor targeting, reducing toxicity, controlling drug release, and reverse tumor multidrug resistance (MDR). This review provides valuable insights into the clinical development and application of PTX-targeted NDDS in the treatment of TNBC.

The establishment of nature reserves (NRs) is widely acknowledged as one of the most effective measures to mitigate the threats on habitat quality (HB) posed by human activities (HAs). Precise and scientific assessment of the effectiveness of NRs holds crucial significance in improving management and promoting conservation. In this study, key indicators were creatively selected and applied to the propensity score matching (PSM) model to comprehensively assess the variations in HAs and HB within national NRs on the Qinghai-Tibet Plateau. The results indicated that between 2000 and 2020, 67.4 % of the NR area experienced a decline in HA-related impacts, while 53.8 % of the area saw improvements in HB. Additionally, with the exclusion of external environmental factors, in 2020, the difference in HAs and HB between NRs and non-protected areas was −0.131 and 0.179, respectively. Finally, based on an assessment of the overall conservation effectiveness, seven NRs were classified as “Class I'', 18 as “Class II'', and another seven as “Class III''. These results not only confirmed the effectiveness of national NRs in alleviating anthropogenic pressure and enhancing HB but also served as an important basis for accurately assessing the conservation effectiveness of other NRs and formulating more scientifically sound and appropriate management policies.

Objectives To explore the effects and mechanisms of bilirubin on mitochondrial function and type of macrophage cell death after exposure to cigarette smoke extract (CSE).Methods RAW264.7 macrophages were treated with different concentrations of CSE and bilirubin solutions and divided into four groups: control, CSE, bilirubin, and bilirubin + CSE groups. The necrotic and apoptotic states of the macrophages were determined using an Annexin V-fluorescein 5-isothiocyanate/propidium iodide (FITC/PI) staining kit. Cytoplasmic NOD-like receptor family, pyrin domain containing 3 (NLRP3) expression in macrophages was detected by immunofluorescence and the levels of IL-1β and IL-18 in the supernatants of culture medium were detected by enzyme linked immunosorbent assay (ELISA) test. A JC-1 mitochondrial membrane potential detection kit was used to assess mitochondrial membrane damage and the adenosine triphosphate (ATP) assay kit was used to determine intracellular ATP levels. After the macrophages were stained with reactive oxygen species (ROS) specific dye, 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA), the fluorescence intensity and proportion of ROS-positive macrophages were measured using flow cytometry.Results We observed that compared with those of 0 μM (control group), concentrations of 5, 10, or 20 μΜ bilirubin significantly decreased cell viability, which was increased by bilirubin exposure below 1 μM. The effect of CSE on macrophage viability was concentration- and time-dependent. Bilirubin of 0.2 μM could alleviate the inhibition of macrophage viability caused by 5% CSE. In addition, bilirubin intervention could reduce the occurrence of necrosis and pyroptosis to a certain extent.Conclusions CSE could cause mitochondrial dysfunction in macrophages, as demonstrated by a decrease in mitochondrial membrane potential and intracellular ATP levels and an increase in ROS production, while bilirubin could relieve mitochondrial dysfunction caused by CSE.

With the rise in popularity of tablets, professional interpreters were among the early adopters who integrated them into their workflow. Tablets have also become an indispensable tool for students, including those studying interpreting, who utilize them in the classroom for various purposes, such as note-taking. However, despite this growing trend, the traditional practice of pen-and-paper note-taking remains prevalent. Additionally, current interpreting textbooks primarily focus on teaching pen-and-paper note-taking skills. As interpreting instructors, it is crucial for us to familiarize ourselves with the use of tablets for note-taking in consecutive interpreting (CI). This will enable us to adapt our teaching methods accordingly and cater to the needs of the “iPad Kids” generation. The purpose of this study is to use quantitative method to examine the factors that contribute to the adoption of tablets for note-taking by instructors in the classroom environment. A questionnaire was developed based on the General Extended Technology Acceptance Model for E-learning (GETAMEL) framework. The questionnaire was distributed to teachers at prominent foreign language universities, foreign language faculties in select comprehensive universities and translation training institutions across Chinese Mainland and Macao Special Administrative Region of China. To provide comprehensive insights into the variables under study, descriptive statistics were generated using both SPSS 25.0 and Excel. These tools facilitated the production of detailed data summaries, offering valuable insights into the research variables. The obtained results provide insights into various aspects, including instructors’ knowledge levels and usage of tablet interpreting in university classrooms, their attitudes toward integrating tablet interpreting into teaching, and the key factors that influence their decisions to adopt tablet interpreting in their classroom practices. The findings suggest the existence of additional external factors that could be incorporated into the existing model. The paper concludes with recommendations on how to promote the integration of technology into teaching practices for interpreting instructors.

Abstract Shape memory alloys (SMAs) with large latent heat absorbed/released during phase transformation at elevated temperatures benefit their potential application on thermal energy storage (TES) in high temperature environment like power plants, etc. The desired alloys can be designed quickly by searching the vast component space of doped NiTi‐based SMAs via data‐driven method, while be challenging with the noisy experimental data. A noise‐aware active learning strategy is proposed to accelerate the design of SMAs with large latent heat at elevated phase transformation temperatures based on noisy data. The optimal noise level is estimated by minimizing the model error with incorporation of a range of noise levels as noise hyper‐parameters into the noise‐aware Kriging model. The employment of this strategy leads to the discovery of the alloy with latent heat of –36.08 J g−1, 9.2% larger than the best value (–33.04 J g−1) in the original training dataset within another four experiments. Additionally, the alloy represents high austenite finish temperature (481.71°C) and relatively small hysteresis. This promotes the latent heat TES application of SMAs in high temperature circumstance. It is expected that the noise‐aware approach can be convenient for the accelerated materials design via the data‐driven method with noisy data.

Deep learning is progressively emerging as a vital tool for image reconstruction in light field microscopy. The present review provides a comprehensive examination of the latest advancements in light field image reconstruction techniques based on deep learning algorithms. First, the review briefly introduced the concept of light field and deep learning techniques. Following that, the application of deep learning in light field image reconstruction was discussed. Subsequently, we classified deep learning-based light field microscopy reconstruction algorithms into three types based on the contribution of deep learning, including fully deep learning-based method, deep learning enhanced raw light field image with numerical inversion volumetric reconstruction, and numerical inversion volumetric reconstruction with deep learning enhanced resolution, and comprehensively analyzed the features of each approach. Finally, we discussed several challenges, including deep neural approaches for increasing the accuracy of light field microscopy to predict temporal information, methods for obtaining light field training data, strategies for data enhancement using existing data, and the interpretability of deep neural networks.

Pesticide residues, resulting from agricultural practices, pose significant health and environmental risks. This review synthesizes the current understanding of pesticide impacts on the immune system, highlighting their role in chronic diseases such as asthma, diabetes, Parkinson's disease (PD) and cancer. We emphasize the significant role of omics technologies in the study of pesticide toxicity mechanisms. The integration of genomics, proteomics, metabolomics, and epigenomics offers a multidimensional strategy for a comprehensive assessment of pesticide effects, facilitating personalized risk management and policy formulation. We advocate for stringent regulatory policies, public education, and global cooperation to enhance food safety and environmental sustainability. By adopting a unified approach, we aim to mitigate the risks of pesticide residues, ensuring human health and ecological balance are preserved.

Heavy metals (HMs) within the soil–water-grain system have substantial effects on both eco-environmental and human health. This study collected 232 samples (58 surface soil, 89 drinking water, and 85 highland barley) from the central Qinghai–Tibet Plateau (QTP) and analyzed the contamination characteristics, source apportionments, and associated risks of arsenic (As), cadmium (Cd), chromium (Cr), mercury (Hg), and lead (Pb). The study employed geochemical normalization factors, biotoxicity assessment methods, ecological risk and health risk assessment models, and the Positive matrix factorization (PMF) model to assess the soil–water-grain system. The results showed no accumulation of HMs in highland barley, and no biotoxicity was observed. Soil was identified as the primary medium contributing to ecological and health risks, with overall risk levels ranging from slight to moderate, particularly higher in the northern and eastern regions of the study area. Cr posed non-carcinogenic risks to local children in 100% of cases and to adults in 27.27% of cases. Pb presented non-carcinogenic risks in 81.82% of cases for children and 36.36% for adults. Furthermore, As, Cd, and Cr were found to pose carcinogenic risks to both children and adults. Non-carcinogenic and carcinogenic risks were more pronounced in children than in adults. Children’s health risks were primarily driven by As concentrations in grains, with a sensitivity contribution exceeding 90%. The Monte Carlo simulation (MCS) indicated that ingestion rates were more sensitive for children, while body weight showed an inverse relationship. The PMF model identified three potential sources of HMs: anthropogenic, geogenic, and environmental. Therefore, to ensure the sustainable development of ecology and the health of residents, it is urgent to conduct routine soil remediation and maintain a balanced diet to mitigate the migration and transformation of HMs in the study area and improve the health level of residents.

Abstract Sphingolipids play vital roles in metabolism and regulation. Previously, the aryl hydrocarbon receptor (AHR), a ligand‐activated transcription factor, was reported to directly regulate ceramide synthesis genes by binding to their promoters. Herein, sphingosine kinase 2 (SPHK2), responsible for producing sphingosine‐1‐phosphate (S1P), was found to interact with AHR through LXXLL motifs, influencing AHR nuclear localization. Through mutagenesis and co‐transfection studies, AHR activation and subsequent nuclear translocation was hindered by SPHK2 LXXLL mutants or SPHK2 lacking a nuclear localization signal (NLS). Similarly, an NLS‐deficient AHR mutant impaired SPHK2 nuclear translocation. Silencing SPHK2 reduced AHR expression and its target gene CYP1A1, while SPHK2 overexpression enhanced AHR activity. SPHK2 was found enriched on the CYP1A1 promoter, underscoring its role in AHR target gene activation. Additionally, S1P rapidly increased AHR expression at both the mRNA and protein levels and promoted AHR recruitment to the CYP1A1 promoter. Using mouse models, AHR deficiency compromised SPHK2 nuclear translocation, illustrating a critical interaction where SPHK2 facilitates AHR nuclear localization and supports a positive feedback loop between AHR and sphingolipid enzyme activity in the nucleus. These findings highlight a novel function of SPHK2 in regulating AHR activity and gene expression.

IntroductionVisual impairment, encompassing low visual acuity and visual field loss, significantly impacts the older adult population worldwide, leading to increased disability and mortality risks. Recent studies suggest a strong association between visual impairment and anxiety, particularly among older adults. This study aims to explore the relationship between visual impairment and anxiety symptoms in older adult individuals in China, and to investigate potential mediating factors.MethodsData for this study were derived from the 2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS), including 11,702 participants aged 65 and older. Visual impairment was assessed through self-reported visual function, while anxiety symptoms were measured using the 7-item Generalized Anxiety Disorder scale (GAD-7). Additional assessments included sleep quality and duration, exercise status, and dietary diversity. Logistic regression models and mediation analysis were employed to explore associations and mediating effects.ResultsThe findings indicate that visual impairment is significantly associated with increased anxiety symptoms among the older adult (OR = 1.51, 95% CI: 1.32–1.72, p

Abstract Background This study aimed to develop a novel six-gene expression biomarker panel to enhance the early detection and risk stratification of peritoneal recurrence and micrometastasis in locally advanced gastric cancer (LAGC). Methods We used genome-wide transcriptome profiling and rigorous bioinformatics to identify a six-gene expression biomarker panel. This panel was validated across multiple clinical cohorts using both tissue and liquid biopsy samples to predict peritoneal recurrence and micrometastasis in patients with LAGC. Results Through genome-wide expression profiling, we identified six mRNAs and developed a risk prediction model using 196 samples from a surgical specimen training cohort. This model, incorporating a 6-mRNA panel with clinical features, demonstrated high predictive accuracy for peritoneal recurrence in gastric cancer patients, with an AUC of 0.966 (95% CI: 0.944–0.988). Transitioning from invasive surgical or endoscopic biopsy to noninvasive liquid biopsy, the model retained its predictive efficacy (AUC = 0.963; 95% CI: 0.926–1.000). Additionally, the 6-mRNA panel effectively differentiated patients with or without peritoneal metastasis in 95 peripheral blood specimens (AUC = 0.970; 95% CI: 0.936–1.000) and identified peritoneal micrometastases with a high efficiency (AUC = 0.941; 95% CI: 0.874–1.000). Conclusions Our study provides a novel gene expression biomarker panel that significantly enhances early detection of peritoneal recurrence and micrometastasis in patients with LAGC. The RSA model's predictive capability offers a promising tool for tailored treatment strategies, underscoring the importance of integrating molecular biomarkers with clinical parameters in precision oncology.

Abstract Objective This study aimed to systematically review epidemiological evidence on associations between screen time exposure and myopia in children and adolescents, and to quantitatively evaluate summary effect estimates from existing literature. Method There were three online databases including PubMed, Embase, and Web of Science, for epidemiological studies on screen time exposure and myopia published before June 1, 2023. The risk of bias was assessed by the Newcastle Ottawa Scale (NOS) checklist. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the correlation between screen time exposure and myopia using random or fixed-effect models by exposure type (categorical/continuous). We also performed subgroup analysis by screen device type, study quality, geographic region, and research period. Results We searched 7,571 records from three databases and identified 19 eligible studies, including 14 high-quality studies and 5 moderate-quality studies. Meta-analyses suggested that there was a statistically significant correlation between screen time (high vs. low) and myopia. The pooled ORs with 95%CIs were respectively 2.24 (1.47–3.42) for cross-sectional studies, and 2.39 (2.07–2.76) for cohort studies. We also found a significant association between continuous exposure to screen time (per 1 h/d increase) and myopia in cohort studies. The pooled ORs with 95%CIs were 1.07 (1.01–1.13). In subgroup analysis stratified by screen device type in cross-sectional studies, screen time exposures from computers (categorical: OR = 8.19, 95%CI: 4.78–14.04; continuous: OR = 1.22, 95%CI: 1.10–1.35) and televisions (categorical: OR = 1.46, 95%CI: 1.02–2.10) were associated with myopia, while smartphones were not. Although publication bias was detected, the pooled results did not show significant changes after adjustment using the trim and fill method. Conclusion Our findings support that screen time exposure was significantly associated with myopia in children and adolescents. Notably, screen time exposure from computers may have the most significant impact on myopia.

Construction of disaster-resilient cities has attracted considerable attention. However, traditional methods of studying urban disaster resilience through experimental approaches are often constrained by various limitations, such as testing sites, costs and ethical considerations. To address these constraints, this paper proposes incorporating digital twin concepts into urban disaster resilience research. By establishing a connection between the physical realm of the city and its virtual counterpart, this approach utilizes digital simulations to overcome the limitations of experimental methods and enables dynamic deduction and control of the disaster process. This paper delves into three key aspects encompassing the acquisition of data from reality to the virtual space, disaster simulation within the virtual space, and translation of virtual insights into effective disaster prevention strategies in reality. It provides a comprehensive summary of relevant research endeavors from the authors’ research group and showcases the effectiveness and potential of the proposed techniques. These findings serve as references for pre-disaster planning, real-time emergency assessments, post-disaster rescue operations, and accident investigations for buildings and cities.

Abstract Molecular computing is an emerging paradigm that plays an essential role in data storage, bio-computation, and clinical diagnosis with the future trends of more efficient computing scheme, higher modularity with scaled-up circuity and stronger tolerance of corrupted inputs in a complex environment. Towards these goals, we construct a spatially localized, DNA integrated circuits-based classifier (DNA IC-CLA) that can perform neuromorphic architecture-based computation at a molecular level for medical diagnosis. The DNA-based classifier employs a two-dimensional DNA origami as the framework and localized processing modules as the in-frame computing core to execute arithmetic operations (e.g. multiplication, addition, subtraction) for efficient linear classification of complex patterns of miRNA inputs. We demonstrate that the DNA IC-CLA enables accurate cancer diagnosis in a faster (about 3 h) and more effective manner in synthetic and clinical samples compared to those of the traditional freely diffusible DNA circuits. We believe that this all-in-one DNA-based classifier can exhibit more applications in biocomputing in cells and medical diagnostics.

Abstract Variations in chromosome number are occasionally observed among oomycetes, a group that includes many plant pathogens, but the emergence of such variations and their effects on genome and virulence evolution remain ambiguous. We generated complete telomere-to-telomere genome assemblies for Phytophthora sojae, Globisporangium ultimum, Pythium oligandrum, and G. spinosum. Reconstructing the karyotype of the most recent common ancestor in Peronosporales revealed that frequent chromosome fusion and fission drove changes in chromosome number. Centromeres enriched with Copia-like transposons may contribute to chromosome fusion and fission events. Chromosome fusion facilitated the emergence of pathogenicity genes and their adaptive evolution. Effectors tended to duplicate in the sub-telomere regions of fused chromosomes, which exhibited evolutionary features distinct to the non-fused chromosomes. By integrating ancestral genomic dynamics and structural predictions, we have identified secreted Ankyrin repeat-containing proteins (ANKs) as a novel class of effectors in P. sojae. Phylogenetic analysis and experiments further revealed that ANK is a specifically expanded effector family in oomycetes. These results revealed chromosome dynamics in oomycete plant pathogens, and provided novel insights into karyotype and effector evolution.

Abstract Formaldehyde (HCHO) is a serious hazardous air pollutant and crucial precursor of PM2.5 and ozone compound pollution. There has been a dearth of HCHO research in Tibet where pressing need to protect the unique ecosystem. Therefore, this study aims to investigate the spatial-temporal distribution of HCHO from 2013 to 2021 and identify its influencing factors using satellite observations. Our findings reveal a noteworthy annual growth rate of 2.25% yr−1 in HCHO vertical column density (VCD) in Tibet. This rate is comparable to that in India and even surpasses levels observed in many other regions worldwide, including eastern China. Furthermore, unlike other areas, the eastern region of Tibet exhibits no discernible seasonal pattern in HCHO VCD. The anomalous variation in HCHO concentrations in Tibet can primarily be attributed to long-distance transnational transport originating from incomplete combustion in India Assam. Our research underscores the urgent need for enhanced atmospheric environmental management in Tibet.

Abstract Background Surgical staplers have been widely used to facilitate surgeries, and this study aimed to examine the real-world effectiveness of a new powered stapling system with Gripping Surface Technology (GST) on intraoperative outcomes of gastrectomy for gastric cancer. Method The data were extracted from the Fourth Hospital of Hebei Medical University’s (FHHMU) medical records system. Participants (N = 121 patients) were classified into the GST (n = 59) or non-GST group (n = 62), based on the use of the GST system. The intraoperative outcomes such as bleeding were assessed by reviewing video records. T-tests, Chi-square tests, and Mann–Whitney-U tests were used to compare the baseline characteristics between groups. Multivariate logistic regression was conducted for adjusting outcomes to study the effect of variables. Results Compared with the non-GST group, the GST group had significantly lower risks for intraoperative bleeding, intraoperative anastomosis intervention rate, intraoperative suture, and intraoperative pression (aORs: 0.0853 (p

Abstract Cholangiocarcinoma (CCA) is a highly malignant biliary tract cancer with currently suboptimal diagnostic and prognostic approaches. We present a novel system to monitor CCA using exosomal circular RNA (circRNA) via serum and biliary liquid biopsies. A pilot cohort consisting of patients with CCA-induced biliary obstruction (CCA-BO, n = 5) and benign biliary obstruction (BBO, n = 5) was used to identify CCA-derived exosomal circRNAs through microarray analysis. This was followed by a discovery cohort (n = 20) to further reveal a CCA-specific circRNA complex (hsa-circ-0000367, hsa-circ-0021647, and hsa-circ-0000288) in both bile and serum exosomes. In vitro and in vivo studies revealed the three circRNAs as promoters of CCA invasiveness. Diagnostic and prognostic models were established and verified by two independent cohorts (training cohort, n = 184; validation cohort, n = 105). An interpreter-free diagnostic model disclosed the diagnostic power of biliary exosomal circRNA signature (Bile-DS, AUROC = 0.947, RR = 6.05) and serum exosomal circRNA signature (Serum-DS, AUROC = 0.861, RR = 4.04) compared with conventional CA19-9 (AUROC = 0.759, RR = 2.08). A prognostic model of CCA undergoing curative-intent surgery was established by calculating early recurrence score, verified with bile samples (Bile-ERS, C-index=0.783) and serum samples (Serum-ERS, C-index = 0.782). These models, combined with other prognostic factors revealed by COX-PH model, enabled the establishment of nomograms for recurrence monitoring of CCA. Our study demonstrates that the exosomal triple-circRNA panel identified in both bile and serum samples serves as a novel diagnostic and prognostic tool for the clinical management of CCA.

Abstract Astragalus mongholicus is a medicinal plant that is known to decrease in quality in response to continuous cropping. However, the differences in the root-associated microbiome and root exudates in the rhizosphere soil that may lead to these decreases are barely under studies. We investigated the plant biomass production, root-associated microbiota, and root exudates of A. mongholicus grown in two different fields: virgin soil (Field I) and in a long-term continuous cropping field (Field II). Virgin soil is soil that has never been cultivated for A. mongholicus. Plant physiological measurements showed reduced fresh and dry weight of A. mongholicus under continuous cropping conditions (i.e. Field II). High-throughput sequencing of the fungal and bacterial communities revealed differences in fungal diversity between samples from the two fields, including enrichment of potentially pathogenic fungi in the roots of A. mongholicus grown in Field II. Metabolomic analysis yielded 20 compounds in A. mongholicus root exudates that differed in relative abundance between rhizosphere samples from the two fields. Four of these metabolites (2-aminophenol, quinic acid, tartaric acid, and maleamate) inhibited the growth of A. mongholicus, the soil-borne pathogen Fusarium oxysporum, or both. This comprehensive analysis enhances our understanding of the A. mongholicus microbiome, root exudates, and interactions between the two in response to continuous cropping. These results offer new information for future design of effective, economical approaches to achieving food security.