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The years we are experiencing are often identified as those of the age of digital technologies, where “digital” is commonly associated with intelligence, efficiency, and convenience. The emergence of digital technologies has significantly impacted and transformed various aspects of our society compared to the past. In this panorama, some arising questions regard transportation infrastructure systems and, first of all, highway infrastructure. This research focuses on one central issue: how highways fit into this digital revolution. Actually, the work in this paper can be described as follows. Although there are many different theoretical model systems for the architecture of the digital twin, we have chosen to review the main body of research on the digital twin in highway infrastructure based on a relatively well-established modeling framework, the five-dimensional model of the digital twin. After discussing the components of the digital twin for highway infrastructure's five-dimensional model, the paper reviews some innovative technologies that make these items effective. In addition to this, the digital twin maturity level of highway infrastructure and the MBSE-based (model-based systems engineering) digital twin model for highway are also discussed in this paper. Therefore, the paper provides a bird's eye view of this extremely dynamic technology for a new system of intelligent highways and discusses some of their criticalities and strengths, allowing for the optimization and development of new transportation functions and services, improving the adaptability of highways to the digital revolution.

Abstract Aims The aim of the research was to look into the connection between the occurrence of gallstones in adult US citizens and lipid accumulation products (LAP). Methods We conducted a cross-sectional study of 3,582 U.S. adults with relevant indicators collected from the 2017–2020 National Health and Nutrition Examination Survey (NHANES) database. Multifactorial logistic regression was used to investigate the linear relationship between LAP and gallstone incidence, while smoothed curve fitting was used to describe the nonlinear relationship, and subgroup and interaction analyses were used to evaluate the potential differences between groups. Results Among the 3582 participants aged ≥ 20 years included, there was a positive association between LAP and gallstones. Following adjustments for all covariates, the likelihood of getting gallstones rose by 29% for each unit rise in log2-LAP (OR = 1.29, 95% CI: 1.13‒1.49). Compared to those in the lowest tertile, those in the highest LAP tertile had a significantly higher risk of developing gallstones (OR = 1.97, 95% CI: 1.31‒2.95). Subgroup analyses indicated that the association between LAP and gallstones was not affected by the stratification of the variables examined. Conclusion Gallstones and LAP exhibited a positive association in our investigation, indicating that LAP may be utilized as a clinical indicator to determine the occurrence of gallstones.

Abstract Intracerebral hemorrhage is a lethal cerebrovascular disease, and the inevitable secondary brain injury (SBI) is responsible for serious disability and death. Perfect therapeutic goal is to minimize SBI and restore neurobehavioral functions. Recently, neuroprotection is highlighted to reduce SBI, but it still faces “Neuronal survival but impaired functions” dilemma. Herein, this work further proposes a novel combinational therapeutic strategy of neuroprotection and neurogenesis toward this goal. However, appropriate therapeutic agents are rarely reported, and their discovery and development are urgently needed. Selenium participates in various physiological/pathological processes, which is hypothesized as a potential targeting molecule. To explore this effect, this work formulates an ultra-small selenium nanodot with a seleno-amino acid derived carbon dot domain and a hydrophilic PEG layer, surprisingly finding that it increases various selenoproteins levels at perihematomal region, to not only exert multiple neuroprotective roles at acute phase but promote neurogenesis and inhibit glial scar formation at recovery phase. At a safe dose, this combinational strategy effectively prevents SBI and recovers neurobehavioral functions to a normal level. Furthermore, its molecular mechanisms are revealed to broaden application scopes in other complex diseases. Graphical abstract

Abstract Background Describing the transmission dynamics of infectious diseases across different regions is crucial for effective disease surveillance. The multivariate time series (MTS) model has been widely adopted for constructing cross-regional infectious disease transmission networks due to its strengths in interpretability and predictive performance. Nevertheless, the assumption of constant parameters frequently disregards the dynamic shifts in disease transmission rates, thereby compromising the accuracy of early warnings. This study investigated the applicability of time-varying MTS models in multi-regional infectious disease monitoring and explored strategies for model selection. Methods This study focused on two prominent time-varying MTS models: the time-varying parameter-stochastic volatility-vector autoregression (TVP-SV-VAR) model and the time-varying VAR model using the generalized additive framework (tvvarGAM), and intended to explore and verify their applicable conditions for the surveillance of infectious diseases. For the first time, this study proposed the time delay coefficient and spatial sparsity indicators for model selection. These indicators quantify the temporal lags and spatial distribution of infectious disease data, respectively. Simulation study adopted from real-world infectious disease surveillance was carried out to compare model performances under various scenarios of spatio-temporal variation as well as random volatility. Meanwhile, we illustrated how the modelling process could help the surveillance of infectious diseases with an application to the influenza-like case in Sichuan Province, China. Results When the spatio-temporal variation was small (time delay coefficient: 0.1–0.2, spatial sparsity:0.1–0.3), the TVP-SV-VAR model was superior with smaller fitting residuals and standard errors of parameter estimation than those of the tvvarGAM model. In contrast, the tvvarGAM model was preferable when the spatio-temporal variation increased (time delay coefficient: 0.2–0.3, spatial sparsity: 0.6–0.9). Conclusion This study emphasized the importance of considering spatio-temporal variations when selecting appropriate models for infectious disease surveillance. By incorporating our novel indicators—the time delay coefficient and spatial sparsity—into the model selection process, the study could enhance the accuracy and effectiveness of infectious disease monitoring efforts. This approach was not only valuable in the context of this study, but also has broader implications for improving time-varying MTS analyses in various applications.

Abstract To adapt to the complex belowground environment, plants make trade-offs between root resource acquisition and defence ability. This includes forming partnerships with different types of root associating microorganisms, such as arbuscular mycorrhizal and ectomycorrhizal fungi. These trade-offs, by mediating root chemistry, exert legacy effects on nutrient release during decomposition, which may, in turn, affect the ability of new roots to re-acquire resources, thereby generating a feedback loop. However, the linkages at the basis of this potential feedback loop remain largely unquantified. Here, we propose a trait-based root ‘acquisition-defence-decomposition’ conceptual framework and test the strength of relevant linkages across 90 angiosperm tree species. We show that, at the plant species level, the root-fungal symbiosis gradient within the root economics space, root chemical defence (condensed tannins), and root decomposition rate are closely linked, providing support to this framework. Beyond the dichotomy between arbuscular mycorrhizal-dominated versus ectomycorrhizal-dominated systems, we suggest a continuous shift in feedback loops, from ‘high arbuscular mycorrhizal symbiosis-low defence-fast decomposition-inorganic nutrition’ by evolutionarily ancient taxa to ‘high ectomycorrhizal symbiosis-high defence-slow decomposition-organic nutrition’ by more modern taxa. This ‘acquisition-defence-decomposition’ framework provides a foundation for testable hypotheses on multidimensional linkages between species’ belowground strategies and ecosystem nutrient cycling in an evolutionary context.

Abstract Background Cancer stem cells (CSCs) are a specific subpopulation of cancer cells with the ability of self‐renewal, infinite proliferation, multidifferentiation and tumorigenicity, and play critical roles in cancer progression and treatment resistance. CSCs are tightly regulated by the tumor microenvironment, such as hypoxia; however, how hypoxia regulates CSCs in non‐small cell lung cancer (NSCLC) remains unclear. Methods The proportion of ALDHhi cells was examined using the Aldefluor assay. Tankyrase inhibitor XAV939 and siRNA were used to inhibit β‐catenin while pcDNA3‐β‐catenin (S33Y) plasmid enhanced the expression of β‐catenin. Western blot was administered for protein detection. The mRNA expression was measured by quantitative real‐time PCR. Results We found that hypoxia led to an increase in the proportion of ALDHhi cells in lung squamous carcinoma (LUSC) H520 cells, while causing a decrease in the ALDHhi cell proportion in lung adenocarcinoma (LUAD) A549 cells. Similarly, β‐catenin expression was upregulated in H520 cells but downregulated in A549 cells upon exposure to hypoxia. Mechanically, the proportion of ALDHhi cells in both cell lines was decreased by β‐catenin inhibitor or siRNA knockdown, whereas increased after β‐catenin overexpression. Furthermore, hypoxia treatment suppressed E‐cadherin expression in H520 cells and enhanced N‐cadherin and β‐catenin expression, while this effect was completely opposite in A549 cells. Conclusion The hypoxia‐EMT‐β‐catenin axis functions as an important regulator for the proportion of CSCs in NSCLC and could potentially be explored as therapeutic targets in the future.

Abstract Background Resistance to immune checkpoint inhibitors (ICIs) represents a major unmet medical need in non-small cell lung cancer (NSCLC) patients. Vascular endothelial growth factor (VEGF) inhibition may reverse a suppressive microenvironment and recover sensitivity to subsequent ICIs. Methods This phase Ib/IIa, single-arm study, comprised dose-finding (Part A) and expansion (Part B) cohorts. Patients with ICIs-refractory NSCLC were enrolled to receive anlotinib (a multi-target tyrosine kinase inhibitor) orally (from days 1 to 14 in a 21-day cycle) and nivolumab (360 mg every 3 weeks, intravenously) on a 21-day treatment cycle. The first 21-day treatment cycle was a safety observation period (phase Ib) followed by a phase II expansion cohort. The primary objectives were recommended phase 2 dose (RP2D, part A), safety (part B), and objective response rate (ORR, part B), respectively. Results Between November 2020 and March 2022, 34 patients were screened, and 21 eligible patients were enrolled (6 patients in Part A). The RP2D of anlotinib is 12 mg/day orally (14 days on and 7 days off) and nivolumab (360 mg every 3 weeks). Adverse events (AEs) of any cause and treatment-related AEs (TRAEs) were reported in all treated patients. Two patients (9.5%) experienced grade 3 TRAE. No grade 4 or higher AEs were observed. Serious AEs were reported in 4 patients. Six patients experienced anlotinib interruption and 4 patients experienced nivolumab interruption due to TRAEs. ORR and disease control rate (DCR) was 19.0% and 76.2%, respectively. Median PFS and OS were 7.4 months (95% CI, 4.3-NE) and 15.2 months (95% CI, 12.1-NE), respectively. Conclusion Our study suggests that anlotinib combined with nivolumab shows manageable safety and promising efficacy signals. Further studies are warranted. Trial registration NCT04507906 August 11, 2020.

Abstract China’s environmental criminal law serves as the strongest legal safeguard for the construction of an ecological civilization, revealing the country’s determination and efforts in environmental protection. Prior to 2011, Article 338 of China’s Criminal Law, which is most closely associated with the punishment of polluters, was rarely applied effectively. However, following the revision of Article 338 to address environmental pollution crime in 2011, more than 10,000 cases were filed in just a few years; thus, this law has played a significant role in the smooth advancement of China’s ecological civilization. An empirical analysis of 1600 instances of environmental pollution crime revealed that Chinese courts continue to give precedence to conventional sentencing factors in the enforcement of this criminal law. Despite the vigorous promotion of the ecological civilization concept in recent years within China, its integration into the judiciary process appears inadequate, and the boundaries of environmental pollution crime remain vaguely delineated. Given these circumstances, there is a pressing need for China to enhance its legislative and judicial frameworks regarding environmental criminal law to ensure robust and enduring support for the nation’s sustainable development.

Abstract Background Existing researches on nurses’ work engagement and job burnout have mostly stayed at the individual level, and limited researches test the cross-level effects of psychosocial safety climate (PSC). The study aimed to explore the cross-level mediating effect of organization-based self-esteem (OBSE) and the moderating effect of psychological detachment between the relationship of PSC and work engagement and job burnout in nurses. Methods The cross-sectional study was conducted during November to December 2022 at a tertiary hospital in a northeastern province of China. Data was collected from 1832 nurses through an online questionnaire. Correlation analyses and hierarchical linear modeling were used to test study hypotheses. Results The results showed that PSC was positively associated with work engagement, and negatively associated with job burnout. OBSE mediated the effect of PSC on work engagement, as well as job burnout. Additionally, psychological detachment played a moderating role between PSC and work engagement, but no moderating effect was found between PSC and job burnout. Conclusions PSC at the organizational level increases work engagement and reduces job burnout by stimulating nurses’ high levels of OBSE. Psychological detachment, as a situational factor, enhances the positive influence of PSC on work engagement. The implementation of measures to improve the PSC levels of the organization, and the levels of OBSE and psychological detachment among nurses could help to promote their good work performance.

Abstract Understanding the temporal dynamics of soil microbial biomass is crucial for assessing soil ecosystem functions and services, yet these dynamics are globally uncertain. Here, we compiled a data set of soil microbial biomass carbon (MBC) and nitrogen (MBN) from 1493 studies between 1988 and 2019 to elucidate their temporal trends and potential drivers. Results showed that global MBC and MBN significantly decreased by 0.033 Mg C ha−1 yr−1 and 0.007 Mg N ha−1 yr−1 at 0–30 cm soil depth, between 1988 and 2019, respectively, which might be primarily attributed to the warming of the climate, the increase in global precipitation, and reduction of soil organic carbon (SOC) stock. The rate of decline in MBC and MBN showed a non‐linear trend: following a decline from 1988 to 1999, it slowed down until 2014, likely due to the global warming hiatus. Afterward, the pace of decline increased again from 2015 to 2019. Boreal biomes experienced the largest decrease in soil microbial biomass with the reduction rate of MBC being 4.3 times higher than in temperate biomes, showing a higher sensitivity in boreal biomes to climate change. Grassland ecosystems also exhibited greater reductions, possibly driven by their degradation. These findings shed valuable insights on the long‐term dynamics of soil microbial biomass on a global scale over the last three decades. Furthermore, this study underscores the importance of preserving soil microbial biomass as a key strategy to mitigate the adverse effects of future climate change, thereby sustaining ecosystem health and resilience.

Summary: Pancreatic ductal adenocarcinoma (PDAC) poses significant clinical challenges, often presenting as unresectable with limited biopsy options. Here, we show that circulating tumor cells (CTCs) offer a promising alternative, serving as a “liquid biopsy” that enables the generation of in vitro 3D models and highly aggressive in vivo models for functional and molecular studies in advanced PDAC. Within the retrieved CTC pool (median 65 CTCs/5 mL), we identify a subset (median content 8.9%) of CXCR4+ CTCs displaying heightened stemness and metabolic traits, reminiscent of circulating cancer stem cells. Through comprehensive analysis, we elucidate the importance of CTC-derived models for identifying potential targets and guiding treatment strategies. Screening of stemness-targeting compounds identified stearoyl-coenzyme A desaturase (SCD1) as a promising target for advanced PDAC. These results underscore the pivotal role of CTC-derived models in uncovering therapeutic avenues and ultimately advancing personalized care in PDAC.

Abstract Background Deep brain stimulation (DBS) is a promising therapy for refractory Gilles de la Tourette syndrome (GTS). However, its long-term efficacy, safety, and recommended surgical age remain controversial, requiring evidence to compare different age categories. Methods This retrospective cohort study recruited 102 GTS patients who underwent DBS between October 2006 and April 2022 at two national centers. Patients were divided into two age categories: children (aged 0.05), and the children group received significantly higher improvement in GTS-QOL scores than adults (55.9% vs. 47.9%, p = 0.049). Conclusions DBS showed acceptable long-term efficacy and safety for both children and adults with GTS. Surgeries performed for patients younger than 18 years seemed to show acceptable long-term efficacy and safety and were not associated with increased risks of loss of benefit compared to patients older than 18 at the time of surgery. However, surgeries for children should also be performed cautiously to ensure their refractoriness and safety.

In order to improve the symptoms of "Shanghuo" and the universality of ginseng, the animals randomly divided into control group, the 2 and 4 g/kg ginseng group and ginseng dandelion root compatibility group were given intragastric administration for 19 days, respectively. Body temperature, blood pressure and 5-hydroxytryptamine (5-HT), thyroid-stimulating hormone (TSH), corticosterone (CORT) and other indicators associated with "Shanghuo" were measured. The results showed that the body temperature and blood pressure of the 2 and 4 g/kg groups were lower than those of the ginseng group, and the effect of the 4 g/kg group was more significant (P

Organic proteins are attractive owing to their unique optical properties, remarkable mechanical characteristics, and biocompatibility. Manufacturing multifunctional structures on organic protein films is essential for practical applications; however, the controllable fabrication of specific structures remains challenging. Herein, we propose a strategy for creating specific structures on silk film surfaces by modulating the bulging and ablation of organic materials. Unique surface morphologies such as bulges and craters with continuously varying diameters were generated based on the controlled ultrafast laser-induced crystal-form transition and plasma ablation of the silk protein. Owing to the anisotropic optical properties of the bulge/crater structures with different periods, the fabricated organic films can be used for large-scale inkless color printing. By simultaneously engineering bulge/crater structures, we designed and demonstrated organic film-based optical functional devices that achieves holographic imaging and optical focusing. This study provides a promising strategy for the fabrication of multifunctional micro/nanostructures that can broaden the potential applications of organic materials.

Long-term permeability experiments have indicated that sorption-induced swelling can switch from internal to bulk depending on the evolutive sorption status. However, this sorption swelling switch mechanism has not been considered in current analytical permeability models. This study introduces a normalized sorption non-equilibrium index (SNEI) to characterize the sorption status, quantify the dynamical variations of matrix swelling accumulation and internal swelling partition, and formulate the sorption swelling switch model. The incorporation of this index into the extended total effective stress concept leads to an analytical transient coal permeability model. Model results show that the sorption swelling switch itself results in the permeability switch under stress-constrained conditions, while the confined bulk swelling suppresses the permeability recovery to the continuous reduction under displacement-constrained conditions. Model verifications show that current experimental observations correspond to the early stages of the transient process, and they could be extended to the whole process with these models. This study demonstrates the importance of the sorption swelling switch in determining permeability evolution using simple boundary conditions. It provides new insights into experimentally revealing the sorption swelling switch in the future, and underscores the requirement of a rigorous model for complex coupled processes in large-scale coal seams.

Objectives: Caner-derived exosomes, containing diverse nucleic acids and proteins, are being exploited in diagnostic biomarker development. This study aims to screen and identify the altered exosomal proteins between epithelial ovarian cancer (EOC) patient and healthy volunteers, and to evaluate their diagnostic accuracy for EOC. Methods: Exosomes were separate by ultracentrifugation, and then subjected to TEM, qNano, and western blot for identification. Exosomal EFEMP1 and SERPINC1 were selected by MS/MS analysis, validated by ELISA in a cohort with 163 healthy donors, 183 EOC patients and 30 patients with benign ovarian tumors. Results: MS/MS analyses identified a total of 207 differential exosomal proteins, including the 122 up-regulated and 85 down-regulated. Exosomal EFEMP1 and SERPINC1 were significantly upregulated in EOC patients compared with those in healthy donors as well as in the benign patients, possessing favorable diagnostic efficiency. The area under the curves (AUCs) were 0.8071, 0.8211, respectively. They also exerted rather high early diagnostic efficiency, as well as the potential to distinguish the malignant patients from the benign individuals. Besides, exosomal SERPINC1 was associated with coagulation index and LE-DVT (lower extremity deep venous thrombosis) in EOC patients. Conclusions: Exosomal EFEMP1 and SERPINC1 are upregulated and serve as the promising diagnostic biomarkers for EOC.

ABSTRACTBackground The biofilm formation in Dental Unit Waterlines (DUWLs) could become an important cause of infection during dental care, which could put immunocompromised individuals at risk of cross-infection. The aim of this study was to characterize the microbial communities of biofilms among DUWLs using high-throughput sequencing technology.Methods Twenty-nine biofilm samples were obtained from 24 dental chair units at 5 hospitals and 2 dental clinics. The genomic DNA of the samples was extracted, then 16S rDNA and ITS2 gene were amplified and sequenced. Alpha-diversity and Beta-diversity were calculated with QIIME2 and the Kruskal – Wallis H-test was adopted for statistical analysis.Results Microbial communities with a high diversity of bacteria (377 genera) and fungi (83 genera) were detected in the biofilm samples. The dominant phylum of bacteria was Proteobacteria (93.27%) and that of fungi was Basidiomycota (68.15%). Potential human pathogens were detected including 7 genera of bacteria (Pseudomonas, Stenotrophomonas, Hafnia-Obesumbacterium, Burkholderia-Caballeronia-Paraburkholderia, Ralstonia, Enterobacter, Klebsiella) and 6 genera of fungi (Malassezia, Candida, Alternaria, Cryptococcus, Rhodotorula, Rhinocladiella).Conclusions This multicenter assessment revealed the infectious risk during dental care. It emphasized the importance of biofilm control due to biofilm accumulation and multiple kinds of opportunistic pathogens in DUWLs.

Abstract Renewable energy‐driven proton exchange membrane water electrolyzer (PEMWE) attracts widespread attention as a zero‐emission and sustainable technology. Oxygen evolution reaction (OER) catalysts with sluggish OER kinetics and rapid deactivation are major obstacles to the widespread commercialization of PEMWE. To date, although various advanced electrocatalysts have been reported to enhance acidic OER performance, Ru/Ir‐based nanomaterials remain the most promising catalysts for PEMWE applications. Therefore, there is an urgent need to develop efficient, stable, and cost‐effective Ru/Ir catalysts. Since the structure‐performance relationship is one of the most important tools for studying the reaction mechanism and constructing the optimal catalytic system. In this review, the recent research progress from the construction of unsaturated sites to gain a deeper understanding of the reaction and deactivation mechanism of catalysts is summarized. First, a general understanding of OER reaction mechanism, catalyst dissolution mechanism, and active site structure is provided. Then, advances in the design and synthesis of advanced acidic OER catalysts are reviewed in terms of the classification of unsaturated active site design, i.e., alloy, core‐shell, single‐atom, and framework structures. Finally, challenges and perspectives are presented for the future development of OER catalysts and renewable energy technologies for hydrogen production.

Study region: Upstream of the Heilongjiang River, located in Northeast Asia, is the transboundary river between China and Russia. Study focus: Using long-term hydrological records provided by the Mohe station in combination with multiple statistical approaches, we investigate how river ice phenology of the Heilongjiang River has varied during the period 1957–2016, and quantitatively assess the individual contribution of changes in different climatic factors to such variation in river ice phenology. New insights for the region: We show the later occurrence for newly formed ice date, ice-on date, and freeze-up date and the earlier occurrence for beak-up date and ice-off date, ultimately leading to a decrease in persistence of river ice in the Heilongjiang River. River ice phenology exhibits a general lag response to climate change, with ranging from 1 to 5 months. Further attribution analysis that explicitly considers time-lag effect suggests that climate change plays a dominant role in regulating river ice phenology. More specifically, compared to other climatic factors, air pressure and maximum and minimum temperature changes have larger contributions to variation in river ice phenology, particularly for the delay of formation time. These findings provide technical basis and beneficial reference to the development of regional river management strategies involved in climate change adaptation framework.

Introduction: Sodium zirconium cyclosilicate (SZC) is a nonabsorbed cation-exchanger approved in China for the treatment of hyperkalemia [HK; serum potassium (sK+) levels >5.0 mmol/L]. This is the first real-world study aimed to assess the effectiveness, safety, and treatment patterns of SZC in Chinese patients with HK. Here we present the results of the first interim analysis.Methods: This multicenter, prospective, cohort study included patients aged ≥18 years with documented HK within 1-year before study enrollment day. These patients were followed up for 6 months from the enrollment day after initiating SZC treatment. The treatment was categorized into correction phase (FAS-P1) and maintenance phase (FAS-P2 new and ongoing users). Subgroup analysis was performed in patients on hemodialysis (FAS-H). The primary objective was evaluation of safety profile of SZC; secondary objectives included assessment of treatment patterns of SZC and its effectiveness.Results: Of 421 screened patients, 193, 354, and 162 patients were enrolled in the FAS-P1, FAS-P2, and FAS-H groups, respectively. sK+ levels were reduced significantly from 5.9 mmol/L to 5.0 mmol/L after the correction phase. For the maintenance phase, the mean sK+ levels were maintained at 5.2 mmol/L and 5.0 mmol/L in the FAS-P2 new and ongoing user, respectively, and 5.3 mmol/L in the FAS-H subgroup. A considerable proportion of patients showed normokalemia after 48 h of SZC treatment (FAS-P1:51.3%) which was maintained up to 6 months in the maintenance phase (FAS-P2:44%). SZC was well-tolerated.Conclusion: SZC was effective and safe for the treatment of HK in real-world clinical practice in China.

Abstract Aberrant tumor mechanical microenvironment (TMME), featured with overactivated cancer‐associated fibroblasts (CAFs) and excessive extracellular matrix (ECM), severely restricts penetration and accumulation of cancer nanomedicines, while mild‐hyperthermia photothermal therapy (mild‐PTT) has been developed to modulate TMME. However, photothermal agents also encounter the barriers established by TMME, manifesting in limited penetration and heterogeneous distribution across tumor tissues and ending with attenuated efficiency in TMME regulation. Herein, it is leveraged indocyanine green (ICG)‐loaded soft nanogels with outstanding deformability, for efficient tumor penetration and uniform distribution, in combination with mild‐PTT to achieve potent TMME regulation by inhibiting CAFs and degrading ECM. As a result, doxorubicin (DOX)‐loaded stiff nanogels gain greater benefits in tumor penetration and antitumor efficacy than soft counterparts from softness‐mediated mild‐PTT. This study reveals the crucial role of nanomedicine mechanical properties in tumor distribution and provides a novel strategy for overcoming the barriers of solid tumors with soft deformable nanogels.

ABSTRACT: This study aims to identify candidate genes related to ovarian development after ovarian tissue transplantation through transcriptome sequencing (RNA-seq) and expression network analyses, as well as to provide a reference for determining the molecular mechanism of improving ovarian development following ovarian tissue transplantation. We collected ovarian tissues from 15 thirty-day-old ducks and split each ovary into 4 equal portions of comparable sizes before orthotopically transplanting them into 2-day-old ducks. Samples were collected on days 0 (untransplanted), 3, 6, and 9. The samples were paraffin sectioned and then subjected to Hematoxylin-Eosin (HE) staining and follicular counting. We extracted RNA from ovarian samples via the Trizol method to construct a transcriptome library, which was then sequenced by the Illumina Novaseq 6000 sequencing platform. The sequencing results were examined for differentially expressed genes (DEG) through gene ontology (GO) function and the Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses, gene set enrichment analysis (GSEA), weighted correlation network analysis (WGCNA), and protein-protein interaction (PPI) networks. Some of the candidate genes were selected for verification using real-time fluorescence quantitative PCR (qRT-PCR). Histological analysis revealed a significant reduction in the number of morphologically normal follicles at 3, 6, and 9 d after ovarian transplantation, along with significantly higher abnormality rates (P < 0.05). The transcriptome analysis results revealed 2,114, 2,224, and 2,257 upregulated DEGs and 2,647, 2,883, and 2,665 downregulated DEGs at 3, 6, and 9 d after ovarian transplantation, respectively. Enrichment analysis revealed the involvement multiple pathways in inflammatory signaling, signal transduction, and cellular processes. Furthermore, WGCNA yielded 13 modules, with 10, 4, and 6 candidate genes mined at 3, 6 and 9 d after ovarian transplantation, respectively. Transcription factor (TF) prediction showed that STAT1 was the most important TF. Finally, the qRT-PCR verification results revealed that 12 candidate genes exhibited an expression trend consistent with sequencing data. In summary, significant differences were observed in the number of follicles in duck ovaries following ovarian transplantation. Candidate genes involved in ovarian vascular remodeling and proliferation were screened using RNA-Seq and WGCNA.

Estrogen receptor-positive (ER+) breast cancer seriously endangers the women's physical and mental health worldwide and ER targeting therapy is vital. Here, we found that a citrus polymethoxyflavones (PMFs)-rich hydrolysate (C–H) and its major components (nobiletin and 3-methoxynobiletin) potently degrade ERα protein via the ubiquitin-proteasome pathway, thereby impairing the proliferation of ER+ breast cancer cells. Moreover, our study exhibited that C–H combined with tamoxifen (TAM) inhibited the cell proliferation of ER+ breast cancer in vitro. It was further confirmed that C–H decreased tumor growth of ER+ breast cancer in tumor-bearing 129 mice in vivo and improved the efficacy of tamoxifen. Our study revealed that the citrus PMFs have potential applications as pharmaceutical and healthcare products in breast cancer treatment by targeting ERα protein degradation.

The raw and steamed products of ginseng exhibit different efficacy, and elucidation of the underlying chemical transformation is significant for their rational application and quality control. This work was designed to holistically depict the chemical variation of Panax ginseng (PG), P. quinquefolius (PQ), and P. notoginseng (PN) induced by the steaming, and to unveil the steaming-associated markers diagnostic for differentiating between the raw and processed products, following a three-step strategy: 1) systematic ginsenosides characterization by hybrid scan (namely HDDIDDA) available on the Vion™ ion mobility-quadrupole time-of-flight mass spectrometer coupled with reversed-phase ultra-high performance liquid chromatography; 2) holistic depiction of the chemical variation and discovery of potential markers by the pattern recognition untargeted metabolomics analysis; and 3) construction of steaming-induced transformation network combined with desorption electrospray ionization-mass spectrometry imaging (DESI-MSI). Consequently, 542 ginsenosides were characterized from the raw and processed PG/PQ/PN. Steaming at 1–10 h could cause significant chemical variation, and separately 26, 28, and 18 potential markers were found for the steaming of PG, PQ, and PN. Steaming-induced transformation network mainly involved hydration of the malonyl group, hydrolysis of the glycosyl moiety, and dehydration at C-20. DESI-MSI further revealed spatial distribution of marker saponins in the cork layer, phloem, and xylem, and primarily confirmed the hydrolysis reactions occurring to ginseng steaming. Conclusively, the established strategy is practical to unveil the holistic ginsenosides variation of ginseng induced by the processing, which is useful in the quality control of both the herbal medicines and foods.

Abstract Amino acid/auxin permease (AAAP) genes encode a large family of protein transporters that play important roles in various aspects of plant growth and development. Here, we performed genome-wide identification of members in the foxtail millet (Setaria italica L.) AAAP family (SiAAAP) and their saline-alkali stress-induced expression patterns, resulting in the identification of 65 SiAAAP genes, which could be divided into eight subfamilies. Except for SiAAAP65, the remaining 64 genes were located on nine chromosomes of foxtail millet. Gene structure and conserved motif analyses indicated that the members in the same subfamily are highly conserved. Gene duplication event analysis suggested that tandem duplication may be the main factor driving the expansion of this gene family, and Ka/Ks analysis indicated that all the duplicated genes have undergone purifying selection. Transcriptome analysis showed differential expression of SiAAAPs in roots, stems, leaves, and tassel inflorescence. Analysis of cis-acting elements in the promoter indicated that SiAAAPs contain stress-responsive cis-acting elements. Under saline-alkali stress, qRT-PCR analysis showed that SiAAP3, SiLHT2, and SiAAP16 were differentially expressed between salt-alkali tolerant millet variety JK3 and salt-alkali sensitive millet variety B175. These results suggest that these genes may be involved in or regulate the response to saline-alkali stress, providing a theoretical basis for further studying the function of SiAAAPs.

In satellite remote sensing imaging, factors such as optical axis shift, image plane jitter, movement of the target object, and Earth's rotation can induce image blur. The unavailability of the image fuzzy kernel makes the necessity for blind remote sensing image deblurring clear. This study introduces a priori constraint based on the maximization of local high-frequency wavelet coefficients in clean remote sensing images, integrated with a graph-based blind deblurring model. This approach aims to produce a skeleton image that retains sharp edge details while eliminating harmful structures, thereby enabling accurate estimation of the fuzzy kernel. An alternating iteration method, combined with a straightforward thresholding approach, is employed to address our proposed nonconvex, nonlinear model. Comparative experiments demonstrate that, relative to several leading blind image deblurring algorithms, our approach demonstrates unparalleled efficacy in enhancing peak signal-to-noise ratio and structural similarity index measurements.

In order to investigate the pharmacological effect of Paeonia suffruticosa Andr. stamens on chronic non-bacterial prostatitis (CNBP) in rats, the rats with chronic abacterial prostatitis induced by castration combined subcutaneous injection of hormone (estradiol benzoate 0.25 mg·kg−1) were used as models. Forty rats with CNBP were randomly divided into five groups (8 per group): Model group (normal saline), positive group (celecoxib 250 mg·kg−1), various doses of lyophilized powder of Paeonia suffruticosa Andr. stamens groups (100, 200, 400 mg·kg−1). Another group of normal mice treated with normal saline as normal group. The therapeutic effect of Paeonia suffruticosa Andr. stamens on CNBP was evaluated by lecithin body density, prostatic index, cytokines in prostate tissue and the expression levels of TXB2 and 6-K-PGF1α in blood. The results showed that the inflammation of prostate tissue in rats was significantly improved. Compared with model group, the number of white blood cells, prostate weight, prostate index, TXB2 and the content of PGE2 in prostate tissue of rats were significantly decreased in each dosage group of Paeonia suffruticosa Andr. stamens (P0.05). The contents of 6-keto-PGF1α and NO in high dose of Paeonia suffruticosa Andr. stamens were significantly increased (P0.05). This study showed that Paeonia suffruticosa Andr. stamens had therapeutic effect on chronic abacterial prostatitis, which would provide a theoretical basis for further development and application of the Paeonia suffruticosa Andr. stamens.

Abstract Introduction Durvalumab is a check‐point inhibitor against programmed death ligand‐1 (PD‐L1), and anlotinib is a new orally administered multitarget tyrosine kinase inhibitor (TKI). Both agents have been approved in China. Preclinical and clinical trials have suggested that antiangiogenic therapy has the potential to alleviate immunosuppression and showed synergetic effect when combined with ICIs. However, it is unclear that whether this combination is effective when initiated as maintenance treatment in ES‐SCLC patients. Methods This is a multicenter, randomized, phase II study. A total of 64 eligible patients who do not experience disease progression after four cycles platinum‐based chemotherapy combined with durvalumab will be randomized to durvalumab with anlotinib or durvalumab alone until disease progression, withdrawal of consent, or unacceptable toxicity. The primary endpoint is PFS (from randomization); secondary endpoint was OS and PFS (from diagnosis), objective response rate (ORR); disease control rate (DCR) and duration of response (DOR), safety and tolerability assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Discussion We conduct a phase II study to investigate the safety and efficacy of durvalumab combined with anlotinib as maintenance treatment in ES‐SCLC patients.

Abstract Background The main aim of this study was to establish the clinicopathological and prognostic correlations between endometriosis-associated and non-endometriosis-associated primary ovarian cancer, with a view to providing a reference guide for revision of diagnostic criteria for malignant transformation of endometriosis. Methods Clinicopathological and follow-up data of 174 patients with clear cell and endometrial ovarian cancer were retrospectively extracted. Cases were divided into endometriosis-associated and non-endometriosis-associated primary ovarian cancer for comparative analysis of clinicopathological characteristics and prognosis. Results Average age and post-menopausal rate in the endometriosis-associated ovarian cancer group were lower relative to the primary ovarian cancer group (P 0.05). Furthermore, rates of resistance to platinum chemotherapy, relapse, progression-free survival and overall survival were comparable between the two groups (P > 0.05). Conclusion Endometriosis-associated and primary ovarian cancers of the same pathological type are speculated to be homologous in terms of origin from malignant transformation of endometriosis. It may therefore be necessary to revise the diagnostic criteria for ovarian endometriosis malignancy.

To improve our understanding of the carbon balance, it is significant to study long-term variations of all components of carbon exchange and their driving factors. Gross primary production (GPP), respiration (Re), and net ecosystem productivity (NEP) from the hourly to the annual sums in a subtropical coniferous forest in China during 2003–2017 were calculated using empirical models developed previously in terms of PAR (photosynthetically active radiation), and meteorological parameters, GPP, Re, and NEP were calculated. The calculated GPP, Re, and NEP were in reasonable agreement with the observations, and their seasonal and interannual variations were well reproduced. The model-estimated annual sums of GPP and Re over 2003–2017 were larger than the observations of 11.38% and 5.52%, respectively, and the model-simulated NEP was lower by 34.99%. The GPP, Re, and NEP showed clear interannual variations, and both the calculated and the observed annual sums of GPPs increased on average by 1.04% and 0.93%, respectively, while the Re values increased by 4.57% and 1.06% between 2003 and 2017. The calculated and the observed annual sums of NEPs/NEEs (net ecosystem exchange) decreased/increased by 1.04%/0.93%, respectively, which exhibited an increase of the carbon sink at the experimental site. During the period 2003–2017, the annual averages of PAR and the air temperature decreased by 0.28% and 0.02%, respectively, while the annual average water vapor pressure increased by 0.87%. The increase in water vapor contributed to the increases of GPP, Re, and NEE in 2003–2017. Good linear and non-linear relationships were found between the monthly calculated GPP and the satellite solar-induced fluorescence (SIF) and then applied to compute GPP with relative biases of annual sums of GPP of 5.20% and 4.88%, respectively. Large amounts of CO2 were produced in a clean atmosphere, indicating a clean atmospheric environment will enhance CO2 storage in plants, i.e., clean atmosphere is beneficial to human health and carbon sink, as well as slowing down climate warming.

The space fractional advection–diffusion equation is a crucial type of fractional partial differential equation, widely used for its ability to more accurately describe natural phenomena. Due to the complexity of analytical approaches, this paper focuses on its numerical investigation. A lattice Boltzmann model for the spatial fractional convection–diffusion equation is developed, and an error analysis is carried out. The spatial fractional convection–diffusion equation is solved for several examples. The validity of the model is confirmed by comparing its numerical solutions with those obtained from other methods The results demonstrate that the lattice Boltzmann method is an effective tool for solving the space fractional convection–diffusion equation.

Abstract Global warming has intensified the intensity of compound drought‐hot extremes (CDHEs), posing more severe impacts on human societies and ecosystems than individual extremes. The vulnerability of global terrestrial ecosystems under CDHEs, along with its key influencing factors, remains poorly understood. Based on multiple remote sensing data, we construct a Vine Copula model to appraise vegetation vulnerability under CDHEs, and attribute it to climatic and biotic factors for five different vegetation types. High vulnerability is detected in central and southern regions of North America, eastern and southern regions of South America, Southern Africa, northern and western Europe, and northern and eastern Australia. The drier the climate, the higher will be the vulnerability. Furthermore, biodiversity and biomass are key biotic factors influencing the vulnerability of various vegetation types, such that ecosystems with richer biodiversity and higher biomass have lower vulnerability to CDHEs. The findings deepen understanding of terrestrial ecosystem response to CDHEs.

Introduction: TT-01025-CL is an oral, irreversible small molecule that potently inhibits vascular adhesion protein-1 (VAP-1) for the treatment of inflammation associated with non-alcoholic steatohepatitis (NASH). The objectives of this study were to evaluate the safety/tolerability, pharmacokinetics, and pharmacodynamics of TT-01025-CL, a VAP-1 inhibitor, in healthy Chinese volunteers.Methods: Double-blind, placebo-controlled, dose-escalation studies were conducted in subjects randomized to receive oral once-daily TT-01025-CL (ranges: 10–300 mg [single dose]; 20–100 mg for 7 days [multiple doses]) or placebo under fasting conditions. Safety and tolerability were monitored throughout the study. Pharmacokinetic (PK) parameters were determined using non-compartment analysis. The activity of semicarbazide-sensitive amine oxidase (SSAO)-specific amine oxidase and the accumulation of methylamine in plasma were evaluated as pharmacodynamic (PD) biomarkers.Results: A total of 36 (single-dose group) and 24 (multiple-dose group) subjects were enrolled in the study. No serious adverse events (AEs) were reported, and no subject discontinued due to an AE. All treatment-emergent adverse events (TEAEs) were mild and moderate in intensity. No dose-dependent increase in the intensity or frequency of events was observed. TT-01025-CL was rapidly absorbed after administration. In the single-ascending dose (SAD) study, median Tmax ranged from 0.5 to 2 h and mean t1/2z ranged from 2.09 to 4.39 h. PK was linear in the range of 100–300 mg. The mean Emax of methylamine ranged from 19.167 to 124.970 ng/mL, with mean TEmax ranging from 13.5 to 28.0 h. The complete inhibition (>90%) of SSAO activity was observed at 0.25–0.5 h post-dose and was maintained 48–168 h post-dose. In the multiple-ascending dose (MAD) study, a steady state was reached by day 5 in the 40 mg and 100 mg dose groups. Negligible accumulation was observed after repeated dosing. PK was linear in the range of 20–100 mg. Plasma methylamine appeared to plateau at doses of 20 mg and above, with mean Emax ranging from 124.142 to 156.070 ng/mL and mean TEmax ranging from 14.2 to 22.0 h on day 7. SSAO activity in plasma was persistently inhibited throughout the treatment period. No evident change in methylamine and SSAO activity was observed in the placebo groups.Conclusion: TT-01025-CL was safe and well-tolerated at a single dose of up to 300 mg and multiple doses of up to 100 mg once daily for 7 consecutive days. Absorption and elimination occurred rapidly in healthy volunteers. Linearity in plasma exposure was observed. TT-01025-CL inhibited SSAO activity rapidly and persistently in humans. The profile of TT-01025-CL demonstrates its suitability for further clinical development.

The online prediction of power system dynamic frequency helps to guide the choice of control measures quickly and accurately after a disturbance, and this then ensures the reliable and stable operations of a power system. However, the prediction performance of the traditional single model is not accurate enough, and the prediction method cannot reflect the dynamic mechanism of the power system. To address these challenges, based on the analysis of the mechanism of the dynamic operation of a power system, a dynamic frequency online prediction method using the autoregressive integrated moving average (ARIMA) model and the deep belief network (DBN) is proposed in this paper. First, according to the mechanism of the dynamic operation of a power system, the dynamic frequency can be regarded as having two stages after the disturbance occurs. In the first stage, the frequency changes monotonously in the short term, which is predicted by the ARIMA model. Furthermore, the second stage is an oscillation phase with changing amplitude, which is predicted by the DBN. The calibration process is used to combine the two predicted results. Second, the three metrics including the frequency nadir (fnadir), the quasi-steady state frequency (fss), and the frequency curve obtained through the prediction are analyzed to measure the accuracy of the prediction results. Finally, to verify the accuracy of the proposed model, the IEEE 10-generator 39-bus benchmark system is used for verification.

In this paper, a past information-based fault detection (FD) interval observer is designed for linear time-invariant discrete-time system with external disturbances. The past outputs, upper and lower estimations in a finite time window are applied to construct observer. Design freedom of the FD observer is raised by introducing the gain matrices of past information. The interval property is realized through time-delay positive systems theory and the undetermined observer matrices is solved with disturbance attenuation, fault sensitivity and nonnegativity conditions. The decision is implemented by residual interval and natural threshold. Finally, simulation is proceeded to declare the FD performance.

Abstract Background Recent studies have shown that mesenchymal stem cell (MSC) therapy has potential therapeutic effects for patients with end-stage liver diseases. However, a consensus on the efficacy and safety of MSCs has not been reached. Methods A systemic literature review was conducted by searching the Cochrane Library and PubMed databases for articles that evaluated the impact of MSC therapy on the outcomes among patients with end-stage liver disease. Various parameters, including pre- and post-treatment model of end-stage liver disease (MELD) score, serum albumin (ALB), total bilirubin (TB), coagulation function, aminotransferase, and survival rate, were evaluated. Results This meta-analysis included a final total of 13 studies and 854 patients. The results indicated improved liver parameters following MSC therapy at different time points, including in terms of MELD score, TB level, and ALB level, compared with conventional treatment. Furthermore, the MSC treatment increased the overall survival rate among patients with liver cirrhosis and acute-on-chronic liver failure (ACLF). The changes in transaminase level and coagulation function differed between the different therapies at various post-treatment time points, indicating that MSC therapy provided no significant benefits in this regard. The further subgroup analysis stratified by liver background revealed that patients with ACLF benefit more from MSC therapy at most time points with improved liver function, including in terms of MELD score, TB level, and ALB level. In addition, no serious side effects or adverse events were reported following MSC therapy. Conclusions The meta-analysis results suggest that MSC therapy is safe and results in improved liver function and survival rates among patients with end-stage liver disease. The subgroup analysis stratified by liver background indicated that patients with ACLF benefit more from MSC therapy than patients with liver cirrhosis at most time points.

The utilization of unmanned sailboats as a burgeoning instrument for ocean exploration and monitoring is steadily rising. In this study, a dual sail configuration is put forth to augment the sailboats’ proficiency in its wind-catching ability and adapt to the harsh environment of the sea. This proposition is based on a thorough investigation of sail aerodynamics. The symmetric rigid wing sails NACA 0020 and NACA 0016 are selected for use as the mainsail and trailing wing sail, respectively, after considering the operational environment of unmanned sailboats. The wing sail structure is modeled using SolidWorks, and computational fluid dynamics (CFD) simulations are conducted using ANSYS Fluent 2022R1 software to evaluate the aerodynamic performance of the sails. Key aerodynamic parameters, including lift, drag, lift coefficient, drag coefficient, and thrust coefficient, are obtained under different angles of attack. Furthermore, the effects of mainsail aspect ratios, mainsail taper ratios, and the positional relationship between the mainsail and trailing sail on performance are analyzed to determine the optimal structure. The thrust provided by the sail to the boat is mainly generated by the decomposition of lift, and the lift coefficient is used to measure the efficiency of an object in generating lift in the air. The proposed sail structure demonstrates a 37.1% improvement in the peak lift coefficient compared to traditional flexible sails and exhibits strong propulsion capability, indicating its potential for widespread application in the marine field.

Phenology and photosynthetic capacity both regulate carbon uptake by vegetation. Previous research investigating the impact of phenology on vegetation productivity has focused predominantly on the start and end of growing seasons (SOS and EOS), leaving the influence of peak phenology metrics—particularly in typical climatic transition zones—relatively unexplored. Using a 24-year (2000–2023) enhanced vegetation index (EVI) dataset from the Moderate Resolution Imaging Spectroradiometer (MODIS), we extracted and examined the spatiotemporal variation for peak of season (POS) and peak growth (defined as EVImax) of forest vegetation in the Funiu Mountain region, China. In addition to quantifying the factors influencing the peak phenology metrics, the relationship between vegetation productivity and peak phenological metrics (POS and EVImax) was investigated. Our findings reveal that POS and EVImax showed advancement and increase, respectively, negatively and positively correlated with vegetation productivity. This suggested that variations in EVImax and peak phenology both increase vegetation productivity. Our analysis also showed that EVImax was heavily impacted by precipitation, whereas SOS had the greatest effect on POS variation. Our findings highlighted the significance of considering climate variables as well as biological rhythms when examining the global carbon cycle and phenological shifts in response to climate change.

BackgroundAs a group of environmental pollutants, polycyclic aromatic hydrocarbons (PAHs) are neurotoxic and may cause mild cognitive impairment (MCI) by inducing inflammation. Whether neutrophil-lymphocyte ratio (NLR), an inflammatory indicator, plays a mediating role in the relationship between PAHs exposure and MCI is unclear yet. ObjectiveTo investigate a potential mediating role of NLR in the association between exposure to PAHs and MCI in coke oven plant workers. MethodsEleven urine hydroxylated PAHs (OH-PAHs) of 530 coke oven plant workers were determined by high performance liquid chromatography tandem mass spectrometry. NLR was derived from participants' routine blood examination results using a fully automated haematology analyser. The associations between urinary OH-PAHs and MCI were analyzed by binary logistic regression, the associations between urinary OH-PAHs and NLR were analyzed by multiple linear regression, and the role of NLR in the relationship between urinary OH-PAHs and MCI was evaluated by mediating effect analysis. ResultsAfter controlling for confounding factors and other OH-PAHs, the results of binary logistic regression showed that for every e-fold (e is the base of the natural logarithm) increase in the concentration of 2-hydroxynaphthalene (2-OHNap) and 1-hydroxyphenanthrene (1-OHPhe), the OR (95%CI) values of reporting MCI positive were 1.21 (1.02, 1.43) and 1.25 (1.04, 1.51) respectively. For each unit increase of NLR, the OR (95%CI) of reporting MCI positive was 1.56 (1.12, 2.18). The results of multiple linear regression showed that each unit increase in natural log-transformed levels of 1-OHPhe was associated with 0.05 (95%CI: 0.01, 0.10) increase of NLR. The results of mediating effect analysis showed that the association between urinary 1-OHPhe and MCI was partially mediated by peripheral blood NLR, with a mediation ratio of 9.8%. ConclusionExposure to PAHs in coke oven plant workers may increase the risk of reporting MCI positive partially through increased NLR in peripheral blood.

Abstract Identifying genes whose expression is associated with schizophrenia (SCZ) risk by transcriptome-wide association studies (TWAS) facilitates downstream experimental studies. Here, we integrated multiple published datasets of TWAS, gene coexpression, and differential gene expression analysis to prioritize SCZ candidate genes for functional study. Convergent evidence prioritized Propionyl-CoA Carboxylase Subunit Beta (PCCB), a nuclear-encoded mitochondrial gene, as an SCZ risk gene. However, the PCCB’s contribution to SCZ risk has not been investigated before. Using dual luciferase reporter assay, we identified that SCZ-associated SNPs rs6791142 and rs35874192, two eQTL SNPs for PCCB, showed differential allelic effects on transcriptional activities. PCCB knockdown in human forebrain organoids (hFOs) followed by RNA sequencing analysis revealed dysregulation of genes enriched with multiple neuronal functions including gamma-aminobutyric acid (GABA)-ergic synapse. The metabolomic and mitochondrial function analyses confirmed the decreased GABA levels resulted from inhibited tricarboxylic acid cycle in PCCB knockdown hFOs. Multielectrode array recording analysis showed that PCCB knockdown in hFOs resulted into SCZ-related phenotypes including hyper-neuroactivities and decreased synchronization of neural network. In summary, this study utilized hFOs-based multi-omics analyses and revealed that PCCB downregulation may contribute to SCZ risk through regulating GABAergic pathways, highlighting the mitochondrial function in SCZ.

Let $ d_k(n) $ denote the k-th divisor function. In this paper, we give the asymptotic formula of the sum $ \sum\limits_{\substack{x-y\le n_i^r \le x+y \\ i = 1,2,\ldots,l} }{d_k(n_1^r+n_2^r+\ldots+n_l^r)}, $ where $ n_1, n_2, \ldots, n_l \in \mathbb{Z}^+ $, $ k\ge2 $, $ r\ge 3 $ and $ l > 2^{r-1} $ are integers.

Abstract Precipitation or dissolution due to geochemical reactions has been observed in the caprocks for CO2 geosequestration. Geochemical reactions modify the caprock sealing efficiency with self‐limiting or self‐enhancement. However, the effect of this modification on the caprock sealing efficiency has not been fully investigated through multiphysical‐geochemical coupling analysis. In this study, a multiphysical‐geochemical coupling model was proposed to analyze caprock sealing efficiency. This coupling model considered the full couplings of caprock deformation, two‐phase flow, CO2 concentration diffusion, geochemical reaction, and CO2 sorption. The two‐phase flow only occurs in the fracture network and the CO2 may partially dissolve into water and diffuse through the concentration difference. The dissolved CO2 has geochemical reactions with some critical minerals, thus altering flow channels. The CO2 in the fracture network diffuses into matrix, causing the matrix swelling. This fully coupling model was validated with a penetration experiment on a cement cube and compared with two other models for CO2 storage plumes. Finally, the effects of geochemical reactions on penetration depth and pore pressure were studied through parametric study. The numerical simulations reveal that the coupling of geochemical reactions and matrix diffusion significantly affect the caprock sealing efficiency. Geochemical reactions occur at a short time after the arrival of CO2 concentration and modify the fracture porosity. The CO2 diffusion into the matrix requires a much longer time and mainly induces matrix swelling. These effects may produce self‐enhancement or self‐limiting depending on the flow rate in the fracture network, thus significantly modifying caprock sealing efficiency.

E3 ubiquitin ligases are central modifiers of plant signaling pathways that regulate protein function, localization, degradation, and other biological processes by linking ubiquitin to target proteins. E3 ubiquitin ligases include proteins with the U-box domain. However, there has been no report about the foxtail millet (Setaria italica L. Beauv) U-box gene family (SiPUB) to date. To explore the function of SiPUBs, this study performed genome-wide identification of SiPUBs and expression analysis of them in response to saline-alkali stress. A total of 70 SiPUBs were identified, which were unevenly distributed on eight chromosomes. Phylogenetic and conserved motif analysis demonstrated that SiPUBs could be clustered into six subfamilies (I–VI), and most SiPUBs were closely related to the homologues in rice. Twenty-eight types of cis-acting elements were identified in SiPUBs, most of which contained many light-responsive elements and plant hormone-responsive elements. Foxtail millet had 19, 78, 85, 18, and 89 collinear U-box gene pairs with Arabidopsis, rice, sorghum, tomato, and maize, respectively. Tissue specific expression analysis revealed great variations in SiPUB expression among different tissues, and most SiPUBs were relatively highly expressed in roots, indicating that SiPUBs may play important roles in root development or other growth and development processes of foxtail millet. Furthermore, the responses of 15 SiPUBs to saline-alkali stress were detected by qRT-PCR. The results showed that saline-alkali stress led to significantly differential expression of these 15 SiPUBs, and SiPUB20/48/70 may play important roles in the response mechanism against saline-alkali stress. Overall, this study provides important information for further exploration of the biological function of U-box genes.

Low-carbon is a part of China's efforts to pursue the national strategy of "carbon peaking and carbon neutrality." Meanwhile, the path of low-carbon transformation of logistics has become a topic of global concern. This study constructs a technical framework of logistics carbon emissions (LCE), which is composed of carbon emission evaluation, carbon emission prediction and low-carbon strategy. All 13 prefecture-level cities in Jiangsu, China, are the application objects in empirical research. Then, the influence analysis of the LCE efficiency based on the panel Tobit model and the evolution of LCE under different scenarios are explored. The results show that: (ⅰ) during the study period (2013-2020), the LCE in Jiangsu showed an overall upward trend, with Xuzhou, Suzhou and Nanjing being the cities with the highest carbon emissions; (ⅱ) the static efficiency of LCE in Jiangsu is at a medium level, with fluctuations in Suzhou, Changzhou, Zhenjiang, Nantong, and Suqian caused by the technical change index; (ⅲ) economic level, industrial structure, fixed asset utilization rate, and ecological environment in Jiangsu are significantly positively correlated with LCE efficiency, while education popularization and energy intensity are negative; (ⅳ) LCE in Jiangsu has been drastically reduced in the low-carbon scenario compared to the baseline scenario. On the above basis, this study proposes suggestions for the low-carbon development strategies of logistics in Jiangsu.

ObjectiveInfection is a major cause of increased mortality in patients with acute-on-chronic liver failure (ACLF). This study aims to examine the potential correlation of the skeletal muscle index at the third lumbar vertebra (L3-SMI) with infections among ACLF patients and to evaluate its impact on the long-term survival.MethodsThis retrospective study included 126 patients who underwent abdominal computed tomography (CT) and were diagnosed with ACLF at our center between December 2017 and December 2021. L3-SMI was calculated using CT, and the clinical and biochemical data as well as MELD scores were also collected, so as to analyze the relationship between L3-SMI and infections in ACLF patients and the impact on long-term prognosis.ResultsOf the 126 ACLF patients enrolled, 50 had infections. In the multivariate logistic regression analysis, both L3-SMI [odds ratio (OR) = 0.89, 95% confidence interval (CI) = 0.81 – 0.97, P = 0.011] and hepatic encephalopathy (OR = 8.20, 95% CI = 1.70 – 39.59, P = 0.009) were independently associated with the risk of infection development. The overall survival (OS) estimates were obtained using Kaplan-Meier curves, and it was found that patients in the lowest tertile of L3-SMI had significantly lower 3-month, 6-month, 1-year, and 2-year survival rates than those in the highest tertile (P = 0.014; log-rank test).ConclusionLow L3-SMI is an independent risk factor for the development of infections and significantly influences the long-term survival in ACLF patients.

ABSTRACTCombined with data from the Broadband China pilots, panel data on financial fraud in prefecture-level cities from China Judgments Online are used to examine the impact of internet technology on financial fraud. We find that internet technology has significantly increased city financial fraud. The causal effect still exists after the model validity test, excluding the selection bias of Broadband China pilot cities and the reporting effect of the internet. Furthermore, the trust effect is an important mechanism, and heterogeneity analysis shows that internet technology has a more significant impact on the financial fraud committed by highly educated and young fraudsters and on high-tech-dependent financial fraud.

Glycosylated protein by transglutaminase-type could alter the structures and functional properties of proteins. However, the beneficial effects of glycosylated proteins against alcohol-induced intestinal injury remain unclear. Herein, the protective role and mechanism of glycosylated casein ameliorating alcohol-induced intestinal injury were assessed in vivo. The results showed that glycosylated casein and casein significantly relieved alcohol-induced oxidative stress and inflammatory responses in a concentration-dependent manner. The interventions of glycosylated casein and casein decreased serum parameters, improved the activities of antioxidant enzymes, reduced levels of inflammatory cytokines, and alleviated histopathological impairment in intestine tissues. Glycosylated casein and casein treatment downregulated protein expressions of TLR4, NF-κB p65, IKB-α, and MyD88 in mice, which activated the TLR4/NF-κB signaling pathway as a protective mechanism. More importantly, glycosylated caseinate showed a better effect against alcohol-induced intestinal injury than casein, suggesting that transglutaminase-mediated glycosylation of proteins is a useful technique to enforce protein biofunctions in the intestine.

A three-dimensional dynamic heat transfer mathematical model of the process when cored wire feed in molten iron is established based on finite volume method (FVM). The calculation area is meshed with triangles and quadrilaterals to determine nodes and control volumes, and implicit time integration method is used to ensure the stability of calculating process. For exposing the dynamic heat transfer behavior, the variation of temperature field and explosion characteristics of cored wires are studied. In addition, the melt loss rate of the top end of cored wire and the correlation among melt explosion depth, molten iron temperature and feeding speed of cored wires are theoretically calculated. More importantly, the influence of different structures of cored wires on the absorption rate of magnesium are considered. The calculation results are in good agreement with the experimental data, which indicate that the existing theoretical model has good validity and can provide theoretical guidance for spheroidization process in molten iron.

Abstract Compared with the traditional permanent magnet synchronous motor (PMSM), the double‐stator permanent magnet synchronous motor (DS‐PMSM) can utilise the internal space adequately and has high power density. In this study, the design method of this kind of motor will be researched. Different rotor magnetic circuit topologies are analysed while keeping the outer diameter of outer stator unchanged, and the rotor magnetic circuit topologies with higher power density are selected. Furthermore, the effects of pole‐arc coefficient and stator split ratio on the power density of the motor are analysed, so a high power density DS‐PMSM can be designed. On this basis, a kind of magnetic pole structure with unequal pole‐arc coefficient is proposed to solve the problem of large torque ripple in DS‐PMSM. Finally, the DS‐PMSM is investigated by the FEA, compared with the traditional single stator PMSM, the average torque of the DS‐PMSM is increased by 62.2%, and the torque ripple is only 3.2%.