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Climate change has exacerbated outbreaks of forest pests worldwide. In recent years, bark beetles have caused significant damage to coniferous forests of the Northern Hemisphere. Polygraphus bark beetles are widely distributed secondary pests. Recently, tree mortality caused by these beetles on the Qinghai-Tibet Plateau has been increasing; however, few studies have focused on their fungal associations. In the present study, we explored the diversity of ophiostomatalean fungi associated with these beetles on the north-eastern and southern Qinghai-Tibet Plateau. We isolated 442 ophiostomatalean strains from adult beetles and their fresh galleries, specifically targeting Polygraphus poligraphus and Polygraphus rudis infesting Picea crassifolia and/or Pinus griffithii. Based on phylogenetic and morphological features, we assigned the 442 strains to 16 species belonging to Grosmannia spp., Leptographium spp. and Ophiostoma spp. Amongst these, Ophiostoma maixiuense and Ophiostoma bicolor were the most frequently isolated species, accounting for 20.8% and 18.1% of the total number of ophiostomatalean assemblages, respectively. By comparing their fungal communities, we found that the different patterns of fungal assemblages of bark beetles from the north-eastern and southern Qinghai-Tibet Plateau may be influenced by biogeographic barriers and host tree species. The results of this study enhance our understanding of bark beetle fungal assemblages, especially Polygraphus, on the Qinghai–Tibet Plateau, with implications for forest management under changing climate.

Abstract In view of the cost and reliability issues caused by mechanical position sensors, position sensorless control (PSC) of permanent magnet synchronous motors (PMSMs) has received widespread attention. A series of rotor position estimation (RPE) schemes have been developed, in which the phase‐locked loop (PLL) plays an important role. However, the conventional phase‐locked loops face two thorny issues, one is the degradation of RPE performance under motor acceleration and deceleration conditions, and the other is high noise sensitivity. To this end, an adaptive gain PLL (AG‐PLL) is proposed for PSC of PMSM drives. The gains of the loop filter in the proposed AG‐PLL are adaptively adjusted with the estimation error in order to find a compromise between the estimation performance under motor acceleration and deceleration conditions and the noise sensitivity. Moreover, the proposed scheme avoids increasing the order of the PLL, so its dynamic performance is also guaranteed. The proposed scheme is tested based on the hardware‐in‐the‐loop platform.

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 Background Horizontal violence can cause serious mental health problems for nurses, particularly anxiety, depression, and post-traumatic stress disorder. However, the intrinsic linkage mechanism between mental symptoms of anxiety, depression, and post-traumatic stress disorder in nurses exposed to horizontal violence is unclear. This study aims to elucidate the characteristics of anxiety, depression, and post-traumatic stress disorder networks among nurses with horizontal violence exposure. Methods Data for this cross-sectional study were obtained from the baseline portion of a short longitudinal survey conducted at four tertiary hospitals in Shandong Province, China. A total of 510 nurses with horizontal violence exposure completed the General Information Scale, the Negative Acts Questionnaire, the Seven-item Generalized Anxiety Disorder Scale, the Nine-item Patient Health Questionnaire, and the Four-item SPAN. The network model was constructed using network analysis. The expected influence and the bridge expected influence of nodes were calculated. The stability and accuracy of the network were estimated. Results The results show that A4 (Trouble relaxing) and P1 (Startle) had the highest expected influence in the network. D9 (Suicidality ideation) and A5 (Restlessness) were the key bridge symptoms. Conclusions “Trouble relaxing”, “Startle”, “Suicidality ideation”, and “Restlessness” are all mental symptoms that need to be urgently improved the most in nurses exposed to horizontal violence. Nursing administrators and policymakers should implement mental health intervention programs for these symptoms as early as possible to maximize nurses’ mental health.

Calcium is one of the essential macro-elements in the human body. The scientific calcium supplementation is greatly significant to maintaining life and health. The peptide-calcium chelates with good calcium binding capacity and high bioavailability have attracted more attention. This work reviews the binding sites, binding modes, and intermolecular forces between calcium and peptides in peptide-calcium chelates. Compared with free calcium, chelated calcium is more easily absorbed in the intestine according to the summarization of the calcium absorption pathways. Peptide-calcium chelates, as a new generation of calcium supplements, have a rich source of raw materials, high bioavailability, good economic value, and broad development prospects. Further research is needed on the safety, physicochemical stability, digestive stability, and Ca2+ release mechanism of peptide-calcium chelates after intestinal absorption. This paper aims to provide new insight into the development of novel calcium supplements.

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 Rheumatoid arthritis (RA) is a common autoimmune disease, and some observational studies have indicated an association between Gastroesophageal Reflux Disease (GERD) and RA. However, the causal relationship between the two remains uncertain. We used Mendelian randomization (MR) to assess the causal relationship between GERD and RA. Two-sample Mendelian randomization analysis was performed using pooled data from large-scale genome-wide association studies. In addition, we performed multivariate MR analyses to exclude confounding factors between GERD and RA, including smoking quantity, drinking frequency, BMI, depression, and education attainment. The MR results for GERD on RA suggested a causal effect of the genetic susceptibility of GERD on RA (discovery dataset, IVW, odds ratio [OR] = 1.41, 95% confidence interval [CI] 1.22–1.63, p = 2.81 × 10−6; validation dataset, IVW, OR = 1.38, 95% CI 1.23–1.55, P = 1.76 × 10−8). Multivariate MR analysis also supports this result. But the results of the reverse MR analysis did not reveal compelling evidence that RA can increase the risk of developing GERD. Our bidirectional Two-Sample Mendelian randomization analysis and multivariate MR analysis provide support for the causal effect of GERD on RA. This discovery could offer new insights for the prevention and treatment of RA.

Abstract Background Social participation is an important index of rehabilitation and social reintegration in patients after total knee arthroplasty (TKA). However, most existing studies focus on improving patients’ functioning and activities, with only a few examining the social participation among patients after TKA. Therefore, the study aims to investigate the heterogeneity of social participation in patients three months after TKA and analyze subgroup influencing factors, to promote functional exercise and postoperative follow-up in specific patients. Methods This cross-sectional study recruited 255 patients who underwent TKA in a Tertiary Hospital in Jinan City, China, from March to July 2022. Three months after having undergone TKA, participants’ data were collected using the Numeric Pain Rating Scale, the Chinese version of the Tampa Scale of Kinesiophobia, the 10-item Kessler Psychological Distress Scale, Hospital for Special Surgery Knee-rating Scale, and Impact on Participation and Autonomy Questionnaire. Latent profile analysis was used to identify categories of patients’ social participation. Multiple logistic regression analysis was used to analyze the influencing factors of the different subgroups. Results Three months after TKA, the patients were divided into three subgroups: low social participation group (17.9%), moderate social participation group (40.8%), and high social participation group (41.3%). The vast majority of patients who underwent TKA exhibited moderate-to-high level of social participation. The multiple logistic regression analysis results showed that age, degree of pain, knee function, and kinesiophobia were the influencing factors of the potential profiles of social participation in patients three months after TKA (p

Abstract Cloud computing was developed by blending virtualization and grid computing technologies. Its purpose is to provide Internet-based, on-demand, and consumption-based access to pools of computing resources in a measurable, adaptable, and scalable manner. Task scheduling is essential to cloud computing to ensure the performance of cloud services. However, inefficient scheduling can lead to resource issues such as under-allocation and over-allocation, which wastes resources and degrades service performance. Therefore, metaheuristic algorithms are incorporated into task scheduling systems to efficiently and timely distribute complex and diverse incoming tasks to limited resources. This study aims to analyze task priorities and precisely assign them to virtual machines. This is achieved by utilizing the Black Widow Optimization (BWO) algorithm. The primary objectives are to reduce time and energy consumption, improve task success rates, and optimize turnaround efficiency. Ultimately, these improvements aim to enhance the overall trustworthiness of the system.

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.

Abstract A key factor contributing to resistance in immune checkpoint blockade (ICB) therapies is CD8+ T-cell tolerance in the tumor microenvironment (TME), partly resulting from upregulating coinhibitory receptors. Here, we describe the role of PGRN as a coinhibitory molecule that modulates the antitumor response of CD8+ T cells, thus presenting a novel immunosuppressive target for lung cancer. The in vivo subcutaneous transplanted lung cancer model showed that PGRN expression was elevated on CD8+ T cells that infiltrated transplanted lung cancers. Furthermore, PGRN deficiency was found to specifically encourage the infiltration of CD8+ T cells, enhance their proliferation, migration, and activation, and resist apoptosis, ultimately inhibiting tumor growth. This was achieved by PGRN knockout, increasing the production of T cell chemokine CCL3, which boosts the antitumor immune response induced by CD8+ T cells. Critically, the PD-L1 inhibitor exhibited a synergistic effect in enhancing the antitumor response in PGRN–/– mice. In summary, our findings highlight the significance of PGRN as a novel target for boosting CD8+ T cells antitumor immunity and its potential to overcome the resistance in ICB therapy.

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.

Abstract Background Rose (Rosa hybrida) is a globally recognized ornamental plant whose growth and distribution are strongly limited by drought stress. The role of Mediator, a multiprotein complex crucial for RNA polymerase II-driven transcription, has been elucidated in drought stress responses in plants. However, its physiological function and regulatory mechanism in horticultural crop species remain elusive. Results In this study, we identified a Tail module subunit of Mediator, RhMED15a-like, in rose. Drought stress, as well as treatment with methyl jasmonate (MeJA) and abscisic acid (ABA), significantly suppressed the transcript level of RhMED15a-like. Overexpressing RhMED15a-like markedly bolstered the osmotic stress tolerance of Arabidopsis, as evidenced by increased germination rate, root length, and fresh weight. In contrast, the silencing of RhMED15a-like through virus induced gene silencing in rose resulted in elevated malondialdehyde accumulation, exacerbated leaf wilting, reduced survival rate, and downregulated expression of drought-responsive genes during drought stress. Additionally, using RNA-seq, we identified 972 differentially expressed genes (DEGs) between tobacco rattle virus (TRV)-RhMED15a-like plants and TRV controls. Gene Ontology (GO) analysis revealed that some DEGs were predominantly associated with terms related to the oxidative stress response, such as ‘response to reactive oxygen species’ and ‘peroxisome’. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment highlighted pathways related to ‘plant hormone signal transduction’, in which the majority of DEGs in the jasmonate (JA) and ABA signalling pathways were induced in TRV-RhMED15a-like plants. Conclusion Our findings underscore the pivotal role of the Mediator subunit RhMED15a-like in the ability of rose to withstand drought stress, probably by controlling the transcript levels of drought-responsive genes and signalling pathway elements of stress-related hormones, providing a solid foundation for future research into the molecular mechanisms underlying drought tolerance in rose.

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.

Abstract Background Brain function and neuronal activity depend on a constant supply of blood from the cerebral circulation. The cerebral venous system (CVS) contains approximately 70% of the total cerebral blood volume; similar to the cerebral arterial system, the CVS plays a prominent role in the maintenance of central nervous system (CNS) homeostasis. Impaired venous autoregulation, which can appear in forms such as cerebral venous congestion, may lead to metabolic abnormalities in the brain, causing severe cerebral functional defects and even chronic tinnitus. However, the role of cerebral venous congestion in the progression of tinnitus is underrecognized, and its pathophysiology is still incompletely understood. This study elucidated the specific pathogenetic role of cerebral venous congestion in the onset and persistence of tinnitus and the possible neurophysiological mechanisms. Results We found that a rat model of cerebral venous congestion exhibited tinnitus-like behavioral manifestations at 14 days postoperatively; from that point onward, they showed signs of persistent tinnitus without significant hearing impairment. Subsequent neuroimaging and neurochemical findings showed CNS homeostatic plasticity disturbance in rats with cerebral venous congestion, reflected in increased neural metabolic activity, ultrastructural synaptic changes, upregulated synaptic efficacy, reduced inhibitory synaptic transmission (due to GABA deficiency), and elevated expression of neuroplasticity-related proteins in central auditory and extra-auditory pathways. Conclusion Collectively, our data suggest that alternations in CNS homeostatic plasticity may play a vital role in tinnitus pathology caused by cerebral venous congestion. These findings provide a new perspective on tinnitus related to cerebral venous congestion and may facilitate the development of precise interventions to interrupt its pathogenesis.

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.

Abstract Background Arthritis primarily affects older people and is a prominent cause of their activity impairment. This study aimed to examine the mediating role of depressive symptoms in the relationship between social participation and activity impairment, as well as to determine whether sex moderated the mediating effect. Methods A total of 2247 older patients with arthritis were included from the China Health and Retirement Longitudinal Study between 2015 and 2018. We first examined a simple mediation model where depressive symptoms were a mediator between social participation and activity impairment. Furthermore, sex was systematically integrated into the model as a moderator. The mediation model and moderated mediation model were analyzed using PROCESS macro. Results Mediation analysis revealed that the association between social participation and activity impairment was partially mediated by depressive symptoms (B = -0.10, 95% CI = [-0.14, -0.06]) with intermediary effect of 28.6%. Moderated mediation analysis indicated that mediation model was moderated by sex. The indirect effect of social participation on activity impairment among female patients (B = -0.15, 95% CI = [-0.21, -0.09]) was stronger than male patients (B = -0.04, 95% CI = [-0.09, -0.01]). Conclusion Social participation was the key protective factor associated with depressive symptoms and activity impairment among arthritis patients. Encouraging arthritis patients to social participation and improving the depressive symptoms might avoid activity impairment, especially for female patients.

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.

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.

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.

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.

ObjectivesSubjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) are considered as the spectrum of preclinical Alzheimer’s disease (AD), with abnormal brain network connectivity as the main neuroimaging feature. Repetitive transcranial magnetic stimulation (rTMS) has been proven to be an effective non-invasive technique for addressing neuropsychiatric disorders. This study aims to explore the potential of targeted rTMS to regulate effective connectivity within the default mode network (DMN) and the executive control network (CEN), thereby improving cognitive function.MethodsThis study included 86 healthy controls (HCs), 72 SCDs, and 86 aMCIs. Among them, 10 SCDs and 11 aMCIs received a 2-week rTMS course of 5-day, once-daily. Cross-sectional analysis with the spectral dynamic causal model (spDCM) was used to analyze the DMN and CEN effective connectivity patterns of the three groups. Afterwards, longitudinal analysis was conducted on the changes in effective connectivity patterns and cognitive function before and after rTMS for SCD and aMCI, and the correlation between them was analyzed.ResultsCross-sectional analysis showed different effective connectivity patterns in the DMN and CEN among the three groups. Longitudinal analysis showed that the effective connectivity pattern of the SCD had changed, accompanied by improvements in episodic memory. Correlation analysis indicated a negative relationship between effective connectivity from the left angular gyrus (ANG) to the anterior cingulate gyrus and the ANG.R to the right middle frontal gyrus, with visuospatial and executive function, respectively. In patients with aMCI, episodic memory and executive function improved, while the effective connectivity pattern remained unchanged.ConclusionThis study demonstrates that PCUN-targeted rTMS in SCD regulates the abnormal effective connectivity patterns in DMN and CEN, thereby improving cognition function. Conversely, in aMCI, the mechanism of improvement may differ. Our findings further suggest that rTMS is more effective in preventing or delaying disease progression in the earlier stages of the AD spectrum.Clinical Trial Registrationhttp://www.chictr.org.cn, ChiCTR2000034533.

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.

To reduce the iron loss and torque ripple of an external rotor consequent pole (ERCP) motor used in an electric vehicle air-conditioning compressor, the magnetic pole structure of the motor was improved, and an unequal piecewise consequent pole (CP) structure was designed. The performance of the motor is optimized by reducing the harmonic content in the air gap flux density and reducing the iron saturation degree of the motor. The designed CP structure can significantly reduce the iron loss and torque ripple of the motor. Based on the Taguchi method, the optimal size parameters of the unequal piecewise CP structure are determined, and the final optimization design scheme is obtained. The results of finite element simulation and high-precision iron loss model show the following: compared with the original motor, the iron loss and torque ripple of the motor with the final optimized design scheme are significantly reduced.