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Abstract Accurate classification of tropical cyclone (TC) tracks is essential for evaluating and mitigating the potential disaster risks associated with TCs. In this study, three commonly used methods (K-means, Fuzzy C-Means, and Self-Organizing Maps) are assessed for clustering historical TC tracks that originated in the South China Sea from 1949 to 2023. The results show that the K-means method performs the best, while the Fuzzy C-Means and Self-Organizing Maps methods are also viable alternatives. By applying the K-means method, the distinct characteristics of the four cluster types are investigated. Each type has different characteristics in terms of lifespan, wind speed, frequency of occurrence, Power Dissipation Index, and the spatial distribution of accumulated rainfall. The influence of El Niño-Southern Oscillation (ENSO) is evident in the patterns of TC activity. Specifically, there is a higher frequency of TC activity during La Niña years, whereas during El Niño years, the activity is reduced. This observation highlights the important role that ENSO plays in shaping the behavior of TCs and provides valuable information for predicting and preparing for these events. Understanding the unique characteristics of each cluster can help authorities and communities in the region better prepare for and respond to the potential impacts of TCs.

Abstract Bacterial transcription activator-like effectors (TALEs) promote pathogenicity by activating host susceptibility (S) genes. To understand the pathogenicity and host adaptation of Xanthomonas citri pv. malvacearum (Xcm), we assemble the genome and the TALE repertoire of three recent Xcm Texas isolates. A newly evolved TALE, Tal7b, activates GhSWEET14a and GhSWEET14b, different from GhSWEET10 targeted by a TALE in an early Xcm isolate. Activation of GhSWEET14a and GhSWEET14b results in water-soaked lesions. Transcriptome profiling coupled with TALE-binding element prediction identify a pectin lyase gene as an additional Tal7b target, quantitatively contributing to Xcm virulence alongside GhSWEET14a/b. CRISPR-Cas9 gene editing supports the function of GhSWEETs in cotton bacterial blight and the promise of disrupting the TALE-binding site in S genes for disease management. Collectively, our findings elucidate the rapid evolution of TALEs in Xanthomonas field isolates and highlight the virulence mechanism wherein TALEs induce multiple S genes to promote pathogenicity.

This study aimed to elucidate the expression patterns of miR-33 and ARC in both a rat model of temporal lobe epilepsy (TLE) and human TLE patients, to explore the role of miR-33 in epilepsy onset through its regulation of ARC expression in the hippocampus. Our findings, supported by a Dual-Luciferase reporter assay, suggest that miR-33 can bind to the 3′ UTR region of ARC. We observed that miR-33 levels were reduced at 1 hour and 60 days post-seizure, while ARC expression notably increased at these time points. In the hippocampal CA1 and CA3 regions of post-seizure rats, ARC expression significantly exceeded that of control groups. Following the transfection of HEK cells with a miR-33 mimic, there was a decrease in both ARC mRNA and protein levels, whereas the group treated with a miR-33 inhibitor displayed the opposite effect. RNA sequencing in TLE patients revealed a similar miR-33 and ARC interaction. The regulation of Arc expression by miR-33 suggests that Arc may be a target gene of miR-33 in the context of epilepsy. Our findings indicate that miR-33 downregulation could contribute to the dysregulation of Arc expression observed in TLE, potentially influencing the disease process. Further studies are required to establish the exact role of miR-33-mediated Arc regulation in the development of epilepsy.

Abstract A potential non-precious metal catalyst for oxygen reduction reaction should contain metal-N4 moieties. However, most of the current strategies to regulate the distances between neighboring metal sites are not pre-designed but depend on the probability by tuning the metal loading or the support. Herein, we report a general method for the synthesis of neighboring metal-Nx moieties (metal = Fe, Cu, Co, Ni, Zn, and Mn) via an interfacial-fixing strategy. Specifically, polydopamine is used to coat nanotemplates made of metal oxides, followed by pyrolysis to form a metal-oxide skeleton coated by rich nitrogen-doped carbon shells. After chemically etching the skeleton, only interfacial metal atoms strongly bonded with the support via nitrogen atoms are retained. The high purity (>95%) of dual Fe sites was confirmed by both the direct visualization of local regions and the indirect evidence of the averaged information. When these neighboring metal-Nx moieties are applied for oxygen reduction reaction, Fe-Nx moieties exhibit the superior activity, even outperforming commercial Pt/C in the aspects of the half-wave potential, methanol tolerance, carbon monoxide tolerance, and robustness.

Abstract Super-enhancers (SEs) represent a distinct category of cis-regulatory elements notable for their robust transcriptional activation capabilities. In tumor cells, SEs intricately regulate the expression of oncogenes and pivotal cancer-associated signaling pathways, offering significant potential for cancer treatment. However, few studies have systematically discussed the crucial role of SEs in hepatocellular carcinoma (HCC), which is one of the most common liver cancers with late-stage diagnosis and limited treatment methods for advanced disease. Herein, we first summarize the identification methods and the intricate processes of formation and organization of super-enhancers. Subsequently, we delve into the roles and molecular mechanisms of SEs within the framework of HCC. Finally, we discuss the inhibitors targeting the key SE-components and their potential effects on the treatment of HCC. In conclusion, this review meticulously encapsulates the distinctive characteristics of SEs and underscores their pivotal roles in the context of hepatocellular carcinoma, presenting a novel perspective on the potential of super-enhancers as emerging therapeutic targets for HCC.

[Objective] The evolution of rural living space system is a crucial aspect of the interactive relationship of rural production, living, and ecological spaces. In the context of rural transformation and development, focusing on the rural living space system at the village scale, exploring their changes, and clarifying the driving mechanisms of their change provide a theoretical basis and case support for enhancing the capacity of rural spatial governance and modernizing the governance system. [Methods] Taking Santuo Village in Anping Town, Fengjie County, Chongqing Municipality, within the Three Gorges reservoir area as a case study, this research utilized GIS spatial analysis, supplemented by land use data, socio-economic data, field visits and household survey data, etc, to systematically analyze the characteristics and driving factors behind of the changes of rural living space system from 2000 to 2022. [Results] (1) The living space system in Santuo Village have experienced significant changes. The period from 2000 to 2010 was marked by a steady change, while the period from 2011 to 2022 experienced an accelerated changes. (2) Key evolution characteristics include the clustering and convenience improvement of settlement-residential space system, diversification of livelihood-employment space system, expansion of consumption-shopping space system, enrichment of leisure-interaction space system, and improvement of public service facilities space system. (3) The core factors that influenced these changes were per capita household income, industrial participation status, proximity to major roads, slope, relocation policies, the improvement level of household facilities, average farming distance, and compensation methods. Secondary factors included altitude, distance to township center, distance to county center, primary forms of employment, distance to main relatives’ residences, and frequency of interaction with these relatives. [Conclusion] In the past 20 years, the rural living spaces in the Three Gorges reservoir area had been gradually optimized due to the combined influence of socioeconomic development, the willingness of rural entities, and post-project implementation support policies of the Three Gorges Project. Summarizing the evolution characteristics of rural living space systems and analyzing their driving factors is a key measure for the construction of livable, business-friendly and beautiful rural areas.

Abstract Background Caroli’s disease, an autosomal recessive, hereditary-related disorder, is a rare disease, in which the diagnosis is based primarily on medical imaging and pathophysiological examinations. It is characterized by intrahepatic cystic dilation or cysts. Hepatic resection of diseased lobes can cure or avoid the risk of malignancy. Case presentation A 65-year-old Asian man was admitted to our hospital with cholangitis and recurrent septicemia. The pathological diagnosis was polycystic bile duct dilation and cholangitis, consistent with the symptoms of Caroli’s disease. In addition, a genetic test report indicated that the autoimmune regulator (AIRE) gene had a c.275G > A variant (p. Arg92Gln hybrid mutation), which was different from the previously reported PKHD1 gene mutation in Caroli’s disease. Conclusion This finding suggests that AIRE mutations may be associated with Caroli’s disease, with a risk of death and difficulty in curing.

Abstract Background Accumulating evidence suggests that the radiographic phenotypes of patients with knee osteoarthritis (KOA) often do not correlate with their clinical findings, which are the primary reason for seeking medical care. Therefore, at OARSI 2024, we proposed a clinical finding staging system—Chinese medicine staging (CMS)—to guide the treatment of KOA. However, the clinical effectiveness and application characteristics of CMS in guiding non-surgical treatment of KOA remain unclear. Methods A total of 14,985 KOA patients were included in the study. Data from 13,983 patients were used to analyze the characteristics of CMS application, while 1465 patients were used to evaluate CMS-guided clinical effectiveness, and 152 patients were included in a comparative analysis of clinical effectiveness without CMS guidance. The demographic characteristics of the CMS-using population were examined, and the correlation between CMS and treatment modalities was analyzed to clarify CMS application characteristics. VAS and WOMAC scores were compared between the CMS-guided and non-CMS-guided groups both before treatment and at week 8 of treatment, using the minimal clinically significant difference as the benchmark. Results In application characteristics, regarding nonsurgical treatments, an increase in the CMS led to a decrease in basic treatment and an increase in nonpharmacological and pharmacological treatments (P 0.05). In clinical effectiveness, at week 8 of treatment, VAS scores and WOMAC scores were significantly lower in CMS-guided group (VSA: 3.51; 95% CI, 3.42–3.60, Pain: 3.55; 95% CI, 3.40–3.70, Stiffness: 1.18; 95% CI, 1.11–1.25, Function: 12.57; 95% CI, 12.07–13.08, Total: 17.31; 95% CI, 16.63–17.99), which had a higher net difference than non-CMS-guided group (VSA: 3.30; 95% CI, 3.05–3.54, Pain: 3.14; 95% CI, 2.68–3.60, Stiffness: 0.95; 95% CI, 0.76–1.15, Function: 11.36; 95% CI, 9.80–12.91, Total: 15.45; 95% CI, 13.40–17.49). The net differences in CMS-guided group were all higher than in MCID. Conclusion CMS is consistent with the patient’s clinical finding, is suitable for guiding non-surgical treatment of KOA and can achieve clinically significant therapeutic effects.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has surged as a major cause of liver transplants in the United States. Existing studies have presented conflicting findings regarding the association between liver characteristics (specifically steatosis and fibrosis) and mortality. This study investigates the relationship between the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) via vibration-controlled transient elastography (VCTE) and all-cause mortality in MASLD patients. Methods: Using the NHANES 2017-2018 database, 3821 individuals representing the United States population with MASLD underwent VCTE for liver stiffness measurement. Exclusion criteria were applied, eliminating ineligible cases, incomplete examinations, underage individuals, and those with hepatitis B or C, along with significant alcohol consumption history. Cox proportional hazard models assessed the hazard ratio (HR) for all-cause mortality in CAP and LSM. Cox regression analysis with interaction terms was employed for deeper exploration. Results: The study unveiled a strong, independent correlation between LSM and all-cause mortality. However, the CAP failed to demonstrate a significant association with mortality in both univariate and adjusted analyses, contrary to recent findings. The analysis underscores the importance of accurately measuring liver stiffness via VCTE in predicting adverse outcomes in MASLD patients, emphasizing the pivotal role of fibrosis in assessing mortality risk. Conclusion: This study reaffirms the robust link between liver fibrosis (measured through VCTE) and mortality among MASLD individuals. The absence of a significant association between steatosis (indicated by CAP) and mortality challenges recent research, urging further comprehensive investigations with larger cohorts to delineate steatosis’ precise impact on MASLD-related mortality.

Abstract Rural Revitalization (RR) is a key national strategy in China aimed at sustainable rural development and has gained significant attention. Given the unique characteristics of different villages, understanding differentiated paths to achieve RR is essential. This study introduces a new “5I Framework” (INDUS-INHAB-INDOC-INFRA-INCOM) to assess RR’s overall development status (ODS) and differentiated paths. Then, using western China as a case, this study employs entropy weight, the technique for order preference by similarity to an ideal solution (TOPSIS), fuzzy set qualitative comparative analysis (fsQCA), and hierarchical clustering to categorize differentiated RR paths into “4L Category” (Lots-Learning-Labor-Living). Context-specific recommendations are provided for each category. “5I” and “4L” are derived from their initial letters for easier recall and global dissemination. Our findings reveal ODS’s temporal fluctuations between Acceptable and Good Grades (0.3 and 0.6), with Chongqing’s villages showing a downward trend (from 0.439 to 0.407); the findings also reveal spatial differences in ODS, as northern villages generally score higher due to distinct characteristics. Seven differentiated paths to RR are identified, highlighting varying dimensions essential for RR success: INFRA is crucial across all high ODS paths, while INHAB and INDOC are not always central. Besides, these paths are grouped into four clusters via hierarchical clustering, indicating that RR can be achieved by integrating “lots” of aspects, enhancing “learning” and cultural status among residents, requiring villagers’ “labor” to support agriculture, or improving the “living” environment. The clustered categories enhance the applicability of our proposed countermeasures in similar contexts. The “5I Framework” facilitates theoretical understanding and evaluation of RR, while the “4L Category” underpinned by the “5I Framework” promotes effective implementation practices—both representing innovations of this study.

Objective To analyze the risk factors of infectious in hepatocellular carcinoma (HCC) patients after transcatheter arterial chemoembolization (TACE), and construct a prediction model.Methods The complete clinical data of HCC patients who received TACE treatment in the department of Interventional Pain of the Second Affiliated Hospital of the Air Force Medical University from January 1, 2020 to December 31, 2023 were retrospectively analyzed. According to whether infection occurred within 30 days after TACE, the patients were divided into the infection group and the non-infection group. According to the visiting time of HCC patients undergoing TACE, they were divided into the training and validation cohorts. Multivariate Logistic regression analysis was used to determine independent risk factors and construct a prediction model. The area under the curve (AUC) of the receiver operating characteristic curve, calibration curve analysis (CCA) and the Brier score, decision curves analysis (DCA) were used to evaluate the performence of the prediction model.Results A total of 592 HCC patients with TACE were included, the infection rate after TACE was 10.30%, with Gram-negative bacteria was most common infection (55.41%). Comorbid diabetes [OR=12.694, 95%CI(4.415, 36.497)], maximum lesion diameter > 5 cm [OR=7.620, 95%CI(1.994, 29.111)], ascites[OR=5.106, 95%CI(2.226, 11.711)], intraoperative blood loss ≥ 500 mL [OR=20.588, 95%CI(7.269, 58.311)], and operation time≥120 minutes [OR=1.284, 95%CI(1.093, 1.872)] were independent risk factors for post-TACE infection. The AUC of the prediction model in the training set and the validation set were 0.907 and 0.931. CCA showed good consistency of the "predicted probability" and the "actual probability" of the post-TACE infection prediction model, and the Brier scores in the training set and the validation set were 0.084 and 0.075. The DCA curve suggested that the prediction model provided good clinical net benefit.Conclusion Comorbid diabetes, maximum lesion diameter > 5 cm, ascites, intraoperative blood loss ≥ 500 mL, and operation time ≥ 120 minutes were independent risk factors for post-TACE infection. The post- TACE infection prediction model can better identify the occurrence of TACE infection in HCC patients and is a useful tool for early identification of post-TACE infection.

Abstract. Sepsis-related organ dysfunction is associated with increased morbidity and mortality. Previous studies have found that the endothelium plays crucial roles in maintaining the vascular permeability during sepsis, as well as in regulating inflammation and thrombosis. During sepsis, endothelial cells may release cytokines, chemokines, and pro-coagulant factors, as well as express adhesion molecules. In general, endothelial responses during sepsis typically inhibit bacterial transmission and coordinate leukocyte recruitment to promote bacterial clearance. However, excessive or prolonged endothelial activation can lead to impaired microcirculation, tissue hypoperfusion, and organ dysfunction. Given the structural and functional heterogeneity of endothelial cells in different organs, there are potential differences in endothelial responses by organ type, and the risk of organ damage may vary accordingly. This article reviews the endothelial response observed in sepsis and its effects on organ function, summarizes current progress in the development of therapeutic interventions targeting the endothelial response, and discusses future research directions to serve as a reference for researchers in the field.

Abstract Background The global incidence of frozen shoulder (FS) (2% ~ 5%) and osteoporosis (OP) is high (9.1%-12.1%). Clinically, postmenopausal women are particularly at risk for both diseases. The main objective of this current research is to investigate the pathogenesis mechanism of FS and explore the connection between FS and OP. Methods We obtained FS and OP datasets from GEO and identified crosstalk genes. Following KEGG and GO enrich analysis, the p38 MAPK signaling pathway was focused and the specific p38α inhibitor TAK715 was screened out. We conducted flow cytometry, western blot, and PCR analyses to assess the treatment effect of TAK715 on FS synovium fibroblasts at different concentrations. Additionally, we employed SD rats to validate the treatment effects of TAK715 in vivo. Results TAK715 was useful in reversing fibrosis at the concentration of 1 μM, 5 μM and 10 μM. The unbalanced apoptosis process in frozen shoulder cell and the activation of osteoclast were inhibited at the concentration of 5 μM by TAK715. Then we successfully established a FS and OP rat model, with the FS with OP rat displaying less range of motion (ROM) and thicker shoulder capsule. In FS rat that was treated with TAK715, the frozen shoulder side was corrected in ROM and bone loss. Conclusions The frozen shoulder with osteoporosis may exhibit more severe symptoms, and TAK715 is effective in protecting fibrosis and osteoporosis both in vitro and vivo. The therapy to correct FS and OP simultaneously by TAK715 provides novel approach in FS treatment and study.

Abstract Background Changes in precipitation alter soil moisture, thereby affecting the aboveground and belowground ecological processes. However, it remains unclear whether plant root systems alter these effects through rhizospheric processes. In this study, a precipitation control experiment was conducted in the alpine grassland of northern Tibet to simulate precipitation changes with a 50% decrease and 50% increase in precipitation. Nutrient and microbial biomass, root traits, and survival strategies in the rhizosphere and bulk soils of the dominant plant, Stipa purpurea, were analyzed for alterations under precipitation changes. Results Increased precipitation (IP) significantly decreased the rhizosphere soil total phosphorus and bulk soil ammonium nitrogen and increased the rhizosphere soil total potassium. Decreasing precipitation (DP) significantly increased the rhizosphere soil total potassium and decreased the bulk soil total potassium. DP significantly reduced microbial biomass carbon, nitrogen and phosphorus in rhizosphere soil, while IP significantly increased the bulk soil MBC:MBP, soil C:P imbalance, and soil N:P imbalance. Along the PC1 axis, where the contribution of the traits was relatively large, it was possible to define the root economic spectrum. The root system of Stipa purpurea from the DP treatment was distributed on the conservative side of the economic spectrum, whereas that from the control and IP treatments were clustered on the acquisition side. Conclusions Increasing and decreasing precipitation mainly affected the contents of total phosphorus and total potassium in rhizosphere soil and the contents of ammonium nitrogen and total potassium in bulk soil of Stipa purpurea. The microbial biomass carbon, nitrogen and phosphorus were mainly affected by a decrease in precipitation. Decreasing precipitation significantly reduced microbial biomass carbon, nitrogen and phosphorus, but the rhizosphere MBC:MBN, MBC:MBP and MBN:MBP remained stable under the change of precipitation. Increasing precipitation exacerbated the C:P imbalance and N:P imbalance in bulk soil, and increased the demand for phosphorus by bulk microorganisms. Increased precipitation promoted root access to resources. The root system of Stipa purpurea in the context of precipitation changes was driven by rhizosphere nutrients and bulk microorganisms. This study is important for revealing plant–microbe–soil interactions in terrestrial ecosystems.

Abstract Background Mobile phone addiction (MPA) has numerous deleterious effects on college students, including depression, anxiety, cognitive impairments, and sleep disorders. Undergraduate nursing students play a crucial role as a significant reserve workforce in clinical nursing practice, and their compromised mental health status significantly influences the quality of nursing work and nurse-patient relationships in the future. Objectives This study aims to investigate the associations between neuroticism and MPA among undergraduate nursing students, the mediating effect of self-control and the moderating effect of psychological capital. Methods A total of 900 undergraduate nursing students participated in the survey, wherein the Eysenck Personality Questionnaire Short Form Scale China Version-Neuroticism Subscale (EPQ-RSC-N), Self-Control Scale (SCS), Positive Psychological Capital Questionnaire (PPQ), and Mobile Phone Addiction Tendency Scale (MPATS) were employed for assessment. To analyze the available data, various statistical methods were utilized, including common method bias test examination, descriptive statistics, chi-square tests, independent samples t-tests, Pearson’s correlation analyses, as well as the Hayes’ PROCESS Macro models 4 and 14. Results (1) The prevalence of MPA in this study was found to be 34.89%. (2) The MPA was positively correlated with neuroticism (r = 0.287, p

Currently, the rapid development of the industrial Internet has led to the creation of a massive number of intelligent agents that are widely and distributively applied in various edge scenarios. The work conditions in these edge scenarios are complex, uncertain, and random. Traditional manual updates or human judgments are used for task decision-making in large-scale distributive intelligent agent edge work scenarios, which lack dynamic perception and autonomous recognition capabilities for edge work conditions. This inevitably leads to low decision-making accuracy, poor reliability, and ultimately, task failure. To address this issue, this study proposes an adaptive task identification strategy based on cloud-edge collaboration. This method utilizes a cloud-edge collaborative industrial intelligent application architecture to achieve cloud-based training and encapsulation of the task model, with online calling at the edge-end. Then, edge-end intelligent agents identify edge work conditions through multi-source data fusion, enabling accurate task decision-making. Finally, the edge-end requests the cloud for task model matching. The effectiveness of the proposed method is validated in an industrial safety situation virtual detection system.

Abstract Debris flows continuously erode the channel downward and sideways during formation and development, which changes channel topography, enlarges debris flow extent, and increases the potential for downstream damage. Previous studies have focused on debris flow channel bed erosion, with relatively little research on lateral erosion, which greatly limits understanding of flow generation mechanisms and compromises calibration of engineering parameters for prevention and control. Sidewall resistance and sidewall shear stress are key to the study of lateral erosion, and the distribution of the flow field directly reflects sidewall resistance characteristics. Therefore, this study has focused on three aspects: flow field distribution, sidewall resistance, and sidewall shear stress. First, the flow velocity distribution and sidewall resistance were characterized using laboratory debris flow experiments, then a debris flow velocity distribution model was established, and a method for calculating sidewall resistance was developed based on models of flow velocity distribution and rheology. A calculation method for the sidewall shear stress of debris flow was then developed using the quantitative relationship between sidewall shear stress and sidewall resistance. Finally, the experiment was validated and supplemented through numerical simulations, enhancing the reliability and scientific validity of the research results. The study provides a theoretical basis for the calculation of the lateral erosion rate of debris flows.

Frozen shoulder (FS) manifests as progressively worsening pain and a reduction in shoulder range of motion (ROM). Salvianolic acid B (SaB) is recently expected to be used in the treatment of fibrosis diseases including FS. We firstly demonstrate that SaB can effectively hinder the progression of oxidative stress, inflammation, and pathological fibrosis within the synovial tissue in FS, potentially leading to the reduction or reversal of capsule fibrosis and joint stiffness. For further clinical application, we design and synthesize a novel, superior, antioxidant and antibacterial CSMA-PBA/OD-DA (CPDA) hydrogel for the delivery of SaB. In vitro experiments demonstrate that the CPDA hydrogel exhibits excellent biocompatibility and rheological properties, rendering it suitable for intra-articular injections. Upon injection into the contracted joint cavity of FS model rat, the SaB-CPDA hydrogel accelerate the recovery of ROM and exhibit superior anti-fibrosis effect, presenting the promise for the treatment of FS in vivo.

Abstract Background The prognostic significance of obstructive sleep apnea (OSA) in patients with unstable angina (UA) based on remnant cholesterol (RC) or triglyceride (TG) levels remains unclear. This study aims to evaluate the effects of the interaction between RC, TG, and OSA on cardiovascular outcomes in UA patients. Methods In this prospective cohort study, OSA was diagnosed when apnea-hypopnea index of ≥ 15 events/h. Patients with high RC (HRC, n = 370) or high TG (HTG, n = 362) included RC or TG in the highest tertile, and those in the middle and lowest tertiles were defined as normal RC (NRC, n = 736) or normal TG (NTG, n = 744). The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including cardiovascular death, myocardial infarction, ischemia stroke, ischemia-driven revascularization, or hospitalization for UA. Results A total of 1,106 eligible UA patients were enrolled, among which 560 (50.6%) had OSA. RC and TG levels were increased in OSA patients, but there was no difference in the prevalence of OSA between the NRC and HRC or NTG and HTG groups. During a median follow-up of 1.9 (1.1, 3.0) years, OSA was associated with an increased risk of MACCE occurrence compared to non-OSA in UA patients with HRC (adjusted HR 2.06; 95% CI 1.20–3.51, P = 0.008), but not in those with NRC (adjusted HR 1.21; 95% CI 0.84–1.75, P = 0.297). The incremental risk in HRC was attributable to higher rates of hospitalization for UA and ischemia-driven revascularization. Results for HTG and NTG were similar. Conclusion OSA was associated with a worse prognosis in UA patients with HRC or HTG, emphasizing the necessity of identifying OSA presence in this population. Trial registration Clinicaltrials.gov; No: NCT03362385.

Abstract Background The ability of socially assistive robots (SARs) to treat dementia and Alzheimer’s disease has been verified. Currently, to increase the range of their application, there is an increasing amount of interest in using SARs to relieve pain and negative emotions among children in routine medical settings. However, there is little consensus regarding the use of these robots. Objective This study aimed to evaluate the effect of SARs on pain and negative affectivity among children undergoing invasive needle-based procedures. Design This study was a systematic review and meta-analysis of randomized controlled trials that was conducted in accordance with the Cochrane Handbook guidelines. Methods The PubMed, CINAHL, Web of Science, Cochrane Library, Embase, CNKI, and WanFang databases were searched from inception to January 2024 to identify relevant randomized controlled trials (RCTs). We used the Cochrane Risk of Bias tool 2.0 (RoB2.0) to assess the risk of bias among the included studies, and we used RevMan 5.4 software to conduct the meta-analysis. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was used to assess the quality of the evidence. Results Ten RCTs involving 815 pediatric subjects were selected for this review and reported outcomes related to pain and emotions during IV placement, port needle insertion, flu vaccination, blood sampling, and dental treatment. Children undergoing needle-related procedures with SARs reported less anxiety (SMD= -0.36; 95% CI= -0.64, -0.09) and fewer distressed avoidance behaviors (SMD= -0.67; 95% CI= -1.04, -0.30) than did those receiving typical care. There were nonsignificant differences between these groups in terms of in pain (SMD = -0.02; 95% CI = − 0.81, 0.78) and fear (SMD = 0.38; 95% CI= -0.06, 0.82). The results of exploratory subgroup analyses revealed no statistically significant differences based on the intervention type of robots or anesthetic use. Conclusions The use of SARs is a promising intervention method for alleviating anxiety and distress among children undergoing needle-related procedures. However, additional high-quality randomized controlled trials are needed to further validate these conclusions. Trial registration The protocol of this study has been registered in the database PROSPERO (registration ID: CRD42023413279).

Between 1958 and 1999, notable lithic localities recorded prehistoric activities in Xiqiao Town of Nanhai District, Foshan City, Guangdong Province, from which double-shouldered and microlith-stone artefacts were uncovered. Currently, the "Xiqiaoshan site" is recognized as a substantial Neolithic quarry and processing location, dating back to 4‒7 ka B P. Subsequently, from 2011 to 2022, we conducted multiple geological environmental surveys and analyses on Xiqiaoshan Mountain. A well-preserved Quaternary stratigraphic profile was discovered north of Fuxian village in the southeast foothills of Xiqiaoshan Mountain. The sedimentological, geochemical, and geochronological results indicate the presence of two primary sedimentary strata in the Fuxian locality. The upper unit comprises the Holocene swamp facies, with a calibrated AMS14C dating range from 5052‒5409 a B P; whereas, the lower unit comprises the late Pleistocene alluvial-diluvial strata, with a calibrated AMS14C dating range from 38420‒40502 a B P, and an optically stimulated luminescence (OSL) dating range of 41.977‒43.796 ka B P. Late Pleistocene strata yielded two sand-gravel layers containing Paleolithic artefacts, which are marked as layers A1 and A2. The predominant artefacts in lower layer A1 include larger scrapers, pointed tools, tongue-shaped edged tools, and small flake tools, such as various scrapers, denticulates, notches, knives, utilized flakes, and cores, including tanged axe-shaped knives. In the upper layer A2, backed or tanged knives appear more frequently. The other small flake tools from this layer (A2) were not significantly different from those in lower layer A1. One bifacially prepared core for producing small elongated flakes is of particular interest for this artefact. Based on the average deposition rate, the computational age of the A1 layer was 46.511‒47.325 ka B P, whereas that of the A2 layer was 41.977‒42.167 ka B P. Although the number of artefacts within the Holocene sediments (>5 ka B P) overlying the late Pleistocene strata is limited, the characteristics of inheritance and development are still evident in the types of artefacts. The discovery presented in this study has completely updated and extended the connotation of Xiqiaoshan National Geopark and "Xiqiaoshan culture,"breaking through the late Pleistocene Paleolithic remains records with exact dating in the Pearl River Delta region for the first time. Therefore, a ground-breaking discovery can accurately trace the footsteps of modern humans in the coastal areas of South China from 40‒50 ka. It also reveals the rich features of lithic industry and the developmental characteristics and evolution of its cultural connotations during this period. The present study shows that during the relatively warm and humid conditions of marine isotope stages 3 (MIS3) interglacial period and the subsequent cold and arid stage of MIS2, human population in the Fuxian locality encountered environmental challenges and adopted new subsistence strategy, which is of great significance for understanding modern human responses and adaptations to global and regional environmental and climate change.

Abstract Autophagy plays a dual role in coronavirus infection, facilitating the elimination of either proviral components (virophagy) or antiviral factors such as mitochondria (mitophagy), leading to complex mechanisms of immune evasion. Understanding the mechanisms that govern the switch between the autophagic degradation of deleterious or beneficial substrates in coronavirus infection is crucial for developing precise drug targets to treat virus-induced diseases. However, this switch remains largely unknown. Using a dual split-fluorescence assay, we identify PDPK1 as a negative regulator of innate immunity, directing the transition from virophagy to mitophagy through the phosphorylation of SQSTM1 at T138. Remarkably, a PDPK1-targeting peptide inhibits the replication of various RNA viruses by restoring innate immunity through enhanced virophagy and suppressed mitophagy, thereby protecting female mice from lethal infections. These findings underscore the detrimental role of PDPK1 in innate immunity by orchestrating the shift from virophagy to mitophagy, positioning PDPK1 as a promising pharmacological target for effectively combating a broad spectrum of virus infections.

Abstract Non-alcoholic fatty liver disease (NAFLD) is becoming a significant global public health threat. Seabuckthorn (Hippophae rhamnoides L.) has been used in traditional Chinese medicine (TCM). The hypolipidemic effects of Seabuckthorn polysaccharides (SP) against high-fat diets (HFD)-induced NAFLD were systematically explored and compared with that of Bifidobacterium lactis V9 (B. Lactis V9). Results showed that HFD-induced alanine transaminase (ALT) and aspartate aminotransferase (AST) levels decreased by 2.8-fold and 4.5-fold, respectively, after SP supplementation. Moreover, the alleviating effect on hepatic lipid accumulation is better than that of B. Lactis V9. The ACC and FASN mRNA levels were significantly reduced by 1.8 fold (P

Abstract The relationship between work and family is essential to sustainability, affecting the fertility intention and fertility behavior of childbearing age. This study aims to explore the following research questions to fill the research gaps: (1) Can WFB improve individuals’ fertility intentions (FI)? (2) How does DW affect individuals’ FI? Drawing on the job demands-resources theory (JD-R) and life history theory, we have developed a theoretical framework of work–family balance (WFB), decent work (DW), fertility intention (FI), organizational support (OS), and family support (FS). Data was collected through a questionnaire in China, and hypotheses were tested. We find that WFB significantly and positively affects DW; DW significantly positively affects FI; WFB significantly influences FI, and DW is a mediator between WFB and FI. However, OS and FS have no significant moderating effects on WFB and DW. The theoretical implications of this study are that it preliminarily explores the spillover effects of DW on family life, enriching the research on DW. The findings can be applied to formulating government policies on fertility support, human resource management practices, and personal work–family development.

Abstract Normal veins could develop to varicose vein (VV) by some risk factors, and might further progress to shallow vein thrombosis (SVT). However, the molecular mechanism of key genes associated with the progression and regression of VV are still not thorough enough. In this study, the healthy control (HC), VV, and SVT vascular samples were collected for transcriptome sequencing. The differentially expressed genes (DEGs) were screened by “DESeq2”, including DEGs1 (HC vs. VV), DEGs2 (HC vs. SVT) and DEGs3 (VV vs. SVT). And their functional enrichment analyses were conducted by “ClusterProfiler”. The receiver operating characteristic (ROC) curve was used to obtain the key genes (KGs) of the pathogenesis of VV and SVT. The qRT-PCR assay was performed to validate the expressions of KGs. Immune cell infiltration analyses were conducted based on ssGSEA method. The competitive endogenous RNAs (ceRNAs) regulatory network was constructed. The target drugs of KGs were predicted using DrugBank database. The biofunctions of DACT3 were further investigated through a series of experiments in vitro. All of these DEGs were associated with inflammation and immunity related functions. Immune cell infiltration was significantly different between VV and SVT. Six key genes including PLP2, DACT3, LRRC25, PILRA, MSX1 and APOD that were associated with the progression and regression of VV were screened. The expression of LRRC25 and PILRA was significantly negatively associated with central memory T cell, and significantly positively associated with B cell. Besides, XIST was the critical regulator of multiple KGs. Cimetidine was potential drug for VV and SVT therapy. Overexpression of DACT3 significantly inhibited the proliferation and migration of vascular smooth muscle cells (VSMCs), and affected their cell cycle and phenotypic transition. This study identified six key genes associated with the progression and regression of VV. Among them, DACT3 was proved to hinder VV progression. These findings may help to deepen understanding its underlying mechanisms.

Abstract Wearable visual bionic devices, fueled by advancements in artificial intelligence, are making remarkable progress. However, traditional silicon vision chips often grapple with high energy losses and challenges in emulating complex biological behaviors. In this study, we constructed a van der Waals P3HT/GaAs nanowires P-N junction by carefully directing the arrangement of organic molecules. Combined with a Schottky junction, this facilitated multi-faceted birdlike visual enhancement, including broadband non-volatile storage, low-light perception, and a near-zero power consumption operating mode in both individual devices and 5 × 5 arrays on arbitrary substrates. Specifically, we realized over 5 bits of in-memory sensing and computing with both negative and positive photoconductivity. When paired with two imaging modes (visible and UV), our reservoir computing system demonstrated up to 94% accuracy for color recognition. It achieved motion and UV grayscale information extraction (displayed with sunscreen), leading to fusion visual imaging. This work provides a promising co-design of material and device for a broadband and highly biomimetic optoelectronic neuromorphic system.

To improve the simulation accuracy and efficiency of crop water models in semi-arid regions and considering climate change, we conducted a sensitivity analysis of the AquaCrop model crop parameters for maize (Zea mays) based on field monitoring data from 2020 to 2021 in the Hetao Irrigation District, China. We simulated soil water and salt dynamics, crop growth, water consumption, and final yield under climate change conditions. Non-conservative parameters, such as the crop growth coefficient (CGC) and maximum effective rooting depth (Zx), significantly influenced soil water content and salt profile sensitivity. Zx was highly sensitive to soil salt content. For maize biomass and yield, maximum canopy cover (CCx) and CGC consistently showed high sensitivity. The standard crop transpiration coefficient (KcTr,x) had a significant impact on yield. Water productivity (WPET) and harvest index (HI) were mainly sensitive to CCx, KcTr,x, normalized water productivity (WP*), and reference HI (HI0). The model simulations, calibrated with these sensitive parameters, indicated that under future climate change scenarios, maize yield is projected to increase by approximately 19 % by mid-21st century due to elevated CO2 concentrations and water productivity increasing by 22–27 %. Soil salinity is expected to rise by 0.2 t ha−1 under high-emission scenarios, indicating that the challenge of soil salinization will become more severe. This study provides scientific evidence for developing agricultural management strategies to adapt to climate change, with the aim of enhancing crop yield and water-use efficiency, thus promoting sustainable agricultural development.

Objective: Cisplatin is the main chemotherapy drug for advanced ovarian cancer, but drug resistance often occurs. The aim of this study is to explore the molecular mechanism by which Guizhi Fuling capsule inhibits cisplatin resistance in ovarian cancer. Methods: First, differences in cisplatin resistance, PA2G4 gene expression, migration, and invasion in A2780 cells and A2780/DDP cells were analyzed by qRT-PCR, scratch assay, transwell, immunofluorescence, and western blotting. Then, LC-MS/MS analysis of GFC chemical composition. qRT-PCR, scratch tests, transwell, pseudopodium formation, immunofluorescence, and western blotting were used to explore the mechanism by which GFC inhibited A2780/DDP cell migration and invasion. Finally, the anti-tumor efficacy of GFC was verified by in vivo experiments. Results: A2780/DDP cells had a greater ability to migrate and invade compared to their parents. Cell viability experiments showed that the migration and invasion ability of A278/DDP cells were significantly inhibited with the increase of GFC concentration. qRT-PCR results showed that compared with the blank control group, cisplatin group and GFC group, the transcription level of PA2G4 gene in the combination treatment group was significantly reduced. We also found that GFC combined with cisplatin inhibited the PI3K/AKT/GSK-3β signaling pathway by targeting PA2G4 gene expression, inhibited the epithelial-mesenchymal transition signaling pathway, decreased cell adhesion and inhibited the formation of cell pseudopodias. Conclusion: GFC combined with cisplatin can target PA2G4 gene to regulate PI3K/AKT/GSK-3β Signaling pathway, inhibiting the invasion and migration of cisplatin resistant A2780/DDP cells in ovarian cancer.

IntroductionThe multi-targeted ligands (MTDL) strategy has been recognized as a promising Approach for the development of effective treatments against Alzheimer’s disease (AD), due to the presence of multiple pathological mechanisms in AD. In this study, a series of bis(7)-harmine derivatives were designed and synthesized as multifunctional drugs for the treatment of AD.MethodsThe derivatives were synthesized by chemical methods and their structure was confirmed by nuclear magnetic resonance (NMR). The Ellman’s assay was utilized to assess the inhibitory potential of derivatives against hAChE and hBuChE. The inhibitory activity of these derivatives on both hMAO-A and hMAO-B was assessed using a fluorescence-based method. The thioflavin T (Th-T) fluorescence assay was used to assess the inhibition of Aβ1−42 self-aggregation. The cytotoxicity was evaluated using the MTT assay. The Surflex-Dock program in Sybyl-X2.0 Software was employed for molecular docking.ResultsIn vitro studies revealed that numerous synthesized compounds exhibited potent inhibitory activity against hAChE, and hMAO-B (IC50 < 1 μM), as well as Aβ1−42 aggregation (IC50 < 20 μM). Importantly, the multitarget compounds 6d, 8c, and 8d exhibited remarkable efficacy in simultaneously mitigating Aβ-induced toxicity in SH−SY5Y cells while demonstrating minimal cytotoxicity. Furthermore, predicted ADMET results suggested that 6d, 8c, and 8d possessed favorable pharmacokinetic properties and demonstrated low toxicity levels. Additionally, molecular docking studies of 6d within the activesites of hAChE, hMAO-B, and Aβ1−42 elucidated the inhibition mechanism.Discussion and conclusionBased on these findings, it is evident that 6d, 8c, and 8d hold potential as promising multi-functional drugs for AD treatment.

BackgroundWet age-related macular degeneration (wAMD) is a vision-threatening eye disease worldwide. The amplitude of low-frequency fluctuation (ALFF) method was used to observe changes in spontaneous brain activity, which may help to investigate the underlying pathological mechanism of AMD.MethodsEighteen patients with wAMD and 18 age- and gender-matched healthy controls (HCs) were recruited. The ALFF method was used on each subject and mean ALFF values were compared between groups. The receiver operating characteristic (ROC) curve was used to compare the two groups.ResultsALFF values in the temporal lobe and limbic lobe/parahippocampal gyrus were significantly higher than controls, while values in the postcentral gyrus were significantly lower. The under the curve of the ROC (AUC) of the three regions shows high accuracy of the diagnosis.ConclusionThe abnormal spontaneous brain activity of patients with AMD suggests scope for the use of ALFF in the diagnosis or prognosis in AMD.

IntroductionGeneralized anxiety disorder (GAD) is the most common type of anxiety disorders. GAD usually occurs in adolescence or early adulthood, and the prevalence of GAD is higher among college-enrolled young adults than in the general adult population. However, there is a lack of evidence regarding the effectiveness of acupuncture in the treatment of GAD. This study's objective is to evaluate the efficacy of acupuncture in the treatment of GAD in college students and its stability.MethodsA total of 142 subjects will be recruited for the randomized controlled trial (RCT) of current undergraduate and graduate students with GAD and will be randomized into treatment and control groups. The treatment group will receive conventional acupuncture, while the control group will receive sham acupuncture using Streitberger needles. Both groups will be administered 8 acupuncture treatment (2 times per week for 4 weeks). The follow-up duration will be 2 months. The Hamilton Anxiety Scale (HAMA) will be used as the primary outcome of the study to measure the severity of anxiety disorder. The secondary outcomes of this study will be included the Pittsburgh Sleep Quality Index (PSQI) and Self-rating anxiety Scale (SAS). The study will also evaluate the success of blinding and the safety.DiscussionsFindings of this RCT will help evaluate the efficacy of acupuncture treatment for GAD in college students, potentially promoting it as an alternative treatment option. The protocol was registered at clinicaltrials.gov (Identifier: ChiCTR2400080688).

To explore the impact of thermal barrier coating (TBC) surface roughness on the cooling effectiveness of film-cooled turbine vanes, the GE-E3 high pressure turbine vane was used. Utilizing the method of conjugate heat transfer (CHT) and Computational Fluid Dynamics (CFD), we employed the SST k-ω two-equation turbulence model to conduct numerical simulations of the film cooling process. Our analysis delves into the effects of varying roughness levels (0 μm, 0.81 μm, 2 μm and 3 μm) on vane cooling efficiency, TBC performance, and vane heat transfer coefficient. Results indicate a notable enhancement in vane film cooling efficiency, particularly in proximity to the leading edge (LE), owing to the presence of TBC. As TBC surface roughness increases, heat transfer coefficients on the suction side (SS) and pressure side (PS) near the trailing edge (TE) generally rise, diminishing both cooling and TBC effectiveness. However, divergent outcomes emerge near the LE due to the inherent uncertainty in heat transfer predictions. Notably, reducing TBC surface roughness from 3 μm to 0 μm yields an average cooling efficiency increase of 2.45 %, with a maximum improvement of 2.1 %.

IntroductionEmotional labor involves regulating one’s emotional state at work to align with organizational expectations. For operating room (OR) nurses, emotional labor is an inherent part of their roles, with different strategies potentially impacting their work-related quality of life (WRQoL) in distinct ways. This study aimed to examine the relationship between emotional labor strategies and WRQoL among OR nurses.MethodsA cross-sectional study was conducted using convenience sampling, recruiting 395 OR nurses from 11 secondary and tertiary hospitals in Shandong Province. Data were collected using the General Information Questionnaire, Emotional Labor Scale, and Work-Related Quality of Life scale. Statistical analyses, including descriptive statistics, Pearson correlation analysis, and multiple stratified regression, were applied to explore the relationships between variables.ResultsA total of 372 valid responses were obtained, with an effective response rate of 94.18%. The mean WRQoL score was 114.17 (SD = 16.54). Among emotional labor strategies, expressing naturally felt emotions was the most frequently used. Surface acting showed a significant negative correlation with WRQoL (r = −0.437, p

Pseudorabies virus (PRV), causing Aujeszky’s disease in swine, has important economic impact on the pig industry in China and even poses a threat to public health. Although this disease has been controlled by vaccination with PRV live attenuated vaccines (LAVs), the potency of PRV LAVs in inducing cellular immunity has not been well characterized. In this study, using PRV Bartha K61 strain (BK61), the most-used PRV LAVs, as a model, we re-examined the cellular immune response elicited by the BK61 in mice and pigs by multicolor flow cytometry. We found that phenotypic activation of T cells, NK cells and B cells was hardly detected after vaccination. However, antigen-specific IFN-γ-producing CD4 T cells rather than CD8 T cells were dominantly detected but at low frequency upon restimulation with live BK61 virus. These BK61-specific CD4 T cells are also able to simultaneously produce TNF-α and IL-2, showing characteristics of multifunctional T cells. However, BK61-specific CD4 T cells showed weak secondary response upon challenge with PRV DX strain. Further vaccination with PRV-infected dendritic cells (DCs) transiently increased the percentage of IFN-γ-positive CD4 and CD8 T cells but eventually restored to low frequency and did not improve the protective efficacy of BK61 against challenge, suggesting that PRV BK61 induced a relatively weak cellular immunity that could not be overcome by the DC vaccination. Similar immune responses were also observed following vaccination with another PRV LAV HD/c in mice and pigs, suggesting that this may be an intrinsic drawback of PRV LAVs in inducing cellular immunity. Our results demonstrated that PRV LAVs elicited a CD4 Th1-biased weak cellular immunity which is implicative for the development of PRV-vectored vaccine.

Circular RNAs (circRNAs) exert diverse biological functions in different processes. However, the role of circRNAs during virus infection is mostly unknown. Herein, we explored the characteristics of host circRNAs using alphaherpesvirus pseudorabies virus (PRV) as a model. PRV infection upregulated the expression of circRNA circ29164, which does not encode a protein. RNA pulldown assays identified that circ29164 interacts with the microRNA ssc-miRNA-24-3p. Further analysis indicated that ssc-miR-24-3p targets the mRNA encoding kelch-like ECH-associated protein 1 (KEAP1), and circ29164 competitively binds to ssc-miR-24-3p to prevent it binding to Keap1. Apoptosis detection demonstrated that circ29164 or Keap1 overexpression, but not knockdown, induced caspase 3 activity and the release of cytochrome C from mitochondria, and inhibited PRV replication. Taken together, these data identified a previously undiscovered circRNA, circ29164, which inhibits PRV replication by competitively binding to ssc-24-3p to maintain KEAP1 levels.

Abstract Infected burn wounds are characterized by persistent drug‐resistant bacterial infection coupled with an inflammatory response, impeding the wound‐healing process. In this study, an intelligent nanoparticle system (CCM+TTD@ZIF‐8 NPs) was prepared using curcumin (CCM), an aggregation‐induced emission luminogens (TTD), and ZIF‐8 for infection‐induced wound healing. The CCM+TTD@ZIF‐8 NPs showed multiple functions, including bacteria targeting, fluorescence imaging and pH response‐guided photodynamic therapy (PDT), and anti‐inflammatory. The positive charges of ZIF‐8 NPs allowed the targeting of drug‐resistant bacteria in infected wounds, thereby realizing fluorescence imaging of bacteria by emitting red fluorescence at the infected site upon blue light irradiation. The pH‐responsive characteristics of the CCM+TTD@ZIF‐8 NPs also enabled controllable CCM release onto the infected wound site, thereby promoting the specific accumulation of ROS at the infected site, with outstanding bactericidal efficacy against drug‐resistant Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) strains in vitro/in vivo. Additionally, due to the excellent bactericidal effect and anti‐inflammatory properties of CCM+TTD@ZIF‐8 NPs combined with blue light irradiation, the regeneration of epidermal tissue, angiogenesis, and collagen deposition was achieved, accelerating the healing process of infected burn wounds. Therefore, this CCM+TTD@ZIF‐8 NPs with multifunctional properties provides great potential for infected burn wound healing.

Abstract A simple wideband magneto‐electric (ME) dipole antenna is presented in this letter. In particular, two pairs of L‐shaped slots with different sizes are successively etched out of the pair of horizontal patches of electric dipole, which can enlarge the bandwidth of ME dipole antenna without increasing the antenna size. Two new resonant frequency points are generated respectively at the lower and upper frequency region. To improve the impedance matching characteristics, two vertical rectangular patches are loaded in the middle of the horizontal portion of the Г‐shaped feed structure. A prototype is fabricated and measured, and an overlapped bandwidth of 101.3% (from 1.36 to 4.15 GHz) in terms of VSWR ≤ 2 is achieved, which can simultaneously cover the n50 (1.432–1.517 GHz), n51 (1.427–1.432 GHz), n78 (3.300–3.800 GHz) and 52.5% of n77 (3.8–4.4 GHz) bands of sub‐6G. It should be highlighted that other excellent properties of ME dipole antenna, such as stable radiation pattern, high gain, and low cross‐polarization level (CRPL), are maintained, which makes the proposed ME dipole antenna a good candidate for sub‐6G applications.

Targeted Protein Degradation (TPD) represented by Proteolysis-Targeting Chimeras (PROTAC) is the frontier field in the research and development of antitumor therapy, in which oral drug HP518 Receives FDA Proceed Authorization for its IND Application for Prostate Cancer Treatment. Recently, molecular glue, functioning via degradation of the target protein is emerging as a promising modality for the development of therapeutic agents, while exhibits greater advantages over PROTAC, including improved efficiency, resistance-free properties, and the capacity to selectively target “undruggable” proteins. This marks a revolutionary advancement in the landscape of small molecule drugs. Given that molecular glue research is still in its early stage, we summarized the mechanisms of molecular glue, the promising drugs in clinical trials and diverse feasible design strategies for molecular glue therapeutics.

Summary: Protected cultivation enables the production of vegetables and fruits throughout the year without compromising of farming field for grain production. However, it is generally associated with high resource consumption, including building materials, consumables, and energy, raising severe concerns about its future sustainability, especially the intensity of its carbon emissions, which is less well-understood. This study focused on the carbon emissions of two typical protected cultivation constructions for tomato cultivation in China, using life cycle assessment (LCA). Tomato production generated 354.4 and 173.1 kg CO2-eq/ton carbon emissions in a typical solar greenhouse in northern China and a typical naturally ventilated polyhouse in southern China, which represented 41.9% and 21.7% reduction, respectively, compared to field production in the same area. Further analysis of protected cultivation inputs revealed that agricultural consumables are the main contributors to carbon emissions. Among them, fertilizers were the dominant contributor to carbon emissions, accounting for 73.0% and 67.5% of the total carbon emissions for solar greenhouses and polyhouses, respectively. Based on this finding, a sensitivity analysis revealed the potential of two advanced fertilizer management practices to reduce carbon emissions. Drip irrigation and slow-release fertilizers in protected cultivation can reduce carbon emissions by 16.5–17.7% and 12.9–13.8%, respectively, compared to traditional chemical fertilizers. In addition, the analysis of environmental effects suggested that protected tomato production can significantly reduce environmental impact. Overall, this research highlighted that protected cultivation can substantially mitigate carbon emissions, demonstrating its high efficiency toward low-carbon agriculture.

Objectives We aimed to prospectively investigate the benefit of using augmented reality (AR) for surgery residents learning aneurysm surgery.Materials and methods Eight residents were included, and divided into an AR group and a control group (4 in each group). Both groups were asked to locate an aneurysm with a blue circle on the same screenshot after their viewing of surgery videos from both AR and non-AR tests. Only the AR group was allowed to inspect and manipulate an AR holographic representation of the aneurysm in AR tests. The actual location of the aneurysm was defined by a yellow circle by an attending physician after each test. Localization deviation was determined by the distance between the blue and yellow circle.Results Localization deviation was lower in the AR group than in the control group in the last 2 tests (AR Test 2: 2.7 ± 1.0 mm vs. 5.8 ± 4.1 mm, p = 0.01, non-AR Test 2: 2.1 ± 0.8 mm vs. 5.9 ± 5.8 mm, p

ABSTRACTInfection-induced SARS-CoV-2 seroprevalence has been studied worldwide. At Juntendo University Hospital (JUH) in Tokyo, Japan, we have consistently conducted serological studies using the blood residue of healthcare workers (HCWs) at annual health examinations since 2020. In this 2023 study (n = 3,594), N-specific seroprevalence (infection-induced) was examined while univariate and multivariate logistic regression analyses were performed to compute ORs of seroprevalence with respect to basic characteristics of participants. We found that the N-specific seroprevalence in 2023 was 54.1%—a jump from 17.7% in 2022, and 1.6% in 2021—with 37.9% as non-PCR-confirmed asymptomatic infection cases. Those younger than 50 (adjusted OR = 1.62; p

Objective To demonstrate the feasibility of using a ring array ultrasound (US) transducer, guided by ultrasound tomography (UST), for generating and monitoring mild hyperthermia (MHTh).Methods In silico and in vitro experiments were designed to evaluate the efficacy of a ring array US transducer for generating MHTh and monitoring changes in temperature. In a series of in silico studies, we compared the acoustic focal profiles produced by a ring array US transducer transmitting at different frequencies and further investigated the effectiveness of UST-guidance in implementing aberration correction to enhance the focal profile. In vitro experiments evaluated the capability of using a ring array US transducer to generate and maintain MHTh and the accuracy of using UST to monitor temperature changes.Results The simulations demonstrated that a ring array US transducer achieves symmetrical and localized acoustic focusing. In a heterogenous tissue model, a ring array US transducer achieved a superior acoustic focus by implementing aberration correction with guidance from UST. In vitro experiments demonstrated the capability of a ring array US transducer to generate MHTh in a tissue-mimicking phantom in an average of 117 ± 18 s and subsequently maintain MHTh. Lastly, a ring array US transducer utilized UST to track temperature changes in a preheated water-filled inclusion while it passively cooled from 45 °C to 25 °C, with a maximum error of 0.58 °C.Conclusion A ring array US transducer can noninvasively generate and monitor MHTh, overcoming many limitations of current clinical systems. The closed geometry of the transducer is optimal for acoustic focusing and UST-guidance allows for improved aberration correction in a heterogenous medium. Utilizing UST thermometry with the same ring array US transducer will allow for implementing an image-guided, temperature-controlled, all-acoustic MHTh system.

Background IgA nephropathy (IgAN) is intimately linked to mucosal immune responses, with nasopharyngeal and intestinal lymphoid tissues being crucial for its abnormal mucosal immunity. The specific pathogenic bacteria in these sites associated with IgAN, however, remain elusive. Our study employs 16S rRNA sequencing and machine learning (ML) approaches to identify specific pathogenic bacteria in these locations and to investigate common pathogens that may exacerbate IgAN.Methods In this cross-sectional analysis, we collected pharyngeal swabs and stool specimens from IgAN patients and healthy controls. We applied 16SrRNA sequencing to identify differential microbial populations. ML algorithms were then used to classify IgAN based on these microbial differences. Spearman correlation analysis was employed to link key bacteria with clinical parameters.Results We observed a reduced microbial diversity in IgAN patients compared to healthy controls. In the gut microbiota of IgAN patients, increases in Bacteroides, Escherichia-Shigella, and Parabacteroides, and decreases in Parasutterella, Dialister, Faecalibacterium, and Subdoligranulum were notable. In the respiratory microbiota, increases in Neisseria, Streptococcus, Fusobacterium, Porphyromonas, and Ralstonia, and decreases in Prevotella, Leptotrichia, and Veillonella were observed. Post-immunosuppressive therapy, Oxalobacter and Butyricoccus levels were significantly reduced in the gut, while Neisseria and Actinobacillus levels decreased in the respiratory tract. Veillonella and Fusobacterium appeared to influence IgAN through dual immune loci, with Fusobacterium abundance correlating with IgAN severity.Conclusions This study revealing that changes in flora structure could provide important pathological insights for identifying therapeutic targets, and ML could facilitate noninvasive diagnostic methods for IgAN.

C21H21MnN6O6S, monoclinic, P21/c (no. 14), a = 13.093(3) Å, b = 23.810(5) Å, c = 7.9852(17) Å, β = 106.882(4)°, V = 2,382.1(9) Å3, Z = 4, Rgt(F) = 0.0498, wRref(F2) = 0.1299, T = 296(2) K.

Abstract Green technology innovation is a critical factor in ensuring the long-term stable development of renewable energy enterprises. Based on the super network theory, this paper constructs a network model of green technology innovation influencing factors of renewable energy enterprises, which includes the knowledge sub-network of green technology innovation of renewable energy enterprises, the research and development member sub-network of green technology innovation team of renewable energy enterprises and the policy sub-network of green technology innovation of renewable energy enterprises. It explores the mechanism of its influence on innovation in the preparation stage. Simulation analysis by Netlogo software concludes that innovation knowledge sharing, R&D membership, and innovation policy all have a significant positive impact on green technology innovation in renewable energy companies.

Abstract Background Continuous glucose monitoring (CGM) devices provide detailed information on daily glucose control and glycemic variability. Yet limited population-based studies have explored the association between CGM metrics and fatty liver. We aimed to investigate the associations of CGM metrics with the degree of hepatic steatosis. Methods This cross-sectional study included 1180 participants from the Guangzhou Nutrition and Health Study. CGM metrics, covering mean glucose level, glycemic variability, and in-range measures, were separately processed for all-day, nighttime, and daytime periods. Hepatic steatosis degree (healthy: n = 698; mild steatosis: n = 242; moderate/severe steatosis: n = 240) was determined by magnetic resonance imaging proton density fat fraction. Multivariate ordinal logistic regression models were conducted to estimate the associations between CGM metrics and steatosis degree. Machine learning models were employed to evaluate the predictive performance of CGM metrics for steatosis degree. Results Mean blood glucose, coefficient of variation (CV) of glucose, mean amplitude of glucose excursions (MAGE), and mean of daily differences (MODD) were positively associated with steatosis degree, with corresponding odds ratios (ORs) and 95% confidence intervals (CIs) of 1.35 (1.17, 1.56), 1.21 (1.06, 1.39), 1.37 (1.19, 1.57), and 1.35 (1.17, 1.56) during all-day period. Notably, lower daytime time in range (TIR) and higher nighttime TIR were associated with higher steatosis degree, with ORs (95% CIs) of 0.83 (0.73, 0.95) and 1.16 (1.00, 1.33), respectively. For moderate/severe steatosis (vs. healthy) prediction, the average area under the receiver operating characteristic curves were higher for the nighttime (0.69) and daytime (0.66) metrics than that of all-day metrics (0.63, P

Abstract Numerous studies have shown that the Krüppel-like factors (KLFs) family of transcription factors regulate various eukaryotic physiological processes including the proliferation, differentiation, senescence, death, and carcinogenesis of animal cells. In addition, they are involved in the regulation of key biological processes such as cell cycle, DNA repair, and immune response. Current studies focus on investigating the role of KLFs in normal physiological conditions and the incidence and development of diseases. However002C the significance of KLFs family genes in clear cell renal cell carcinoma (ccRCC) remains partly understood; therefore, an in-depth investigation of their role and clinical value in this cancer is desired. The study aimed to investigate the role of KLF family genes in the incidence, development, and prognosis of ccRCC, and to identify the related potential biomarkers and therapeutic targets. The expression of KLFs in the RNA sequencing data of 613 ccRCCs from the TCGA database was analyzed using R software, and UALCAN and GEPIA assessed the expression of KLF genes in ccRCC. Real-time fluorescence quantitative PCR analysis was performed using 10 pairs of paired ccRCC sample tissues and renal cancer cell lines from the First Affiliated Hospital of Nanchang University. Overall survival (OS), progression-free interval (PFI), and disease-specific survival (DSS) of Kidney Clear Cell Carcinoma (KIRC) samples at differential expressions of KLFs in the TCGA database were analyzed using the R software, followed by generating a nomogram prediction model. GSCALite assessed the interactions of KLF genes with miRNAs and generated network maps. Protein interaction network maps of 50 neighboring genes associated with KLF mutations were analyzed using STRING with GO and KEGG functional enrichment analyses. The cBioPortal determined the probability of KLF gene mutations and their impact on OS and disease-free survival (DFS) in patients with ccRCC. Immune cell infiltration of KLFs was analyzed using TIMER. Finally, GSCALite was used to analyze the drug sensitivity and associated pathways of action of KLFs. Correlation validation using cellular experiments. KLF3/5/9/15 were significantly downregulated in ccRCC tissues, whereas KLF16/17 were upregulated compared with the adjacent tissues. Patients with high mRNA levels of KLF16/17 showed significantly lower OS, PFI, and DSS, whereas KLF3/5/9 showed a reverse trend. In patients with ccRCC, a significant correlation was observed between KLF mutations and OS and DSS. Furthermore, the correlation of KLF3/5/9 with immune cell infiltration was stronger than that of KLF15/16, while KLF17 was significantly associated with the Epithelial-Mesenchymal Transition (EMT) pathway. Overexpression of KLF5 inhibits the proliferative and migratory capacity of renal cancer cells (786-O and OS-RC-2), as well as their sensitivity to relevant small molecule drugs. Our research revealed the expression levels and biological significance of KLF genes in ccRCC, particularly highlighting the potential of KLF5 as a promising biomarker and therapeutic target for effective prognosis and diagnosis of ccRCC.

Purpose – Model-based systems engineering (MBSE) is an important approach for the transforming process from “document-centered” to “model centered” systems engineering mode in equipment development, which can effectively shorten the equipment development cycle and improve product design quality. This paper aims to understand if MBSE enables to support manufacturing and equipment development. Design/methodology/approach – The paper opted a bibliometric analysis of MBSE in domain of advanced manufacturing from different perspectives such as publication volume, research team, sources and keyword co-occurrence. Findings – Firstly, the application of MBSE in advanced manufacturing can be roughly divided into three stages. And MBSE has been widely implemented globally and has gradually formed several noteworthy teams. Secondly, this article has identified some high-quality sources, with a large number of publications and citations, the most influential publications focus on the practice or guidance of digital twins and intelligent manufacturing. Thirdly, research can be divided into six categories, including systems engineering, digitalization, intelligent manufacturing, product design, model and architecture and MBSE applications. Research limitations/implications – Because of the chosen research approach, the visualized network tends to lose certain information such as a few keywords may be inaccurately categorized. Practical implications – This paper comprehensively study the research status of MBSE in advanced manufacturing and forecasts future research trends, emphasizing the combination of intelligent manufacturing and digitization. Originality/value – This paper fulfills an identified need to understand the current application status and future development trends of MBSE.

At the end of 2023, a large-scale rainfall/snowfall and freezing event occurred in northern and central Henan, featuring variable precipitation phases and accompanied by regional thunderstorms, which was relatively rare. This paper analyzed this process by using the data from conventional observations, ERA5 reanalysis, wind profile radar, and dual-polarization radar with a focus on the characteristics of precipitation phases and cause. The results are as follows. (1) At 500 hPa, the horizontal trough turned vertical, and the south branch trough moved eastward, while at 700 hPa, the southwest jet developed. Meanwhile, the ground was affected by the cold air from the east and the west successively, which led to the persistent large-scale freezing rain and snow weather in northern and central Henan. (2) The conditional instability above the cold cushion, the conditional symmetry instability near the frontal zone, and the upward branch of strong frontogenesis circulation provided a favorable condition for the occurrence and development of convective weather, which were the main causes of heavy rain and snow, thunderstorm, and hail. (3) During the process, the freezing rain corresponded to a "thick warm layer (100-200 hPa)-cold layer" stratification, with the ice pellets linking to a "layer of ice crystals - thin warm layer (50-100 hPa) - cold layer" stratification. While the pure snow and sleet corresponded to an entirely cold layer stratification and a shallow warm layer near the ground, respectively. (4) The horizontal wind field products of wind profile radar can qualitatively reflect the changes in the low-level southwest jet stream and the intensity of cold air near the ground. The differences in the vertical velocity products of different precipitation phases are significant, providing a reference for the monitoring and forecasting of short-term phase transitions. (5) The dual-polarization products revealed that the freezing rain and pure snow had the highest correlation coefficients (≥0.99), while the sleet had the lowest (0.85~0.9). The ice pellets showed a significant middle-layer melting, with a maximum differential reflectivity and a minimum correlation coefficient at that level.

Background and purpose: Rectal cancer occurs on the inner wall of the rectum, and metastasis-associated in colon cancer 1 (MACC1) can promote drug resistance in colon cancer cells. This study aimed to investigate the effect of MACC1 on oxaliplatin resistance in rectal cancer and its mechanism. Methods: Biosignal analysis of MACC1 and TCF7 expressions in rectal cancer tissues and signaling pathways enriched for MACC1 were carried out. The expressions of MACC1 and TCF7 in rectal cancer cells and rectal cancer oxaliplatin-resistant cells were detected by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR), cell viability was detected by cell counting kit-8 (CCK-8), and cell proliferation was detected by cell colony formation assay. ECAR values, lactate production and glucose consumption were detected by Seahorse Biosciences XF96. Western blot was used to detect the expressions of glycolysis-related proteins. Dual luciferase reporter gene and ChIP were used to validate the regulatory relationship between MACC1 and TCF7. Normality test and homogeneity of variance analysis was performed on the data of each group by GraphPad Prism 8.0. If it conformed to normal distribution, one-way ANOVA or t-test would be used for inter group comparison, otherwise the comparison between groups would be conducted using Wilcoxon rank sum test. Using a two-sided test, P