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Background: Coronary atherosclerosis (CAS) is a complex chronic inflammatory disease with significant genetic and environmental contributions. While genome-wide association studies (GWAS) have pinpointed many risk loci, over 75 % are in non-coding regions, complicating functional analysis and understanding gene-disease mechanisms. Methods: We conducted a cross-tissue transcriptome-wide association study (TWAS) using data from the GWAS Catalog (16,041 cases, 440,307 controls) and the Genotype-Tissue Expression (GTEx) v8 eQTL dataset. Initially, we used the Unified Test for Molecular Signatures (UTMOST) for analysis, followed by validation with Functional Summary-based Imputation (FUSION) and conditional and joint (COJO) analyses. Candidate genes were further refined using Multi-marker Analysis of Genomic Annotation (MAGMA). Causal relationships were assessed through Summary Data-Based Mendelian Randomization (SMR), colocalization analysis (COLOC), and Mendelian Randomization (MR). GeneMANIA was used to identify interacting genes, and Phenome-Wide Association Study (PheWAS) was employed to enhance the results. Results: UTMOST identified 33 susceptibility genes for CAS. Out of these, 17 met stringent criteria in both UTMOST and FUSION analyses. Combining results from UTMOST, FUSION, and MAGMA, we identified four critical candidate genes. WDPCP was the only gene to pass SMR, COLOC, and MR analyses, confirming its causal role in CAS. GeneMANIA revealed additional interacting genes, and PheWAS validated WDPCP's role as a susceptibility gene. Conclusion: WDPCP is a potential novel susceptibility gene for CAS, influencing endothelial function, lipid metabolism, and coronary artery development. This study extends GWAS findings, highlighting WDPCP's potential as a therapeutic target and its consistent expression across different tissues. Further validation studies are warranted.

Abstract Background The disease impact of breast cancer is to view the couple as a whole, breast cancer is a disease shared by the couple. Cancer coping has evolved from an individual perspective to a dyadic coping perspective for couples. The purpose of this study was to identify and describe the dyadic coping categories of couples with breast cancer and to analyze the relationship between dyadic coping categories and post-traumatic growth (PTG) in couples with breast cancer. Method In this study, breast cancer patients and their spouses were selected as the study population from several tertiary hospitals in Jinzhou City using convenience sampling method in 2023. A general information questionnaire, Dyadic Coping Inventory (DCI), and Post-traumatic Growth Inventory (PTGI) were used to survey 254 couples with breast cancer. Latent profile analysis (LPA) was performed using Mplus (version 8.3). SPSS 26.0 was used for data entry, and data were analyzed using one-way analysis of variance and multifactor logistic regression. Significance level α = 0.05. Result The study examines the influence of various factors such as educational attainment, age, income, residence, medical insurance, surgical procedure type, disease stage, and breast cancer recurrence on patients' coping strategies. Multiple logistic regression analysis showed that education level, age at marriage, place of residence, form of health care coverage, stage of the disease, and whether or not the disease recurred were significant predictors of each indicator (P

Abstract Thermometric techniques with high accuracy, fast response and ease of implementation are desirable for the study of dynamic combustion environments, transient reacting flows, and non-equilibrium plasmas. Herein, single-shot single-beam coherent Raman scattering (SS-CRS) thermometry is developed, for the first time to our knowledge, by using air lasing as a probe. We show that the air-lasing-assisted CRS signal has a high signal-to-noise ratio enabling single-shot measurements at a 1 kHz repetition rate. The SS-CRS thermometry consistently exhibits precision of

Abstract Roof breaking is the root cause of rock burst and mine earthquake. However, the classical “thin plate theory” and “thick plate theory” cannot fully reveal the mechanical mechanism of the influence of roof thickness-span ratio on the fracture mode. In this paper, based on the cohesive element technology, the mechanical behavior of cohesive element failure was studied according to the maximum nominal stress criterion and BK fracture criterion, and the fracture mechanical behavior of roofs with different thicknesses fixed on four sides under uniform load was numerically simulated. The fracture pattern and the maximum principal stress evolution laws of roofs with different thicknesses were obtained. The results show that there are three fracture modes of the plates with different thickness: pure tensile fracture mode at the bottom surface, mixed fracture mode around the “X” shape crack, and pure shear fracture mode along the long edge boundary. The crack morphology of thin plate is the transverse “O−X” type, and the crack morphology of thick plate is the “O−❋” type. With the increase of thickness, the tensile-shear mixed failure mode gradually changes from the tensile dominant to the shear dominant.

Abstract Background Hereditary hemochromatosis (HH) is an iron overload disorder and can be caused by variants in non-HFE genes in Chinese patients. However, there is still a considerable proportion of patients suffering from unexplained iron overload. In our previous study, we had identified the p.R269Q variant in exon 4 of the Bone morphogenetic protein 4 (BMP4) gene in Chinese patients with unexplained primary iron overload by Whole Exome sequencing, and then the BMP4 p.H251Y variant was identified by Sanger sequencing in a Chinese patient with secondary iron overload. Our study aimed to explore the pathogenicity and underlying mechanism of BMP4 p.H251Y and BMP4 p.R269Q variants in patients with iron overload. Methods Sanger sequencing was conducted to identify the novel variants in the BMP4 gene of patients with unexplained iron overload. MRI and liver biopsy were used to display iron overload in the liver of the patient harboring the BMP4 p.H251Y variant. The BMP4 and hepcidin levels in BMP4 knockdown and BMP4 variant cells were examined by enzyme-linked immunosorbent assay. The effects of BMP4 p.H251Y and BMP4 p.R269Q variants on the hepcidin-regulation pathway were studied. Results One of 54 HH patients (1.85%) harbored the BMP4 p.R269Q variant. One of 148 patients (0.68%) with secondary hemochromatosis harbored the BMP4 p.H251Y variant, and these two variants were not found in 100 Chinese general population. For the patient harboring the BMP4 p.H251Y variant, abdominal MRI and Perl's staining of liver tissue displayed iron overload in the liver. Cells transfected with the BMP4 p.H251Y and p.R269Q variants showed down-regulation of hepcidin level and BMP/SMAD pathway compared with cells transfected with the wild-type BMP4 vector. Conclusion The BMP4 p.H251Y and p.R269Q variants can downregulate hepcidin levels by inhibiting the BMP/SMAD axis, suggesting they may play pathogenic roles in iron overload.

Abstract Objective Isolated REM sleep behavior disorder (iRBD) is considered as the strongest predictor of Parkinson's disease (PD). Reliable and accurate biomarkers for iRBD detection and the prediction of phenoconversion are in urgent need. This study aimed to investigate whether α‐Synuclein (α‐Syn) species in plasma neuron‐derived extracellular vesicles (NDEVs) could differentiate between iRBD patients and healthy controls (HCs). Methods Nanoscale flow cytometry was used to detect α‐Syn‐containing NDEVs in plasma. Results A total of 54 iRBD patients and 53 HCs were recruited. The concentrations of total α‐Syn, α‐Syn aggregates, and phosphorylated α‐Syn at Ser129 (pS129)‐containing NDEVs in plasma of iRBD individuals were significantly higher than those in HCs (p

Abstract Background The benefits of low-pressure laparoscopic cholecystectomy (LPLC) in patients with cardiopulmonary comorbidities remain unclear. This study aimed to explore the feasibility and pulmonary effects of LPLC in patients with cardiopulmonary comorbidities. Methods This was a multicenter, parallel, double-blind, randomized controlled trial. Eligible patients included patients with cardiac or pulmonary comorbidities, who were randomly assigned (1:1) to undergo LPLC (10 mmHg) or standard-pressure laparoscopic cholecystectomy (SPLC) (14 mmHg). The primary outcome was postoperative partial pressure of carbon dioxide (CO2). Surgical safety variables, patient recovery, pulmonary function parameters, and surgeon comfort were also compared between groups. Results This study enrolled 144 participants, with 124 participants extracted for the final analysis (62 in LPLC and 62 in SPLC group, respectively). The median postoperative PaCO2 was similar in the LPLC (43.3 mmHg) and SPLC (43.0 mmHg) groups (p = 0.988). Pulmonary parameters including postoperative pH, PaCO2, HCO3, and lactate levels were similar between the two groups. Postoperative base excess was significantly higher in the LPLC group (− 0.6 mmol/L [− 6.9 ~ 7.5] vs. −1.9 mmol/L [− 6.6 ~ 5.4]; p = 0.031). There was no between-group difference regarding intraabdominal operative time, rate of intraoperative bile spillage, blood loss, surgeon comfort during surgery, and conversion rate. Moreover, postoperative major complication rates, the median time to the first flatus, postoperative hospital stay, or mean postoperative visual analog scale score for pain were similar in both groups. Conclusions This study found no reduction of partial pressure of CO2 with LPLC compared with SPLC for patients with cardiopulmonary comorbidities. LPLC with a pneumoperitoneum pressure of 10 mmHg may be safe and feasible for these patients when performed by experienced surgeons, although it does not improve pulmonary parameters. Registration The trial is retrospectively registered at ClinicalTrials.gov (NCT04670952) on December 17, 2020.

Abstract The relative risk and benefits of Laparoscopic liver resection (LLR) are still controversial. This study aimed to evaluate perioperative and survival outcomes for three primary malignant liver tumors related outcomes following LLR. Data from three Homogeneous-High-Volume-Expert-Centers were collected. Multivariable logistic regression analysis was performed for the association between LLR, and major complications defined as Clavien-Dindo Classification grade ≥ II. Multivariable Cox proportional hazards regression was used to explore the impact of LLR on primary malignant liver tumor survival. Overall, 5886 patients underwent liver resection, of which 1991 underwent LLR. After adjusting for covariables, LLR had significantly lower rate of CDC grade ≥ II (OR = 0.56, 95% CI: 0.48–0.67, P 0.05). LLR was associated with lower rate of major complications, especially in women, non-drinkers, those without a history of abdominal surgery, and those with normal platelet. For primary malignant liver tumors, the survival outcomes did not differ significantly between LLR and OLR.

Abstract Double-atom catalysts (DACs) have opened distinctive paradigms in the field of rapidly developing atomic catalysis owing to their great potential for promoting catalytic performance in various reaction systems. However, increasing the loading and extending the service life of metal active centres represents a considerable challenge for the efficient utilization of DACs. Here, we rationally design asymmetric nitrogen, sulfur-coordinated diatomic iron centres on highly defective nitrogen-doped carbon nanosheets (denoted A-Fe2S1N5/SNC, A: asymmetric), which possess the atomic configuration of the N2S1Fe-FeN3 moiety. The abundant defects and low-electronegativity heteroatoms in the carbon-based framework endow A-Fe2S1N5/SNC with a high loading of 6.72 wt%. Furthermore, A-Fe2S1N5/SNC has a low overpotential of 193 mV for the oxygen evolution reaction (OER) at 10 mA cm−2, outperforming commercial RuO2 catalysts. In addition, A-Fe2S1N5/SNC exhibits extraordinary stability, maintaining > 97% activity for over 2000 hours during the OER process. This work provides a practical scheme for simultaneously balancing the activity and stability of DACs towards electrocatalysis applications.

Abstract The identification of predictors for immunotherapy is often hampered by the absence of control groups in many studies, making it difficult to distinguish between prognostic and predictive biomarkers. This study presents biomarker analyses from the phase 3 CONTINUUM trial (NCT03700476), the first to show that adding anti-PD-1 (aPD1) to chemoradiotherapy (CRT) improves event-free survival (EFS) in patients with locoregionally advanced nasopharyngeal carcinoma. A dynamic single-cell atlas was profiled using mass cytometry on peripheral blood mononuclear cell samples from 12 pairs of matched relapsing and non-relapsing patients in the aPD1-CRT arm. Using a supervised representation learning algorithm, we identified a Ki67+ proliferating regulatory T cells (Tregs) population expressing high levels of activated and immunosuppressive molecules including FOXP3, CD38, HLA-DR, CD39, and PD-1, whose abundance correlated with treatment outcome. The frequency of these Ki67+ Tregs was significantly higher at baseline and increased during treatment in patients who relapsed compared to non-relapsers. Further validation through flow cytometry (n = 120) confirmed the predictive value of this Treg subset. Multiplex immunohistochemistry (n = 249) demonstrated that Ki67+ Tregs in tumors could predict immunotherapy benefit, with aPD1 improving EFS only in patients with low baseline levels of Ki67+ Tregs. These findings were further validated in the multicenter phase 3 DIPPER trial (n = 262, NCT03427827) and the phase 3 OAK trial of anti-PD-L1 immunotherapy in NSCLC, underscoring the predictive value of Ki67+ Treg frequency in identifying the beneficiaries of immunotherapy and potentially guiding personalized treatment strategies.

Foamed lightweight soil has become an effective material to solve subgrade problems such as uneven settlement in the traffic field because of its advantages of light weight, high strength, good fluidity, and high construction efficiency. The traditionally foamed lightweight soil is mainly made of cement prepared by foaming. With a strong transportation network, carbon peaking, and carbon neutrality, foamed lightweight soil prepared using industrial solid wastes instead of cement has gradually become a research hotspot. Bayer red mud is one of the industrial solid wastes that are most difficult to reuse. Guided by the resource utilization of industrial wastes and the demand for green construction of traffic engineering, this study proposes to use Bayer red mud instead of cement to prepare foamed lightweight soil, and its application in traffic engineering construction has huge engineering value and ecological benefits. Aiming at the problems in the engineering application of red mud-based foamed lightweight soil, this study examined the regulation methods of the rheological properties of red mud-based foamed lightweight soil and revealed the effects of the water–binder ratio and superplasticizers on rheological properties and compressive strength of red mud-based foamed lightweight soil. The optimal water–binder ratio and optimal type and dosage of superplasticizers were determined, and the dynamic control of the performance of red mud-based foamed lightweight soil was realized. In this study, naphthalene superplasticizers significantly improved the fluidity of fresh slurry. The fluidity of the slurry increased with the increase in the water–binder ratio; when the water–binder ratio is 0.6, the fluidity of the slurry is too thick or watery. When the water–binder ratio is 0.5–0.6, the fluidity is between 165 and 212 mm, which is beneficial for construction. Both polycarboxylate and naphthalene superplasticizers can increase the fluidity of slurry. Naphthalene superplasticizers can increase the fluidity of slurry more remarkably, and the fluidity of 0.3% naphthalene superplasticizers increased from 165 to 176 mm when the water–binder ratio was 0.5. If the water–binder ratio is increased, the compressive strength first increases and then decreases. Polycarboxylate superplasticizers can weaken the compressive strength, whereas naphthalene superplasticizers can improve the compressive strength. An infrared spectrogram analysis showed that geopolymer gel is the main hydration product of red mud-based foamed lightweight soil, naphthalene superplasticizers can promote geopolymerization and increase the amounts of hydration products, and the optimum design values of the water–binder ratio and superplasticizers are determined.

Abstract Phenotypes play a fundamental role in medical genetics, serving as external manifestations of underlying genotypes. Deep phenotyping, a cornerstone of precision medicine, involves precise multi-system phenotype assessments, facilitating disease subtyping and genetic understanding. Despite their significance, the field lacks standardized protocols for accurate phenotype evaluation, hindering clinical comprehension and research comparability. We present a comprehensive workflow of deep phenotyping for rare bone diseases from the Genetics Clinic of Skeletal Deformity at Peking Union Medical College Hospital. Our workflow integrates referral, informed consent, and detailed phenotype evaluation through HPO standards, capturing nuanced phenotypic characteristics using clinical examinations, questionnaires, and multimedia documentation. Genetic testing and counseling follow, based on deep phenotyping results, ensuring personalized interventions. Multidisciplinary team consultations facilitate comprehensive patient care and clinical guideline development. Regular follow-up visits emphasize dynamic phenotype reassessment, ensuring treatment strategies remain responsive to evolving patient needs. In conclusion, this study highlights the importance of deep phenotyping in rare bone diseases, offering a standardized framework for phenotype evaluation, genetic analysis, and multidisciplinary intervention. By enhancing clinical care and research outcomes, this approach contributes to the advancement of precision medicine in the field of medical genetics.

Abstract Background Previous studies have established a positive link between nurse managers’ caring leadership and nurses’ work engagement, but the processes and conditions through which this leadership style influences positive work behaviors remain largely unexplored. To address this gap and contribute to the existing body of knowledge, we developed a chain-mediated effects model to elucidate the impact of caring leadership on nurses’ work engagement and the underlying mechanisms. In this model, we identified professional mission and affective organizational commitment as the mediating variables, offering a novel perspective on the relationship between caring leadership and work engagement. Methods A robust multi-center and large-sample cross-sectional survey was conducted, involving 2502 first-line nurses from six general tertiary hospitals across the eastern, central, and western regions of China. The data collection instruments included a comprehensive questionnaire covering demographic information, the caring leadership scale, the Chinese calling scale, the affective organizational commitment scale, and the Utrecht work engagement scale. Data were meticulously screened and analyzed, employing descriptive analysis to summarize the demographic information, correlation analysis to test the relationship among the variables, stepwise regression analysis to explore the mediating role of calling and affective organization commitment, and the bootstrap method to test the chain mediating effect. This rigorous methodology not only ensures the reliability and validity of research findings but also instills confidence in the robustness of this research. Results The results indicated a positive relationship among caring leadership, calling, affective organizational commitment, and nurses’ work engagement (p

Abstract Background Clear cell renal cell carcinoma (ccRCC) is one of the most common urological diseases and the most common subtype of renal cell carcinoma. Nuclear mitochondria‐related genes (MTRGs) play an essential role in cancer, but their effect on ccRCC has not been clarified. This work aimed to investigate the role of nuclear MTRGs in ccRCC. Methods We collected nuclear MTRGs from the MITOMAP database and obtained the ccRCC profile from the TCGA database. Gene expression validation came from the GEO database. The ccRCC subtypes were determined by unsupervised clustering analysis based on the nuclear MTRGs. Immune scores were computed using the EPIC algorithm. The drug sensitivity scores were calculated using GDSC resources. A nomogram explored the diagnostic value of the nuclear MTRGs. Results In total, 11 nuclear MTRGs were identified as both related to prognosis and differentially expressed in ccRCC, showing a significant positive correlation with CD274 expression. We determined two subtypes of ccRCC based on these genes and found remarkable differences in survival status, immune infiltration, mutation landscape, and drug sensitivity between the two subtypes. The high‐MTRG group had a better prognosis and a lower tumor stage than the low‐MTRG group. Immune checkpoint blockade therapy was more effective for the high‐MTRG group. A nomogram based on the nuclear MTRGs concluded that patients with a higher score had poorer survival. SUCLA2 (succinate‐CoA ligase ADP‐forming subunit beta) was identified as the hub gene linked to ccRCC. High SUCLA2 expression showed a correlation with better survival and a negative correlation with the tumor mutation burden in ccRCC. Pan‐cancer analysis revealed wide‐ranging roles for SUCLA2 across human tumors. Conclusions Nuclear MTRGs play vital roles in determining the molecular features, immune infiltration, and drug sensitivity of ccRCC. High levels of nuclear MTRGs may indicate a better prognosis for patients with ccRCC. SUCLA2 is a representative nuclear MTRG and may serve as a protective biomarker in ccRCC. Our study provides therapeutic guidance and potential biomarkers for ccRCC patients, and contributes to the advancement of precision medicine.

Abstract Coherent optics has profoundly impacted diverse applications ranging from communications, LiDAR to quantum computations. However, developing coherent systems in integrated photonics comes at great expense in hardware integration and energy efficiency. Here we demonstrate a high-coherence parallelization strategy for advanced integrated coherent systems at minimal cost. By using a self-injection locked microcomb to injection lock distributed feedback lasers, we achieve a record high on-chip gain of 60 dB with no degradation in coherence. This strategy enables highly coherent channels with linewidths down to 10 Hz and power over 20 dBm. The overall electrical-to-optical efficiency reaches 19%, comparable to that of advanced semiconductor lasers. This method supports a silicon photonic communication link with an unprecedented data rate beyond 60 Tbit/s and reduces phase-related DSP consumption by 99.99999% compared to traditional III-V laser pump schemes. This work paves the way for realizing scalable, high-performance coherent integrated photonic systems, potentially benefiting numerous applications.

Abstract Background Plant growth-promoting rhizobacteria (PGPR), as a group of environmentally friendly bacteria growing in the rhizosphere of plants, play an important role in plant growth and development and resistance to environmental stresses. However, their limited understanding has led to the fact that their large-scale use in agriculture is still scarce, and the mechanisms by which beneficial bacteria are selected by plants and how they interact with them are still unclear. Method In this study, we investigated the interaction between the auxin-producing strain Bacillus aryabhattai LAD and maize roots, and performed transcriptomic and metabolomic analyses of Bacillus aryabhattai LAD after treatment with maize root secretions(RS). Results Our results show that there is a feedback effect between the plant immune system and bacterial auxin. Bacteria activate the immune response of plant roots to produce reactive oxygen species(ROS), which in turn stimulates bacteria to synthesize IAA, and the synthesized IAA further promotes plant growth. Under the condition of co-culture with LAD, the main root length, seedling length, root surface area and root volume of maize increased by 197%, 107%, 89% and 75%, respectively. In addition, the results of transcriptome metabolome analysis showed that LAD was significantly enriched in amino acid metabolism, carbohydrate metabolism and lipid metabolism pathways after RS treatment, including 93 differentially expressed genes and 45 differentially accumulated metabolites. Conclusion Our findings not only provide a relevant model for exploring the effects of plant-soil microbial interactions on plant defense functions and thereby promoting plant growth, but also lay a solid foundation for the future large-scale use of PGPR in agriculture for sustainable agricultural development.

High nitrogen austenitic stainless steels (HNASSs) have received widespread attention owing to their outstanding corrosion resistance, excellent weldability and workability. However, these materials usually exhibit insufficient yield strength to satisfy the requirement in service because of their face-centered cubic (fcc) structure. Here, we report a novel material design strategy of constructing both grain-scaled and atomic-scaled heterostructure through applying appropriate thermo-mechanical treatment to improve the comprehensive mechanical properties of HNASS. The optimal comprehensive mechanical properties with a yield strength of 1361 MPa and a uniform elongation of 10.6% are achieved. The results show that the ultrahigh yield strength mainly originates from the lath structure consisting of local chemical order domains (∼490 MPa), and the satisfactory ductility benefits from both deformation twinning and dislocation slip. This work proposes for the first time the strategy to improve mechanical properties of HNASS by introducing the multi-scaled heterostructure, and guides the development of high-performance steels and many other advanced fcc materials.

Background: Romosozumab is a novel monoclonal antibody that binds to sclerostin, and has dual effects of increasing bone formation and decreasing bone resorption, giving it a unique mechanism of action. The objective of this study was to perform a systematic review and meta-analysis based on existing worldwide data on treatment effects and safety of romosozumab in randomized controlled trials. Methods: A systematic search was carried out on four databases including PubMed, Embase, Web of Science and Cochrane Central Register of Controlled Trials (CENTRAL). The keywords used for search was “(romosozumab) AND (osteoporosis OR safety)”. Randomized controlled trial or post-hoc studies of the included randomized controlled trial which studied the effects and safety of romosozumab were included. The quality of selected studies was assessed with the Cochrane collaboration tool and the PEDro scale. Results: 20 studies were included for qualitative analysis. 14 studies were included for meta-analysis. In total, there were 13,507 (n = 13,507) participants with 637 men and 12,870 women from original cohorts. The overall mean difference was in favor of romosozumab treatment for lumbar spine (10.04 (95 % confidence interval (CI) = 7.51–12.57; p

Background: Skeleton involvement is one of the most significant aspects of Gaucher disease (GD). However, the treatment for spinal involvement in GD among patients undergoing enzyme replacement therapy (ERT) is poorly characterized. We present a case of progressive kyphotic spinal deformity in a young child caused by vertebral involvement, which was managed by posterior spinal fusion without anterior spinal release under ERT. Case presentation: This is a retrospective study. A 10-year-old boy presenting with progression kyphosis (thoracic kyphotic angle of 113°) associated with type-IIIb GD had undergone posterior spinal fusion with segmental pedicle screw fixation (from T6-L3) and Ponte osteotomy. The patient went back to school without further brace protection. Proximal junctional kyphosis (PJK) was observed at 4 months postoperatively. Revision surgery was performed to prevent neurological impairment. Additional posterior spinal fusion from T2–T6 and decompressive laminectomy were performed during the revision surgery. A 2-year follow-up showed no recurrence of PJK and solid fusion was achieved in the patient under ERT and brace protection. Conclusions: Posterior spinal fusion without anterior spinal release is a good treatment option for severe spinal deformity in patients with GD. However, the fusion level and reinforced fixation require careful consideration. Revision surgery and brace protection is needed as long as PJK is observed.

Abstract Urban governance aims to enhance overall social welfare, while residents’ happiness frequently falls by the wayside. Civilization, as a critical factor influencing residents’ happiness, has not yet been fully understood regarding its impact and mechanisms. This paper uses the China Family Panel Studies data, which includes around 50,000 samples ranging from 2010 to 2020, to construct a multi-period difference-in-differences model. It finds that China’s highest honor for urban brands, the civilized city program, leads to an average increase of 2.6% in residents’ happiness as measured by life satisfaction. This happiness effect is robust but temporary, gradually diminishing within five years following the honor. The happiness effect is heterogeneous across different waves and city sizes and is effective only for urban residents. Mechanism analysis indicates the happiness effect of the civilized city program through three channels: government efforts, social trust, and identity recognition. Additionally, our research indicates that the civilized city initiative improves residents’ perception of environmental quality and reduces income inequality. These findings provide insights into understanding how the civilization tournament policy promotes happiness.

Abstract Background Medical device-related pressure injures (MDRPIs) are common in critically ill patients and associated with negative clinical outcomes and elevated healthcare expenses. We aim to estimate worldwide incidence of MDRPI and explore associated factors through systemic review and meta-analysis. Methods The PubMed, Web of Science, Cochrane Library, and Ovid EMBASE databases were systematically queried to identify relevant studies published from Jan 1, 2010 up until June 30, 2024. Studies were included if they provided data on the incidence or prevalence of MDRPI. Random-effect models were utilized to calculate the overall or domain-specific aggregated estimates of MDRPI. A meta-regression analysis was additionally performed to investigate the heterogeneity among studies. Results We included 28 observational studies on 117,624 patients in the meta-analysis. The overall incidence of MDRPI was 19.3% (95% confidence interval (CI) 13.5–25.2%). The incidence of MDRPI in Europe, North America, Asia, South America, and Oceania was 17.3% (95% CI 12.7–21.9%), 3.6% (95% CI 0.0–8.5%), 21.9% (95% CI 14.3–29.6%), 48.3% (95% CI 20.8–75.7%), and 13.0% (95% CI 5.0–21.1%), respectively (p

Abstract Diagnosing liver lesions is crucial for treatment choices and patient outcomes. This study develops an automatic diagnosis system for liver lesions using multiphase enhanced computed tomography (CT). A total of 4039 patients from six data centers are enrolled to develop Liver Lesion Network (LiLNet). LiLNet identifies focal liver lesions, including hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), metastatic tumors (MET), focal nodular hyperplasia (FNH), hemangioma (HEM), and cysts (CYST). Validated in four external centers and clinically verified in two hospitals, LiLNet achieves an accuracy (ACC) of 94.7% and an area under the curve (AUC) of 97.2% for benign and malignant tumors. For HCC, ICC, and MET, the ACC is 88.7% with an AUC of 95.6%. For FNH, HEM, and CYST, the ACC is 88.6% with an AUC of 95.9%. LiLNet can aid in clinical diagnosis, especially in regions with a shortage of radiologists.

Abstract The Montreal Protocol has been successful in safeguarding the ozone layer and curbing climate change. However, accurately estimating and reducing the time-lagged emissions of ozone-depleting substances or their substitutes, such as produced but not-yet-emitted fluorocarbon banks, remains a significant challenge. Here, we use a dynamic material flow analysis model to characterize the global stocks and flows of two fluorocarbon categories, hydrochlorofluorocarbons (HCFCs) and hydrofluorocarbons (HFCs), from 1986 to 2060. We assess emission pathways, time-lagged emission sizes, and potential abatement measures throughout different life cycle stages while focusing on the role of banked fluorocarbons in global and regional decarbonization efforts in the post-Kigali Amendment era. Although fluorocarbon releases are expected to decline, the cumulative global warming potential (GWP)-weighted emissions of HCFCs and HFCs are significant; these will be 6.4 (±1.2) and 14.8 (±2.5) gigatons CO2-equivalent, respectively, in 2022–2060 in our business-as-usual (BAU) scenario. Scenario analysis demonstrates that implementing currently available best environmental practices in developed economies can reduce cumulative GWP-weighted emissions by up to 45% compared with the BAU scenario.

Abstract Sarcopenia is a complex age-associated syndrome of progressive loss of muscle mass and strength. Although this condition is influenced by many factors, age-related changes in immune function including immune cell dynamics, and chronic inflammation contribute to its progression. The complex interplay between the immune system, gut-muscle axis, and autophagy further underscores their important roles in sarcopenia pathogenesis. Immunomodulation has emerged as a promising strategy to counteract sarcopenia. Traditional management approaches to treat sarcopenia including physical exercise and nutritional supplementation, and the emerging technologies of biophysical stimulation demonstrated the importance of immunomodulation and regulation of macrophages and T cells and reduction of chronic inflammation. Treatments to alleviate low-grade inflammation in older adults by modulating gut microbial composition and diversity further combat sarcopenia. Furthermore, some pharmacological interventions, nano-medicine, and cell therapies targeting muscle, gut microbiota, or autophagy present additional avenues for immunomodulation in sarcopenia. This narrative review explores the immunological underpinnings of sarcopenia, elucidating the relationship between the immune system and muscle during ageing. Additionally, the review discusses new areas such as the gut-muscle axis and autophagy, which bridge immune system function and muscle health. Insights into current and potential approaches for sarcopenia management through modulation of the immune system are provided, along with suggestions for future research directions and therapeutic strategies. We aim to guide further investigation into clinical immunological biomarkers and identify indicators for sarcopenia diagnosis and potential treatment targets to combat this condition. We also aim to draw attention to the importance of considering immunomodulation in the clinical management of sarcopenia.

Abstract Background Large-scale sequencing plays important roles in revealing the genomic map of ccRCC and predicting prognosis and therapeutic response to targeted drugs. However, the relevant clinical data is still sparse in Chinese population. Methods Fresh tumor specimens were collected from 66 Chinese ccRCC patients, then the genomic RNAs were subjected to whole transcriptome sequencing (WTS). We comprehensively analyzed the frequently mutated genes from our hospital’s cohort as well as TCGA-KIRC cohort. Results VHL gene is the most frequently mutated gene in ccRCC. In our cohort, BAP1 and PTEN are significantly associated with a higher tumor grade and DNM2 is significantly associated with a lower tumor grade. The mutant type (MT) groups of BAP1 or PTEN, BAP1 or SETD2, BAP1 or TP53, BAP1 or MTOR, BAP1 or FAT1 and BAP1 or AR had a significantly correlation with higher tumor grade in our cohort. Moreover, we identified HMCN1 was a hub mutant gene which was closely related to worse prognosis and may enhance anti-tumor immune responses. Conclusions In this preliminary research, we comprehensively analyzed the frequently mutated genes in the Chinese population and TCGA database, which may bring new insights to the diagnosis and medical treatment of ccRCC.

The preparation process of soy hull nanocellulose hydrogel was optimized by Box-Behnken response surface. The structure and properties of soy hull nanocellulose hydrogel were studied. On the basis of single factor experiment, the preparation process of soy hull nanocellulose hydrogel was optimized through response surface with three factors and three levels when the maximum stress was used as the index. The structure and properties of soy hull nanocellulose hydrogel were characterized by Fourier transform infrared spectroscopy, X ray polycrystalline diffractometer, scanning electron microscopy, UV spectrophotometer, etc. The optimal process parameters were as follows: gelling temperature 191 ℃, freezing time 102 h, CaCl2 concentration 7%. Under this condition, the actual maximum stress of soy hull nanocellulose hydrogel was 84.11 kPa, which was close to the predicted value of 83.7 kPa. The nanocellulose of soy hull/sodium alginate/CaCl2 (SCNFs/SA/CaCl2) hydrogel showed uniform 3D network structure, excellent tensile performance (elongation at break was 220%), mechanical strength (83.97 kPa), transmittance (82%), and electrical conductivity (1.58 S/cm). The SCNFs/SA/CaCl2 hydrogel also had excellent mechanical strength and fatigue resistance after five cycles of stretching, so the service life of hydrogel was increased. This study provides a new method for preparing a tough, transparent, conductive and fatigue-resistant nanocellulose hydrogel.

Abstract Breast cancer remains a significant global health challenge, and its mechanisms of progression and metastasis are still not fully understood. In this study, analysis of TCGA and GEO datasets revealed a significant increase in CCT2 expression in breast cancer tissues, which was associated with poor prognosis in breast cancer patients. Functional analysis revealed that CCT2 promoted breast cancer growth and metastasis through activation of the JAK2/STAT3 signaling pathway. Additionally, the E3 ubiquitin ligase Trim21 facilitated CCT2 ubiquitination and degradation, significantly reversing the protumor effects of CCT2. Most interestingly, we discovered that exosomal CCT2 derived from breast cancer cells suppressed the activation and proinflammatory cytokine secretion of CD4+ T cell. Mechanistically, exosomal CCT2 constrained Ca2+-NFAT1 signaling, thereby reducing CD40L expression on CD4+ T cell. These findings highlight CCT2 upregulation as a potential driver of breast cancer progression and immune evasion. Our study provides new insights into the molecular mechanisms underlying breast cancer progression, suggesting that CCT2 is a promising therapeutic target and prognostic predictor for breast cancer.

Abstract The debates over the requirement of the International Code of Nomenclature for algae, fungi, and plants (ICNafp) for a viable specimen to represent the name-bearing type material for a species or infraspecific taxon have a long history. Taxonomy of fungi commonly studied as living cultures exemplified by yeasts and moulds, strongly depend on viable reference material. The availability of viable cultures is also particularly useful for several groups of filamentous and dimorphic fungi. While the preservation of metabolically inactive cultures is permitted and recommended by the ICNafp, there is room for improvement. Below, we review the history and current status of cultures as the name-bearing type material under the Code. We also present a roadmap with tasks to be achieved in order to establish a stable nomenclatural system that properly manages taxa typified by viable specimens. Furthermore, we propose setting up rules and defining the nomenclatural status of ex-type cultures under Chapter F, the section of the ICNafp that includes provisions specific to names of fungi.

Abstract Background The role of lifestyle factors and their relative contributions to the development and mortality of cardio-renal-metabolic multimorbidity (CRMM) remains unclear. Methods A study was conducted with 357,554 UK Biobank participants. CRMM was defined as the coexistence of two or three cardio-renal-metabolic diseases (CRMDs), including cardiovascular disease (CVD), type 2 diabetes (T2D) and chronic kidney disease (CKD). The prospective study examined the associations of individual and combined lifestyle scores (diet, alcohol consumption, smoking, physical activity, sedentary behavior, sleep duration and social connection) with longitudinal progression from healthy to first cardio-renal-metabolic disease (FCRMD), then to CRMM, and ultimately to death, using a multistate model. Subsequently, quantile G-computation was employed to assess the relative contribution of each lifestyle factor. Results During a median follow-up of 13.62 years, lifestyle played crucial role in all transitions from healthy to FCRMD, then to CRMM, and ultimately to death. The hazard ratios (95% CIs) per score increase were 0.91 (0.90, 0.91) and 0.90 (0.89, 0.91) for healthy to FCRMD, and for FCRMD to CRMM, and 0.84 (0.83, 0.86), 0.87 (0.86, 0.89), and 0.90 (0.88, 0.93) for mortality risk from healthy, FCRMD, and CRMM, respectively. Among the seven factors, smoking status contributed to high proportions for the whole disease progression, accounting for 19.88–38.10%. High-risk diet contributed the largest proportion to the risk of transition from FCRMD to CRMM, with 22.53%. Less-frequent social connection contributed the largest proportion to the risk of transition from FCRMD to death, with 28.81%. When we further consider the disease-specific transitions, we find that lifestyle scores had slightly stronger associations with development to T2D than to CVD or CKD. Conclusions Our study indicates that a healthy lifestyle may have a protective effect throughout the longitudinal progression of CRMM, informing more effective management and treatment. Smoking status, diet, and social connection played pivotal roles in specific disease transitions.

Abstract Background The link between nonalcoholic fatty liver disease and type 2 diabetes has not been fully established. We investigated the temporal relationship between nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D), quantitatively assessed the impact, and evaluated the related mediation effect. Methods This study involved participants from the China Multi-Ethnic Cohort Study and the UK Biobank. We performed cross-lagged path analysis to compare the relative magnitude of the effects between NAFLD and T2D using two-period biochemical data. Hepatic steatosis and fasting blood glucose elevation (FBG) represented NAFLD and T2D respectively. We fitted two separate Cox proportional-hazards models to evaluate the influence of hepatic steatosis on T2D. Furthermore, we applied the difference method to assess mediation effects. Results In cross-lagged path analyses, the path coefficients from baseline hepatic steatosis to first repeat FBG (β CMEC = 0.068, β UK−Biobank = 0.033) were significantly greater than the path coefficients from baseline FBG to first repeat hepatic steatosis (β CMEC = 0.027, β UK−Biobank = -0.01). Individuals with hepatic steatosis have a risk of T2D that is roughly three times higher than those without the condition (HR = 3.478 [3.314, 3.650]). Hepatic steatosis mediated approximately 69.514% of the total effect between obesity and follow-up T2D. Conclusions Our findings contribute to determining the sequential relationship between NAFLD and T2D in the causal pathway, highlighting that the dominant pathway in the relationship between these two early stages of diseases was the one from hepatic steatosis to fasting blood glucose elevation. Individuals having NAFLD face a significantly increased risk of T2D and require long-term monitoring of their glucose status as well.

Background: The interaction between muscle and bone is shown to be clinically important but the underlying mechanisms are largely unknown. The canonical Wnt/β-catenin signaling pathway is reported to be involved in muscle-bone crosstalk, but its detailed function remains unclear. This systematic review aims to investigate and elucidate the role of the Wnt/β-catenin signaling pathways in muscle-bone crosstalk. Methods: We conducted a literature search on the Web of Science, PubMed, EBSCO and Embase with keywords “Wnt*”, “bone*” and “muscle*”. A systematic review was completed according to the guideline of preferred reporting items of systematic reviews and meta-analyses (PRISMA). Data synthesis included species (human, animal or cell type used), treatments involved, outcome measures and key findings with respect to Wnts. Results: Seventeen papers were published from 2007 to 2021 and were extracted from a total of 1529 search results in the databases of Web of Science (468 papers), PubMed (457 papers), EBSCO (371) and Embase (233). 12 Wnt family members were investigated in the papers, including Wnt1, Wnt2, Wnt2b, Wnt3a, Wnt4, Wnt5a, Wnt8a, Wnt8b, Wnt9a, Wnt10a, Wnt10b and Wnt16. Many studies showed that muscles were able to increase or decrease osteogenesis of bone, while bone increased myogenesis of muscle through Wnt/β-catenin signaling pathways. Wnt3a, Wnt4 and Wnt10b were shown to play important roles in the crosstalk between muscle and bone. Conclusions: Wnt3a, Wnt4 and Wnt10b are found to play important mediatory roles in muscle-bone crosstalk. The role of Wnt4 was mostly found to regulate muscle from the bone side. Whilst the role of Wnt10b during muscle ageing was proposed, current evidence is insufficient to clarify the specific role of Wnt/β-catenin signaling in the interplay between sarcopenia and osteoporosis. More future studies are required to investigate the exact regulatory roles of Wnts in muscle-bone crosstalk in musculoskeletal disease models such as sarcopenia and osteoporosis. Translational potential of this article: The systematic review provides an extensive overview to reveal the roles of Wnt/β-catenin signaling pathways in muscle-bone crosstalk. These results provide novel research directions to further understand the underlying mechanism of sarcopenia, osteoporosis, and their crosstalk, finally helping the future development of new therapeutic interventions.

Sclerostin emerges as a novel target for bone anabolic therapy in bone diseases. Osteogenesis imperfecta (OI) and X-linked hypophosphatemia (XLH) are rare bone diseases in which therapeutic potential of sclerostin inhibition cannot be ignored. In OI, genetic/pharmacologic sclerostin inhibition promoted bone formation of mice, but responses varied by genotype and age. Serum sclerostin levels were higher in young OI-I patients, while lower in adult OI-I/III/IV. It's worth investigating whether therapeutic response of OI to sclerostin inhibition could be clinically predicted by genotype and age. In XLH, preclinical/clinical data suggested factors other than identified FGF23 contributing to XLH. Higher levels of circulating sclerostin were detected in XLH. Sclerostin inhibition promoted bone formation in Hyp mice, while restored phosphate homeostasis in age-/gender-dependent manner. The role of sclerostin in regulating phosphate metabolism deserves investigation. Sclerostin/FGF23 levels of XLH patients with/without response to FGF23-antibody warrants study to develop precise sclerostin/FGF23 inhibition strategy or synergistic/additive strategy. Notably, OI patients were associated with cardiovascular abnormalities, so were XLH patients receiving conventional therapy. Targeting sclerostin loop3 promoted bone formation without cardiovascular risks. Further, blockade of sclerostin loop3-LRP4 interaction while preserving sclerostin loop2-ApoER2 interaction could be a potential precise sclerostin inhibition strategy for OI and XLH with cardiovascular safety.The Translational Potential of this Article.Preclinical data on the molecular understanding of sclerostin inhibition in OI and therapeutic efficacy in mouse models of different genotypes, as well as clinical data on serum sclerostin levels in patients with different phenotypes of OI, were reviewed and discussed. Translationally, it would facilitate to develop clinical prediction strategies (e.g. based on genotype and age, not just phenotype) for OI patients responsive to sclerostin inhibition. Both preclinical and clinical data suggested sclerostin as another factor contributing to XLH, in addition to the identified FGF23. The molecular understanding and therapeutic effects of sclerostin inhibition on both promoting bone anabolism and improving phosphate homostasis in Hyp mice were reviewed and discussed. Translationaly, it would facilitate the development of precise sclerostin/FGF23 inhibition strategy or synergistic/additive strategy for the treatment of XLH. Cardiovascular risk could not be ruled out during sclerostin inhibition treatment, especially for OI and XLH patients with cardiovascular diseases history and cardiovascular abnormalities. Studies on the role of sclerostin in inhiting bone formation and protecting cardiovascular system were reviewed and discussed. Translationaly, blockade of sclerostin loop3-LRP4 interaction while preserving sclerostin loop2-ApoER2 interaction could be a potential precise sclerostin inhibition strategy for OI and XLH with cardiovascular safety.

Low back pain is among the most grave public health concerns worldwide and the major clinical manifestation of intervertebral disc degeneration (IVDD). The destruction of annulus fibrosus (AF) is the primary cause of IVDD. A sustainable and stable treatment system for IVDD is lacking because of the special organizational structure and low nutrient supply of AF. We here found that IVDD results in the impaired mitochondrial function of AF tissue, and mitochondrial autophagy (mitophagy) plays a protective role in this process. We therefore reported a thread-structural microneedle (T-MN) matching the ring structure of AF. Based on the adsorption effect of laminin, our T-MN could load with bone marrow mesenchymal stem cell-derived exosomes to envelope the regulating mitophagy microRNA (miRNA 378), named as T-MN@EXO@miR−378. In general, we offered in situ locking in the defect site of AF to prevent nucleus pulposus leakage and promoted AF repair. The design of the thread structure was aimed at bionically matching the layered AF structure, thereby providing stronger adhesion. The T-MN@EXO@miR−378 effectively attached to AF and slowly released therapeutic engineered exosomes, and prevented IVDD progression by restoring mitophagy, promoting AF cell proliferation and migration, and inhibiting the pathological remodeling of the extracellular matrix. This functional system can be used as an excellent tool for sustained drug release and has a certain prospect in substituting the conventional treatment of IVDD.

Engagement in healthy lifestyles is pivotal for early adolescents’ growth and healthy development. Despite burgeoning research on the determinants of healthy lifestyles among adolescents, there is a dearth of research investigating the role of adolescents’ health mindsets. This study examined whether and how implicit theories of health and future self-continuity affect adolescents’ (N = 440; 49.5% girls; Mage = 10.8, SD = 0.6) engagement in healthy lifestyles. The results indicated that implicit theories of health and future self-continuity accounted for 2.5–5.8% of the variances in behaviour indicators (i.e. (un)healthy eating, physical activity, and sleep quality) and more than 20.3% of the variances in mental well-being indicators (i.e. flourishing and emotional balance) of healthy lifestyles among adolescents. Future self-continuity explained the positive effects of implicit theories of health on adolescents’ engagement in healthy lifestyles. The results have implications for tailoring effective interventions to promote healthy living among adolescents.

AbstractTargeting Heat shock protein 90 (HSP90) C-terminus is an important strategy to develop HSP90 inhibitors without inducing heat shock response. The development of C-terminal inhibitors, however, is hampered by a lack of understanding regarding the interaction between the HSP90 C-terminus and the present inhibitors. We collected seven classical and structurally diverse HSP90 C-terminal inhibitors and constructed a ligand-based pharmacophore model. The subsequent virtual screening and structural optimisation led to the identification of 2-heteroarylthio-N-arylacetamides as novel HSP90 C-terminal inhibitors. 9 and 27 exhibited strong antitumour activity in vitro by inhibiting proliferation and inducing apoptosis in multiple cancer cell lines. These compounds disrupted the interaction between HSP90 C-terminus and peptidylprolyl isomerase D, exerting a stronger inhibitory effect than novobiocin. 27 significantly induced the degradation of HSP90 clients without triggering heat shock response. In an in vivo study using 4T1 mice breast cancer models, 9 showed a potent antitumour effect without obvious toxicity.

Background and objectives: Atypical thymic carcinoids (ATCs) are rare mediastinal malignancies that lack established treatment guidelines. Capecitabine and temozolomide (CapTem) has demonstrated significant efficacy in pancreatic neuroendocrine neoplasms (NENs), while its applicability and effectiveness in ATCs remain underexplored. This study seeks to investigate the efficacy, safety, and prognostic factors associated with CapTem in ATC patients. Design and methods: Thirty-eight ATC patients treated with CapTem at our center were analyzed. We assessed the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse effects. We also examined patients’ clinicopathological characteristics and their correlations with CapTem efficacy. Results: The cohort achieved a 15.8% ORR and 89.5% DCR, with a median PFS of 13.0 months. Multivariate analysis identified the platelet-to-lymphocyte ratio (PLR) as a significant independent prognostic factor for PFS, with a PLR ⩾ 235 associated with shorter PFS (7 months vs. undefined, p = 0.0004). Age was an independent prognostic factor for OS, with patients over 50 years experiencing shorter OS (36 months vs. undefined, p = 0.015). Safety analysis showed rare severe toxicities and no treatment-related fatalities. Conclusion: CapTem is an effective and well-tolerated treatment for ATC patients. Pretreatment PLR and age appear to be potential prognostic markers for CapTem therapy; however, these results warrant validation in larger patient cohorts.

Resumo Fundamento A hipertrofia cardíaca patológica (HC) sustentada é um fator de risco independente para aumento da incidência e mortalidade de eventos cardiovasculares. Objetivos Esta pesquisa foi projetada para desvendar o papel do RNA não codificante longo (LncRNA) CCAT2 na progressão da HC. Métodos Procedimentos de constrição aórtica transversal (TAC) foram conduzidos para construir um modelo de HC in vivo induzido por sobrecarga de pressão. O tratamento com angiotensina II (Ang II) foi utilizado para induzir células hipertróficas de cardiomiócitos de rato H9c2. Resultados Os resultados in vivo mostraram que o silenciamento de CCAT2 reduziu a área de superfície dos cardiomiócitos, aliviou a fibrose cardíaca e diminuiu os níveis de β-MHC, ANP e BNP em modelos de camundongos HC. Os resultados in vitro revelaram que o knockdown de CCAT2 reduziu a área de superfície celular e atenuou os níveis de β-MHC, ANP e BNP em células hipertróficas H9c2. Além disso, o silenciamento de CCAT2 diminuiu os níveis de β-catenina ativa, GSK-3β fosforilada e genes alvo Wnt (c-Myc, ciclinaD1 e c-Jun) em camundongos HC e células H9c2 hipertróficas. É importante ressaltar que o tratamento com o ativador da via Wnt / β-catenina LiCl reverteu a supressão do knockdown de CCAT2 na área de superfície celular H9c2 e nos níveis de MHC, ANP e BNP. Conclusões Coletivamente, o silenciamento do CCAT2 desempenha um papel protetor contra a HC através da inativação da sinalização Wnt/β-catenina, o que sugere que o CCAT2 pode se tornar um alvo terapêutico promissor para o HC.

Objectives To evaluate and analyse the quality of clinical practice guidelines for Peripherally Inserted Central Catheter-related thrombosis (PICC-related thrombosis) to identify the most current and effective prophylactic measures recommended in the guidelines.Design Scoring and analysis of the guidelines using the Appraisal of Guidelines for Research and Evaluation II (AGREE II).Data sources Cochrane Library, PubMed, EMBASE, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Chinese databases (China National Knowledge Infrastructure and Wan Fang) and the relevant websites of the guideline were searched through 8 August 2024.Eligibility criteria for selecting studies Studies that primarily clinical practice guidelines on the prevention of PICC-related thrombosis were included.Data extraction and synthesis Two reviewers independently screened the searched items and extracted data and scored documents using AGREE II. Findings were summarised in Grading of Recommendation, Assessment, Development and Evaluation (GRADE) evidence profiles and synthesised qualitatively.Results The analysis incorporated a total of nine guidelines, all rated as ‘recommended’ or ‘recommended with modifications’. Standardised scores revealed elevated performance in the domains of Scope and Purpose, Clarity of Presentation and Editorial Independence. Conversely, the Stakeholder Involvement and Applicability domains yielded the lowest average standardised scores. Disparities in standardised scores across guidelines were particularly evident in the domains of Rigour of Development, Stakeholder Involvement and Applicability. The agreement between the two appraisers was almost perfect (intraclass correlation coefficients higher than 0.80). A considerable proportion of recommendations relied on evidence of low-quality, in certain instances, were derived from expert opinions within working groups.Conclusions The review reveals that a significant portion of recommendations relies on low-quality evidence. Guideline developers are urged to prioritise methodological quality, with a specific focus on refining Stakeholder Involvement and Applicability domains. Addressing these aspects will enhance the overall quality and reliability of PICC-related thrombosis prevention guidelines. One potential way to mitigate these challenges is to endorse a standardised approach to guideline development and to synthesise reliable clinical evidence to reduce variation in recommendations.PROSPERO registration number CRD42023495519.

Increasing evidence indicates that 2-hydroxyglutarate (2HG) is an oncometabolite that drives tumour formation and progression. Due to mutations in isocitrate dehydrogenase (IDH) and the dysregulation of other enzymes, 2HG accumulates significantly in tumour cells. Due to its structural similarity to α-ketoglutarate (αKG), accumulated 2HG leads to the competitive inhibition of αKG-dependent dioxygenases (αKGDs), such as KDMs, TETs, and EGLNs. This inhibition results in epigenetic alterations in both tumour cells and the tumour microenvironment. This review comprehensively discusses the metabolic pathways of 2HG and the subsequent pathways influenced by elevated 2HG levels. We will delve into the molecular mechanisms by which 2HG exerts its oncogenic effects, particularly focusing on epigenetic modifications. This review will also explore the various methods available for the detection of 2HG, emphasising both current techniques and emerging technologies. Furthermore, 2HG shows promise as a biomarker for clinical diagnosis and treatment. By integrating these perspectives, this review aims to provide a comprehensive overview of the current understanding of 2HG in cancer biology, highlight the importance of ongoing research, and discuss future directions for translating these findings into clinical applications.

Non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD)-related mortality have increased dramatically in past decades. Our study aims to investigate the association between plain water and this prevalent metabolic disease, as water plays a crucial role in regulating metabolic processes. A total of 3,543/3,428 individuals with NAFLD/MASLD were included in this study from National Health and Nutrition Examination Survey (NHANES). Daily plain water intake was recorded, and mortality status was tracked until December 31, 2019. Multivariate Cox regression models and restricted cubic spline (RCS) regression models were used to assess the association between plain water intake and long-term all-cause as well as cause-specific mortality among participants with NAFLD/MASLD. Furthermore, we investigated the relationship between substituting other beverages with plain water intake and the risk of mortality. The multivariate Cox regression analyses revealed a significant association between higher plain water intake and lower all-cause mortality, cerebrovascular diseases mortality, and cancer mortality in both NAFLD or MASLD patients. Dose-response analyses revealed a non-linear trend between plain water intake and mortality among NAFLD/MASLD patients. Additionally, replacing sugar or artificial beverages with plain water was linked to reduced all-cause mortality, cerebrovascular diseases mortality, and cancer mortality in patients with NAFLD/MASLD. Higher plain water intake is independently linked to lower risk of all-cause, cerebrovascular diseases mortality, and cancer mortality in NAFLD/MASLD patients. Increasing plain water intake may be an effective way for these patients to reduce their risk of mortality.

Abstract One key source of uncertainty for weather and climate models is structural uncertainty arising from the fact that these models must simplify or approximate complex physical, chemical, and biological processes that occur in the real world. However, structural uncertainty is rarely examined in the context of simulated effects of anthropogenic heat flux in cities. Using the Weather Research and Forecasting (WRF) model coupled with a single‐layer urban canopy model, it is found that the sensitivity of urban canopy air temperature to anthropogenic heat flux can differ by an order of magnitude depending on how anthropogenic heat flux is released to the urban environment. Moreover, varying model structures through changing the treatment of roof‐air interaction and the parameterization of convective heat transfer between the canopy air and the atmosphere can affect the sensitivity of urban canopy air temperature by a factor of 4. Urban surface temperature and 2‐m air temperature are less sensitive to the methods of anthropogenic heat flux release and the examined model structural variants than urban canopy air temperature, but their sensitivities to anthropogenic heat flux can still vary by as much as a factor of 4 for surface temperature and 2 for 2‐m air temperature. Our study recommends using temperature sensitivity instead of temperature response to understand how various physical processes (and their representations in numerical models) modulate the simulated effects of anthropogenic heat flux.

Abstract Study objective The aim of our study was to elucidate differences in brain activity patterns among obstructive sleep apnea (OSA) patients, OSA patients with depressive symptoms, and healthy controls (HCs). We also investigated the relationship between brain function and depression in OSA patients. Methods A total of 95 subjects were included in the study, including 34 OSA patients without depressive symptoms, 31 OSA patients with depressive symptoms, and 30 HCs. The 53‐channel functional near‐infrared spectroscopy (fNIRS) was used to monitor the concentration of oxy‐hemoglobin (Oxy‐Hb) in the brain, whereas the participants performed the verbal fluency task, and the degree of depression was scored using the 17‐item Hamilton Rating Scale for Depression (HAMD‐17). Hierarchical regression models were conducted to analyze the association of fNIRS features with depressive symptom. Results The Oxy‐Hb changes of the three groups were significantly different in Channels 25 (H = 9.878, p = .007) and 43 (H = 6.957, p = .031). Inter‐group comparisons showed that the Oxy‐Hb change of Channel 25 (located in the dorsolateral prefrontal cortex [DLPFC]) in OSA group was less than that in HC group (p = .006), and the Oxy‐Hb change of Channel 43 (located in the right frontal polar region) in OSA group with depression was less than that in OSA group (p = .025). Spearman's test showed that there was a significant negative correlation between HAMD‐17 scores and mean Oxy‐Hb changes in Channel 43 (r = −.319, p

Sacha Inchi (Plukenetia volubilis L) (SI) is a traditional natural medicine from tropical rainforests of Amazon region in South America. As a raw material for edible oil, it has various pharmacological effects such as antioxidant, anti-inflammatory, hypolipidemia, and blood pressure lowering, which have attracted increasing attentions of pharmacists. This has prompted researchers to explore its pharmacological effects for potential applications in certain diseases. Among these, the study of its anti-inflammatory effects has become a particularly interesting topic, especially in rheumatoid arthritis (RA). RA is a systemic autoimmune disease, and often accompanied by chronic inflammatory reactions. Despite significant progress in its treatment, there is still an urgent need to find effective anti-RA drugs in regard to safety. This review summarizes the potential therapeutic effects of SI on RA by modulating gut microbiota, targeting inflammatory cells and pathways, and mimicking biologic antibody drugs, predicting the application prospects of SI in RA, and providing references for research aimed at using SI to treat RA.

Abstract The Beishan Exploration Tunnel (BET) is a facility built to develop technologies associated with the safety of China's first high‐level radioactive nuclear waste(HLW) disposal. The surrounding rock discontinuity identification is a key research topic in BET, which could provide essential geological data for future HLW disposal stability and integrity research. This article presents the rock discontinuity identification research progress in BET based on Structure from Motion (SfM) photogrammetry technology. The discontinuity identification algorithm is improved by introducing the region‐growing algorithm to optimize the candidate subplane. This algorithm automatically picks the seed, avoids human intervention, and thus increases the work efficiency of the discontinuity identification. The FCM method is improved by embedding with the CFSFDP algorithm in the discontinuity sets grouping. The CFSFDP algorithm coincides well with the Fisher distribution of discontinuity orientations, which is suitable for the Beishan situation. A parallel scheme is used when implementing the method, which accelerates the discontinuity calculation. This improved rock discontinuity identification method was tested on a slope above the BET and applied in the BET. The discontinuity identification results were compared with the results from the manual field measurement and the open‐source software DSE. The results show that the improved discontinuity identification method obtains reliable discontinuity data and costs less time and human workload than the other two methods. The surrounding rock discontinuity identification research provides a powerful tool for the Beishan HLW disposal geological investigation.

ObjectiveThis study aimed to determine the 50% effective dose (ED50) of ciprofol when combined with different doses of remifentanil for upper gastrointestinal endoscopy of school-age children and to evaluate its safety.MethodsThis study involved school-aged children who were scheduled to undergo upper gastrointestinal endoscopy under deep sedation. The children were randomly assigned to two groups: remifentanil 0.3 μg/kg (R0.3) and remifentanil 0.5 μg/kg (R0.5). Anesthesia was induced with remifentanil, followed by ciprofol. The dose of ciprofol for each patient was determined using the Dixon up-down sequential method. If the MOAA/S score was ≤1 and the child did not exhibit significant movement or coughing during the endoscopy process, sedation was considered successful. The first patient in each group received 0.5 mg/kg ciprofol. The dose of ciprofol was adjusted by 0.05 mg/kg based on the response of the previous patient. The primary outcome was the ED50 of the ciprofol-induction dose. The total ciprofol doses, onset times, awakening times, and adverse reactions were recorded.Results1) The Dixon method was used to collect crossovers data from each group, and the ED50 values of the R0.3 and R0.5 groups were calculated to be 0.390 mg/kg (95% CI 0.356–0.424 mg/kg) and 0.332 mg/kg (95% CI 0.291–0.374 mg/kg), respectively. The ED50 of ciprofol in the R0.3 group was significantly higher than that in the R0.5 group (p < 0.05). 2) The onset time and recovery time of the R0.5 group were shorter than those of the R0.3 group (p < 0.05). When the two groups were compared, the total dose of ciprofol in the R0.5 group decreased (p < 0.05). 3) Compared with the R0.3 group, the incidence of respiratory depression during induction in the R0.5 group increased (p < 0.05).ConclusionThis study explored the ED50 of ciprofol combined with different doses of remifentanil for successful sedation in upper gastrointestinal examinations in school-aged children. Compared to the use of remifentanil 0.3 μg/kg, the combination of ciprofol with remifentanil 0.5 μg/kg significantly reduced the ED50 required to prevent body movement or cough during endoscope insertion but increased the incidence of respiratory depression.

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

Background: Cellular senescence is pivotal in the occurrence and progression of atrial fibrillation (AF). This study aimed to identify senescence-related genes that could be potential therapeutic biomarkers for AF. Methods: AF-related differentially expressed genes (DEGs) were identified using the Gene Expression Omnibus dataset. Weighted gene co-expression network analysis (WGCNA) was used to analyze important modules and potential hub genes. Integrating senescence-related genes, potential biomarkers were identified. Their differential expression levels were then validated in human atrial tissue, HL-1 cells, and Angiotensin II-infused mice. Finally, molecular docking analysis was conducted to predict potential interactions between potential biomarkers and the senolytic drug Navitoclax. Results: We identified seven genes common to AF-related DEGs and senescence-related genes. Three significant modules were selected from WGCNA analysis. Taken together, three senescence-related genes (ETS1, SP1, and WT1) were found to be significantly associated with AF. Protein-protein interaction network analysis revealed biological connections among the predicted target genes of ETS1, SP1, and WT1. Notably, ETS1, SP1, and WT1 exhibited significant differential expression in clinical samples as well as in vitro and in vivo models. Molecular docking revealed favorable binding affinity between senolytic Navitoclax and these potential biomarkers. Conclusions: This study highlights ETS1, SP1, and WT1 as crucial senescence-related genes associated with AF, offering potential therapeutic targets, with supportive evidence of binding affinity with senolytic Navitoclax. These findings provide novel insights into AF pathogenesis from a senescence perspective.

Biochar has been recognised as an efficacious amendment for the remediation of compound heavy metal contamination in soil. However, the molecular mechanism of biochar-mediated tolerance to compound heavy metal toxicity in cotton is unknown. The objective of this research was to investigate the positive impact of biochar (10 g·kg−1) on reducing damage caused by compound heavy metals (Cd, Pb, and As) in cotton (Gossypium hirsutum L.). The results revealed that biochar reduced Cd concentrations by 24.9 % (roots), and decreased Pb concentrations by 37.1 % (roots) and 59.53 % (stems). Biochar maintained ionic homoeostasis by regulating the expression of metal transporter proteins such as ABC, HIPP, NRAMP3, PCR, and ZIP, and genes related to the carbon skeleton and plasma membrane. Biochar also downregulated genes related to photosynthesis, thereby increasing photosynthesis. Biochar re-established redox homoeostasis in cotton by activating signal transduction, which regulated the activity of the enzymes POD, SOD, and CAT activity; and the expression of related genes. This research revealed the molecular mechanism by which biochar confers resistance to the harmful effects of compound heavy metal toxicity in cotton. The application of biochar as a soil amendment to neutralise the toxicity of compound heavy metals is recommended for cash crop production.

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