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Abstract Purpose This study analyzed antibiotic resistance mechanisms and molecular epidemiology of multidrug-resistant Pseudomonas aeruginosa (MDR-PA), aiming at providing clues for prevention and control of MDR-PA infections. Methods The carbapenemase resistance genes (VIM, IMP, NDM, KPC, GES, OXA-40) of MDR-PA strains were detected by polymerase chain reaction (PCR) and sequencing. The efflux pump system (MexA, MexC, MexE, MexX), AmpC and OprD2 were detected by real-time fluorescent quantitative PCR (qPCR) in MDR-PA group and sensitive-Pseudomonas aeruginosa (S-PA) group. The homology analysis of MDR-PA strains was performed by multilocus sequence typing (MLST). Results A total of 81 MDR-PA strains were collected from the First Affiliated Hospital of Guangxi Medical University from October 2022 to October 2023. Among the carbapenemase detected, the detection rate of NDM-1 was the highest, with a rate of 34.57% (28/81). MexA had a higher expression in MDR-PA group than that in S-PA group (P

Abstract Following the publication of the 2021 WHO Classification of Central Nervous System Tumors (CNS5), Following the publication of the 2021 WHO Classification of Central Nervous System Tumors (CNS5), prognostic markers of glioblastoma (GBM) need to be further explored. Radiomics is a non-invasive and reproducible method for the prognostic assessment of multiple solid tumors. This study aimed to explore the prognostic value and biological significance of MRI T1-weighted enhancement (CE-T1) based radiomics in GBM (CNS5). A six-features radiomics prognostic model was created to calculate the radiomics score (RS). High RS (HR = 3.718, 95%CI: 2.222 − 6.220, P

Purpose – Assessing the efficiency of fresh food cold chain logistics as accurately as possible is essential for industry development planning. This study was designed to analyze the efficiency of fresh food cold chain logistics in China. Design/methodology/approach – A three-stage data envelopment analysis (DEA) model was used to analyze the efficiency of fresh food cold chain logistics in 30 provinces of China from 2013 to 2019. The stochastic frontier analysis (SFA) model in the second stage was used to eliminate the influence of external environmental factors and random disturbances on efficiency analysis results. Findings – (1) The overall actual efficiency of fresh food cold chain logistics in China is unsatisfactory, with an average technical efficiency of 0.382 over the 7-year period. (2) The national average technical efficiency and average scale efficiency were overestimated by 29.9% and 40.0%, respectively, compared with the actual values. (3) The efficiency of fresh food cold chain logistics does not align with the level of regional economic development. (4) Distinct regional variations exist in the efficiency of fresh food cold chain logistics in China, with higher efficiencies observed in Northwest China and the Central Yangtze River regions, and the lowest efficiencies in the northeast regions. Originality/value – This study applies a three-stage DEA model to assess the development and regional differences of fresh food cold chain logistics in China, enriching the application of models and empirical analysis in this field. By analyzing the situation in China, it provides ideas and references for other developing countries to develop cold chain logistics.

Let $ \mathcal{G} $ be a generalized matrix algebra. We show that under certain conditions, each generalized Lie $ n $-derivation associated with a linear map on $ \mathcal{G} $ is a sum of a generalized derivation and a central map vanishing on all $ (n-1) $-th commutators and is also a sum of a generalized inner derivation and a Lie $ n $-derivation. As an application, generalized Lie $ n $-derivations on von Neumann algebras are characterized.

Self-regulation is crucial for student success in scientific inquiry and engineering design. However, it remains unclear how students dynamically engage in self-regulated learning (SRL) processes to achieve high performance. In this study, we investigated the temporal nature of self-regulation during engineering design by leveraging computer trace data from 101 high school students who designed an energy-plus house in a simulated learning environment. Using sequential mining, we found that high-performing students were more engaged in the Observation, Analysis, and Evaluation phases of SRL than low-performing students. Additionally, high-performing students demonstrated consecutive sequential patterns between Observation and Analysis, Reformation and Evaluation, and Analysis and Evaluation behaviors. These findings provide insights into students’ SRL processes and the design of scaffoldings.

Abstract Background Corynebacterium striatum (C. striatum), a common skin and mucosal colonizer, is increasingly considered as an opportunistic pathogen causing bloodstream infections (BSIs). This study aims to investigate the clinical features and outcomes of C. striatum-BSI. Methods We included hospitalized cases with C. striatum-positive blood cultures from January 2014 to June 2022 and classified them into C. striatum-BSI group and contamination group; Clinical characteristics, treatments, and outcomes were compared between the C. striatum-BSI group and contamination group, Methicillin-resistant Staphylococcus aureus (MRSA)-BSI and Methicillin-resistant Staphylococcus epidermidis (MRSE)-BSI. Results Fifty-three patients with positive C. striatum blood cultures were identified. Among them, 25 patients were classified as C. striatum-BSI, with 21 as contamination cases. And 62 cases of MRSA-BSI and 44 cases of MRSE-BSI were identified. Compared to the contaminated group, the C. striatum-BSI group had a shorter time to positivity of blood cultures (27.0 h vs. 42.5 h, P = 0.011). C. striatum-BSI group had a longer time to positivity (27 h) when compared to both the MRSA (20 h) and MRSE groups (19 h) (p

Abstract Background Serum (1,3)-β-D-glucan (BDG) detection for diagnosis of Pneumocystis jirovecii pneumonia (PJP) in non-human immunodeficiency virus (HIV) immunocompromised patients lacks intensive care unit (ICU)-specific data. We aimed to assess its performance and determine the optimal cutoff for PJP in ICU population. Methods This retrospective study included critically ill non-HIV immunocompromised patients admitted to a medical ICU with suspected pneumonia, undergoing simultaneous microbiological testing for P. jirovecii on lower respiratory tract specimens and serum BDG. Confounders affecting BDG positivity were explored by multivariable logistic regression. Optimal cut-offs were derived from Youden’s index for the entire cohort and subgroups stratified by confounders. Diagnostic performance of serum BDG was estimated at different cutoffs. Results Of 400 patients included, 42% were diagnosed with PJP and 58.3% had positive serum BDG. Serum BDG’s area under the receiver operating characteristic curve was 0.90 (0.87–0.93). At manufacturer’s 150 pg/ml cut-off, serum BDG had high sensitivity and negative predictive value (94%), but low specificity and positive predictive value (67%). Confounders associated with a positive serum BDG in PJP diagnosis included IVIG infusion within 3 days (odds ratio [OR] 9.24; 95% confidence interval [CI] 4.09–20.88, p

Abstract The current selection of ligands for both proteins of interest (POI) and E3 ubiquitin ligase significantly restricts the scope of targeted protein degradation (TPD) technologies. This study introduces cell-penetrating peptide-induced chimera conjugates (cp-PCCs) targeting the DHHC3 enzyme involved in PD-L1 palmitoylation. This approach disrupts PD-L1’s immunosuppressive function, enhancing anti-tumor immunity. We developed cp-PCCs to degrade DHHC3, directly linking DHHC3-mediated PD-L1 palmitoylation to PD-L1 stability on tumor cells. Our research utilized both in vitro assays and in vivo experiments in immune checkpoint blockade-resistant mouse models. We focused on a CRBN-based cp-PCC named PCC16, which demonstrated a DC50 of 102 nmol for DHHC3 degradation and significantly reduced PD-L1 levels. In resistant models, PCC16 not only robustly downregulated PD-L1 but also exhibited substantial anti-tumor activity in vivo without significant toxicity. This outperformed traditional inhibitors, showcasing the potential of cp-PCC technology to bypass current PROTAC limitations. Our findings suggest that cp-PCCs offer a promising method for targeting PD-L1 through DHHC3 inhibition and support their continued exploration as a versatile tool in cancer immunotherapy, especially for tumors resistant to standard treatments.

Abstract Objective To evaluate the efficacy and safety of definitive radiotherapy in selected patients with local recurrence of Kimura disease of the head and neck after surgery. Methods This retrospective study collected the clinical data of 14 patients with postoperative recurrence of Kimura disease of the head and neck who received definitive radiotherapy at the First Affiliated Hospital of Fujian Medical University between 2006 and 2022. The radiation dose ranged from 28 to 40 Gy. Its efficacy and safety were analyzed. Results During follow‐up, ranging from 17 to 168 months, local control was achieved in 13 (92.9%) of the 14 patients with postoperative recurrence. There were no serious late toxicities except for mild xerostomia in four (28.6%) patients; the patients’ peripheral blood eosinophil count dropped from 1.73×109/L before treatment to 0.42×109/L after treatment, and the eosinophil percentage dropped from 20.64% to 9.78%. Both changes were statistically significant (p

The diterpene ent-copalol is an important precursor to the synthesis of andrographolide and is found only in green chiretta (Andrographis paniculata). De novo biosynthesis of ent-copalol has not been reported, because the catalytic activity of ent-copalyl diphosphate synthase (CPS) is very low in microorganisms. In order to achieve the biosynthesis of ent-copalol, Saccharomyces cerevisiae was selected as the chassis strain, because its endogenous mevalonate pathway and dephosphorylases could provide natural promotion for the synthesis of ent-copalol. The strain capable of synthesizing diterpene geranylgeranyl pyrophosphate was constructed by strengthening the mevalonate pathway genes and weakening the competing pathway. Five full-length ApCPSs were screened by transcriptome sequencing of A. paniculata and ApCPS2 had the best activity and produced ent-CPP exclusively. The peak area of ent-copalol was increased after the ApCPS2 saturation mutation and its configuration was determined by NMR and ESI-MS detection. By appropriately optimizing acetyl-CoA supply and fusion-expressing key enzymes, 35.6 mg/L ent-copalol was generated. In this study, de novo biosynthesis and identification of ent-copalol were achieved and the highest titer ever reported. It provides a platform strain for the further pathway analysis of andrographolide and derivatives and provides a reference for the synthesis of other pharmaceutical intermediates.

Abstract Hepatocellular carcinoma (HCC) is the primary malignant tumor of the liver. c-Myc is one of the most common oncogenes in clinical settings, and amplified levels of c-Myc are frequently found in HCC. Histone deacetylase inhibitors (HDACi), such as Trichostatin A (TSA), hold enormous promise for the treatment of HCC. However, the potential and mechanism of TSA in the treatment of c-Myc-induced HCC are unclear. In this study, we investigated the effects of TSA treatment on a c-Myc-induced HCC model in mice. TSA treatment delayed the development of HCC, and liver function indicators such as ALT, AST, liver weight ratio, and spleen weight ratio demonstrated the effectiveness of TSA treatment. Oil red staining further demonstrated that TSA attenuated lipid accumulation in the HCC tissues of mice. Through mRNA sequencing, we identified that TSA mainly affected cell cycle and fatty acid degradation genes, with alcohol dehydrogenase 4 (ADH4) potentially being the core molecular downstream target. QPCR, immunohistochemistry, and western blot analysis revealed that ADH4 expression was repressed by c-Myc and restored after TSA treatment both in vitro and in vivo. Furthermore, we observed that the levels of total NAD+ and NADH, NAD+, NAD+/NADH, and ATP concentration increased after c-Myc transfection in liver cells but decreased after TSA intervention. The levels of phosphorylated protein kinase B (p-AKT) and p-mTOR were identified as targets regulated by TSA, and they governed the ADH4 expression and the downstream regulation of total NAD+ and NADH, NAD+, NAD+/NADH, and ATP concentration. Overall, our study suggests that TSA has a therapeutic effect on c-Myc-induced HCC through the AKT-mTOR-ADH4 pathway. These findings provide valuable insights into the potential treatment of HCC using TSA and shed light on the underlying molecular mechanisms involved.

Abstract Background Although triglyceride-glucose (TyG) index is a reliable indicator of insulin resistance and cardiometabolic disease, its effectiveness in predicting mortality risk has not been adequately validated. We aimed to investigate the association between the TyG-related indices and all-cause and cause-specific mortality in the general population. Methods A total of 27,642 individuals were included from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018. Three indicators were constructed, including the TyG index, TyG combined with waist-to-height ratio (TyG-WHtR), and TyG combined with waist circumference (TyG-WC). Mortality data was acquired through the linkage of NHANES data with National Death Index records. Weighted Cox proportional hazards models were used to estimate the independent association between the TyG-related indices and mortality. Nonlinear associations were explored using restricted cubic splines. Results Multivariable adjusted models showed a progressive increase in all-cause and cause-specific mortality across quartiles of the TyG-related indices. Compared with the lowest quartile of the TyG index, the highest quartile had adjusted hazard ratios of 1.26 (95% CI 1.04–1.52) for all-cause mortality, 1.38 (1.04–1.74) for cardiovascular mortality, and 1.23 (1.01–1.50) for non-cardiovascular mortality, respectively. For the TyG-WHtR index, the corresponding hazard ratios were 1.60 (1.25–2.05), 1.86 (1.26–2.50), and 1.48 (1.10–1.99), respectively. For the TyG-WC index, the corresponding hazard ratios were 1.42 (1.11–1.75), 1.48 (1.04–1.96), and 1.38 (1.05–1.72), respectively. The associations between the three TyG-related indices and all-cause, cardiovascular and non-cardiovascular mortality were J-shaped. Interaction tests revealed significant effect modification by age, low-density lipoprotein cholesterol (LDL-C) level, and statin use (all P values

Abstract Human p97 ATPase is crucial in various cellular processes, making it a target for inhibitors to treat cancers, neurological, and infectious diseases. Triazole allosteric p97 inhibitors have been demonstrated to match the efficacy of CB-5083, an ATP-competitive inhibitor, in cellular models. However, the mechanism is not well understood. This study systematically investigates the structures of new triazole inhibitors bound to both wild-type and disease mutant forms of p97 and measures their effects on function. These inhibitors bind at the interface of the D1 and D2 domains of each p97 subunit, shifting surrounding helices and altering the loop structures near the C-terminal α2 G helix to modulate domain-domain communications. A key structural moiety of the inhibitor affects the rotameric conformations of interacting side chains, indirectly modulating the N-terminal domain conformation in p97 R155H mutant. The differential effects of inhibitor binding to wild-type and mutant p97 provide insights into drug design with enhanced specificity, particularly for oncology applications.

Abstract Whether small nucleolar RNAs (snoRNAs) are involved in the regulation of liver cancer stem cells (CSCs) self-renewal and serve as therapeutic targets remains largely unclear. Here we show that a functional snoRNA (SNORD88B) is robustly expressed in Hepatocellular carcinoma (HCC) tumors and liver CSCs. SNORD88B deficiency abolishes the self-renewal of liver CSCs and hepatocarcinogenesis. Mechanistically, SNORD88B anchors WRN in the nucleolus, promoting XRCC5 interacts with STK4 promoter to suppress its transcription, leading to inactivation of Hippo signaling. Moreover, low expression of STK4 and high expression of XRCC5 are positively correlated with HCC poor prognosis. Additionally, snord88b knockout suppresses mouse liver tumorigenesis. Notably, co-administration of SNORD88B antisense oligonucleotides (ASOs) with MST1 agonist adapalene (ADA) exert synergistic antitumor effects and increase overall murine survival. Our findings delineate that SNORD88B drives self-renewal of liver CSCs and accelerates HCC tumorigenesis via non-canonical mechanism, providing potential targets for liver cancer therapy by eliminating liver CSCs.

Abstract We aimed to assess the cumulative incidences of cancer-specific mortality (CSM) in non-metastatic patients with non‑muscle invasive urothelial bladder cancer (NMIUBC) and establish competing risk nomograms to predict CSM. Patient data was sourced from the Surveillance, Epidemiology, and End Results database, as well as the electronic medical record system in our institution to form the external validation cohort. Sub-distribution proportional hazards model was utilized to determine independent risk factors influencing CSM in non-metastatic NMIUBC patients. Competitive risk nomograms were constructed to predict 3-year, 5-year, and 8-year cancer-specific survival (CSS) in all patients group, TURBT group and cystectomy group, respectively. The discrimination and accuracy of the model were validated through the concordance index (C-index), the area under the receiver operating characteristic curve (AUC), and calibration curves. Decision curve analysis (DCA) and a risk stratification system was employed to evaluate the clinical utility of the model. Race, age, marital status, surgery in other sites, tumor size, histological type, histological grade, T stage and N stage were identified as independent risk factors to predict CSS in all patients group. The C-index for 3-year CSS was 0.771, 0.770 and 0.846 in the training, testing and external validation sets, respectively. The ROC curves showed well discrimination and the calibration plots were well fitted and consistent. Moreover, DCA demonstrated well clinical effectiveness. Altogether, the competing risk nomogram displayed excellent discrimination and accuracy for predicting CSS in non-metastatic NMIUBC patients, which can be applied in clinical practice to help tailor treatment plans and make clinical decisions.

Abstract Background Multiple epiphyseal dysplasia-4 (MED-4, MIM 226900) is a rare autosomal recessive disease characterized by disproportionate height and early onset osteoarthritis of the lower limbs. MED-4 is caused by homozygous or compound heterozygous pathogenic variants in the SLC26A2 gene. However, the underlying pathogenic mechanisms in chondrocytes remains unknown. This study aimed to identify the pathogenic variants within a MED-4 family and explore the molecular etiology of this condition in human primary chondrocyte cells. Methods Clinical data were recorded and peripheral blood samples were collected for analysis. Whole exome sequencing (WES) and bioinformatic analyses were performed to determine causative variants. Wild-type SLC26A2 and corresponding mutant expression plasmids were constructed and transfected into human primary chondrocytes. The expression and subcellular distribution of SLC26A2 protein in chondrocytes were detected by immunoblotting and immunofluorescence. Effects of these variants on chondrocytes viability and apoptosis were measured by Cell Counting Kit-8 (CCK-8) assay. Expression of genes related to cartilage homeostasis was subsequently analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Results We identified two compound heterozygous variants c.1020_1022delTGT(p.Val341del) and c.1262 T > C(p.Ile421Thr) in the SLC26A2 gene in the patients. Mutant SLC26A2Val341del and SLC26A2Ile421Thr proteins were distributed in relatively few cells and were observed only within the nucleus. The viability of chondrocytes with the SLC26A2 variant group was similar to the wild-type (WT) group. However, the protein expressions of SLC26A2Val341del and SLC26A2Ile421Thr were decreased compared with SLC26A2WT. Expression levels of matrix metallopeptidase 13 (MMP13), α-1 chain of type X collagen (COL10A1), and Runt-related transcription factor 2 (RUNX2) were significantly decreased in the variant group. However, aggrecan (ACAN) expression was higher in the variant group than the WT group. Conclusions Overall, our data demonstrate that the variants p.Val341del and p.Ile421Thr in SLC26A2 cause MED-4 and that these two variants promote chondrocyte proliferation while inhibiting chondrocyte differentiation.

Freeway work zone forms as a result of traffic crash or road rehabilitation. To ascertain the effects of work zone with lane II completely blocked on vehicular flow on ring freeways with a tunnel, a three-lane continuum model is put forward. The mandatory net lane-changing rate from lane II to lane I or III just upstream of the work zone is described by a random number model, with the random number being produced within a small range around a median based on a golden section analysis. The net-changing rate between adjacent lanes is described using a lane-changing time on the basis of an assumption: the time ratio to relaxation time equals infinity when the absolute value of traffic densities between the two adjacent lanes is less than 1 veh/km, implying that the net-changing rate is zero; otherwise, the time ratio is inversely proportional to the vehicular spatial headway, which is equal to unity for traffic flow at saturation state, but infinity when the traffic flow is completely jammed. It is assumed that the freeway is a three lane ring with a total length of 100 km, and has a tunnel with a speed limit of 60 km/h and a length of 1.6 km located downstream the work zone with a length of 0.16 km. The free flow speeds on lanes I, II, and III are 120 km/h, 100 km/h, and 85 km/h, respectively. For the vehicular flow on the ring freeway with a tunnel, numerical simulations based on the three-lane continuum model are carried out with a reliable numerical method of high accuracy. It is found that the vehicular flow has two thresholds of traffic jam formation, one depending upon the tunnel and the other upon the work zone. The tunnel triggers a traffic jam when the initial density normalized by jam density is equal to the first threshold 0.15, and the work zone originates another traffic jam when the normalized initial density equals the second threshold 0.19. The freeway tunnel plays a dominant role in the prediction of mean travel time as soon as the tunnel has generated a traffic jam at the tunnel entrance. For the vehicular flow at unsaturated state, the average speed through the tunnel is about 26.67 km/h. When the normalized initial density exceeds the second threshold 0.19, the mean travel time through every lane increases with the initial density linearly. Vehicle fuel consumption can be estimated by interpolation with the time averaged grid traffic speed and an assumed vehicle performance curve. It is found that the vehicle fuel consumption is lane number dependent, and distributes with the initial density concavely, as well as has a value in the range of 6.5 to 8.3 l.

Abstract Prevention of subsequent fracture is a major public health challenge in the field of osteoporosis prevention and treatment, and older women are at high risk for osteoporotic fractures. This study aimed to examine factors associated with subsequent fracture in older Chinese women with osteoporosis. We collected data on 9212 older female patients with osteoporotic fractures from 580 medical institutions in 31 provinces of China. Higher odds of subsequent fractures were associated with age of 70–79 years (OR 1.218, 95% CI 1.049–1.414), age ≥ 80 (OR 1.455, 95% CI 1.222–1.732), index fracture site was vertebrae (OR 1.472, 95% CI 1.194–1.815) and hip (OR 1.286, 95% CI 1.041–1.590), index fracture caused by fall (OR 1.822, 95% CI 1.281–2.591), strain (OR 1.587, 95% CI 1.178–2.139), no inducement (OR 1.541, 95% CI 1.043–2.277), and assessed as high risk of fracture (OR 1.865, 95% CI 1.439–2.416), BMD T-score ≤ −2.5 (OR 1.725, 95% CI 1.440–2.067), history of surgery (OR 3.941, 95% CI 3.475–4.471) and trauma (OR 8.075, 95% CI 6.941–9.395). Low risk of fall (OR 0.681, 95% CI 0.513–0.904), use of anti-osteoporosis medication (AOM, OR 0.801, 95% CI 0.693–0.926), and women who had received fall prevention health education (OR 0.583, 95% CI 0.465–0.730) associated with lower risk. The areas under the curve of the prediction model was 0.818. The sensitivity was 67.0% and the specificity was 82.0%. The prediction model showed a good ability to predict the risk of subsequent fracture in older women with osteoporotic fractures and are suitable for early self-measurement which may benefit post-fracture management.

Abstract Polymer-based circularly polarized luminescence (CPL) materials with the advantage of diversified structure, easy fabrication, high thermal stability, and tunable properties have garnered considerable attention. However, adequate and precise tuning over CPL in polymer-based materials remains challenging due to the difficulty in regulating chiral structures. Herein, visualized full-color CPL is achieved by doping red, green, and blue quantum dots (QDs) into reconfigurable blue phase liquid crystal elastomers (BPLCEs). In contrast to the CPL signal observed in cholesteric liquid crystal elastomers (CLCEs), the chiral 3D cubic superstructure of BPLCEs induces an opposite CPL signal. Notably, this effect is entirely independent of photonic bandgaps (PBGs) and results in a high g lum value, even without matching between PBGs and the emission bands of QDs. Meanwhile, the lattice structure of the BPLCEs can be reversibly switched via mechanical stretching force, inducing on-off switching of the CPL signals, and these variations can be further fixed using dynamic disulfide bonds in the BPLCEs. Moreover, the smart polymer-based CPL systems using the BPLCEs for anti-counterfeiting and information encryption have been demonstrated, suggesting the great potential of the BPLCEs-based CPL active materials.

Abstract Background Life’s Essential 8 (LE8), the recently updated construct for quantifying cardiovascular health, is related to the risks of cardiovascular events. The present study aimed to evaluate associations of LE8 score with the multi-territorial extent of atherosclerosis in a community-dwelling population. Methods Data were derived from the baseline cross-sectional survey of the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study in Lishui City. The LE8 included overall, medical and behavior LE8 scores, and were categorized as low (

This study challenges the generally accepted principle that some degree of as-cast microstructure heritability (CMH), marked by -oriented dendrite-associated inhomogeneity, is tolerable in conventional [001]-oriented Ni-based single crystal (SX) superalloys. Our findings reveal that this principle does not hold for newly developed [111]-oriented SX superalloys, where -directed dendrites experience significant resolved shear stress under [111] applied loads. This work examines the stress rupture behaviors of a [111]-oriented low-Re Ni-based SX superalloy under various CMH conditions at 1100 °C/160 MPa and 760 °C/800 MPa. In the absence of CMH, the alloy achieves rupture properties comparable to fourth-generation SX superalloys. However, the presence of CMH drastically shortens rupture life and alters multi-scale deformation behaviors. High-temperature damage involves submicroscopic dislocation shearing, microscopic crack initiation, mesoscopic inter-dendritic crack connections, and macroscopic fractures. Intermediate-temperature damage is marked by submicroscopic stacking fault shearing, microscopic shear zone deformation, mesoscopic crack propagation, and macroscopic lattice rotation. Moreover, this research investigates the degradation mechanism of stress rupture property when the CMH is combined with slow cooling and reveals unique deformation behaviors, such as high-temperature subgrain formation and intermediate-temperature isolated micro-twins. This work provides new insights into the influence mechanism of the CMH.

Climate warming and human disturbance are supposed to have significantly impacted the alpine grasslands. However, it is still unclear how human activity affects the community composition and niche characteristics in response to warming. We conducted a two-factorial experiment in an alpine meadow, and set up four treatments: warming, mowing, warming with mowing, and control. Based on the investigation of community composition and niche characteristics, we evaluated the impacts of soil carbon, nitrogen, and phosphorus on species niche overlap. The results showed that mowing significantly increased species richness of Grass, Sedge, Forbs and the importance value of Sedge compared to warming (P < 0.05). The niche breadth of species (>50 %) was reduced by warming, but increased under mowing. The niche overlap mainly occurred between Grass and Forbs in warming, while it was evenly distributed among species after mowing, which alleviated the negative effects of warming on interspecific competitiveness. Warming increased the number of species pairs with a niche overlap value >0.9 by 24.15 %, while warming with mowing decreased it by 2.7 %. The number of species pairs with niche overlap was significantly correlated with soil total nitrogen and soil available nitrogen (P < 0.05). In particular, the species pairs with highly competitive showed a greater dependency on soil nitrogen. Our work highlights that moderate utilization and soil nitrogen are two crucial factors influencing the response of community structure in alpine meadows to future climate change. The study provides an important reference for predicting and addressing the impact of global climate change on adaptive management and grassland protection.

IntroductionTetrastigma hemsleyanum is a folk and rare medicinal plant, and specifically, it is distributed in the south, China. To investigate the cumulative properties of its medicinal components, we examined the effect of UV light on flavonoid content and related enzyme activity changes in T. hemsleyanum.MethodsThe leaves and tubers were treated with UV-A, UV-B and UV-C for 1 h, 1L/23D h, 3 h and 3L/21D h (D represents darkness treatment). High-performance liquid chromatography (HPLC) analysis showed that the content of many flavonoids decreased significantly during UV-A treatment, increased after UV-B and UV-C irradiation and accumulated again after darkness treatment.ResultsIn the root tubers of the UV-A group, naringin content in the 3L/21D h group (0.069 μg/g) was 16.30 times higher than that of 3 h group (0.0042 μg/g). The rutin content was elevated after UV irradiation but was not detected in the CK group. The test results of the enzyme-linked kit indicated that the activities of many enzymes were higher in the UV-A and UV-B irradiation groups than those in the CK group, but the results were reversed in the UV-C treatment. After darkness treatment, the activities of most enzymes were higher than those with UV irradiation alone; F3’5’H activity in the 3L/21D h group (97.25 U/L) was 1.24 times higher than that in the 3 h group (78.12 U/L) in the UV-A-treated group.DiscussionThe study results suggest that appropriate UV-B and UV-C irradiation, as well as darkness supplementation, had a promotive effect on flavonoids in the leaves and root tubers of T. hemsleyanum. Additionally, UV irradiation and darkness treatment enhanced the activity of most enzymes.

Gastrointestinal (GI) cancers are the most common malignancies, while surgical intervention remains the sole therapeutic approach offering the possibility of a definite cure for cancer. Perioperative anxiety negatively impacts the recovery of GI cancers. Recently, mounting studies have demonstrated that proper nursing interventions may alleviative perioperative anxious illnesses in patients with GI cancers. We conducted a first comprehensive review to summarize all the current evidence on this topic. After a systematically search in the six common databases, eighteen relevant studies were included for further analysis. The present review highlighted that there is a high prevalence of perioperative anxiety in patients with GI cancers (e.g., colorectal cancer, gastric/stomach cancer, hepatocellular carcinoma, gallbladder cancer, and esophageal cancer), while specific nursing interventions are the reliable methods to reduce postoperative anxiety. These nursing strategies include, but are not limited to, therapeutic listening intervention, implementing perioperative music, predictive nursing, progressive relaxation exercises, psychological interventions in the nursing care, comprehensive nursing, continuous nursing care, video-based nursing education, multidisciplinary cooperative continuous care, accelerated rehabilitation nursing, TCM nursing, evidence-based early warning nursing, target nursing care, and high-quality nursing. Since several limitations existed in the eligible studies as well as in this review, a well-designed multicenter RCT with large sample size is still warranted for the confirmation of nursing intervention for managing perioperative anxiety in patients with GI cancers. Also, future studies should focus on the long-term effects of relevant interventions, specific patient populations, multidisciplinary approaches, technological innovations, and educational programs.

In recent years, China has gradually begun restoring native salt marsh vegetation such as Suaeda salsa (S. salsa) in coastal wetlands that were damaged by the long-term invasion of Spartina alterniflora. Chlorophyll content (Cab), an important indicator of vegetation health, necessitates extensive and long-term monitoring using Sentinel-2. However, due to the influence of betacyanin (Beta), S. salsa exhibits different phenotypes (red and green) under various stress conditions, making remote sensing mechanism studies of this unique vegetation more challenging. In particular, satellite multispectral images are significantly affected by soil background in mixed pixels, making it imperative to mitigate this influence. This study explores the applicability of a recently proposed spectral separation of soil and vegetation (3SV) in Sentinel-2 multispectral and S. salsa vegetation from a remote sensing mechanism perspective, and further improves it. Additionally, a comparative analysis was conducted on the effectiveness of combining 3SV with several mainstream chlorophyll-sensitive indices. The advantages of machine learning algorithms were leveraged to develop a high-precision hybrid semi-empirical model for estimating Cab in different S. salsa phenotypes. The research findings indicate that: (1) The 3SV algorithm, adjusted with slope compensation and B2 and B4 bands, is applicable to green S. salsa scenarios. For red S. salsa scenarios, further adjustment using B2 and B3 bands and coverage fraction is required. (2) The MTCI, MRENDVI, MND, and MNDRE indices combined best with the modified 3SV, significantly reducing the RMSE of the semi-empirical models, especially under wet soil conditions with soil fraction fsoil

BackgroundWhile the correlation between physical activity (PA) and mental health is well known, the mediating mechanism of resilience between the two variables remains unclear.ObjectivesTo systematically evaluate the relationship between PA and mental health, and explore the mediating role of resilience between them.MethodsA systematic search of electronic databases (PubMed, Web of Science, ProQuest, Ebsco, China Knowledge, and China Biomedical Database) was conducted to identify relevant studies, and meta-analytic procedures were used to assess the strength of the relationships between PA and mental health. Furthermore, a meta-analytic structural equation model (MASEM) was used to assess the mediating effects of resilience, ensuring the reliability of our findings.ResultsThe findings of 15 studies (17,043 subjects) were subjected to meta-analysis and route analysis. The findings of the meta-analysis revealed a statistically significant positive correlation of 0.288 (95% CI, 0.166–0.402) between PA and positive indicators of mental health, as well as a statistically significant negative correlation (95% CI, −0.342 to −0.171) with negative indicators of mental health. Furthermore, the results of MASEM path analysis indicated that PA may indirectly impact both positive and negative indicators of mental health through the mediating factor of resilience. The indirect effect values were 0.108 (95% CI, 0.080–0.141) and −0.074 (95% CI, −0.100 to −0.051), respectively, accounting for 40.15% of the total effect value and 28.91%.ConclusionPhysical activity is positively correlated with positive indicators of mental health and negatively correlated with negative indicators of mental health. Moreover, PA can positively influence mental health through the mediating role of resilience.

Abstract Enzymes with active sites involving histidine selectively utilize either the δ‐ or ε‐nitrogen atom (Nδ or Nε) of the histidine imidazole for catalysis. However, evaluating the impact of Nδ and Nε is difficult, and directly integrating noncanonical N‐methylated histidine within enzymes poses risks due to laborious procedures. In this study, we present the self‐assembly of Fmoc‐Histidine (Fmoc‐His) with hemin to create a peroxidase‐mimetic catalyst, in which either the Nε or Nδ of histidine is methylated to modify the tautomeric preferences, thereby tuning hemin catalysis. UV‐vis spectra, 1H‐NMR, and fluorescence experiments elucidate that the N‐methylation of histidine alters the self‐assembly propensity of Fmoc‐His, and affects the binding affinity of histidine to hemin iron, with Fmoc‐δmHis/hemin exhibiting stronger binding than Fmoc‐εmHis/hemin. Theoretical simulation results suggest that εmHis and δmHis ligation produce a saddled structure and planar structure of hemin, respectively, stemming from the disparity of steric hindrance at the Nε and Nδ positions. The significant inhibition of hemin's oxidative activity by Fmoc‐δmHis is observed, likely due to the strong binding of Fmoc‐δmHis, potentially hindering access of the substrate, H2O2, to the hemin iron. Conversely, Fmoc‐εmHis enhances hemin catalysis, surpassing even Fmoc‐His alone. This differential impact of Fmoc‐εmHis and Fmoc‐δmHis on hemin activity is further corroborated by apparent activation energy and kinetic parameters (kcat, kcat/Km). This study sheds light on the heterogeneous biological effects at the nitrogen positions of histidine imidazole and offers insights into designing supramolecular metalloenzymes.

IntroductionOsteoarthritis (OA) is a globally prevalent joint disorder affecting approximately 240 million individuals worldwide. Cinnamaldehyde, known for its broad anti-inflammatory and anti-aging effects across various cell types, has not been investigated for its potential impact on apoptosis in OA chondrocytes.MethodsTo explore the effectiveness of cinnamaldehyde in mitigating knee osteoarthritis by reducing chondrocyte apoptosis, bioinformatics analysis was first conducted to identify apoptosis-associated differentially expressed genes (APDEGs). Gene expression datasets GSE55235 and GSE114007 were analyzed using weighted gene co-expression network analysis (WGCNA). Gene modules of interest were cross-referenced with APDEGs to identify those specific to OA. LASSO regression analysis was employed to build a risk model, and this model, along with datasets GSE114007, GSE55457, and GSE12021, was validated using ROC analysis. Cellular experiments and blood analyses from OA patients were performed to evaluate the effects of cinnamaldehyde on apoptosis-related gene expression.ResultsCinnamaldehyde administration was found to rectify the abnormal expression of key apoptosis-related genes in OA patients. Specifically, cinnamaldehyde may affect knee osteoarthritis by regulating apoptosis-related genes such as ZFAND5, BCL6, ELL2, FOSL2, MARCKS, and SGCD. Additionally, three novel apoptotic targets in OA chondrocytes—ZFAND5, ELL2, and SGCD—were identified.DiscussionThese findings provide significant theoretical support for the clinical use of cinnamaldehyde in OA treatment. The discovery of novel apoptotic targets presents new therapeutic possibilities for future OA interventions.

Water-soluble salt-based ceramic cores can be recycled and have excellent high-temperature chemical stability. In this work, vat photopolymerization was successfully applied to water-soluble salt-based ceramic cores for the first time. The powder raw materials of the printing suspension were sodium chloride and alumina. High-precision green bodies were manufactured by optimizing suspensions and parameters. In addition, the postprocessing method was optimized according to the microstructure and mechanical properties. The sintered part had a high bending strength and smooth surface. Finally, the dissolution rate and moisture resistance were compared under different dissolution and storage conditions. Compared to traditional manufacturing methods, vat photopolymerization enables the production of complex structures without molds and reduces production costs. This technology is suitable for the rapid iteration of complex structural parts and can be applied to precision parts in aerospace, military, and other technical fields with high cost-effectiveness and sustainability.

Abstract Backgrounds Increased respiratory drive has been demonstrated to correlate with weaning failure, which could be quantified by electrical activity of the diaphragm (EAdi). We described the physiological process of EAdi-based parameters during the spontaneous breathing trial (SBT) and evaluated the change of EAdi-based parameters as potential predictors of weaning failure. Methods We conducted a prospective study in 35 mechanically ventilated patients who underwent a 2-hour SBT. EAdi and ventilatory parameters were continuously measured during the SBT. Diaphragm ultrasound was performed before the SBT and at the 30 min of the SBT. Three EAdi-based parameters were calculated: neuro-ventilatory efficiency, neuro-excursion efficiency and neuro-discharge per min. Results Of the thirty 35 patients studied, 25 patients were defined as SBT success, including 22 patients weaning successfully and 3 patients reintubated. Before the SBT, neuro-excursion efficiency differed significantly between two groups and had the highest predictive value for SBT failure (AUROC 0.875, p

Abstract Atrial fibrillation (AF) is the most common arrhythmia and its incidence increases with sepsis. However, data on new-onset AF during sepsis hospitalization remain limited in China. We aimed to evaluate the incidence, risk factors, and associated mortality of new-onset AF in sepsis patients in China. We conducted a retrospective study using the National Data Center for Medical Service system, from 1923 tertiary and 2363 secondary hospitals from 31 provinces in China from 2017 to 2019.In total we included 1,425,055 sepsis patients ≥ 18 years without prior AF. The incidence of new-onset AF was 1.49%. Older age, male sex, hypertension, heart failure, coronary disease, valvular disease, and mechanical ventilation were independent risk factor. New-onset AF was associated with a slight increased risk of mortality (adjusted RR 1.03, 95% CI 1.01–1.06). Population attributable fraction suggested AF accounted for 0.2% of sepsis deaths. In this large nationwide cohort, new-onset AF occurred in 1.49% of sepsis admissions and was associated with a small mortality increase. Further research should examine whether optimized AF management can improve sepsis outcomes in China.

Abstract The protection of the replication fork structure under stress conditions is essential for genome maintenance and cancer prevention. A key signaling pathway for fork protection involves TRPV2-mediated Ca2+ release from the ER, which is triggered after the generation of cytosolic DNA and the activation of cGAS/STING. This results in CaMKK2/AMPK activation and subsequent Exo1 phosphorylation, which prevent aberrant fork processing, thereby ensuring genome stability. However, it remains poorly understood how the TRPV2 channel is activated by the presence of cytosolic DNA. Here, through a genome-wide CRISPR-based screen, we identify TRPM8 channel-associated factor 1 (TCAF1) as a key factor promoting TRPV2-mediated Ca2+ release under replication stress or other conditions that activate cGAS/STING. Mechanistically, TCAF1 assists Ca2+ release by facilitating the dissociation of STING from TRPV2, thereby relieving TRPV2 repression. Consistent with this function, TCAF1 is required for fork protection, chromosomal stability, and cell survival after replication stress.

Abstract Background Emerging evidences have demonstrated that gut microbiota composition is associated with pulmonary arterial hypertension (PAH). However, the underlying causality between intestinal dysbiosis and PAH remains unresolved. Method An analysis using the two-sample Mendelian randomization (MR) approach was conducted to examine the potential causal relationship between gut microbiota and PAH. To assess exposure data, genetic variants associated with 196 bacterial traits were extracted from the MiBioGen consortium, which included a sample size of 18,340 individuals. As for the outcomes, summary statistics for PAH were obtained from the NHGRI-EBI GWAS Catalog, which conducted a meta-analysis of four independent studies comprising a total of 11,744 samples. Causal effects were estimated employing various methods, including inverse variance weighted (IVW), MR-Egger, weighted median, weight mode and simple mode, with sensitivity analyses also being implemented with Cochran’s Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis, and funnel plots. Results Following false discovery rate (FDR) correction, the genetically predicted genus Eubacterium fissicatena group (odds ratio (OR) 1.471, 95% confidence interval (CI) 1.178–1.837, q = 0.076) exhibited a causal association with PAH. In addition, the genus LachnospiraceaeUCG004 (OR 1.511, 95% CI 1.048–2.177) and genus RuminococcaceaeUCG002 (OR 1.407, 95% CI 1.040–1.905) showed a suggestive increased risk of PAH, while genus Eubacterium eligens group (OR 0.563, 95% CI 0.344–0.922), genus Phascolarctobacterium (OR 0.692, 95% CI 0.487–0.982), genus Erysipelatoclostridium (OR 0.757, 95% CI 0.579–0.989) and genus T–yzzerella3 (OR 0.768, 95% CI 0.624–0.945) were found to have nominal protective effect against PAH. Conclusion The findings from our MR study have revealed a potential causal relationship between gut microbiota and PAH. Specifically, we have identified four types of gut microbiota that exhibit a protective effect on PAH, as well as three types that have a detrimental impact on PAH, thereby offering valuable insights for future mechanistic and clinical investigations in the field of PAH.

Abstract Emotions play a crucial role in the learning process, yet there is a scarcity of studies examining emotion dynamics in problem-solving with fine-grained data and advanced tools. This study addresses this gap by investigating the emotional trajectories during self-regulated learning (SRL) phases (i.e., forethought, performance, and self-reflection) among 47 medical students utilizing an intelligent tutoring system. Real-time facial expressions were analyzed through recurrence quantification analysis alongside an examination of electrodermal activities (EDA) across the SRL phases. The findings reveal that emotion stability varied across SRL phases, with students exhibiting more stable emotions during the performance phase. Compared to the forethought and self-reflection phases, students had less frequent and lower intensity of emotional arousal in the performance phase. Moreover, we found that students with better performance demonstrated more stable emotions in the forethought phase, less stable emotions in the self-reflection phase, and a higher level of emotional arousal in the self-reflection phase. These insights highlight the temporal and dynamic nature of emotions in SRL, offering methodological and educational implications for leveraging facial expressions and EDA to monitor and enhance students’ emotional experience during problem-solving.

Abstract In mines, tunnel ventilation is monitored using wind speed sensors to measure the stability of the mine ventilation system. However, opening and closing the air door will cause violent fluctuations in the monitoring data of the wind speed sensors. When false alarms are triggered, the staff can diagnose only the mine ventilation system based on their experience. A numerical simulation method is adopted to explore the changes in the flow field during the opening and closing of the air door to address this issue. In addition, a method that is based on the wind speed data of a single sensor is proposed to identify the time and divide the stages of air door opening and closing. The experimental results showed that the proposed method can successfully identify the air door opening and closing time and apply stage division when needed.

Abstract Background Small nucleolar RNAs (snoRNAs) play key roles in ribosome biosynthesis. However, the mechanism by which snoRNAs regulate cancer stemness remains to be fully elucidated. Methods SNORA68 expression was evaluated in breast cancer tissues by in situ hybridization and qRT‒PCR. Proliferation, migration, apoptosis and stemness analyses were used to determine the role of SNORA68 in carcinogenesis and stemness maintenance. Mechanistically, RNA pull-down, RNA immunoprecipitation (RIP), cell fractionation and coimmunoprecipitation assays were conducted. Results SNORA68 exhibited high expression in triple-negative breast cancer (TNBC) and was significantly correlated with tumor size (P = 0.048), ki-67 level (P = 0.037), and TNM stage (P = 0.015). The plasma SNORA68 concentration was significantly lower in patients who achieved clinical benefit. The SNORA68-high patients had significantly shorter disease-free survival (DFS) (P = 0.036). Functionally, SNORA68 was found to promote the cell stemness and carcinogenesis of TNBC in vitro and in vivo. Furthermore, elevated SNORA68 expression led to increased nucleolar RPL23 expression and retained RPL23 in the nucleolus by binding U2AF2. RPL23 in the nucleolus subsequently upregulated c-Myc expression. This pathway was validated using a xenograft model. Conclusion U2AF2-SNORA68 promotes TNBC stemness by retaining RPL23 in the nucleolus and increasing c-Myc expression, which provides new insight into the regulatory mechanism of stemness.

Abstract Objective Previous studies have shown that the obesity paradox exists in a variety of clinical settings, whereby obese individuals have lower mortality than their normal-weight counterparts. It remains unclear whether the association between obesity and mortality risk varies by anthropometric measures. The purpose of this study is to examine the association between various anthropometric measures and all-cause and cause-specific mortality in US adults. Methods This cohort study included data from the National Health and Nutrition Examination Survey between 2009 and 2018, with a sample size of 28,353 individuals weighted to represent 231 million US adults. Anthropometric measurements were obtained by trained technicians using standardized methods. Mortality data were collected from the date of enrollment through December 31, 2019. Weighted Cox proportional hazards models, restricted cubic spline curves, and cumulative incidence analyses were performed. Results A total of 2091 all-cause deaths, 606 cardiovascular deaths, 519 cancer deaths, and 966 other-cause deaths occurred during a median follow-up of 5.9 years. The association between body mass index (BMI) and mortality risk was inversely J-shaped, whereas the association between waist-to-height ratio (WHtR) and mortality risk was positively J-shaped. There was a progressive increase in the association between the WHtR category and mortality risk. Compared with the reference category of WHtR

Abstract Introduction The impact of immunosuppression on prognosis of carbapenem-resistant organism (CRO) bloodstream infection (BSI) remains unclear. The aim of this study was to clarify the relationship between immunosuppression and mortality of CRO-BSI and to identify the risk factors associated with mortality in immunosuppressed patients. Methods This retrospective study included 279 patients with CRO-BSI from January 2018 to March 2023. Clinical characteristics and outcomes were compared between the immunosuppressed and immunocompetent patients. The relationship between immunosuppression and 30-day mortality after BSI onset was assessed through logistic-regression analysis, propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). Factors associated with mortality in immunosuppressed patients were analyzed using multivariable logistic regression analysis. Results A total of 88 immunocompetent and 191 immunosuppressed patients were included, with 30-day all-cause mortality of 58.8%. Although the 30-day mortality in immunosuppressed patients was significantly higher than in immunocompetent patients (46.6% vs. 64.4%, P = 0.007), immunosuppression was not an independent risk factor for mortality in multivariate logistic regression analysis (odds ratio [OR] 3.53, 95% confidence interval [CI] 0.74–18.89; P = 0.123), PSM (OR 1.38, 95% CI 0.60–3.18; P = 0.449,) or IPTW (OR 1.40, 95% CI 0.58–3.36; P = 0.447). For patients with CRO-BSI, regardless of immune status, appropriate antibiotic therapy was associated with decreased 30-day mortality, while Charlson comorbidity index (CCI), intensive care unit (ICU)-acquired infection and thrombocytopenia at CRO-BSI onset were associated with increased mortality. Conclusion Despite the high mortality rate of CRO-BSI, immunosuppression did not affect the mortality. Appropriate antibiotic therapy is crucial for improving the prognosis of CRO-BSI, regardless of the immune status.

Exercise rehabilitation has been proven as a promising intervention for recovery of patients after percutaneous coronary intervention for acute myocardial infarction. Based on the analysis of individual’s condition, early exercise rehabilitation plan should be designed systematically and logically to reduce the mortality due to acute myocardial infarction, prevent complications, promote the early rehabilitation and improve the exercise tolerance and quality of life of the patient. This paper summarized the status quo of exercise rehabilitation and its research status, potential problems and clinical practice in patients with acute myocardial infarction after percutaneous coronary intervention, and provided reference for the establishment of exercise rehabilitation plan after percutaneous coronary intervention. (运动康复是急性心肌梗死患者经皮冠状动脉介入(PCI)术恢复行之有效的方法。早期运动康复应该基于个体的特殊状况, 有层次有逻辑设计并推进活动方案, 降低因急性心肌梗死而造成的死亡率, 规避其他症状并发, 压缩患者的治疗康复周期, 优化患者的运动耐量与生活水平。本研究针对运动康复疗法在国内外的发展、研究应用、存在的问题及其用于急性心肌梗死PCI术后的展望进行综述, 旨在为制定更完善的PCI术后运动康复方案提高可靠参考。)

Abstract Investigating the impact of train-induced vibration loads on soil hydraulic properties, this study conducted experiments using a self-designed indoor soil seepage platform that incorporates vibration loads. The experiments were complemented with scanning electron microscopy to analyze the influence of train-induced vibration loads on soil hydraulic conductivity and its evolutionary characteristics under different vibration frequencies. The experimental results indicated that as the vibration frequency increases from no vibration (0 Hz) to 20 Hz, the time required for the soil volumetric moisture content to reach its peak and stabilize decreases rapidly. However, after the vibration frequency exceeds 20 Hz, the rate at which the time required for the volumetric moisture content to reach its peak and stabilize decreases slows down. Furthermore, the soil pore water pressure increases with the increase in vibration frequency. At a vibration frequency of 80 Hz, the peak value of pore water pressure increases by 105% compared to the non-vibration state, suggesting that higher vibration frequencies promote the development and acceleration of soil pore moisture migration. Additionally, as the vibration frequency increases, the soil hydraulic conductivity initially experiences a rapid increase, with a growth rate ranging from 40.1 to 47.4%. However, after the frequency exceeds 20 Hz, this growth rate significantly decreases, settling to only 18.6% to 7.8%. When the soil was subjected to a vibration load, the scanning electron microscopy test revealed alterations in its pore structure. Micropores and small pores transformed into macropores and mesopores. Additionally, the microstructural parameters indicated that vibration load decreased the complexity of soil pores, thereby speeding up the hydraulic conduction process. This, in turn, affected the hydraulic properties of the soil and established a relationship between pore structure complexity and soil hydraulic properties.

Abstract Background The recently identified methylation patterns specific to cell type allows the tracing of cell death dynamics at the cellular level in health and diseases. This study used COVID-19 as a disease model to investigate the efficacy of cell-specific cell-free DNA (cfDNA) methylation markers in reflecting or predicting disease severity or outcome. Methods Whole genome methylation sequencing of cfDNA was performed for 20 healthy individuals, 20 cases with non-hospitalized COVID-19 and 12 cases with severe COVID-19 admitted to intensive care unit (ICU). Differentially methylated regions (DMRs) and gene ontology pathway enrichment analyses were performed to explore the locus-specific methylation difference between cohorts. The proportion of cfDNA derived from lung and immune cells to a given sample (i.e. tissue fraction) at cell-type resolution was estimated using a novel algorithm, which reflects lung injuries and immune response in COVID-19 patients and was further used to evaluate clinical severity and patient outcome. Results COVID‑19 patients had globally reduced cfDNA methylation level compared with healthy controls. Compared with non-hospitalized COVID-19 patients, the cfDNA methylation pattern was significantly altered in severe patients with the identification of 11,156 DMRs, which were mainly enriched in pathways related to immune response. Markedly elevated levels of cfDNA derived from lung and more specifically alveolar epithelial cells, bronchial epithelial cells, and lung endothelial cells were observed in COVID-19 patients compared with healthy controls. Compared with non-hospitalized patients or healthy controls, severe COVID-19 had significantly higher cfDNA derived from B cells, T cells and granulocytes and lower cfDNA from natural killer cells. Moreover, cfDNA derived from alveolar epithelial cells had the optimal performance to differentiate COVID-19 with different severities, lung injury levels, SOFA scores and in-hospital deaths, with the area under the receiver operating characteristic curve of 0.958, 0.941, 0.919 and 0.955, respectively. Conclusion Severe COVID-19 has a distinct cfDNA methylation signature compared with non-hospitalized COVID-19 and healthy controls. Cell type-specific cfDNA methylation signature enables the tracing of COVID-19 related cell deaths in lung and immune cells at cell-type resolution, which is correlated with clinical severities and outcomes, and has extensive application prospects to evaluate tissue injuries in diseases with multi-organ dysfunction.

Abstract Background We aimed to identify some potential biomarkers for elderly osteoporosis (OP) by integral analysis of lncRNA and mRNA expression data. Methods A total of 8 OP cases and 5 healthy participants were included in the study. Fasting peripheral venous blood samples were collected from individuals, and total RNA was extracted. RNA-seq library was prepared and sequenced on the Illumina HiSeq platform. Differential gene expression analysis was performed using “DESeq2” package in R language. Functional enrichment analysis was conducted using the “clusterProfiler” package, and the cis- and trans-regulatory relationships between lncRNA and target mRNA were analyzed by the lncTar software. A protein-protein interaction (PPI) network was constructed using the STRING database, and hub genes were identified through the MCODE plugin in Cytoscape. Results We identified 897 differentially expressed lncRNAs (DELs) and 1366 differentially expressed genes (DEGs) between normal and OP samples. After co-expression network analysis and cis-trans regulatory genes analysis, we identified 69 candidate genes regulated by lncRNAs. Then we further screened 7 genes after PPI analysis. The target gene DOCK4, trans-regulated by two lncRNAs, was found to be significantly upregulated in OP samples. Additionally, 4 miRNAs were identified as potential regulators of DOCK4. The potential diagnostic value of DOCK4 and its two trans-regulatory lncRNAs was supported by ROC analysis, indicating their potential as biomarkers for OP. Conclusion DOCK4 is a potential biomarker for elderly osteoporosis diagnostic. It is identified to be regulated by two lncRNAs and four miRNAs.

The rational assessment of the urban green space supply–demand relationship is crucial aspect to achieving Sustainable Development Goals. However, previous research predominantly focused on evaluative and indirect exposure calculations for the lack of precise geographic boundaries for urban green space and their refined visitation data. This has led to an evaluation of the supply–demand relationship that may deviate from the actual condition. In this study, the precise geographic boundaries, functional characteristics, and scale information of planned urban green space in Guangzhou were utilized. Then, the supply–demand relationship of urban green space was assessed using mobile signal data to capture real-time exposure. The results show that 20.8% of the urban green space in Guangzhou suffers from undersupply, which is especially pronounced in the central urban areas. The imbalance is more pronounced on weekends compared to weekdays, with 10.6% higher undersupply rates. In addition, the Gini for the monthly average of green space exposure is 0.71, indicating a highly unequal of green space exposure in Guangzhou. The real exposure inequality of urban green space in the central urban area is better than in the peripheral area. In particular, small-scale urban green space documents a more severe imbalance, and the exposure is significantly correlated with the scale of urban green space. Based on these findings, this study provides scientific recommendations for urban green space supply planning including scale, spatial arrangement, and indicator optimization.

The gastrointestinal tract (GIT) is an important and complex system by which humans to digest food and absorb nutrients. The GIT is vulnerable to diseases, which may led to discomfort or even death in humans. Therapeutics for GIT disease treatment face multiple biological barriers, which significantly decrease the efficacy of therapeutics. Recognizing the biological barriers and pathophysiological characteristics of GIT may be helpful to design innovative therapeutics. Nanotherapeutics, which have special targeting and controlled therapeutic release profiles, have been widely used for the treatment of GIT diseases. Herein, we provide a comprehensive review of the biological barrier and pathophysiological characteristics of GIT, which may aid in the design of promising nanotherapeutics for GIT disease treatment. Furthermore, several typical diseases of the upper and lower digestive tracts, such as Helicobacter pylori infection and inflammatory bowel disease, were selected to investigate the application of nanotherapeutics for GIT disease treatment.

In order to improve the efficiency of emergency repair for multiple faults in distribution networks, a method for allocating emergency repair resources for multiple faults in distribution networks based on parallel convolutional neural network (CNN) algorithm is studied. This method uses a matrix operation based multiple fault detection method for distribution networks. After determining the location of multiple faults based on the direction of fault power, the principle is to allocate emergency repair resources nearby for multiple faults, with the goal of minimizing economic losses caused by the fault point and minimizing fault repair time. The objective function for allocating emergency repair resources nearby is constructed, and parallel CNN algorithm is used to solve the problem by classification, to find the feasible solution with the minimum mean square error between the objective function and the feasible solution set for nearby allocation of emergency repair resources, and it is used as the optimal solution for nearby allocation of repair resources. The experimental results show that when the proposed method is used to allocate emergency repair resources for multiple faults in the distribution network, the optimal time for setting the repair plan is 0.53 and 0.96 s, respectively, with an average allocation accuracy of 91%. It has been confirmed that this method can achieve the optimal decision of resource allocation plan in a short period of time, improving the efficiency of emergency repair.

Osteoarthritis (OA) is a prevalent chronic degenerative disease that affects the bones and joints, particularly in middle-aged and elderly individuals. It is characterized by progressive joint pain, swelling, stiffness, and deformity. Notably, treatment with a heat shock protein 90 (HSP90) inhibitor has significantly curtailed cartilage destruction in a rat model of OA. Although the monoclonal antibody 9B8 against HSP90 is recognized for its anti-tumor properties, its potential therapeutic impact on OA remains uncertain. This study investigated the effects of 9B8 on OA and its associated signaling pathways in interleukin-1β (IL-1β)−stimulated human chondrocytes and a rat anterior cruciate ligament transection (ACLT) model. A specific concentration of 9B8 preserved cell viability against IL-1β−induced reduction. In vitro, 9B8 significantly reduced the expression of extracellular matrix-degrading enzyme such as disintegrin and metallopeptidase-4 (ADAMTS4) of thrombospondin motifs, matrix metalloproteinase-13 (MMP-13), as well as cellular inflammatory factors such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), which were upregulated by IL-1β.In vivo, 9B8 effectively protected the articular cartilage and subchondral bone of the rat tibial plateau from ACLT-induced damage. Additionally, gene microarray analysis revealed that IL-1β substantially increased the expression of SLC2A1, PFKP, and ENO2 within the HIF-1 signaling pathway, whereas 9B8 suppressed the expression of these genes. Thus, 9B8 effectively mitigates ACLT-induced osteoarthritis in rats by modulating the HIF-1 signaling pathway, thereby inhibiting overexpression involved in glycolysis.These results collectively indicate that 9B8 is a promising novel drug for the prevention and treatment of OA.

Background: Osteoarthritis (OA) is a common chronic joint disease. This study aimed to investigate possible OA diagnostic biomarkers and to verify their significance in clinical samples. Methods: We exploited three datasets from the Gene Expression Omnibus (GEO) database, serving as the training set. We first determined differentially expressed genes and screened candidate diagnostic biomarkers by applying three machine learning algorithms (Random Forest, Least Absolute Shrinkage and Selection Operator logistic regression, Support Vector Machine-Recursive Feature Elimination). Another GEO dataset was used as the validation set. The test set consisted of RNA-sequenced peripheral blood samples collected from patients and healthy donors. Blood samples and chondrocytes were collected for quantitative real-time PCR to confirm expression levels. Receiver operating characteristic curves were generated for individual and combined biomarkers. Results: In total, 251 DEGs were screened, where B3GALNT1, SCRG1 and ZNF423 were screened by all three algorithms. The area under the curve (AUC) of various biomarkers in our test set did not reach as high as that in public datasets. GRB10 exhibited highest AUC of 0.947 in the training set but 0.691 in our test set, while the favorable combined model comprising B3GALNT1, GRB10, KLF9 and SCRG1 demonstrated an AUC of 0.986 in the training set, 1.000 in the validation set and 0.836 in our test set. Conclusion: We identified a combined model for early diagnosis of OA that includes B3GALNT1, GRB10, KLF9 and SCRG1. This finding offers new avenues for further exploration of mechanisms underlying OA.