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Huanggan decoction ameliorates cholestatic hepatic fibrosis in rats via TGF-β1/Smad3 signaling pathway
Background Huanggan Decoction (HGD), as a special Chinese medicine preparation, has good effects in clearing heat, removing dampness, eliminating jaundice. HGD has been used in medical institutions for more than 40 years, and shows an outstanding curative effect in jaundice and cholestatic liver diseases (CLD), makes up for the deficiency of the treatment of CLD. However, the underlying mechanisms of HGD for its therapeutic effects are still not well understood. Methods The hepatoprotective properties of HGD were assessed using a cholestatic liver fibrosis (CLF) rat model induced by ANIT. Serum liver function index was analyzed by automatic chemical analyzer. Serum biomarkers of liver fibrosis and inflammatory factors were detected by ELISA kits. Liver pathology and collagen fiber extent were assessed using HE and Masson’s stains. Expressions of pro-fibrotic cytokine TGF-β1 and the indicator of HSC activation α-SMA in liver were assayed by immunohistochemistry. The levels of Smad3, phosphorylated Smad3, MMP1 and TIMP1 were assayed by western blotting. Results HGD dramatically decreased the serum biochemical indexes, down-regulated the serum biomarkers of liver fibrosis and inflammatory cytokines, reduced the collagen deposition, ameliorated pathological damage. At the same time, HGD notably reduced the level of α-SMA. Additionally, HGD increased MMP1 protein level while decreasing TIMP1 protein level and the p-Smad3 to Smad3 ratio. Conclusions Findings suggest that HGD demonstrated a remarkable liver-protective effect, potentially linked to halting liver fibrosis progression by maintaining the equilibrium between MMP1 and TIMP1, modulating TGF-β1/Smad signal pathway, suppressing HSC activation, and exhibiting anti-inflammatory characteristics.
Community detection framework based on 3D shape descriptors for tree species classification in point cloud data
Abstract Accurate tree species classification from remote sensing data, such as LiDAR point clouds, is important for various applications, including vegetation monitoring and forest growth prediction. Although numerous machine learning algorithms are used widely for these tasks, several challenges remain. These include the need for extensive training datasets, over-fitting to specific geographic areas and environmental conditions during tree growth, the requirement for post-processing adjustments, and unreliable performance with rare tree species and shapes. This paper presents a robust framework for classifying tree species directly from diverse point cloud datasets, eliminating the need for training machine learning models or manually preparing the training datasets. The proposed approach performs community detection on a graph using features extracted from point clouds of individual trees. Multiple shape descriptors are proposed as feature vectors that consider 3D tree crown structure and are rotationally invariant. Community detection groups the trees into distinct communities based on these feature vectors. Tree species classification is performed by classifying these communities, reducing the manual effort significantly, as only a few trees from each community need inspection. The proposed framework was validated using both real-world terrestrial LiDAR and synthetic point clouds. The results demonstrate its competitiveness with established methods, while surpassing the performance of traditional clustering techniques applied to the same feature vectors. Additionally, the results confirm the effectiveness of the proposed feature vectors for achieving competitive tree species classification accuracy.
Correction: Boomerang and bones: Refining the chronology of the Early Upper Paleolithic at Obłazowa Cave, Poland
Controlled hot pressing for functional upcycling of waste polyethylene materials
In vivo evaluation of the antibacterial properties of a poly-ε-lysine and hyaluronic acid coated intramedullary implant in a New Zealand White rabbit model
Peri-prosthetic joint infection (PJI) is a severe complication that can arise following joint replacement surgery. PJI treatment is extremely complex due to the formation of bacterial biofilms and the emergence of antimicrobial resistance (AMR) to antibiotic classes commonly used in the treatment of PJI. This critical development highlights the urgent need for novel prophylactic strategies that do not rely on conventional antibiotic agents to prevent bacterial adherence and subsequent biofilm formation on implant surfaces. This study evaluated the contact-killing properties of a supramolecular poly-epsilon-lysine and hyaluronic acid (PEL-10/HA-1) coating on an intramedullary nail in a New Zealand White (NZW) rabbit model. Fifteen female NZW rabbits were inoculated with Staphylococcus aureus (JAR 060131, 5.9 x 10 4 CFU in 100 µL PBS) in the right humerus. Seven received an uncoated nail, while eight received a PEL-10/HA-1 coated titanium alloy nail. After 7 days, the rabbits were euthanized for microbiological analysis of the nail and surrounding tissues. Remarkably, microbiological analysis showed that 4/8 of the rabbits with a coated nail had 0 CFU on the nail, versus 1/8 of the rabbits with an uncoated nail. The rinsing solution, soft tissue, and bone samples from the rabbits with a coated nail were more often culture-negative than the samples from rabbits with an uncoated nail. However, no statistically significant differences were observed between the CFUs of the coated and uncoated groups. There were no statistically significant differences between the coated and uncoated groups in other infection indicators, including white blood cell count, C-reactive protein, and plasma protein electrophoresis. While the PEL-10/HA-1 coating had a bacteriostatic and bactericidal effect in vitro , this effect did not translate to in vivo , highlighting a translational gap. The PEL-10/HA-1 coating must be optimized to enhance its antimicrobial effect, ensuring the same promising in vivo effect as previously observed in vitro.
Multifunctional Asymmetric Soluble Covalent Organic Frameworks: A Versatile Medium for Stabilizing Lithium Anode Interfaces
Application of representation learning in detecting botnet attacks
Clinical outcomes with lower versus conventional dose polymyxin B regimens in dialysis dependent and non-dialysis patients with gram-negative sepsis: A real-world propensity-score matched cohort study
Background Polymyxin B remains a key treatment option for infections caused by multidrug-resistant gram-negative bacilli, particularly in critically ill patients. However, its optimal dosing strategy recommendation remains uncertain, especially in those undergoing renal replacement therapy. This study aimed to compare the clinical and microbiological outcomes of low, usual and high dose polymyxin B in a real-world ICU population. Methods This 5-year retrospective cohort study included critically ill adult patients with gram-negative sepsis who received polymyxin B. Patients were categorized into low-, usual- and high-dose groups based on loading and total daily maintenance dose. Pairwise propensity score matching was performed to adjust for baseline differences. Primary outcome was 28-day all-cause mortality. Secondary outcomes included microbiological clearance, ventilator-free days, ICU-free days, and vasopressor-free days. Subgroup and sensitivity analyses were conducted, including within patients requiring dialysis. All the statistical analysis was performed using R software. Results A total of 674 patients were included. After matching, usual-dose polymyxin B (61%) was associated with significantly higher 28-day mortality compared to the low-dose group (48.04%) (HR = 1.47;95% CI:[1.11–1.95];p = 0.007). Vasopressor, ventilator and ICU-free days were also significantly higher in the low-dose group were compared to the other groups. No significant survival advantage was observed with high-dose regimens. Among dialysis-dependent patients (n = 254), mortality did not differ significantly across dosing groups, though microbiological clearance was better with low dosing. Sensitivity and subgroup analysis also supported the results to be robust. Conclusion Low dose polymyxin B regimens were associated with lower mortality and comparable clinical outcomes compared to higher doses and may be feasible in critically ill patients with renal impairment. However, these findings should be interpreted cautiously given the observational design and residual confounding, warranting confirmation in future randomized trials.
Research on the relationships among transformational leadership, job crafting and psychological empowerment of teachers in medical universities
War-related vicarious trauma among healthcare providers in the war-torn tigray, Northern Ethiopia
Background Tigray War, which started in November 2020, has doubled the burden on healthcare professionals, causing both direct violence and indirect effects as they care for trauma survivors. Vicarious trauma refers to harmful changes that occur in professionals’ views of themselves and/or others as a result of deep empathic engagement and repeated exposure to details of trauma survivors. There is insufficient data to determine the prevalence of vicarious trauma among healthcare workers in the region. Therefore, this study assessed the extent of vicarious trauma among healthcare providers working in the war-torn Tigray region of Ethiopia. Method A health facility-based cross sectional study design was used to recruit 2,374 healthcare providers from August to September 2023 in the war affected Tigray region of Ethiopia and the study participants were selected using stratified random sampling techniques. Data were collected using the Open Data Kit (ODK) and exported to SPSS version 23.0 for analysis. Vicarious trauma was assessed using a 7-item standard tool with likert scale responses ranging from very often (5) to rarely (0). The total score from the responses on these 7 items was categorized as low risk (0–14), moderate risk (15–21), high risk (22–28), and extremely high risk (29–35). Ordinal multivariable logistic regression was used to identify the association of various factors with vicarious trauma. Statistical significance was reported when p-value was less than 0.05. Result Prevalence of moderate and above vicarious trauma was revealed as 81.6% (95% CI: 80.0, 83.1). Specifically, the burden was identified as 32.4%, 33.3%, and 15.8% for moderate, high,and extremely high levels of vicarious trauma respectively, with significant variability across the administrative zones of the region. Risk of vicarious trauma increases with increasing age 30–39 years (AOR = 1.3, p-value = 0.002), 40–49 years (AOR = 1.5, p-value = 0.01), 50 years and above (AOR = 2.3, p-value = 0.0001), having a larger family size (AOR = 1.2, p-value = 0.03), among those who live far from their work place (AOR = 1.3, p-value = 0.04), and among those in leadership positions (AOR = 1.5, p-value = 0.0001). Conclusion Healthcare workers in Tigray region experienced high level of vicarious trauma (8 out of 10). This was worse for older workers with larger families, those living and walking farther to work, and those working in heavily conflict-affected central and northwest Tigray. This calls for the government and stakeholders urgently collaborate to provide training on mental resilience, coping strategies, and support resources, offer age-specific psychoeducation, consider adjusting work hours for older employees, support affected employees and their families, improve transportation, and reduce administrative burdens on managers to prioritize staff well-being.
Decreased metallothionein-3 expression in the human spinal cord is a common feature of amyotrophic lateral sclerosis and multiple sclerosis
Abstract Amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) are devastating adult-onset neurological diseases with distinct pathological manifestations. Although growing evidence implicates copper dysregulation in both diseases, our understanding of this connection remains incomplete. In this study, we investigated metallothionein-3 (MT3), which is a key regulator of copper metabolism in the central nervous system (CNS), and its relationship to copper in the ALS and MS spinal cord. Using combined quantitative mass spectrometry approaches and immunohistochemical observations, we found a significant decrease in ALS and MS spinal cord MT3 levels compared to controls. This was correlated with levels of copper and MT3-copper binding, highlighting a strong relationship between copper and MT3 levels. These findings demonstrate decreased MT3 expression alongside copper as a common feature of ALS and MS supporting previously reported evidence for copper dysregulation in these diseases.
Cost-effectiveness of primary HPV genotyping and dual-stain or cytology reflex testing versus cytology-based screening for cervical cancer in Chile
Testing for high-risk human papillomavirus with genotyping for types 16 and 18 (HPV16/18) and triage by p16/Ki-67 dual-stain immunocytochemistry improves diagnostic performance in cervical cancer screening. We estimated the cost-effectiveness of HPV DNA–based primary screening strategies that detect high-risk genotypes every 5 years with either reflex cytology (hrHPV–Pap-5) or reflex dual stain (CINtec® PLUS, Roche; hereafter hrHPV–CINtec-5) versus cytology every 3 years (SoC (PAP-3)) among women aged 25–64 years, from the Chilean public healthcare perspective. A state-transition microsimulation reflected the natural history of cervical cancer in screening-eligible Chilean women, using local epidemiology and literature-informed inputs. Direct medical costs were obtained from official Chilean sources and converted to USD (1 USD = 938 CLP). Deterministic and probabilistic sensitivity analyses were conducted; a 30–64 years initiation scenario was also evaluated. Both high-risk HPV DNA-based strategies were more effective and cost-saving than SoC (PAP-3). In the 25–64 base case, hrHPV–CINtec-5 yielded the greatest health gain (13,003 incremental Quality-Adjusted Life Year, hereafter QALYs) with $16.65 saved per woman, while hrHPV–Pap-5 saved $32.57 with 12,844 QALYs. Probabilistic sensitivity analysis confirmed dominance (most simulations in the southeast quadrant) and cost-effectiveness acceptability >90% across willingness-to-pay ranges. Deterministic analysis highlighted progression risk from HPV16/18 and the discount rate as key drivers. Transitioning from PAP-3 to high-risk HPV DNA-based primary screening in Chile is projected to improve health outcomes while reducing costs. Among HPV DNA-based strategies detecting high-risk genotypes evaluated, triage with hrHPV–CINtec-5 provided the largest health gain while remaining cost-saving; hrHPV–Pap-5 maximized cost savings. These findings support modernizing the national screening program.
Quality and reliability of hyperlipidemia-related short videos on mainstream social media platforms: a cross-sectional study
Retraction: FoxO3a Modulates Hypoxia Stress Induced Oxidative Stress and Apoptosis in Cardiac Microvascular Endothelial Cells
MSA-2 Loaded Three-Dimensional Metal Covalent Organic Framework for Synergistic Radiosensitization and Innate Immune Activation
Air classification of copper granules from recycled electrical cables using a zig-zag separator
Abstract Recycling copper electrical power cable scrap presents challenges in achieving high purity of the final product, which is typically in the form of copper granules. To obtain copper granules of the highest possible purity, it is necessary to separate impurities, primarily tin-contaminated copper granules (from tinned elements), from pure copper granules. To investigate the feasibility of separating tin-contaminated (tinned) copper using a zig-zag air classifier, numerical CFD analyses of the process were conducted. These simulations were subsequently validated against experimental studies performed with a laboratory-scale zig-zag air classifier. The conducted research demonstrated that the application of a zig-zag air classifier allows to produce copper granules with a final copper content exceeding 99% Cu. A comparison of the numerical CFD separation process analysis results with the actual experimental data revealed that the model’s error is dependent on the morphology of the analyzed granules.
A longitudinal comparison of symptom-distress and person-centeredness between a fast-track programme for cardiac surgery and conventional care
Aim and design Impaired recovery in the post-operative phase after cardiac surgery predicts long-term recovery, making it important to identify and treat symptoms immediately. A fast-track programme after cardiac surgery was implemented. When developing such programmes, the patients’ perspective of perioperative care is of major importance. This is a non-randomized longitudinal observational study in which symptom distress, perceived person-centeredness and pain level were prospectively compared after cardiac surgery. The aim of this non-randomized longitudinal observational study is to prospectively compare symptom-distress, perceived person-centeredness and pain level after cardiac surgery between a fast-track group and those undergoing conventional postoperative care. Methods Symptom distress was explored and compared between a fast-track group and those undergoing conventional postoperative care. A total of 149 participants, 75% men and 25% women, with a mean age of 67 years (SD 9.9 years), were included. The control group comprised 117 patients and the fast-track group 31. Symptom distress was assessed by the Post-Operative Recovery Profile Instrument, person-centeredness by the Being Taken Seriously Questionnaire, while a Numerical Rating Scale was employed to measure self-rated pain. Results Regarding symptom distress, the control group felt significantly (p = .041) more restricted in physical activity in the thoracic intensive care unit (TICU) compared to the fast-track group. However, no differences in symptom distress between the groups were reported in the surgical ward. Longitudinally, an increase in symptom distress was found in the TICU, followed by improvements at the surgical ward. The fast-track group demonstrated lower pain ratings at all time points compared to the control group. The pain intensity score was relatively high during the first six hours after extubation. There was no difference between the control group and the fast-track group regarding their experiences of receiving person-centred care at either of the two time points. Conclusions A fast-track programme is equivalent to conventional care in terms of perceived symptom-distress and person-centeredness and also reduces the duration of ICU care. Impact and patient contribution Detailed information regarding symptom distress could be used as an evidence-based foundation for symptom management support. The results contribute to an understanding of expected symptom patterns during cardiac surgery, which might increase self-efficacy when used to inform and educate patients perioperatively.
Investigation of the relationship between physical activity levels and mental health in adolescents after February 6th earthquakes
Selective culinary uses of plant foods by Northern and Eastern European hunter-gatherer-fishers
Carbonised food deposits preserved in pottery vessels, often termed ‘foodcrusts,’ are frequently encountered on hunter-gatherer-fisher (HGF) pottery throughout Northern and Eastern Europe. While lipid residue analysis is frequently employed to determine their composition, this technique favours the identification of animal products. In this study, we present a combined analytical approach, including high resolution microscopic analysis (Digital Microscopy and Scanning Electron Microscopy) together with molecular and isotopic analysis of lipids (GC-MS and GC-C-IRMS) and bulk isotope analysis (EA-IRMS) to further understand the composition of foodcrusts. Eighty-five pottery vessels with foodcrusts were analysed from 13 archaeological sites dating from the 6th to the 3rd millennium BC, of which 58 have allowed for identification of plant tissues, such as wild grasses and legumes, fruits, and the roots, tubers, leaves and stems of herbaceous plants. The results demonstrate that the choice of plant foods was remarkably selective, with hunter-gatherers favouring certain plant species and even their parts over others and combining these with specific animal ingredients. The results also reveal that our knowledge of plant processing in pottery is likely to be grossly under-represented by relying on lipid residue analysis alone.
Exploring molecular mechanisms of aminoglycoside resistance in Escherichia coli MG1655 using the antibiotic resistance growth plate
Abstract The overuse of antibiotics in human and animal health has driven the rapid emergence of multi-drug-resistant bacterial strains. To investigate the molecular mechanisms underlying resistance, we developed the Antibiotic Resistance Growth Plate (ARGP), an experimental evolution tool that imposes a spatiotemporal antibiotic gradient. Using the ARGP, Escherichia coli MG1655 populations developed resistance to gentamicin up to 10x MIC within two days. Whole-genome sequencing of wildtype and resistant strains revealed mutations in 16 S rRNA genes and the fusA gene. Bioinformatic, phylogenetic, and molecular docking analyses were used to demonstrate the mechanical significance of the fusA gene in the molecular pathways of gentamicin resistance in E. coli MG1655, where mutations in fusA alter EF-G function, disrupting gentamicin’s inhibition of ribosomal translocation. These results highlight the rapidity and specificity of adaptive responses to aminoglycosides and establish the ARGP as a versatile tool for studying the molecular pathways driving antibiotic resistance.