Nanozyme-Enhanced Electrochemical Biosensors: Mechanisms and Applications.

Nanozymes, as innovative materials, have demonstrated remarkable potential in the field of electrochemical biosensors. This article provides an overview of the mechanisms and extensive practical applications of nanozymes in electrochemical biosensors. First, the definition and characteristics of nanozymes are introduced, emphasizing their significant role in constructing efficient sensors. Subsequently, several common categories of nanozyme materials are delved into, including metal-based, carbon-based, metal-organic framework, and layered double hydroxide nanostructures, discussing their applications in electrochemical biosensors. Regarding their mechanisms, two key roles of nanozymes are particularly focused in electrochemical biosensors: selective enhancement and signal amplification, which crucially support the enhancement of sensor performance. In terms of practical applications, the widespread use of nanozyme-based electrochemical biosensors are showcased in various domains. From detecting biomolecules, pollutants, nucleic acids, proteins, to cells, providing robust means for high-sensitivity detection. Furthermore, insights into the future development of nanozyme-based electrochemical biosensors is provided, encompassing improvements and optimizations of nanozyme materials, innovative sensor design and integration, and the expansion of application fields through interdisciplinary collaboration. In conclusion, this article systematically presents the mechanisms and applications of nanozymes in electrochemical biosensors, offering valuable references and prospects for research and development in this field.

One-year mortality risk in older individuals with femoral intertrochanteric fracture: a tertiary center in China.

BACKGROUND: The accelerated growth of older individuals worldwide has increased the number of patients presenting with fragility hip fractures. Having a hip fracture can cause excess mortality, and patients with hip fracture have a higher risk of death than those without hip fracture. Most studies have treated hip fracture as a single, homogeneous condition, but hip fracture includes two major anatomic types: intertrochanteric fracture and femoral neck fracture. Few studies have specifically evaluated 1-year mortality risk in older individuals with femoral intertrochanteric fracture. The aim of this study was to evaluate 1-year mortality and factors associated with mortality in older individuals with femoral intertrochanteric fracture. METHODS: A retrospective review was conducted of 563 patients ≥ 65 years old who underwent surgery for femoral intertrochanteric fractures at our institution between January 2010 and August 2018. Patient demographics, comorbidities, and treatment were collected by retrospective chart review. Age, sex, Body Mass Index (BMI), American Society of Anesthesiologists (ASA) classification, Charlson comorbidity index (CCI), Arbeitsgemeinschaft Für Osteosynthesefragen (AO) fracture classification, haemoglobin value at admission, time to surgery, operation time, and intraoperative blood loss were risk factors to be tested. Multivariable logistic regression was used to evaluate associations between variables and death. RESULTS: Among the 563 patients, 49 died within 1 year after surgery, and the 1-year mortality rate was 8.7%. Multivariate analysis identified age > 80 years (OR = 4.038, P = 0.011), haemoglobin < 100 g/l (OR = 2.732, P = 0.002), ASA score ≥ 3 (OR = 2.551, P = 0.005), CCI ≥ 3 (OR = 18.412, P = 0.018) and time to surgery > 14 d (OR = 3.907, P = 0.030) as independent risk factors for 1-year mortality. Comorbidities such as myocardial infarction and chronic pulmonary disease were associated with 1-year mortality after adjusting for age > 80 years and time to surgery > 14 days. CONCLUSIONS: Patients over 80 years old with haemoglobin < 100 g/l, ASA score ≥ 3, CCI ≥ 3, and multiple comorbidities, especially myocardial infarction and chronic pulmonary disease before surgery, are at a higher risk of 1-year mortality. Doctors should pay more attention to these vulnerable patients, and a surgical delay greater than 14 days should be avoided.

Incidence, clinical features, and risk factors for acute pancreatitis following posterior instrumented fusion surgery for lumbar degenerative disease: a single-center, retrospective analysis of 20,929 patients.

PURPOSE: The aim of this study is to identify the incidence, clinical features, and risk factors for postoperative acute pancreatitis (PAP) after lumbar surgery. METHODS: We retrospectively analyzed patients who developed PAP after posterior lumbar fusion surgery. For each PAP patient, data were collected for four controls who underwent procedures in the same period and did not develop PAP. Statistical methods included univariate and multivariate analyses. RESULTS: Totally, 21 out of 20,929 patients were diagnosed with PAP (0.10%) after posterior lumbar fusion surgery. Patients with degenerative lumbar scoliosis were at higher risk of developing PAP (P < 0.05). With atypical clinical features, PAP occurred within 3 days (0-5) after surgery. PAP patients had significantly higher incidence of osteoporosis (47.6 vs. 22.6%, P = 0.030) and fusion of L1/2(42.9 vs. 4.3%, P = 0.010), lower albumin (42.2 ± 4.1 vs. 44.3 ± 3.2 g/L, P = 0.010), more fusion segments (median 4 vs. 3, P = 0.022), larger surgical invasiveness index (median 9 vs. 8, P = 0.007), longer operation duration (232 ± 109 vs. 185 ± 90 min, P = 0.041), greater estimated blood loss (median 600 vs. 400 mL, P = 0.025), lower intraoperative mean arterial pressure (87.2 ± 9.9 vs. 92.1 ± 8.8 mmHg, P = 0.024). Multivariate logistic regression analysis found three independent risk factors: fusion of L1/2, surgical invasiveness index > 8, and intraoperative mean arterial pressure < 90 mmHg. All patients were treated with conservative therapy and fully recovered after 8.1 (4-22) days. CONCLUSION: The incidence of PAP following posterior surgery for degenerative lumbar disease was 0.10%, and its clinical features were not typical. The fusion of L1/2, high surgical invasiveness index, and low intraoperative mean arterial pressure were independent risk factors for PAP after surgery for lumbar degenerative disease.

A Molybdenum Disulfide Nanozyme with Charge-Enhanced Activity for Ultrasound-Mediated Cascade-Catalytic Tumor Ferroptosis.

The deficient catalytic activity of nanozymes and insufficient endogenous H2 O2 in the tumor microenvironment (TME) are major obstacles for nanozyme-mediated catalytic tumor therapy. Since electron transfer is the basic essence of catalysis-mediated redox reactions, we explored the contributing factors of enzymatic activity based on positive and negative charges, which are experimentally and theoretically demonstrated to enhance the peroxidase (POD)-like activity of a MoS2 nanozyme. Hence, an acidic tumor microenvironment-responsive and ultrasound-mediated cascade nanocatalyst (BTO/MoS2 @CA) is presented that is made from few-layer MoS2 nanosheets grown on the surface of piezoelectric tetragonal barium titanate (T-BTO) and modified with pH-responsive cinnamaldehyde (CA). The integration of pH-responsive CA-mediated H2 O2 self-supply, ultrasound-mediated charge-enhanced enzymatic activity, and glutathione (GSH) depletion enables out-of-balance redox homeostasis, leading to effective tumor ferroptosis with minimal side effects.

Antibiotic resistance genes in gut of breast-fed neonates born by caesarean section originate from breast milk and hospital ward air.

The human gut is a reservoir of antibiotic resistance genes (ARGs). Even in the absence of antibiotics, ARGs are present in large quantities in faeces of adults, children and even newborns. However, where and when ARGs are acquired remains unclear, as does the types of ARGs acquired. Herein, we recruited 82 pairs of women and their caesarean section newborns. Conventional culture methods and quantitative PCR were employed to detect nine species and six ARG types in meconia, faeces from 3-day-old newborns, amniotic fluid, colostrum, and hospital ward air samples. Furthermore, ARG transfer was explored by tracking Staphylococcus epidermidis isolated from faeces of 3-day-old newborns, colostrum and ward air samples using multi-locus sequence typing (MLST). No ARGs or microorganisms were detected in meconia or amniotic fluid. One or more ARGs were detected in 90.2% of faeces from 3-day-old newborns, and the mecA gene exhibited the highest detection rate (45.1%). ARGs were detected in 85.4% of colostra consistent with ARGs in faeces from 3-day-old newborns. Some ARGs were detected in ward air, and might also be a source of ARGs in neonatal faeces. Isolation of S. epidermidis from neonatal faeces was consistent with antibiotic resistance and gene profiles for colostrum samples. Traceability analysis of S. epidermidis showed that ARGs in neonatal faeces mainly originated from colostrum, and partly from ward air. After birth, neonates born by caesarean section obtain a variety of ARGs mainly from colostrum, and partly from ward air.

Serum periostin level is not sufficient to serve as a clinically applicable biomarker of osteoarthritis.

BACKGROUND: Emerging knowledge has highlighted the role of periostin (POSTN) in osteoarthritis (OA) process; however, whether POSTN is suitable as a biomarker of OA remains unclear. This study aimed to investigate the potential value of POSTN as a biomarker of OA. METHODS: Ten 6-month-old female Sprague-Dawley (SD) rats were used in this study. Five rats underwent ovariectomy (OVX) operation and the others were carried out sham operation. Thirty-two patients with OA and eighteen patients who had meniscus injuries or ligament injuries but with intact articular cartilages were recruited in this study from January to July 2019 at the Peking University International Hospital. We first detected the expression of POSTN in the cartilage of OVX induced OA rats and different compartments of the knee joint in patients with OA using immunohistochemistry. Besides, serum POSTN levels in patients with or without OA were examined using enzyme-linked immunosorbent assay (ELISA). The associations among serum POSTN levels, clinical symptoms, and radiological severity were assessed according to the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and, Kellgren-Lawrence (KL) grading, respectively. Finally, multivariable cumulative link models were established to evaluate the validity of serum POSTN level as a predictor of knee OA. RESULTS: The significantly higher POSTN expression was found in OVX-OA rats than Sham rats, while, the expression of POSTN was significantly higher in the torn cartilage of patients with OA. However, the serum POSTN level did not differ significantly between patients with and without OA. Additionally, we found no remarkable associations between serum POSTN level and WOMAC scores and KL grading. Subsequent analysis revealed that serum POSTN was not a significant predictor of OA. CONCLUSION: Thus, although POSTN may be involved OA process and local POSTN is valuable in disease diagnosis and distinguishing of the severity of disease, its serum level is not sufficient to serve as a candidate biomarker of OA given the current analysis technology.

Repair of critical diaphyseal defects of lower limbs by 3D printed porous Ti6Al4V scaffolds without additional bone grafting: a prospective clinical study.

The repair of critical diaphyseal defects of lower weight-bearing limbs is an intractable problem in clinical practice. From December 2017, we prospectively applied 3D printed porous Ti6Al4V scaffolds to reconstruct this kind of bone defect. All patients experienced a two-stage surgical process, including thorough debridement and scaffold implantation. With an average follow-up of 23.0 months, ten patients with 11 parts of bone defects were enrolled in this study. The case series included three females and seven males, their defect reasons included seven parts of osteomyelitis and four parts of aseptic nonunion. The bone defects located at femur (five parts) and tibia (six parts), with an average defect distance of 12.2 cm. Serial postoperative radiologic follow-ups displayed a continuous process of new bone growing and remodeling around the scaffold. One patient suffered tibial varus deformity, and he underwent a revision surgery. The other nine patients achieved scaffold stability. No scaffold breakage occurred. In conclusion, the implantation of 3D printed Ti6Al4V scaffold was feasible and effective to reconstruct critical bone defects of lower limbs without additional bone grafting. Graphical abstract.

Full Solar-Spectrum-Driven Antibacterial Therapy over Hierarchical Sn3 O4 /PDINH with Enhanced Photocatalytic Activity.

Antibacterial photocatalytic therapy (APCT) is considered to be a potential treatment for administrating antibiotic-resistant bacteria. However, due to the low photocatalytic efficiency and weak ability to capture bacteria, it is not practically applied. In this work, an organic-metal oxide hybrid semiconductor heterostructure is fabricated for the photocatalytic generation of reactive oxygen species (ROS) to kill the drug-resistant bacteria. The organic semiconductor, perylene diimide (PDI), can self-assemble on Sn3 O4 nanosheets to form a "hook-and-loop" sticky surface that can capture bacteria, via large numbers of hydrogen bonding and π-π stacking interactions, which are not possible in inorganic semiconductors. This easy-to-fabricate hybrid semiconductor also possesses improved photocatalytic activity, which is owing to the formation of heterostructure that achieves full-spectrum absorption, and the reduction of the photocarrier recombination rate to produce more reactive oxygen species. It has a good promoting effect on the wounds of mice infected by Staphylococcus aureus. This work shows new ideas for fabricating smart full-spectrum inorganic-organic hybrid adhesive heterostructure photocatalysts for antibacterial photocatalytic therapy.

Clinical predictors for deep vein thrombosis on admission in patients with intertrochanteric fractures: a retrospective study.

BACKGROUND: Limited studies were available to investigate the prevalence of deep vein thrombosis (DVT) on admission in elderly patients with intertrochanteric fractures. The aim of present study was to evaluate risk factors and the prevalence of pre-admission DVT in elderly patients with intertrochanteric fractures. METHODS: This retrospective study included 788 elderly patients with intertrochanteric fracture who were eligible for this study from January 1, 2010, to December 31, 2019. Color doppler ultrasonography was performed for DVT detection at admission. All patients' clinical data were collected. Univariate analysis and stepwise backward multivariate logistic regression were used to identify the risk factors contributing to the occurrence of DVT. RESULTS: The overall prevalence of pre-admission DVT in patients with intertrochanteric fractures was 20.81% (164 of 788 patients). The mean time from injury to admission was 2.1 days in the total population, 2.96 and 1.87 days in patients with and without DVT. Univariate analysis showed that significantly elevated risk of DVT were found in patients with longer time from injury to admission, high energy injury, lower Hb value, higher BMI, diabetes, chronic obstructive pulmonary disease (COPD), atrial fibrillation, dementia, varicose veins, higher age-adjusted CCI, higher ASA class and A3 type intertrochanteric fractures (P < 0.05). The adjusted multivariate logistic regression analysis demonstrated that longer time from injury to admission, high energy trauma, COPD, lower Hb, diabetes and A3 type intertrochanteric fractures were independent risk factors of pre-admission DVT. CONCLUSIONS: A high prevalence of pre-admission DVT was found in elderly Chinese patients with intertrochanteric fractures. Therefore, surgeons should be aware of the high prevalence of DVT for elderly patients with intertrochanteric fractures in order to prevent intraoperative and postoperative PE and other lethal complications.

An innovative strategy to treat large metaphyseal segmental femoral bone defect using customized design and 3D printed micro-porous prosthesis: a prospective clinical study.

Five patients with segmental irregular-shaped bone defect of the femur were recruited in this study from 2017.12 to 2018.11. All patients were treated by customized design and 3D printed micro-porous prosthesis. And the procedure was divided into stages: radical debridement and temporary fixation (the first stage); the membrane formation and virtual surgery (intervening period for 6-8 weeks); definite reconstruction the defects (the second stage). Routine clinical follow-up and radiographic evaluation were done to assess bone incorporation and complications of internal fixation. The weight-bearing time and the joint function of the patients were recorded. The patients were followed up for an average of 16.4 months. The average length of bone defect and the distal residual bone was 12 cm and 6.5 cm. The average time of partial weight-bearing and full weight-bearing was 12.7 days and 2.6 months. X-ray demonstrated good osseous integration of the implant/bone interface. No complications occurred such as implant loosening, subsidence, loss of correction and infection. At the last follow-up, Harris score of hip joint was excellent in 2 cases, good in 2 cases, fair in 1 case; HSS score of knee joint was good in 4 cases, middle in 1 case. From our study, we concluded that meticulous customized design 3D printed micro-porous prosthesis combined with intramedullary nail may be a promising and an alternative strategy to treat metaphyseal segmental irregular-shaped femoral bone defect, especially for cases with massive juxta-articular bone loss.

Putative environmental levels of levofloxacin facilitate the dissemination of antibiotic-resistant Escherichia coli via plasmid-mediated transformability.

Antibiotic residues in the environment pose a great risk to global public health. They increase antibiotic resistance by enhancing plasmid conjugation among bacteria or mutations within bacterial genomes. However, little is known about whether the putative environmental levels of antibiotics are sufficient to influence plasmid-mediated transformability. In this study, we explored the effect of eight kinds of representative antibiotics and several other compounds on the plasmid transformability of competent Escherichia coli. Only levofloxacin (LEV) at the putative environmental levels was found to facilitate the frequency of PBR322-or RP4-plasmid-mediated transformation by up to 5.3-fold. Additionally, PBR322 transformation frequency could be further enhanced by copper ion or ammonia nitrogen but inhibited by humic acid. However, when competent E. coli was exposed to the minimal inhibitory concentrations (MIC) of the antibiotics, an enhanced plasmid-assimilation ability was observed and plasmid transformation frequency was increased by up to 98.6-fold for all the tested antibiotics. Furthermore, E. coli exhibited a preference for the uptake of plasmids harbouring the resistance genes to the antibiotics it had been exposed to. Among these antibiotics, cephalexin, tetracycline, and kanamycin induced the highest uptake of RP4. The putative environmental levels of LEV enhanced plasmid transformability regardless of the presence of corresponding antibiotic resistance gene (ARG) on the genetic elements, suggesting environmental LEV residues may facilitate dissemination of antibiotic resistance by any plasmid-mediated transformability, thereby posing a great risk to health.

NLRP3/ASC-mediated alveolar macrophage pyroptosis enhances HMGB1 secretion in acute lung injury induced by cardiopulmonary bypass.

Our previous study showed that high levels of HMGB1 existed in rats following cardiopulmonary bypass (CPB)-induced acute lung injury (ALI) and neutralization of high-mobility group box 1(HMGB1) reduced CPB-induced ALI. However, the mechanism by which CPB increases HMGB1 secretion is unclear. Recent studies have shown that inflammasome-mediated cell pyroptosis promotes HMGB1 secretion. This study aimed to investigate the relationship between inflammasome-mediated pyroptosis and HMGB1 in CPB-related ALI. We employed oxygen-glucose deprivation (OGD)-induced alveolar macrophage (AM) NR8383 pyroptosis to measure HMGB1 secretion. We found that OGD significantly increased the levels of caspase-1 cleaved p10, IL-1ß and ASC expression, caspase-1 activity and the frequency of pyroptotic AM, and promoted the cytoplasm transportation and secretion of HMGB1, which were significantly mitigated by ASC silencing or pre-treatment with glyburide (a Nlrp3 inhibitor) in AM. CPB also increased the expression levels of Nlrp3, ASC, caspase-1 P10, and IL-1ß, and the percentages of AM pyroptosis in the lungs of experimental rats accompanied by increased levels of serum and bronchoalveolar lavage fluid (BALF) HMGB1. Treatment with glyburide significantly mitigated the CPB-increased ASC, caspase-1 p10 and IL-1ß expression, and the percentages of AM pyroptosis in the lungs, as well as the levels of HMGB1 in serum and BALF in rats. Therefore, our data indicated that the Nlrp3/ASC-mediated AM pyroptosis increased HMGB1 secretion in ALI induced by CPB. These findings may provide a therapeutic strategy to reduce lung injury and inflammatory responses during CPB.

Total coliforms as an indicator of human enterovirus presence in surface water across Tianjin city, China.

BACKGROUND: Enteric viruses in surface water pose considerable risk to morbidity in populations living around water catchments and promote outbreaks of waterborne diseases. However, due to poor understanding of the correlation between water quality and the presence of human enteric viruses, the failure to assess viral contamination through alternative viral indicators makes it difficult to control disease transmission. METHODS: We investigated the occurrence of Enteroviruses (EnVs), Rotaviruses (HRVs), Astroviruses (AstVs), Noroviruses GII (HuNoVs GII) and Adenoviruses (HAdVs) from Jinhe River over 4 years and analyzed their correlation with physicochemical and bacterial parameters in water samples. RESULTS: The findings showed that all target viruses were detected in water at frequencies of 91.7% for HAdVs, 81.3% for HuNoVs GII, 79.2% for EnVs and AstVs, and 70.8% for HRVs. These viruses had a seasonal pattern, which showed that EnVs were abundant in summer but rare in winter, while HAdVs, HRVs, AstVs, and HuNoVs GII exhibited opposite seasonal trends. Pearson correlation analysis showed that total coliforms (TC) was significantly positively correlated with EnVs concentrations while no consistent significant correlations were observed between bacterial indices and viruses that precipitate acute gastroenteritis. CONCLUSIONS: Taken together, the findings provide insights into alternative viral indicators, suggesting that TC is a potentially promising candidate for assessment of EnVs contamination. However, it failed to predict the presence of HAdVs, HRVs, AstVs, and HuNoVs GΙΙ in surface water across the city of Tianjin.

Enhanced itaconic acid production by self-assembly of two biosynthetic enzymes in Escherichia coli.

Here, we described a novel strategy for the production of itaconic acid in Escherichia coli by self-assembly of aconitase (ACO) and cis-aconitate decarboxylase (CAD) existing in the metabolic pathway of itaconic acid via the protein-peptide interactions of PDZ domain and PDZ ligand. Co-expression of ACO and CAD in E. coli (uCA) resulted in low levels of itaconate (117.25 mg/L) after 48 h fermentation while the itaconate titre was significantly improved up to 222.15 mg/L by self-assembly of ACO-PDZ (APd) and CAD-PDZlig (CPl) in E. coli (sPP) under the same conditions. To further confirm the effect of self-assembly, the itaconate catalyzed from sodium citrate was determined. The sPP was extra efficacious in the early catalytic period, showing approximately threefold itaconate yields increased after 2 h catalysis, when compared to uCA. Furthermore, the itaconate production of sPP was increased from 5 to 8.7 g/L after 30 h of reaction compared to uCA. This self-assembly strategy showed remarkable potential for the further improvement of itaconate production. Biotechnol. Bioeng. 2017;114: 457-462. © 2016 Wiley Periodicals, Inc.

In vivo study of a bioactive nanoparticle-gelatin composite scaffold for bone defect repair in rabbits.

The purpose is to study the in vivo bioactivity of this scaffold and verify its ability to simulate the characteristics of cancellous bone. Twenty-four adult New Zealand white rabbits were divided into three groups. Bone defects above the femoral condylar of both sides were created. A newly designed bioactive nanoparticle-gelatin composite scaffold was implanted to the experimental side, while the control side was left without implantation. The repair of bone defect was monitored by X-ray examination, gross observation, Micro-CT examination and histological observation of the area of bone defect 4, 8 and 12 weeks after surgery. There was void of new bone tissue in medullary cavity in the bone defect area of the control side. In the experimental side, the composite scaffold displayed excellent biodegradability, bioactivity and cyto-compatibility. With the time laps, new bone tissue grew from the edge to center as revealed by both Micro-CT image and staining biopsy, which complies with the "creeping substitution" process. The mechanical properties of the newly designed bioactive nanoparticle-gelatin composite scaffold and the 3-D structure of new bone tissue are comparable to the surrounding cancellous bones. This newly developed bioactive nanoparticle-gelatin composite scaffold possesses good biocompatibility and in vivo osteogenic capability for bone defect repair. It may be a promising artificial bone grafts.

High-mobility group box 1 accelerates lipopolysaccharide-induced lung fibroblast proliferation in vitro: involvement of the NF-κB signaling pathway.

The mechanism underlying lipopolysaccharide (LPS)-induced aberrant proliferation of lung fibroblasts in Gram-negative bacilli-associated pulmonary fibrosis is unknown. High-mobility group box 1 (HMGB1) is a ubiquitous nuclear protein that is released from the nuclei of lung fibroblasts after LPS stimulation. It can exasperate LPS-induced inflammation and hasten cell proliferation. Thus, this study investigated the effects of LPS- and/or HMGB1-stimulating murine lung fibroblasts on gene expression using various assays in vitro. Thiazolyl-diphenyl-tetrazolium bromide (MTT) assay data showed that either LPS or HMGB1 could induce lung fibroblast proliferation. Endogenous HMGB1 secreted from lung fibroblasts was detected by enzyme-linked immunosorbent assay (ELISA) 48 h after LPS stimulation. Pretreatment with an anti-HMGB1 antibody inhibited the proliferative effects of LPS on lung fibroblasts. DNA microarray data showed that the NF-κB signaling genes were upregulated in cells after stimulated with LPS, HMGB1, or both. Secretion of matrix metalloproteinase (MMP)-2 and MMP-9, and tissue inhibitor of metalloproteinase 2 (TIMP-2) was significantly upregulated after treatment with LPS, HMGB1, or their combination. However, an NF-κB inhibitor was able to downregulate levels of these proteins. In addition, levels of Toll-like receptor 4 (TLR4), Toll-like receptor 2 (TLR2), and receptors for advanced glycation end products (RAGE) mRNA and proteins were also upregulated in these cells after LPS treatment and further upregulated by LPS plus HMGB1. In conclusion, the data from the current study demonstrate that LPS-induced lung fibroblast secretion of endogenous HMGB1 can augment the proproliferative effects of LPS and, therefore, may play a key role in exacerbation of pulmonary fibrosis. The underlying molecular mechanisms are related to the activation of the TLR4/NF-κB signaling pathway and its downstream targets.

HDAC is essential for epigenetic regulation of Thy-1 gene expression during LPS/TLR4-mediated proliferation of lung fibroblasts.

Lipopolysaccharide (LPS)-induced proliferation of lung fibroblasts is closely correlated with loss of gene expression of thymocyte differentiation antigen-1 (Thy-1), accompanied with deacetylation of histones H3 and H4 at the Thy-1 gene promoter region; however, the mechanism remains enigmatic. We report here that LPS downregulates Thy-1 gene expression by activating histone deacetylases (HDACs) via Toll-like receptor 4 (TLR4) signaling. Treatment of primary cultured mouse lung fibroblasts with LPS resulted in significant upregulation of TLR4 and enhanced cell proliferation that was abolished by silencing TLR4 with lentivirus-delivered TLR4 shRNA. Interestingly, LPS increased the mRNA and protein levels of HDAC-4, -5, and -7, an effect that was abrogated by HDAC inhibitor trichostatin A (TSA) or TLR4-shRNA-lentivirus. Consistent with these findings, Ace-H3 and Ace-H4 were decreased by LPS that was prevented by TSA. Most importantly, chromosome immunoprecipitation (ChIP) analysis demonstrated that LPS decreased the association of Ace-H4 at the Thy-1 promoter region that was efficiently restored by pretreatment with TSA. Accordingly, LPS decreased the mRNA and protein levels of Thy-1 that was inhibited by TSA. Furthermore, silencing the Thy-1 gene by lentivirus-delivered Thy-1 shRNA could promote lung fibroblast proliferation, even in the absence of LPS. Conversely, overexpressing Thy-1 gene could inhibit lung fibroblast proliferation and reduce LPS-induced lung fibroblast proliferation. Our data suggest that LPS upregulates and activates HDACs through TLR4, resulting in deacetylation of histones H3 and H4 at the Thy-1 gene promoter that may contribute to Thy-1 gene silencing and lung fibroblast proliferation.

Cross-border dual-channel supply chain decision-making under random demand and tariff conditions.

Given the cross-border e-commerce import tariff and random demands, this study establishes a pricing decision model for cross-border e-commerce dual-channel supply chain, which is composed of domestic manufacturers and overseas retailers, so as to analyze the effects of import tariff and random demand on the pricing, demand and profit of cross-border e-commerce. According to the research, import tariffs have a positive correlation with retailers' retail prices and a negative correlation with manufacturers' direct prices, wholesale prices, demand and profit from direct channels, and profit from retail channels. The export tax rebate policy will lessen the negative effects of import tariffs and maximize the best choices made by manufacturers and retailers.

Psychological status of medical security teams in Winter Olympic Games and Paralympics under COVID-19.

Background: Medical security work for the 2022 Beijing Winter Olympic and Paralympics faced enormous challenges under COVID-19. This study aimed to investigate the mental status of those medical team members to provide a reference for scientifically implementing medical security services for large-scale events. Methods: In this prospective cohort study, the Patient Health Questionnaire-9, Self-rating Anxiety Scale, General Self-Efficacy Scale, and Psychological Questionnaire for Emergent Events of Public Health (PQEEPH) were administered to 145 members of the medical team. A generalized mixed linear model was used to analyze the impact of work duration, position, on/off rotation, and gender on psychological status. Results: Work duration significantly impacted depression, anxiety, self-efficacy, and all dimensions of PQEEPH. Women scored higher than men in the PQEEPH dimensions of depression, neurasthenia, fear, and total score. Working status affected the dimensions of depression, neurasthenia, and total score. Deterioration in emotional state became apparent in the fourth week and recovered 1 week after the task concluded, while self-efficacy decreased from beginning to end. Conclusion: All the medical team members experienced emotional deterioration and decreased self-efficacy in medical security tasks. To maintain a medical team's psychological wellbeing during large-scale activities, rotation times should be set reasonably, and adequate mental health services should be provided.

Machine learning models to predict osteonecrosis in patients with femoral neck fractures undergoing internal fixation.

OBJECTIVE: This study aimed to use machine learning (ML) to establish risk factor and prediction models of osteonecrosis of the femoral head (ONFH) in patients with femoral neck fractures (FNFs) after internal fixation. METHODS: We retrospectively collected clinical data of patients with FNFs who were followed up for at least 2 years. Only intracapsular FNFs were included. In total, 437 patients and 24 variables were enrolled. The entire dataset was divided into training (89.5 %) and test (10.5 %) datasets. Six models-logistic regression, naive Bayes, decision tree, random forest, multilayer perceptron, and AdaBoost-were established and validated for predicting postoperative ONFH. We compared the area under the receiver operating characteristic curve (AUC), accuracy, recall, and F1 score of different models. In addition, a confusion matrix, density curve, and learning curve were used to evaluate the model performance. RESULTS: The logistic regression model performed best at predicting ONFH in patients with FNFs undergoing internal fixation surgery, with an AUC, accuracy, recall, F1 score, and prediction value of 0.84, 0.89, 1.00, 0.94, and 89.1 %, respectively. The learning and density curves demonstrated a good prediction fitting degree and distinct separation. When establishing the ML models, the reduction quality, internal fixation removal, American Society of Anesthesiologists classification, injury mechanism, and displacement distance of the medial cortex were the top five risk factors positively correlated with the occurrence of ONFH. CONCLUSIONS: The logistic regression model had excellent performance in predicting ONFH in patients with FNFs after internal fixation and could provide valuable guidance in clinical decision-making. When choosing treatment options for patients with FNFs, doctors should identify the risk factors and consider using the presented models to help anticipate outcomes and select individualised treatment.