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Abstract Background Lipid management based on cardiovascular risk level is the cornerstone of primary prevention of coronary artery disease (CAD), while the accuracy and adherence of traditional cardiovascular risk stratification have been questioned. Prevention strategies based on imaging screening for atherosclerotic plaques are found to be more objective and adherent in recent studies. This trial aims to investigate the role of coronary computed tomography angiography (CCTA) in guiding the primary prevention of CAD in a randomized controlled design. Methods Approximately 3400 middle-aged asymptomatic community participants will be recruited and randomized in a 1:1 ratio to a traditional cardiovascular risk score-guided (usual care group) or CCTA-guided (CCTA group) strategy. Participants with cardiovascular disease, prior lipid-lowering therapy, CCTA contraindication, or serious diseases that affect life span will be excluded. The intervention strategy includes blood pressure, blood glucose, and lipid management and lifestyle modifications. Blood pressure and glucose targets and lifestyle modification recommendations keep the same in both strategies, while lipid management is personalized based on traditional risk level or CCTA results, respectively. The primary outcome is the proportion of participants taking lipid-lowering medication regularly at both 6 and 12 months. The secondary outcomes include the proportion of participants achieving low-density lipoprotein cholesterol lowering targets at 12 months, mean changes in lipid levels from baseline to 12 months, barriers to adherence, adverse reactions related to CCTA examination, and cardiovascular events. Discussion The study is the first randomized clinical trial to examine the effectiveness of a CCTA-guided versus a traditional risk score-guided primary prevention strategy in an asymptomatic community-based population. Trial registration ClinicalTrials.gov NCT05725096. Registered on 2 February 2023.

Summary: Ferroptosis is implicated in several diseases, including iron overload-induced osteoarthritis (IOOA), which is marked by oxidative stress, iron imbalance, and lipid peroxidation. Given rosiglitazone’s (RSG) ability to inhibit lipid peroxidation and ferroptosis, this study aims to assess its therapeutic potential for treating IOOA. Our in vitro results show that RSG targets acyl-CoA synthetase long-chain family member 4 to mitigate impairments induced by interleukin-1 beta and ferric ammonium citrate, including cell apoptosis, senescence, inflammatory responses, extracellular matrix degradation, and ferroptosis. RSG reduced intracellular iron content, alleviated oxidative stress and lipid peroxidation, mitigated damage to membrane-bound organelles, and enhanced glucose transport. Additionally, pre-treatment with RSG imparted anti-ferroptotic properties to chondrocytes. In vivo, RSG alleviated cartilage degradation, inflammatory responses, and ferroptosis in mice with IOOA. In conclusion, RSG exhibits chondroprotective and anti-ferroptotic effects by suppressing lipid peroxidation and restoring iron homeostasis, highlighting its potential for treating IOOA.

Abstract Background It is well known that high-fat diet (HFD)-induced metabolic syndrome plays a crucial role in cognitive decline and brain-blood barrier (BBB) breakdown. However, whether the bone-brain axis participates in this pathological process remains unknown. Here, we report that platelet-derived growth factor-BB (PDGF-BB) secretion by preosteoclasts in the bone accelerates neuroinflammation. The expression of alkaline phosphatase (ALPL), a nonspecific transcytosis marker, was upregulated during HFD challenge. Main body Preosteoclast-specific Pdgfb transgenic mice with high PDGF-BB concentrations in the circulation recapitulated the HFD-induced neuroinflammation and transcytosis shift. Preosteoclast-specific Pdgfb knockout mice were partially rescued from hippocampal neuroinflammation and transcytosis shifts in HFD-challenged mice. HFD-induced PDGF-BB elevation aggravated microglia-associated neuroinflammation and interleukin-1β (IL-1β) secretion, which increased ALPL expression and transcytosis shift through enhancing protein 1 (SP1) translocation in endothelial cells. Conclusion Our findings confirm the role of bone-secreted PDGF-BB in neuroinflammation and the transcytosis shift in the hippocampal region during HFD challenge and identify a novel mechanism of microglia-endothelial crosstalk in HFD-induced metabolic syndrome.

Abstract Objectives To determine the mandibular anatomical structures by observing cone-beam computed tomography (CBCT) from multiple angles. Materials and methods This retrospective study analyzed 1593 consecutive CBCT images. Ultimately, 95 CBCTs met the inclusion criteria. The mandibular, inferior lingual, and bony canals at the tooth apex were studied by multi-angle observation CBCT. Descriptive statistics were used for statistical analysis. Results It is beneficial to further observe the anastomosis of the mandibular, lingual, and mandibular canals when the course of the mandibular lingual canal is observed on CBCT cross-section. The frequency of the inferior lingual canal anastomosis with the mandibular canal was 43.2% (95% confidence interval (CI) 33, 53.3) in the sample. The mental foramen was located below the long axis of the tooth in a few samples, with an occurrence rate of 29.5% (95% CI 20.1, 38.8). The occurrence rate of various types of the bony canal at the apex of the tooth in canines, first premolars, second premolars, first molars, and second molars under the root apex was recorded through the multi-angle observation of the dental volume reformat (DVR) and three-dimensional (3D) levels in CBCT. Conclusion This study demonstrates the utility of CBCT imaging in examining mandibular anatomy from multiple angles, providing valuable insights into anatomical variations, and enhancing our understanding of mandibular structures. This research emphasizes the crucial role of meticulous CBCT examination in precisely identifying and understanding key anatomical structures, ultimately reducing the risk of surgical complications. Critical relevance statement By examining cone-beam computed tomography scans from various perspectives, it is possible to determine the precise position of anatomical structures within the jaw. This allows for a more accurate assessment, reducing the risk of harm to these structures during treatment. Key points • It is crucial to utilize image data effectively to enhance the comprehension of human anatomy. • We captured detailed images of the mandible from different angles and orientations utilizing cone-beam computed tomography (CBCT). • This study provides essential anatomical information for procedural planning to ensure optimal outcomes and patient safety. Graphical Abstract

ABSTRACTThe 2nd China Vaccinology Integrated Innovation & Teaching Development Conference was held in Sun Yat-sen University, Shenzhen, 18–19, November 2023. Over 200 participants in the field of Vaccinology gathered together to address challenges and issues relevant to vaccine education and training courses, research, and public health programs in China. The conference themed “Promoting the Integrated and Innovative Development of Vaccinology through Collective Efforts.” The conference was organized by the China Association of Vaccine (CAV) and hosted by Vaccinology Education Professional Committee of CAV, and School of Public Health (Shenzhen), Sun Yat-sen University. Other partners included the Medical Virology Branch of the Chinese Medical Association, the editorial committee of the Chinese Journal of Preventive Medicine, Human Vaccines & Immunotherapeutics, and the People’s Medical Publishing House. The 1st conference was held in Hangzhou, in October 2020.

BackgroundThe association between dietary zinc intake and epilepsy remains unclear. This study aimed to investigate the relationship between zinc intake from the diet and epilepsy, employing Mendelian randomization (MR) to explore potential causal links between zinc and epilepsy.MethodsThe cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2013 and 2018. Among the 4,434 participants included, 1.5% (67/4,434) reported having epilepsy. Restricted cubic spline models and logistic regression models were employed to examine the relationships between dietary zinc intakes and epilepsy. Subsequently, a 2-sample Mendelian randomization (MR) analysis was conducted using the inverse variance weighted (IVW) approach as the primary analysis.ResultsIn the restricted cubic spline (RCS) analysis, the relationship between dietary zinc consumption and epilepsy displayed an L-shaped curve (nonlinear, p = 0.049). After multivariate adjustments, the adjusted odds ratios for epilepsy in T2 (5.0–11.0 mg/day) and T3 (≥11.0 mg/day) were 0.49 (95% confidence interval [CI]: 0.26–0.92, p = 0.026) and 0.60 (95% CI: 0.31–1.17, p = 0.132), respectively, compared to the lowest dietary zinc consumption tertile (T1, ≤5.0 mg/day). The IVW method indicated that genetically predicted zinc intake per standard-deviation increase was inversely associated with three types of epilepsy, including all types of epilepsy (OR = 1.06, 95% CI: 1.02–1.11, p = 0.008), generalized epilepsy (OR = 1.13, 95% CI: 1.01–1.25, p = 0.030), and focal epilepsy (documented hippocampal sclerosis) (OR = 1.01, 95% CI: 1.00–1.02, p = 0.025).ConclusionOur findings suggest that a daily zinc intake ranging from 5.0 to 11.0 mg is associated with the lowest risk of epilepsy. Furthermore, Mendelian randomization (MR) studies provide additional support for the existence of a causal relationship between zinc and epilepsy.

BackgroundPrevious studies suggest a link between diet-derived circulating antioxidants and epilepsy, but the causal relationship is unclear. This study aims to investigate the causal effect of these antioxidants on epilepsy.MethodsTo assess the causal link between dietary antioxidants and epilepsy risk, we conducted a two-sample Mendelian randomization (MR) analysis. This involved examining antioxidants such as zinc, selenium, α- and γ-tocopherol, vitamin A (retinol), vitamin C (ascorbate), and vitamin E (α-tocopherol). We utilized instrumental variables (IVs) which were genetic variations highly associated with these commonly used antioxidants. Exposure data were sourced from a comprehensive genome-wide association study (GWAS). We aggregated data from the International League Against Epilepsy (ILAE) Consortium sample, which included various types of epilepsy, as an outcome variable. Finally, we applied the inverse variance weighting method and conducted sensitivity analyses for further validation.ResultsBased on the primary MR estimates and subsequent sensitivity analyses, the inverse variance weighting (IVW) method revealed that a genetically predicted increase in zinc per standard deviation was positively associated with three types of epilepsy. This includes all types of epilepsy (OR = 1.06, 95% CI: 1.02–1.11, p = 0.008), generalized epilepsy (OR = 1.13, 95% CI: 1.01–1.25, p = 0.030), and focal epilepsy (documented hippocampal sclerosis) (OR = 1.01, 95% CI: 1.00–1.02, p = 0.025). However, there is no evidence indicating that other antioxidants obtained from the diet affect the increase of epilepsy either positively or negatively.ConclusionOur research indicates that the risk of developing epilepsy may be directly linked to the genetic prediction of zinc, whereas no such association was found for other antioxidants.

Boar semen is commonly used in artificial insemination (AI) for pig breeding, but its quality can be negatively affected by liquid preservation and transportation, leading to reduced fertility rates. Vibration and temperature fluctuations are critical factors that significantly impact semen quality during storage and transportation, influencing the success rate of AI procedures. Betaine, a naturally occurring compound known for its role in maintaining male fertility, demonstrates potential for improving the preservation and transportation of liquid-preserved boar sperm. The present study demonstrated that betaine supplementation in the semen extenders at 0.5 mg/mL had a significant protective effect on boar sperm motility during storage at 17 °C for 3 to 5 days. During road transportation, 2.5 mg/mL betaine showed significant protective effects on boar sperm progressive motility, while 0.4 mg/mL betaine notably improved boar sperm mitochondrial activity and antioxidant capacity, and reduced lipid peroxidation damage. Simulation models also demonstrated that betaine supplementation increased the proportion of sperm displaying progressive motility and possessing intact acrosomes, regardless of the storage temperature (17 °C or 25 °C), and effectively mitigated the damage caused by vibration at a speed of 200 r/min. Overall, supplementing liquid-preserved boar semen extenders with betaine shows promise in mitigating damage to sperm quality during storage and transportation.

Abstract The quality of green tea changes rapidly due to the oxidation and degradation of polyphenols during storage. Herein, a simple and fast Surface-enhanced Raman spectroscopy (SERS) strategy was established to predict changes in green tea during storage. Raman spectra of green tea with different storage times (2020–2015) were acquired by SERS with silver nanoparticles. The PCA-SVM model was established based on SERS to quickly predict the storage time of green tea, and the accuracy of the prediction set was 97.22%. The Raman peak at 730 cm−1 caused by myricetin was identified as a characteristic peak, which increased with prolonged storage time and exhibited a linear positive correlation with myricetin concentration. Therefore, SERS provides a convenient method for identifying the concentration of myricetin in green tea, and myricetin can function as an indicator to predict the storage time of green tea.

In the past 11 years, there has been a surge in studies exploring the regulatory effect of Traditional Chinese Medicine (TCM) on ferroptosis. However, a significant gap persists in comprehensive scientometric analysis and scientific mapping research, especially in tracking the evolution, primary contributors, and emerging research focal points. This study aims to comprehensively update the advancements in targeting ferroptosis with various TCMs during the previous 11 years. The data, covering the period from 1 January 2012, to 30 November 2023, were retrieved from the Web of Science database. For in-depth scientometric and visualized analyses, a series of advanced analytical instruments were employed. The findings highlight China’s predominant role, accounting for 71.99% of total publications and significantly shaping research in this domain. Noteworthy productivity was observed at various institutions, including Guangzhou University of Chinese Medicine, Chengdu University of Traditional Chinese Medicine, and Zhejiang University. Thomas Efferth emerged as the foremost author within this field, while Frontiers in Pharmacology boasted the highest publication count. This study pinpointed hepatocellular carcinoma, chemical and drug-induced liver injury, mitochondrial diseases, acute kidney injury, and liver failure as the most critical disorders addressed in this research realm. The research offers a comprehensive bibliometric evaluation, enhancing our understanding of the present status of TCM therapy in managing ferroptosis-related diseases. Consequently, it aids both seasoned researchers and newcomers by accelerating access to vital information and fostering innovative concept extraction within this specialized field.

Abstract Due to the intrinsic contradiction of electrical conductivity and Seebeck coefficient in thermoelectric materials, the enhancement for the power factor (PF) is limited. Since the PF decides the output power, strategies to the enhancement of PF are of paramount importance. In this work, Bi2Te3/Sb and Bi2Te3/W multilayer films are proposed to enhance the thermoelectric properties. Both systems possess extremely high conductivity of ≈5.6 × 105 S m−1. Moreover, the electrical conductivity and Seebeck coefficient simultaneously increase as temperature rising, showing the overcome of the intrinsic contradiction. This results in ultrahigh PFs of 1785 µWm−1 K−2 for Bi2Te3/W and of 1566 µWm−1 K−2 for Bi2Te3/Sb at 600 K. Thermal heating of the Bi2Te3/Sb multilayer system shows compositional changes with subsequent formation of Bi‐Te‐Sb phases, Sb‐rich Bi‐Te precipitates, and cavities. Contrary, the multilayer structure of the Bi2Te3/W films is maintained, while Bi2Te3 grains of high‐crystalline quality are confined between the W layers. In addition, bilayer defects in Bi2Te3 and smaller cavities at the interface to W layers are also observed. Thus, compositional and confinement effects as well as structural defects result in the ultrahigh PF. Overall, this work demonstrates the strategies on how to obtain ultrahigh PFs of commercial Bi2Te3 material by microstructure engineering using multilayer structures.

Abstract Intra-articular injection of therapeutics is an effective strategy for treating osteoarthritis (OA), but it is hindered by rapid drug diffusion, thereby necessitating high-frequency injections. Hence, the development of a biofunctional hydrogel for improved delivery is required. In this study, we introduce a liposome-anchored teriparatide (PTH (1–34)) incorporated into a gallic acid-grafted gelatin injectable hydrogel (GLP hydrogel). We show that the GLP hydrogel can form in situ and without affecting knee motion after intra-articular injection in mice. We demonstrate controlled, sustained release of PTH (1–34) from the GLP hydrogel. We find that the GLP hydrogel promotes ATDC5 cell proliferation and protects the IL-1β-induced ATDC5 cells from further OA progression by regulating the PI3K/AKT signaling pathway. Further, we show that intra-articular injection of hydrogels into an OA-induced mouse model promotes glycosaminoglycans synthesis and protects the cartilage from degradation, supporting the potential of this biomaterial for OA treatment.

Abstract Background Treatment options for pretreated triple-negative breast cancer (TNBC) are limited. This study aimed to evaluate the efficacy and safety of apatinib, an antiangiogenic agent, in combination of etoposide for pretreated patients with advanced TNBC. Methods In this single-arm phase II trial, patients with advanced TNBC who failed to at least one line of chemotherapy were enrolled. Eligible patients received oral apatinib 500 mg on day 1 to 21, plus oral etoposide 50 mg on day 1 to 14 of a 3-week cycle until disease progression or intolerable toxicities. Etoposide was administered up to six cycles. The primary endpoint was progression-free survival (PFS). Results From September 2018 to September 2021, 40 patients with advanced TNBC were enrolled. All patients received previous chemotherapy in the advanced setting, with the median previous lines of 2 (1–5). At the cut-off date on January 10, 2022, the median follow-up was 26.8 (1.6–52.0) months. The median PFS was 6.0 (95% confidence interval [CI]: 3.8–8.2) months, and the median overall survival was 24.5 (95%CI: 10.2–38.8) months. The objective response rate and disease control rate was 10.0% and 62.5%, respectively. The most common adverse events (AEs) were hypertension (65.0%), nausea (47.5%) and vomiting (42.5%). Four patients developed grade 3 AE, including two with hypertension and two with proteinuria. Conclusions Apatinib combined with oral etoposide was feasible in pretreated advanced TNBC, and was easy to administer. Clinical trial registration Chictr.org.cn, (registration number: ChiCTR1800018497, registration date: 20/09/2018)

Background: Although rheumatoid arthritis (RA) is a common autoimmune disease, the precise pathogenesis of the disease remains unclear. Recent research has unraveled the role of autophagy in the development of RA. This research aims to explore autophagy-related diagnostic biomarkers in the peripheral blood of RA patients.Methods: The gene expression profiles of GSE17755 were retrieved from the gene expression ontology (GEO) database. Differentially expressed autophagy-related genes (DE-ARGs) were identified for the subsequent research by inserting autophagy-related genes and differentially expressed genes (DEGs). Three machine learning algorithms, including random forest, support vector machine recursive feature elimination (SVM-RFE), and least absolute shrinkage and selection operator (LASSO), were employed to identify diagnostic biomarkers. A nomogram model was constructed to assess the diagnostic value of the biomarkers. The CIBERSORT algorithm was performed to investigate the correlation of the diagnostic biomarkers with immune cells and immune factors. Finally, the diagnostic efficacy and differential expression trend of diagnostic biomarkers were validated in multiple cohorts containing different tissues and diseases.Results: In this study, 25 DE-ARGs were identified between RA and healthy individuals. In addition to “macroautophagy” and “autophagy-animal,” DE-ARGs were also associated with several types of programmed cell death and immune-related pathways according to GO and KEGG analysis. Three diagnostic biomarkers, EEF2, HSP90AB1 and TNFSF10, were identified by the random forest, SVM-RFE, and LASSO. The nomogram model demonstrated excellent diagnostic value in GSE17755 (AUC = 0.995, 95% CI: 0.988–0.999). Furthermore, immune infiltration analysis showed a remarkable association between EEF2, HSP90AB1, and TNFSF10 expression with various immune cells and immune factors. The three diagnostic biomarkers also exhibited good diagnostic efficacy and demonstrated the same trend of differential expression in multiple validation cohorts.Conclusion: This study identified autophagy-related diagnostic biomarkers based on three machine learning algorithms, providing promising targets for the diagnosis and treatment of RA.

Osteomyelitis is a chronic inflammatory bone disease caused by infection of open fractures or post-operative implants. Particularly in patients with open fractures, the risk of osteomyelitis is greatly increased as the soft tissue damage and bacterial infection are often more severe. Staphylococcus aureus, one of the most common pathogens of osteomyelitis, disrupts the immune response through multiple mechanisms, such as biofilm formation, virulence factor secretion, and metabolic pattern alteration, which attenuates the effectiveness of antibiotics and surgical debridement toward osteomyelitis. In osteomyelitis, immune cells such as neutrophils, macrophages and T cells are activated in response to pathogenic bacteria invasion with excessive inflammatory factor secretion, immune checkpoint overexpression, and downregulation of immune pathway transcription factors, which enhances osteoclastogenesis and results in bone destruction. Therefore, the study of the mechanisms of abnormal immunity will be a new breakthrough in the treatment of osteomyelitis.

BackgroundNoise energy has been well-established to increase the risk of occupational noise-induced hearing loss (NIHL). However, the role of noise temporal structure (expressed by kurtosis) or its combination with energy metrics (e.g., kurtosis-adjusted cumulative noise exposure, adj-CNE) in occupational NIHL was still unclear.MethodsA cross-sectional survey of 867 Chinese workers, including 678 metal manufacturing workers and 189 workers exposed to Gaussian noise, was conducted. Noise energy metrics, including LAeq,8h and CNE, kurtosis (β), and adj-CNE were used to quantify noise exposure levels. Noise-induced permanent threshold shift at frequencies 3, 4, and 6 kHz (NIPTS346) and the prevalence of high-frequency NIHL (HFNIHL%) were calculated for each participant. The dose–response relationship between kurtosis or adj-CNE and occupational NIHL was observed.ResultsAmong 867 workers, different types of work had specific and independent noise energy and kurtosis values (p > 0.05). HFNIHL% increased with an increase in exposure duration (ED), LAeq,8h, CNE, or kurtosis (p 2, p R2CNE). After CNE was adjusted by kurtosis, average differences in NIPTS346 or HFNIHL% between the complex and Gaussian noise group were significantly reduced (p

Background: The repair of wounds usually caused by trauma or other chronic diseases remained challenging in clinics due to the potential risk of inflammation and inadequate tissue regenerative properties. Among them, the behaviour of immune cells, such as macrophages, is critical in tissue repair.Materials and methods: In this study, a water-soluble phosphocreatine-grafted methacryloyl chitosan (CSMP) was synthesized with a one-step lyophilization method, followed by the fabrication of CSMP hydrogel with a photocrosslinked method. The microstructure, water absorption and mechanical properties for the hydrogels were investigated. Then, the macrophages were co-cultured with hydrogels and the pro-inflammatory factors and polarization markers for these macrophages were detected through real-time quantitative polymerase chain reaction (RT-qPCR), Western blot (WB), and flow cytometry methods. Finally, the CSMP hydrogel was implanted in a wound defect area in mice to test its ability to promote wound healing.Results: The lyophilized CSMP hydrogel had a porous structure with pores ranging in size from 200 to 400 μm, which was larger than the CSM hydrogel’s. The lyophilized CSMP hydrogel possessed a higher water absorption rate compared with the CSM hydrogel. The compressive stress and modulus of these hydrogels were increased in the initial 7 days immersion and then gradually decreased during the in vitro immersion in PBS solution up to 21 days; the CSMP hydrogel showed a higher value in these parameters versus the CSM hydrogel. The CSMP hydrogel inhibited the expression of inflammatory factors such as interleukin-1β (IL-1β), IL-6, IL-12, and tumor necrosis factor-α (TNF-α) in an in vitro study cocultured with pro-inflammatory factors in pre-treated bone marrow-derived macrophages (BMM). The mRNA sequencing results showed that the CSMP hydrogel might inhibit the macrophages’ M1 type polarization through the NF-κB signaling pathway. Furthermore, when compared to the control group, the CSMP hydrogel promoted more skin area repair in the mouse wound defect area, and inflammatory factors such as IL-1β, IL-6, and TNF-α were lower in the repaired tissue for the CSMP group.Conclusion: This phosphate-grafted chitosan hydrogel showed great promise for wound healing through regulating the macrophage’s phenotype via the NF-κB signaling pathway.

BackgroundOccupational noise-induced hearing loss (NIHL) is one of the most prevalent occupational diseases in the world. With the development of industry, noise sources in the workplace have become increasingly complex.ObjectiveTo apply kurtosis-adjusted cumulative noise exposure (CNE) to assess the occupational hearing loss among furniture manufacturing workers, and to provide a basis for revising noise measurement methods and occupational exposure limits in China.MethodsA cross-sectional survey was conducted to select 694 manufacturing workers, including 542 furniture manufacturing workers exposed to non-Gaussian noise, and 152 textile manufacturing workers and paper manufacturing workers exposed to Gaussian noise. The job titles involving non-Gaussian noise were gunning and nailing, and woodworking, while those involving Gaussian noise were weaving, spinning, and pulping. High frequency noise-induced hearing loss (HFNIHL) and noise exposure data were collected for each study subject. Noise energy metrics included eight-hour equivalent continuous A-weighted sound pressure level (LAeq,8 h) and CNE. Kurtosis was a noise temporal structure metric. Kurtosis-adjusted CNE was a combined indicator of noise energy and temporal structure.ResultsThe age of the study subjects was (35.64±10.35) years, the exposure duration was (6.71±6.44) years, and the proportion of males was 75.50%. The LAeq,8 h was (89.43±6.01) dB(A). About 81.42% of the study subjects were exposed to noise levels above 85 dB(A), the CNE was (95.85±7.32) dB(A)·year, with a kurtosis of 99.34 ± 139.19, and the prevalence rate of HFNIHL was 35.59%. The mean kurtosis of the non-Gaussian noise group was higher than that of the Gaussian noise group (125.33±147.17 vs. 5.86±1.94, t=−21.04, P

Abstract Braided neurovascular flow diverters (FDs) have revolutionized the treatment of aneurysms. However, dual antiplatelet therapy is mandatory for patients with FDs, which increases the risk of adverse side effects like bleeding complications. Surface modification would be of critical relevance to improve the biocompatibility and therefore clinical performance of FDs. Herein, a titanium dioxide (TiO2) covalently immobilized citric acid (CA) nanohybrid coating is fabricated on nitinol (NiTi) braided FDs by liquid phase deposition and dip‐coating, to inhibit thrombosis and promote re‐endothelialization. The CA molecules are covalently bound onto the pre‐deposited TiO2 nanoparticulate coating. The coating has a unique homogenously nanostructured morphology as well as super‐hydrophilicity. Both in vitro and in vivo results verify that the coated samples inhibit platelets and fibrinogen adhesion, delay coagulation time, and concomitantly promote re‐endothelialization. Such appealing properties are ascribed to the nature of CA and TiO2 per se as well as the nanostructured morphology. The present strategy may not only provide a new avenue to surface‐modify braided neurovascular FDs but also shed light on advanced nanohybrid materials for biomedical applications among others.

The strong survival ability of Salmonella in low-moisture foods (LMFs) has been of public concern, and is considered a threat to people’s health. Recently, the development of omics technology has promoted research on the molecular mechanisms of the desiccation stress response of pathogenic bacteria. However, multiple analytical aspects related to their physiological characteristics remain unclear. We explored the physiological metabolism changes of S. enterica Enteritidis exposed to a 24 h-desiccation treatment and a subsequent 3-month desiccation storage in skimmed milk powder (SMP) with an approach of gas chromatography–mass spectrometry (GC–MS) and ultra-performance liquid chromatography-Q Exactive-mass spectrometry (UPLC-QE-MS). A total of 8,292 peaks were extracted, of which 381 were detected by GC–MS and 7,911 peaks were identified by LC–MS/MS, respectively. Through analyses of differentially expressed metabolites (DEMs) and key pathways, a total of 58 DEMs emerged from the 24 h-desiccation treatment, which exhibited the highest relevance for five metabolic pathways, involving glycine, serine, and threonine metabolism, pyrimidine metabolism, purine metabolism, vitamin B6 metabolism, and pentose phosphate pathway. After 3-month SMP storage, 120 DEMs were identified, which were related to several regulatory pathways including arginine and proline metabolism, serine and threonine metabolism, β-alanine metabolism, glycerolipid metabolism, and glycolysis. The analyses of key enzyme activities of XOD, PK, and G6PDH and ATP content provided further evidence that supported the metabolic responses such as nucleic acid degradation, glycolysis, and ATP production played an important role in Salmonella’s adaptation to desiccation stress. This study enables a better understanding of metabolomics-based responses of Salmonella at the initial stage of desiccation stress and the following long-term adaptive stage. Meanwhile, the identified discriminative metabolic pathways may serve as potentially useful targets in developing strategies for the control and prevention of desiccation-adapted Salmonella in LMFs.

Background: Increasing evidence indicates a crucial role for N7-methylguanosine (m7G) methylation modification in human disease development, particularly cancer, and aberrant m7G levels are closely associated with tumorigenesis and progression via regulation of the expression of multiple oncogenes and tumor suppressor genes. However, the role of m7G in sarcomas (SARC) has not been adequately evaluated.Materials and methods: Transcriptome and clinical data were gathered from the TCGA database for this study. Normal and SARC groups were compared for the expression of m7G-related genes (m7GRGs). The expression of m7GRGs was verified using real-time quantitative PCR (RT-qPCR) in SARC cell lines. Then, differentially expressed genes (DEGs) were identified between high and low m7GRGs expression groups in SARC samples, and GO enrichment and KEGG pathways were evaluated. Next, prognostic values of m7GRGs were evaluated by Cox regression analysis. Subsequently, a prognostic model was constructed using m7GRGs with good prognostic values by Lasso regression analysis. Besides, the relationships between prognostic m7GRGs and immune infiltration, clinical features, cuproptosis-related genes, and antitumor drugs were investigated in patients with SARC. Finally, a ceRNA regulatory network based on m7GRGs was constructed.Results: The expression of ten m7GRGs was higher in the SARC group than in the control group. DEGs across groups with high and low m7GRGs expression were enriched for adhesion sites and cGMP-PKG. Besides, we constructed a prognostic model that consists of EIF4A1, EIF4G3, NCBP1, and WDR4 m7GRGs for predicting the survival likelihood of sarcoma patients. And the elevated expression of these four prognostic m7GRGs was substantially associated with poor prognosis and elevated expression in SARC cell lines. Moreover, we discovered that these four m7GRGs expressions were negatively correlated with CD4+ T cell levels, dendritic cell level and tumor purity, and positively correlated with tumor mutational burden, microsatellite instability, drug sensitivity and cuproptosis-related genes in patients with sarcomas. Then, a triple regulatory network of mRNA, miRNA, and lncRNA was established.Conclusion: The current study identified EIF4A1, EIF4G3, NCBP1, and WDR4 as prognostic genes for SARC that are associated with m7G.These findings extend our knowledge of m7G methylation in SARC and may guide the development of innovative treatment options.

By virtue of the hedging and price discovery function, carbon futures trading may help carbon market function more effectively. Is it necessary to establish carbon futures trading in China? The authorities have endorsed the idea since 2015, however, the scheme has not yet started; no antecedent pre-assessment quantitative research has been carried out. Therefore this study that attempts to fill this gap in the literature, could be of real significance. Through deriving a potential decarbonization roadmap, this study tries to give some clues pertaining to the converted mitigation strategy imposed by carbon futures trading in China. A model chain has been proposed, which is composed of the Optimal Production Decision-making Model for Producers, Life Cycle Impact Assessment, Monetization, and Genetic Algorithm based optimization, to quantify the environmental benefits (including improvements to human health, ecosystem damage and increased temperature induced GDP losses) of the assumed mitigation trajectories. By setting the maximization of environmental benefits as the objective, the optimal decarbonization roadmap with carbon futures trading is derived. Results show that the optimal emission reductions for power enterprises (covered by the carbon market) for the next 10 years (2021–2030) are around 3.27 billion tonnes CO2e. If 36% of this amount is assigned to previously discussed mitigation trajectories, it is found that 106.98 GW ultra-super critical units, 160.85 GW mono-Si PV facilities and 167.26 GW doubly-fed induction generator wind capacity should be installed. Overall environmental benefits are 4.6 trillion CNY2018, over 5% of China’s 2018 GDP. Results demonstrate the optimal emission reductions and potential decarbonization roadmap for China’s power enterprises (those covered by the carbon market) under the context of carbon futures trading, which can be an important reference for the authorities and therefore encourage the establishment of the scheme.

Abstract Background Although the relationship between deqi sensations and curative effect has always been controversial, deqi sensations has been regarded as the key indicator of clinical efficacy of acupuncture therapy. There is little evidence for standardization or visualization of the mechanism of acupuncture’s therapeutic effect. This trial aims to evaluate the effect of needling at Zusanli (ST36) on antral contraction function as visualized by ultrasound. Methods This is a two-arm, single-blind, randomized, controlled trial. A total of 116 acupuncture-naïve healthy subjects will be randomly allocated to the acupuncture group or sham acupuncture group in a 1:1 ratio. Participants in the acupuncture group will receive manual acupuncture at Zusanli (ST36) with the needling depth at crural interosseous membrane. Those in the sham acupuncture group will be given penetrating needling depth at the superficial fascia layer. The primary outcome will be the changes in antral contraction frequency (ACF) before and after acupuncture. The secondary outcomes will be the changes in the thermal infrared spectrum of gastric area skin, the antral contraction amplitude (ACA), the antral movement index (AMI), and the scores on the Chinese version of Massachusetts General Hospital Acupuncture Sensation Scale (C-MASS). The adverse events will be evaluated and recorded in detail. Discussion This study may provide visual and objective evidence regarding the safety and efficacy of manual acupuncture at Zusanli (ST36). In addition, the results of this study will help to identify the role of Zusanli (ST36)in the inducing deqi. Trial registration Chinese Clinical Trial Registry ChiCTR2000040686 . Registered on 8 December 2020

As clean renewable energy with strong advantages, hydropower plays an extremely important role in promoting green development and energy allocation patterns. Hydropower project construction is characterized by long duration, large scale, high cost, many participants, and complex construction conditions, and is closely related to the economy, society, and ecological environment, and its construction management mode and construction risk management have become the focus of extensive attention from all walks of life. In this paper, the risk evaluation index system of hydropower engineering EPC project is constructed, and the linear weighted combination method is introduced to determine the comprehensive weights based on the calculation of weights by sequential relationship method and entropy weight method, and the improved fuzzy normal distribution is introduced as the subordinate function distribution of fuzzy evaluation level based on DS evidence theory and fuzzy theory. The risk evaluation model of a hydropower engineering EPC project is also established. Meanwhile, the model was analyzed with hydropower project examples to verify the accuracy and practicality of the model, which can guide hydropower project stakeholders to manage hydropower project risks comprehensively, collaboratively, and efficiently, and provide decision support for hydropower project construction risk management.

Non-traumatic osteonecrosis of the femoral head (NONFH) remains a common refractory disease with poorly understood pathogenesis. Macrophage M1/M2 imbalance and chronic inflammatory microenvironment have been suggested to be closely related to osteonecrosis. Here we describe direct visual evidence for the involvement of dynamic changes in macrophages and the chronic inflammatory microenvironment in human NONFH. Osteonecrosis induces inflammatory responses and macrophage enrichment in the reparative area, and the number of inflammatory cells and macrophages falls during progressive-to end-stage NONFH. Multiplex immunohistochemistry demonstrated that macrophage M1/M2 ratio increased from 3 to 10 during progressive-to end-stage. During the progressive-stage, new blood vessels formed in the reparative area, M2 macrophages accumulated in perivascular (M1/M2 ratio ∼0.05), while M1 macrophages were enriched in avascular areas (M1/M2 ratio ∼12). Furthermore, inflammatory cytokines were detected in synovial fluid and plasma using cytometric bead arrays. Interleukin (IL)-6 and IL-1β were persistently enriched in synovial fluid compared to plasma in patients with NONFH, and this difference was confirmed by immunohistochemistry staining. However, only IL-6 levels in plasma were higher in patients with progressive-stage NONFH than in osteoarthritis. Moreover, fibrosis tissues were observed in the necrotic area in progressive-stage and end-stage NONFH based on Sirius Red staining. Together, these findings indicate that macrophage M1/M2 imbalance facilitates the progression of NONFH, a chronic inflammatory disease characterized by chronic inflammation, osteonecrosis and tissue fibrosis in the local lesion. Inhibiting inflammation, promoting the resolution of inflammation, switching macrophages to an M2 phenotype, or inhibiting their adoption of an M1 phenotype may be useful therapeutic strategies against NONFH.

Although some fungal mitochondria lack the calcium uniporter, many intriguingly encode homologs of the uniporter assembly factor MCUR1. Here, the authors show that in budding yeast, the MCUR1 homologs Put6 and Put7 regulate mitochondrial proline metabolism, a function also conserved in human MCUR1.

In this paper, we built a method of verifying the 4 retinols of vitamin A and 8 tocopherol isomers of vitamin E in the food industry based on RP-HPLC-PDA-FLR. The effect of laboratory light conditions on the target components was considered for the first time, and it was found that the loss rate of the target components was the smallest in the case of a white laboratory bench with red or LED light in the dark room. There was no finding of extraction recoveries of the target components with a significant difference under different saponification conditions. Meanwhile, it was found that using ethyl acetate/n-hexane mixed solvent as the extraction solvent could ensure the effective extraction of the target components. Finally, baseline separation of 12 components was achieved within 45 min using the C30 column. With the help of methodological verification, we found that the recovery rate ranged from 76.45% to 93.52%, and RSD was between 0.19% and 12.99%; the Limit of Detection minimum value was 0.01 mg/100 g and the Limit of Quantitation minimum value was 0.03 mg/100 g. The detection method was successfully applied to the distribution detection of 4 kinds of retinols and 8 kinds of vitamin E in egg and dairy products and provided technical support for the accurate nutritional evaluation of vitamin A and vitamin E.

BackgroundLung cancer is the third most frequently diagnosed cancer in the world, with lung adenocarcinoma (LUAD) as the most common pathological type. But studies on the predictive effect of a single gene on LUAD are limited. We aimed to discover new predictive markers for LUAD.MethodsDifferentially high-expressed genes at each stage were obtained from the TCGA and GTEx databases. The functions of these genes were investigated through GO enrichment and KEGG pathway analyses. Then, the key genes were selected by applying whole gene overall survival time. The expression of the key gene was studied in LUAD, and survival analysis was performed using Kaplan-Meier mapper, followed by univariate and multifactorial COX analysis. Finally, the gene expression and its prognostic significance in the pan-cancer were examined.ResultsA total of 10,106 DEGs were obtained from the two datasets. The top 266 differentially upregulated genes intersected with the top 1,497 overall survival-related genes, and 87 key genes were identified. High-expressed HMMR was associated with a poor prognosis of LUAD. Univariate and multifactorial Cox analysis showed that HMMR was an independent prognostic factor for LUAD patients. A high HMMR expression was strongly associated with the overall survival (OS) and disease-specific survival (DSS) in 11 cancer types and with poorer OS, DSS, and PFI in 10 cancer types.ConclusionHMMR may be an independent prognostic indicator and an important biomarker in diagnosing and predicting the survival of LUAD patients. Also, HMMR may be a key predictor of a variety of cancers.

Epithelial-mesenchymal transition (EMT) process, which is regulated by genes of inducible factors and transcription factor family of signaling pathways, transforms epithelial cells into mesenchymal cells and is involved in tumor invasion and progression and increases tumor tolerance to clinical interventions. This study constructed a multigene marker for lung predicting the prognosis of lung adenocarcinoma (LUAD) patients by bioinformatic analysis based on EMT-related genes. Gene sets associated with EMT were downloaded from the EMT-gene database, and RNA-seq of LUAD and clinical information of patients were downloaded from the TCGA database. Differentially expressed genes were screened by difference analysis. Survival analysis was performed to identify genes associated with LUAD prognosis, and overlapping genes were taken for all the three. Prognosis-related genes were further determined by combining LASSO regression analysis for establishing a prediction signature, and the risk score equation for the prognostic model was established using multifactorial COX regression analysis to construct a survival prognostic model. The model accuracy was evaluated using subject working characteristic curves. According to the median value of risk score, samples were divided into a high-risk group and low-risk group to observe the correlation with the clinicopathological characteristics of patients. Combined with the results of one-way COX regression analysis, HGF, PTX3, and S100P were considered as independent predictors of LUAD prognosis. In lung cancer tissues, HGF and PTX3 expression was downregulated and S100P expression was upregulated. Kaplan-Meier, COX regression analysis showed that HGF, PTX3, and S100P were prognostic independent predictors of LUAD, and high expressions of all the three were all significantly associated with immune cell infiltration. The present study provided potential prognostic predictive biological markers for LUAD patients, and confirmed EMT as a key mechanism in LUAD progression.

Permanent magnet linear motors (PMLM) have gained increased popularities in a wide range of applications. However, they generally suffer from considerably lower force densities. In this paper, a novel doubly yokeless PMLM equipped with quasi-Halbach trapezoidal-shape permanent magnets is presented to both increase the thrust force density and suppress the thrust ripple. Both the stator and the translator are yoke-free, and therefore, the increase of the installation space for the windings is conducive to enhancing the magneto-motive force and the thrust density of the motor. An analytical model is developed to predict the magnetic field distribution and electromagnetic performance of the doubly yokeless PMLM, and finite element computations are undertaken to validate the effectiveness and accuracy of the proposed model. The thrust performance is then optimized against magnet parameters under a specific set of volumetric constraints to the improve the thrust force quality. It is shown that the Halbach ratio and bottom angle of the trapezoidal magnets have significant impacts on the thrust force quality (in terms of both the average thrust and thrust ripple), and optimal values for the two parameters are obtained. The benefits of the doubly yokeless PMLM are highlighted by comparisons with a conventional PMLM with iron yokes.

Microbiota especially Bifidobacterium play an important role in adjusting and maintaining homeostatic balance within the infant intestine. The aim of this study was to elucidate the relationship between maternal and infant gut microbiota and identify the Bifidobacterium species that may transfer from mother to infant over the first 42 days of the infant’s life. Nineteen mother-infant-pair fecal samples were collected and the diversity and composition of the total bacterial and Bifidobacterium communities were analyzed via 16S rDNA and bifidobacterial groEL gene high throughput sequencing. The results revealed that the relative abundance of Bifidobacterium was significantly higher in the infant gut while Parabacteroides, Blautia, Coprococcus, Lachnospira and Faecalibacterium were at lower relative abundance in 7-day and 42-day infant fecal samples compared to the maternal samples. The maternal gut has more B. pseudocatenulatum. In the infant group, B. breve and B. dentium relative abundance increased while B. animalis subsp. lactis decreased from days 7 to 42. Additionally, B. longum subsp. longum isolated from FGZ16 and FGZ35 may have transferred from mother to infant and colonized the infant gut. The results of the current study provide insight toward the infant gut microbiota composition and structure during the first 42 days and may help guide Bifidobacterium supplementation strategies in mothers and infants.

The influenza pandemic causes a large number of hospitalizations and even deaths. There is an urgent need for an efficient and effective method for detecting the outbreak of influenza so that timely, appropriate interventions can be made to prevent or at least prepare for catastrophic epidemics. In this study, we proposed a computational method, the shortest-path-based dynamical network marker (SP-DNM), to detect the pre-outbreak state of influenza epidemics by monitoring the dynamical change of the shortest path in a city network. Specifically, by mapping the real-time information to a properly constructed city network, our method detects the early-warning signal prior to the influenza outbreak in both Tokyo and Hokkaido for consecutive 9 years, which demonstrate the effectiveness and robustness of the proposed method.

Our objective was to investigate the effects of different delivery and feeding modes on the gut microbiota composition of early infants with special emphasis on Bifidobacterium and Lactobacillus profiles at species level. 16S rRNA V3-V4 regions, bifidobacterial, and lactobacilli groEL genes from infant feces were sequenced by Illumina MiSeq. Gut microbiota abundance was significantly different, where standard vaginally delivered (SVD) and breast-fed (BF) groups were higher in comparison with caesarean section (CS), milk-powder-fed (MPF), and mixed-fed (MF) groups. The genus unclassified Enterobacteriaceae was dominant, followed by Bifidobacterium, which was highly abundant in SVD and BF groups. The dominant Bifidobacterium species in all groups were B. longum subsp. longum, B. longum subsp. infantis and B. animalis subsp. lactis. B. dentium and the diversity of Bifidobacterium in SVD and BF groups were significantly higher. For Lactobacillus profiles, L. rhamnosus and L. gasseri were dominant among all the groups, while Lactobacillus species in CS and MPF groups were more diverse. Functional predictions showed significant differences between delivery mode and feeding groups, such as phosphotransferase system as well as taurine and hypotaurine metabolism. In early infants with different delivery and feeding methods, gut microbiota—particularly bifidobacteria and lactobacilli communities—showed significant differences, with strong implications for physiological functions.

5-Aza-2'-deoxycytidine (5-aza-CdR) is used extensively as a demethylating agent and acts in concert with histone deacetylase inhibitors (HDACI) to induce apoptosis or inhibition of cell proliferation in human cancer cells. Whether the action of 5-aza-CdR in this synergistic effect results from demethylation by this agent is not yet clear. In this study we found that inhibition of cell proliferation was not observed when cells with knockdown of DNA methyltransferase 1 (DNMT1), or double knock down of DNMT1-DNMT3A or DNMT1-DNMT3B were treated with HDACI, implying that the demethylating function of 5-aza-CdR may be not involved in this synergistic effect. Further study showed that there was a causal relationship between 5-aza-CdR induced DNA damage and the amount of [(3)H]-5-aza-CdR incorporated in DNA. However, incorporated [(3)H]-5-aza-CdR gradually decreased when cells were incubated in [(3)H]-5-aza-CdR free medium, indicating that 5-aza-CdR, which is an abnormal base, may be excluded by the cell repair system. It was of interest that HDACI significantly postponed the removal of the incorporated [(3)H]-5-aza-CdR from DNA. Moreover, HDAC inhibitor showed selective synergy with nucleoside analog-induced DNA damage to inhibit cell proliferation, but showed no such effect with other DNA damage stresses such as gamma-ray and UV, etoposide or cisplatin. This study demonstrates that HDACI synergistically inhibits cell proliferation with nucleoside analogs by suppressing removal of incorporated harmful nucleotide analogs from DNA.

Objective: To assess the effect of Traditional Chinese Medicine (TCM) nutrition treatment (Bushenhuoxue nutritional decoction) in overweight patients with polycystic ovary syndrome (PCOS). Methods: Retrospective analysis of 96 overweight patients with PCOS who received treatment in our hospital from October 2020 to June 2022 was done. Among them, 46 patients received routine drug treatment and daily dietary intervention (control group), while 50 patients received additional TCM nutrition support in addition to routine treatment (observation group). Glucose and lipid metabolism indicators and hormone levels were compared between the two groups before and after the treatment. Ovulation rate, pregnancy rate, and adverse reactions were compared between both groups one year after the treatment. Results: After treatment, the improvement of glucose and lipid metabolism indicators and hormone levels in the observation group was significantly better than in the control group (P<0.05). After treatment, the TCM syndrome scores of the two groups were lower than that before treatment (P < 0.001), and the TCM syndrome scores of the observation group was lower than that of the control group (P < 0.001).Ovulation and pregnancy rates were significantly higher in the observation group compared to the control group at 1-year follow up (P<0.05), and the incidence of adverse reactions in the observation group was significantly lower than that in the control group (P<0.05). Conclusions: Combined with conventional drug treatment, TCM nutrition treatment can significantly improve glucose and lipid metabolism, hormone levels, and TCM syndrome of overweight PCOS patients, increase the ovulation and pregnancy rates, and reduce potential adverse reactions. [ABSTRACT FROM AUTHOR]