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Abstract Background Higher dietary quality, including increased vegetable consumption, was associated with a reduced risk of metabolic syndrome (MetS). However, specific vegetable consumption in the development of MetS remains obscure. Our study aimed to investigate the correlation between starchy and non-starchy vegetables and MetS. Methods Secondary data analysis from the National Health and Nutrition Examination Survey (NHANES 1999–2018). MetS was defined by National Cholesterol Education Program-Adult treatment Panel III (NCEP ATPIII) and dietary consumption was assessed by trained staff using two 24-h diet recall methods. Weighted logistic regression analysis was carried out to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses and restricted cubic spline (RCS) regression were performed to further investigate specific vegetable subtypes and MetS. Results This research enrolled 24,646 individuals (11,725 females and 12,921 males), with an average age of 45.84 ± 0.23 years. Approximately 15,828(64.22%) participants were defined to be with non-MetS and 8818(35.78%) were with MetS. Both total starchy vegetables and potatoes were associated with increased MetS risk, with the corresponding OR per standard deviation (SD) (95%CI, p-trend) being 1.06(1.02–1.11, p-trend = 0.028) and 1.08(1.04–1.13, p-trend = 0.011), respectively. However, an inverse correlation was found between dark-green vegetables and MetS, and the OR per SD (95%CI, p-trend) was 0.93(0.90–0.97, p-trend = 0.010). Subgroup analyses showed that the positive associations of starchy vegetables and potatoes on MetS risk were stronger in non-Hispanic White participants (p for interaction

Highlights Critical issues including mechanical stability, water and oxygen resistance, transparent electrodes for flexible perovskite solar cells are discussed. Roll-to-Roll technology presents a promising avenue for fabrication of flexible perovskite solar cells fabricated for large-scale commercial application. Balancing the transmittance and conductivity of transparent electrodes has become a significant issue in developing efficient flexible perovskite solar cells.

Abstract Liver regeneration is a dynamic and regulated process that involves inflammation, granulation, and tissue remodeling. Hepatic macrophages, abundantly distributed in the liver, are essential components that actively participate in each step to orchestrate liver regeneration. In the homeostatic liver, resident macrophages (Kupffer cells) acquire a tolerogenic phenotype and contribute to immunological tolerance. Following toxicity-induced damage or physical resection, Kupffer cells as well as monocyte-derived macrophages can be activated and promote an inflammatory process that supports the survival and activation of hepatic myofibroblasts and thus promotes scar tissue formation. Subsequently, these macrophages, in turn, exhibit the anti-inflammatory effects critical to extracellular matrix remodeling during the resolution stage. However, continuous damage-induced chronic inflammation generally leads to hepatic macrophage dysfunction, which exacerbates hepatocellular injury and triggers further liver fibrosis and even cirrhosis. Emerging macrophage-targeting strategies have shown efficacy in both preclinical and clinical studies. Increasing evidence indicates that metabolic rewiring provides substrates for epigenetic modification, which endows monocytes/macrophages with prolonged “innate immune memory”. Therefore, it is reasonable to conceive novel therapeutic strategies for metabolically reprogramming macrophages and thus mediate a homeostatic or reparative process for hepatic inflammation management and liver regeneration.

Tbx18, Wt1, and Tcf21 have been identified as epicardial markers during the early embryonic stage. However, the gene markers of mature epicardial cells remain unclear. Single-cell transcriptomic analysis was performed with the Seurat, Monocle, and CellphoneDB packages in R software with standard procedures. Spatial transcriptomics was performed on chilled Visium Tissue Optimization Slides (10x Genomics) and Visium Spatial Gene Expression Slides (10x Genomics). Spatial transcriptomics analysis was performed with Space Ranger software and R software. Immunofluorescence, whole-mount RNA in situ hybridization and X-gal staining were performed to validate the analysis results. Spatial transcriptomics analysis revealed distinct transcriptional profiles and functions between epicardial tissue and non-epicardial tissue. Several gene markers specific to postnatal epicardial tissue were identified, including Msln, C3, Efemp1, and Upk3b. Single-cell transcriptomic analysis revealed that cardiac cells from wildtype mouse hearts (from embryonic day 9.5 to postnatal day 9) could be categorized into six major cell types, which included epicardial cells. Throughout epicardial development, Wt1, Tbx18, and Upk3b were consistently expressed, whereas genes including Msln, C3, and Efemp1 exhibited increased expression during the mature stages of development. Pseudotime analysis further revealed two epicardial cell fates during maturation. Moreover, Upk3b, Msln, Efemp1, and C3 positive epicardial cells were enriched in extracellular matrix signaling. Our results suggested Upk3b, Efemp1, Msln, C3, and other genes were mature epicardium markers. Extracellular matrix signaling was found to play a critical role in the mature epicardium, thus suggesting potential therapeutic targets for heart regeneration in future clinical practice.

The shale oil and gas exploitation in China is technically benchmarked with the United States in terms of development philosophy, reservoir stimulation treatment, fracturing parameters, fracturing equipment and materials, oil/gas production technology, and data/achievements sharing. It is recognized that the shale oil and gas exploitation in China is weak in seven aspects: understanding of flow regimes, producing of oil/gas reserves, monitoring of complex fractures, repeated stimulation technology, oil/gas production technology, casing deformation prevention technology, and wellbore maintenance technology. Combined with the geological and engineering factors of shale oil and gas in China, the development suggestions of four projects are proposed from the macro- and micro-perspective, namely, basic innovation project, exploitation technology project, oil/gas production stabilization project, and supporting efficiency-improvement project, so as to promote the rapid, efficient, stable, green and extensive development of shale oil and gas industry chain and innovation chain and ultimately achieve the goal of “oil volume stabilizing and gas volume increasing”.

Abstract Background While it is known that klotho has negative regulatory effects in a variety of diseases such as metabolic disorders and kidney disease, the specific role of klotho in rheumatoid arthritis (RA) and its effect on mortality are unclear. This study investigated the association between serum klotho levels and mortality in patients with RA. Methods This study included 841 adults with RA from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016 to extract the concentrations of serum klotho. The association between klotho and RA was determined using Cox regression, Kaplan–Meier (KM) curves, and restricted cubic spline (RCS) models. Results A total of 841 patients with RA were included in this study, who were divided into four groups based on the quartiles of serum klotho levels (Q1, Q2, Q3, and Q4). Cox regression analysis with adjustment for covariates revealed that high levels of klotho lowered the risk of both all-cause and cardiovascular mortality compared to the Q1 group. The KM curve analysis suggested that this effect was more pronounced for all-cause mortality. The RCS-fitted Cox regression model indicated a U-shaped correlation between serum klotho levels and RA mortality. The risk of all-cause mortality increased with decreasing serum klotho levels below a threshold of 838.81 pg/mL. Subgroup analysis revealed that the protective effect of klotho was more pronounced in patients with the following characteristics: male, white ethnicity, age ≥ 60 years, body mass index

Enteroviruses (EVs) are classified into 15 species according to their sequence diversity. They include four human EV (A, B, C, and D) and three rhinoviruses (A, B, and C), and cause diseases in millions of people worldwide. Generally, individuals with enteroviral infections have mild clinical symptoms, including respiratory illness, vomiting, diarrhea, dizziness, and fever. More importantly, some members of the human EV family are neurotropic pathogens that may cause a wide range of clinical diseases, such as aseptic meningitis and encephalitis. Previously, the EV that caused the most severe neurotropic symptoms was poliovirus (PV), a member of the EV C group. Poliovirus has been eliminated in most countries through a global vaccination campaign. Non-PV EVs infect the central nervous system (CNS) and are the major EVs causing neurological diseases. These human non-PV EVs include EV A (e.g., EV-A71, CVA6, and CVA16), B (e.g., CVA9 and CVB3, CVB5, echovirus 11 [E11], E30, and E7), C (e.g., CVA24), and D (e.g., EV-D68). Here, we review the relationship between EV infection and CNS diseases and advance in the use of cellular receptors and host immune responses during viral infection.

Objective Studies on extremely severe elbow stiffness after chronic dislocation in children are scarce. This study aims to investigate the choice of surgical treatment modalities and to analyze their treatment efficacy in children with chronic elbow dislocation with extremely severe periarticular stiffness. Methods Data of 21 children with chronic elbow dislocation with extremely severe periarticular stiffness diagnosed and treated in our department between February 2015 and February 2021 were retrospectively analyzed. Twenty boys and one girl were included in the study, their mean age was 11 ± 2.5 years, and they had concomitant distal humerus fractures. For the treatment protocol, all children with extremely severe elbow stiffness were treated with open arthrolysis, and elbow joint stability was intraoperatively assessed. All children performed passive functional exercises the day after surgery. The elbow flexion and extension angles, range of motion (ROM), and Mayo score were evaluated preoperatively and at the final follow‐up. Results Of the 21 children, only one had recurrent severe stiffness of the elbow joint after surgery; nevertheless, the function was still improved compared with that before surgery. Preoperatively, the mean elbow extension and flexion angles were 72.2° ± 12.7° and 93.6° ± 11.1°, respectively, and the range of motion (ROM) of the elbow joint was 17.8° ± 8.3°. At the final follow‐up, the mean elbow extension and flexion angles were 22.7° ± 18.6° and 118.8° ± 15.4°, respectively, and the elbow joint ROM was 96.1° ± 17.4°. The differences in the preoperative and postoperative ROMs, flexion angles, and extension angles of the elbow joint were significant (p

Abstract Negative thermal expansion (NTE) alloys possess great practical merit as thermal offsets for positive thermal expansion due to its metallic properties. However, achieving a large NTE with a wide temperature range remains a great challenge. Herein, a metallic framework-like material FeZr2 is found to exhibit a giant uniaxial (1D) NTE with a wide temperature range (93-1078 K, $${\bar{\alpha }}_{l}=-34.01\times {10}^{-6}\,{{{{{{\rm{K}}}}}}}^{-1}$$ α ¯ l = − 34.01 × 10 − 6 K − 1 ). Such uniaxial NTE is the strongest in all metal-based NTE materials. The direct experimental evidence and DFT calculations reveal that the origin of giant NTE is the couple with phonons, flexible framework-like structure, and soft bonds. Interestingly, the present metallic FeZr2 excites giant 1D NTE mainly driven by high-frequency optical branches. It is unlike the NTE in traditional framework materials, which are generally dominated by low energy acoustic branches. In the present study, a giant uniaxial NTE alloy is reported, and the complex mechanism has been revealed. It is of great significance for understanding the nature of thermal expansion and guiding the regulation of thermal expansion.

Abstract Background Nearly 80% of patients with pancreatic cancer suffer from glucose intolerance or diabetes. Pancreatic cancer complicated by diabetes has a more immunosuppressive tumor microenvironment (TME) and is associated with a worse prognosis. The relationship between glucose metabolism and programmed cell death-Ligand 1 (PD-L1) is close and complex. It is important to explore the regulation of high glucose on PD-L1 expression in pancreatic cancer and its effect on infiltrating immune effectors in the tumor microenvironment. Methods Diabetic murine models (C57BL/6) were used to reveal different immune landscape in euglycemic and hyperglycemic pancreatic tumor microenvironment. Bioinformatics, WB, iRIP [Improved RNA Binding Protein (RBP) Immunoprecipitation]-seq were used to confirm the potential regulating role of peptidyl-tRNA hydrolase 1 homolog (PTRH1) on the stability of the PD-L1 mRNA. Postoperative specimens were used to identify the expression of PD-L1 and PTRH1 in pancreatic cancer. Co-culturing T cells with pancreatic cancer cells to explore the immunosuppressive effect of pancreatic tumor cells. Results Our results revealed that a high dose of glucose enhanced the stability of the PD-L1 mRNA in pancreatic tumor cells by downregulating PTRH1 through RAS signaling pathway activation following epidermal growth factor receptor (EGFR) stimulation. PTRH1 overexpression significantly suppressed PD-L1 expression in pancreatic cells and improved the proportion and cytotoxic function of CD8+ T cells in the pancreatic TME of diabetic mice. Conclusions PTRH1, an RBP, plays a key role in the regulation of PD-L1 by high glucose and is closely related to anti-tumor immunity in the pancreatic TME.

Abstract In order to reveal the dynamic mechanical properties of resin-molded parts prepared from photosensitive resin composition at different temperatures, four typical service temperatures (26 °C, 50 °C, 70 °C and 90 °C) were selected, and the mechanical properties of photosensitive resin specimens under quasi-static and high strain rate (1200 s−1, 1500 s−1 and 1800 s−1) loading were tested by universal material testing machine and split Hopkinson pressure bar (SHPB) experimental device. The stress–strain data of the material were obtained. Results show that the stress of photosensitive resin specimens decreases with the increase of temperature under quasi-static and high strain rate loading conditions, reflecting a certain temperature softening effect. Two typical stages of strain softening and strain hardening exist in the quasi-static compression process of the specimens at room temperature, while the specimens only exhibit strain hardening at 50 °C, 70 °C and 90 °C. Under dynamic loading, the elastic modulus, peak stress and peak strain of the photosensitive resin increase with the increase of the strain rate, reflecting an obvious effect of strain rate strengthening. The nonlinear thermo-viscoelastic constitutive model can better describe the mechanical behavior of the material under high strain rates and service temperatures, and the experimental values are in good agreement with the fitted values of the model. The results can provide theoretical model and method support for the design and development of resin-based materials and the optimization of their mechanical properties.

Regarding the replacement and maintenance of submarine buried cables, a piece of equipment, i.e., a submarine buried cable detection and hanging device, was specifically designed in this study that can be used to hook and mark a submarine buried cable, with the aim of facilitating underwater operation tools in completing future maintenance and repair. To verify the equipment design, a test bench was prepared for technical testing. During the test, feedback signals of the detection and hanging device were collected through an integrated displacement sensor and a pressure sensor. From the signal data, the operation window diagram corresponding to submarine buried cable detection and hanging information was established. Finally, the operation window diagram was used to guide and judge whether the detection and hanging device successfully marked the hook of submarine buried cable or not. The research results could provide important technical support as well as experimental basis for further design and application of underwater operation tools.

Benzoxaborole, a five-membered oxaborole ring fused with a phenyl ring, has demonstrated potent pharmacological activity. In order to explore their potential applications in agriculture, five-membered and six-membered benzoxaborole derivatives were synthesized and evaluated for their fungicidal activity against six common plant pathogenic fungi in vitro. The bioassay results showed that most of the target compounds exhibited significant fungicidal activity at concentrations below 50 μg/mL, particularly the highlighted compounds 4b and 4e, which demonstrated impressive fungicidal activity superior to those of the positive controls. Molecular docking was also performed to confirm the practical value of the active compound as a potential inhibitor of Leucyl-tRNA Synthetase (LeuRS). This study indicates that the designed benzoxaborole derivatives could serve as template molecules for the development of novel fungicides.

Abstract Accuracy of planned corneal stromal thickness (CST) reduction is essential to the safety of laser vision correction. This study was to compare the accuracy of the planned central CST reduction in small incision lenticule extraction (SMILE) and femtosecond laser-assisted in situ keratomileusis (FS-LASIK). A total of 77 patients (43 for SMILE, 34 for FS-LASIK using Custom-Q algorithm) were included in this retrospective study. At postoperative 6–18 months, the central CST reduction was overestimated by 18.49 ± 6.42 μm in the SMILE group (P

Abstract The efficiency of homology-directed repair (HDR) plays a crucial role in the development of animal models and gene therapy. We demonstrate that microhomology-mediated end-joining (MMEJ) constitutes a substantial proportion of DNA repair during CRISPR-mediated gene editing. Using CasRx to downregulate a key MMEJ factor, Polymerase Q (Polq), we improve the targeted integration efficiency of linearized DNA fragments and single-strand oligonucleotides (ssODN) in mouse embryos and offspring. CasRX-assisted targeted integration (CATI) also leads to substantial improvements in HDR efficiency during the CRISPR/Cas9 editing of monkey embryos. We present a promising tool for generating monkey models and developing gene therapies for clinical trials.

Abstract Previous studies have shown that Ogt-mediated O-GlcNAcylation is essential for neuronal development and function. However, the function of O-GlcNAc transferase (Ogt) and O-GlcNAcylation in astrocytes remains largely unknown. Here we show that Ogt deficiency induces inflammatory activation of astrocytes in vivo and in vitro, and impairs cognitive function of mice. The restoration of O-GlcNAcylation via GlcNAc supplementation inhibits the activation of astrocytes, inflammation and improves the impaired cognitive function of Ogt deficient mice. Mechanistically, Ogt interacts with NF-κB p65 and catalyzes the O-GlcNAcylation of NF-κB p65 in astrocytes. Ogt deficiency induces the activation of NF-κB signaling pathway by promoting Gsk3β binding. Moreover, Ogt depletion induces the activation of astrocytes derived from human induced pluripotent stem cells. The restoration of O-GlcNAcylation inhibits the activation of astrocytes, inflammation and reduces Aβ plaque of AD mice in vitro and in vivo. Collectively, our study reveals a critical function of Ogt-mediated O-GlcNAcylation in astrocytes through regulating NF-κB signaling pathway.

Abstract Introduction The cannabinoid receptor 2 (CB2) is mainly involved in the immune system. However, although CB2 has been reported to play an anti‐tumor function in breast cancer (BC), its specific mechanism in BC remains unclear. Methods We examined the expression and prognostic significance of CB2 in BC tissues by qPCR, second‐generation sequencing, western blot, and immunohistochemistry. We assessed the impacts of overexpression and a specific agonist of CB2 on the growth, proliferation, apoptosis, and drug resistance of BC cells in vitro and in vivo using CCK‐8, flow cytometry, TUNEL staining, immunofluorescence, tumor xenografts, western blot, and colony formation assays. Results CB2 expression was significantly lower in BC compared with paracancerous tissues. It was also highly expressed in benign tumors and ductal carcinoma in situ, and its expression was correlated with prognosis in BC patients. CB2 overexpression and treatment of BC cells with a CB2 agonist inhibited proliferation and promoted apoptosis, and these actions were achieved by suppressing the PI3K/Akt/mTOR signaling pathway. Moreover, CB2 expression was increased in MDA‐MB‐231 cell treated with cisplatin, doxorubicin, and docetaxel, and sensitivity to these anti‐tumor drugs was increased in BC cells overexpressing CB2. Conclusions These findings reveal that CB2 mediates BC via the PI3K/Akt/mTOR signaling pathway. CB2 could be a novel target for the diagnosis and treatment of BC.

Abstract Background We aimed to evaluate whether extracellular vesicles (EV)-derived microRNAs (miRNAs) can be used as biomarkers for advanced adenoma (AA) and colorectal cancer (CRC). Methods We detected the changes in the plasma EV-delivered miRNA profiles in healthy donor (HD), AA patient, and I-II stage CRC patient groups using miRNA deep sequencing assay. We performed the TaqMan miRNA assay using 173 plasma samples (two independent cohorts) from HDs, AA patients, and CRC patients to identify the candidate miRNA(s). The accuracy of candidate miRNA(s) in diagnosing AA and CRC was determined using the area under the receiver-operating characteristic curve (AUC) values. Logistic regression analysis was performed to evaluate the association of candidate miRNA(s) as an independent factor for the diagnosis of AA and CRC. The role of candidate miRNA(s) in the malignant progression of CRC was explored using functional assays. Results We screened and identified four prospective EV-delivered miRNAs, including miR-185-5p, which were significantly upregulated or downregulated in AA vs. HD and CRC vs. AA groups. In two independent cohorts, miR-185-5p was the best potential biomarker with the AUCs of 0.737 (Cohort I) and 0.720 (Cohort II) for AA vs. HD diagnosis, 0.887 (Cohort I) and 0.803 (Cohort II) for CRC vs. HD diagnosis, and 0.700 (Cohort I) and 0.631 (Cohort II) for CRC vs. AA diagnosis. Finally, we demonstrated that the upregulated expression of miR-185-5p promoted the malignant progression of CRC. Conclusion EV-delivered miR-185-5p in the plasma of patients is a promising diagnostic biomarker for colorectal AA and CRC. Trial registration The study protocol was approved by the Ethics Committee of Changzheng Hospital, Naval Medical University, China (Ethics No. 2022SL005, Registration No. of China Clinical Trial Registration Center: ChiCTR220061592).

Abstract Background This retrospective study aimed to characterize the distribution of HIV-1 genotypes and the prevalence of drug resistance mutations in people with antiretroviral treatment (ART) failure in Suzhou City, China. Methods Pol gene of HIV-1 viruses in blood samples of EDTA anticoagulants from 398 patients with failed antiviral treatment was successfully amplified by using an in-house assay. Drug resistance mutations were analyzed by using the Stanford HIV Drug Resistance Database system ( https://hivdb.stanford.edu/hivdb/by-mutations/ ). HIV-1 genotypes were determined by the REGA HIV subtyping tool (version 3.46, https://www.genomedetective.com/app/typingtool/hiv ). Near full-length genomes (NFLG) of HIV-1 viruses were obtained by next generation sequencing method. Results Sequences analysis of the pol gene revealed that CRF 01_AE (57.29%, 228/398) was the dominant subtype circulating in Suzhou City, followed by CRF 07_BC (17.34%, 69/398), subtype B (7.54%, 30/398), CRF 08_BC (6.53%, 26/398), CRF 67_01B (3.02%, 12/398) and CRF55_01B (2.51%, 10/398). The overall prevalence of drug-resistant mutations in cases with ART failure was 64.57% (257/398), including 45.48% (181/398) for nucleotide reverse transcriptase inhibitors (NRTIs) mutations, 63.32% (252/398) for non-nucleoside reverse transcriptase inhibitors (NNRTIs) mutations, and 3.02% (12/398) for protease inhibitors (PIs) mutations. Ten near full-length genomes (NFLG) of HIV-1 viruses were identified, including six recombinants of CRF 01_AE and subtype B, two recombinants of CRF 01_AE, subtype B and subtype C sequences, one recombinant of CRF 01_AE and subtype C and one recombinant of CRF 01_AE, subtype A1 and subtype C. Conclusions The high prevalence of drug-resistant HIV-1 viruses was a serious challenge for HIV prevention and treatment of people with HIV infection. Treatment regimens for ART failure patients should be adjusted over time based on the outcome of drug resistance tests. NFLG sequencing facilitates the identification of new recombinants of HIV-1.

Abstract Background The study was designed to evaluate the interobserver reliability and intraobserver repeatability of the 2021 Association Research Circulation Osseous (ARCO) classification and explore its guiding significance in the treatment of nontraumatic osteonecrosis of the femoral head (ONFH). Methods In this retrospective study, we randomly selected and investigated 50 sets of preoperative computed tomography or magnetic resonance imaging scans from 96 patients (139 hips) to validate the reliability and repeatability of the 2021 ARCO classification. Patients with a nano-hydroxyapatite/polyamide-66 support rod were included in the clinical efficacy study. The Harris hip score (HHS) was used to assess hip function. Femoral head collapse of > 2 mm was considered radiological failure. Total hip arthroplasty (THA) was performed for clinical failure, and follow-up was discontinued. Results The average kappa value of interobserver consistency was 0.652. The average rate of consistency was 90.25%, and the average kappa value of intraobserver consistency was 0.836. Eighty-two patients (122 hips) were enrolled and followed up for a mean of 43.57 ± 9.64 months. There was no significant difference in the HHS among the three groups before surgery, but the difference was statistically significant at the last follow-up. Among them, types 1 and 2 had significantly higher scores at the last follow-up than preoperatively (P 0.05).According to the imaging evaluation, the failure rate of type 1, 2, and 3 at the last follow-up was 0%, 19%, and 87%, respectively. Univariate analysis showed that the femoral head survival rate of radiography was significantly affected by the new classification system (P = 0.00). At the last follow-up, the incidence rate of THA in type 1, 2, and 3 was 5%, 7%, and 31%, respectively. Univariate analysis showed that the femoral head survival rate was significantly affected by the new classification system (P = 0.001). Conclusions The 2021 ARCO classification for early-stage ONFH shows substantial consistency and repeatability. We do not recommend femoral head-preserving surgery for patients with type 3 ONFH.

Chromium yeast (CY) supplementation has the potential to alleviate the negative effects of heat stress in dairy cows, but the mechanism remains elusive. We aimed to identify the metabolic mechanisms whereby CY supplementation alleviates the negative effects of heat stress in mid-lactation dairy cows. Twelve Holstein dairy cows with similar milk yield (24.6 ± 1.5 kg/d), parity (2 or 3) and days in milk (125 ± 8 d) were fed the same basal diet containing 0.09 mg of Cr/kg DM. They were allocated randomly to 2 groups: a control group (CON, without CY supplementation) and a CY group (CY, administered 0.36 mg Cr/kg DM). The experiment was performed over 8 weeks during a hot summer, in which the mean temperature-humidity index was 79.0 ± 3.13 (>72), indicating that the dairy cows were exposed to heat stress. Chromium yeast supplementation reduced rectal temperature (P = 0.032), and increased the lactation performance by increasing the yield of milk (+2.6 kg/d), protein, lactose and total solid, and protein and lactose percentages in the milk of the heat-stressed dairy cows (P 1.0, P

Abstract The desert ecosystem of the Qinghai–Tibet Plateau (QTP) is an important component of China's desert ecosystem. Studying the mechanisms shaping the taxonomic, phylogenetic, and functional beta diversity of plant communities in the QTP desert will help us to promote scientific conservation and management of the region's biodiversity. This study investigated the effects of environmental (including altitude, climate factors, and soil factors) and geographic distances on three facets of beta diversity as well as their turnover and nestedness components based on field survey data. The results showed that turnover components dominate the three facets of beta diversity. However, the turnover contributions to phylogenetic and functional beta diversity were lower than for taxonomic beta diversity. Environmental distance had a greater influence than geographic distance, with the former uniquely explaining 15.2%–22.8% of beta diversity and the latter explaining only 1.7%–2.4%. Additionally, the explanatory power of different factors for beta diversity differed between herbs and shrubs, with environmental distance being more important for the latter. Distance‐based redundancy analysis suggested that soil total potassium content had a substantial impact on the beta diversity of three dimensions, with mean temperature of the coldest month and soil total phosphorus content having a substantial impact on taxonomic and functional beta diversity as well. Our results support that environmental sorting plays a predominant role in shaping plant community composition across QTP desert ecosystems. To maintain the plant diversity of this region, it is crucial to prioritize the conservation of its diverse environmental conditions and actively mitigate its degradation by anthropogenic pressures.

ObjectiveOptimal neck management remains unclear in head and neck cutaneous squamous cell carcinoma (HNcSCC) with parotid metastasis. Our goal was to compare the impact of different cervical treatments on HNcSCC with parotid metastasis.MethodsPatients were retrospectively included. The primary outcome variables were regional control (RC) and disease-specific survival (DSS). The impacts of observation, elective neck irradiation (ENI), and elective neck dissection (END) were analyzed using the Cox model and presented as hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsIn total, 268 patients were enrolled. In the Cox model for RC, compared with ENI, observation was associated with a significantly higher risk of regional recurrence (p = 0.001, HR = 2.50, 95%CI = 1.45–4.30). However, END showed a comparable influence on regional recurrence (p = 0.246, HR = 0.70, 95%CI = 0.38–1.28). In the Cox model for DSS, END demonstrated a similar HR of 0.62 (95%CI = 0.30–1.26) compared to ENI (p = 0.184). However, patients who underwent observation were associated with an additional nearly twofold risk of cancer-related mortality (HR = 2.85, 95%CI = 1.55–5.23). Subgroup analysis showed that ENI predicted comparable RC (p = 0.389) and DSS (p = 0.346) in patients with one or two metastatic parotid lymph nodes, but worse RC (p = 0.007) and DSS (p = 0.024) in patients with more than three positive lymph nodes.ConclusionIn HNcSCC with parotid metastasis, elective treatment of neck lymph nodes with END or ENI should always be performed.

Objective: Clear cell renal cell carcinoma (ccRCC) is the most common subtype among renal cell carcinomas and has the worst prognosis, originating from renal tubular epithelial cells. Toll-like receptor 4 (TLR4) plays a crucial role in ccRCC proliferation, infiltration, and metastasis. The aim of this study was to construct a prognostic scoring model for ccRCC based on TLR4 expression heterogeneity and to explore its association with immune infiltration, thereby providing insights for the treatment and prognostic evaluation of ccRCC. Methods: Using R software, a differential analysis was conducted on normal samples and ccRCC samples, and in conjunction with the KEGG database, a correlation analysis for the clear cell renal cell carcinoma pathway (hsa05211) was carried out. We observed the expression heterogeneity of TLR4 in the TCGA-KIRC cohort and identified its related differential genes (TRGs). Based on the expression levels of TRGs, consensus clustering was employed to identify TLR4-related subtypes, and further clustering heatmaps, principal component, and single-sample gene set enrichment analyses were conducted. Overlapping differential genes (ODEGs) between subtypes were analysed, and combined with survival data, univariate Cox regression, LASSO, and multivariate Cox regression were used to establish a prognostic risk model for ccRCC. This model was subsequently evaluated through ROC analysis, risk factor correlation analysis, independent prognostic factor analysis, and intergroup differential analysis. The ssGSEA model was employed to explore immune heterogeneity in ccRCC, and the performance of the model in predicting patient prognosis was evaluated using box plots and the oncoPredict software package. Results: In the TCGA-KIRC cohort, TLR4 expression was notably elevated in ccRCC samples compared to normal samples, correlating with improved survival in the high-expression group. The study identified distinct TLR4-related differential genes and categorized ccRCC into three subtypes with varied survival outcomes. A risk prognosis model based on overlapping differential genes was established, showing significant associations with immune cell infiltration and key immune checkpoints (PD-1, PD-L1, CTLA4). Additionally, drug sensitivity differences were observed between risk groups. Conclusion: In the TCGA-KIRC cohort, the expression of TLR4 in ccRCC samples exhibited significant heterogeneity. Through clustering analysis, we identified that the primary immune cells across subtypes are myeloid-derived suppressor cells, central memory CD4 T cells, and regulatory T cells. Furthermore, we successfully constructed a prognostic risk model for ccRCC composed of 17 genes. This model provides valuable references for the prognosis prediction and treatment of ccRCC patients.

BackgroundThe aim of this study was to assess the clinical and radiographic outcomes of cubitus varus treatments based on different fixation methods: Locking plate vs. Kirschner-wires (K-wires) and cast fixation.MethodsThis retrospective study of 28 patients was performed in lateral-wedge osteotomy for cubitus varus deformity in our hospital from July 2018 to July 2020. 14 patients in group A were treated by locking plate after lateral closing-wedge osteotomy, whereas other 14 patients were treated by K-wires in group B. We measured the bony union and carrying angle. The clinical and radiographic outcomes were assessed according to the Bellemore criteria.ResultsNo nonunion, neurovascular injury or myositis ossificans was noted at follow-up. In group A, 1 patient with lateral condylar prominence was found. In group B, 2 patients with pinning site infection were treated successfully with oral antibiotics and 2 patients needed revision surgery for residual varus. According to the Bellemore criteria, statistically significant difference was noted between the two groups (P = 0.0458). In the present study, no statistically significant difference was noted in the length of incision and operation time between the 2 groups (P > 0.05). However, the postoperative carrying angle was significantly different at final follow-up between the 2 groups (P

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third human coronavirus to cause acute respiratory distress syndrome (ARDS) and contains four structural proteins: spike, envelope, membrane, and nucleocapsid. An increasing number of studies have demonstrated that all four structural proteins of SARS-CoV-2 are capable of causing lung injury, even without the presence of intact virus. Therefore, the topic of SARS-CoV-2 structural protein-evoked lung injury warrants more attention. In the current article, we first synopsize the structural features of SARS-CoV-2 structural proteins. Second, we discuss the mechanisms for structural protein-induced inflammatory responses in vitro. Finally, we list the findings that indicate structural proteins themselves are toxic and sufficient to induce lung injury in vivo. Recognizing mechanisms of lung injury triggered by SARS-CoV-2 structural proteins may facilitate the development of targeted modalities in treating COVID-19.

Sensors are important tools in the fields of biology and chemistry. Highly sensitive, robust and low-cost sensors and their preparation methods have always constituted a research topic. In this paper, an all-dielectric metasurface with a double-opening resonant ring is proposed. The metasurfaces can support MD and ED modes to excite three q-BIC modes. And the Q-factor can reach 4.97×104, 2.02×105 and 1.39×106 respectively. For the asymmetric structure, the three excited peaks have certain polarization-insensitive characteristics. With the introduction of graphene, the dynamic regulation of transmission peak can be realized, specifically the regulation of resonance wavelength, and the intensity of transmittance. Since the all-dielectric metasurfaces assist in enhancing the interaction of the light field with dielectric materials, and the field enhancement effect is obvious, so we analyze the sensing properties of the metasurface. It has a sensitivity of up to 1340 nm/RIU and FOM can reach 1.17×106. Finally, we additionally analyze another asymmetric form, which enables the excitation of the q-BIC by changing the polarization angle, making the structure potentially valuable for optical switching as well.

Background: A considerable number of patients with breast cancer will suffer from brain metastasis in the advanced setting. The HER2 status serves as a significant prognostic factor and the reference of applying treatment for patients with breast cancer brain metastasis (BCBM). Methods: Between January 2010 and July 2021, patients with BCBM who had available HER2 status were identified. The patients with HER2 1+ in immunohistochemistry (IHC) or IHC 2+ and fluorescence in situ hybridization (FISH) negative were categorized as HER2-low. Comparisons were conducted between the HER2-low and HER2-zero population. The primary endpoint was overall survival (OS) after the diagnosis of BCBM. Survival outcomes were assessed using Kaplan-Meier curves with log-rank test and Cox proportional hazards model. Results: In this study, we analyzed 71 patients with the HER2-low breast cancer subtype and 64 patients with the HER2-zero subtype. Despite the limited sample size, our findings revealed a significantly better OS for patients with HER2-low cancer compared to their HER2-zero counterparts (26 m vs 20 m, p = 0.0017). This trend was particularly notable in the HR-negative group (26 m vs 13 m, p = 0.0078), whereas no significant difference was observed among the HR-positive patients. Furthermore, Cox regression analysis revealed that the HER2-low status was an independent prognostic factor for better survival in the HR-negative patients (p = 0.046 in multivariate analysis). Conclusions: Patients diagnosed with HER2-low BCBM exhibited a more favorable prognosis than those with HER2-zero BCBM, particularly within the HR-negative subgroup. The low expression of HER2 is supposed to be linked to the prolonged survival of BCBM patients.

Background: Antiviral granules (AG) is a classic traditional Chinese medicine commonly employed for influenza treatment. However, there is an urgent need to improve its quality control standards. Purpose: The quality markers (Q-markers), guided by the Effect-constituent Index (ECI), were screened through in vitro and in vivo component identification, molecular docking, and neuraminidase (NA) inhibition experiments. Methods: The chemical components in AG underwent analysis using UPLC-Q-Orbitrap HRMS and GC–MS, and serum pharmacochemistry was employed to analyze the components absorbed into the bloodstream. Molecular docking was used to evaluate the affinity of the prototype components to NA, and the inhibitory activity of the candidate components was later confirmed through NA inhibitor experiments. Following this, a UHPLC-MS/MS method was developed to screen and quantify the Q-markers in 20 sample batches. Lastly, the ECI was formulated using a multi-index comprehensive evaluation method that combines composition, content, and activity. Results: A total of 246 compounds were identified in AG, and 89 prototype components and 19 metabolic components were detected in the serum of the rats. Molecular docking revealed that the binding energy of 35 candidate active ingredients was better than that of the original ligand and the target protein. Among these candidate active ingredients, 12 candidate Q-markers demonstrated significant inhibitory effects in NA inhibition experiments, with IC50 values ranging from 0.954 to 3.408 mM. A UHPLC-MS/MS content determination method was established for the quantification of 11 Q-markers, including Forsythiaside A, Pogostone, Verbascoside, Mangiferin, 5-methoxy-8-hydroxypsoralen, Curcumenol, Luteolin-7-glucuronide, Kaempferol-3-O-rutinoside, Baicalin, Rutin, and Bergaptol, in 20 batches of samples. The ECI was calculated based on activity and content of these Q-markers. Pearson's correlation analysis of the NA inhibitory effect of the samples and the ECI resulted in an R value of 0.859, indicating a good correlation. Furthermore, this correlation coefficient surpassed those observed between the content of each Q-marker and the NA inhibitory effect. Conclusion: The Q-markers for treating influenza with AG have been successfully screened, and the ECI of AG has been constructed. These findings will provide beneficial strategies for improving the quality control level of AG.

Chylous leakage is an uncommon and serious clinical condition, especially occurring after retroperitoneal operations. Here, we report a case of cervical chylous leakage combined with chylothorax in a 57-year-old woman postretroperitoneal surgery, and our conservative approach led to resolution/clinical improvement. The causes of this rare complication are discussed. We considered that the venous thrombosis, the increased intra-abdominal pressure, or the patient positioning during the surgery may lead to the chylous particles leakage and chylothorax. Because of its rarity, we hope this case report will improve clinicians’ understanding of cervical chylous leakage combined with chylothorax and provide suitable treatment options for future clinical reference.

Nicotinamide mononucleotide (NMN) is an intermediate in biosynthesis pathway of Nicotinamide adenine dinucleotide (NAD+), an essential cofactor in all living cells involved in fundamental biological processes. Evidence stemming from recent studies have unveiled numerous roles of NAD+ metabolism on aging, longevity, delaying the progression of age-related diseases. A three-study genetic toxicity (genetox) battery (bacterial mutagenesis, in vitro cytogenetics, and in vivo mammalian test) is usually required to confirm safety of a new dietary ingredient and this study showed the data from in vivo mutagenicity test for the first time.The acute oral LD50 of NMN was greater than 2000 mg/kg body weight with 5000 mg/kg body weight as LD50 cut-off value and was classified under “Category 5 or Unclassified” as per Globally Harmonized System of Classification and Labelling of Chemicals (GHS). Based on 90 days repeated dose toxicity test the NOAEL was considered to be NLT 800 mg NMN/kg body weight in Wistar rats. The bacterial reverse mutation test, the in vitro and in vivo chromosomal aberration test, found NMN to be non-mutagenic. In the mammalian bone marrow chromosomal aberration test, it was concluded that NMN is non clastogenic at and up to 2,000 mg/kg body weight in all the animals tested to confirm safety of a new dietary ingredient and this study showed the data from in vivo mutagenicity test for the first time.

The new insulated single-sided composite shear wall (NISCSW) composition involves setting a precast wall panel on one side and an insulation panel on the other side, with a middle cavity for casting concrete. To investigate the seismic performance of NISCSW under different shear spans and axial compression ratios, eight specimens are made, including six composite and two cast-in-place walls. The shear span ratio is controlled at 1.2 and 1.9, and the axial compression ratio is controlled at 0.1, 0.3, and 0.4. The specimens are subjected to quasistatic tests to analyze failure modes, hysteresis characteristics, stiffness degradation, displacement ductility, and energy dissipation capacity and to compare the seismic performance of the composite and cast-in-place walls. Results show that for each composite specimen, under the same axial compression ratio, the large shear span ratio specimen has a lower ultimate bearing capacity and faster stiffness degradation but better ductility and postyield energy dissipation capacity. Under the same shear span ratio, the high axial compression ratio specimen had a higher ultimate bearing capacity, slightly worse ductility, and similar stiffness degradation and energy dissipation capacity compared to other specimens. Compared with the cast-in-place specimen with the same axial compression ratio, the composite specimen failure mode and hysteresis characteristics are similar, and the ductility and energy dissipation capacity are comparable to the cast-in-place shear wall specimen, indicating that NISCSW has similar seismic performance to the cast-in-place shear wall under conditions of a large shear span ratio and high axial compression ratio. Based on the test results, the program ABAQUS is used to simulate the specimens. Compared with the test results, the simulated specimen failure mode is consistent with the test results, and the hysteresis and skeleton curves are consistent with the test curve, indicating that the model is correct, reliable, and can be verified with test results.

BackgroundTo investigate the correlation between albumin-corrected anion gap(ACAG) within the first 24 hours of admission and in-hospital mortality in trauma patients in intensive care unit(ICU).Materials and methodsWe utilized the MIMIC-Ⅲ and MIMIC-Ⅳ databases to examine trauma patients admitted to the ICU. The relationship between ACAG and in-hospital mortality in trauma patients was analyzed using Receiver Operating Characteristic(ROC) curve, Kaplan-Meier (K-M) survival curve, and Cox regression model. Propensity score matching (PSM) and subgroup analysis were conducted to enhance stability and reliability of the findings. Mortality at 30-day and 90-day served as secondary outcomes.ResultsThe study enrolled a total of 1038 patients. The AUC for ACAG (0.701, 95%CI: 0.652-0.749) was notably higher than that for anion gap and albumin. The Log-rank test revealed that the optimal cut-off point of ACAG for predicting in-hospital mortality was determined to be 20.375mmol/L. The multivariate Cox regression analysis demonstrated an independent association between high ACAG level and a higher risk of in-hospital mortality (HR = 3.128, 95% CI: 1.615-6.059). After PSM analysis, a matched cohort consisting of 291 subjects was obtained. We found no signifcant interaction in most stratas. Finally, The in-hospital, 30-day, and 90-day survival rates in the high ACAG group exhibited a statistically decrease compared to those in the low ACAG group both pre- and post-matching.ConclusionThe elevated level of ACAG was found to be independently associated with increased in-hospital mortality among trauma patients in the ICU.

Abstract BackgroundAlthough evidence-based medicine proposes personalized care that considers the best evidence, it still fails to address personal treatment in many real clinical scenarios where the complexity of the situation makes none of the available evidence applicable. “Medicine-based evidence” (MBE), in which big data and machine learning techniques are embraced to derive treatment responses from appropriately matched patients in real-world clinical practice, was proposed. However, many challenges remain in translating this conceptual framework into practice. ObjectiveThis study aimed to technically translate the MBE conceptual framework into practice and evaluate its performance in providing general decision support services for outcomes after congenital heart disease (CHD) surgery. MethodsData from 4774 CHD surgeries were collected. A total of 66 indicators and all diagnoses were extracted from each echocardiographic report using natural language processing technology. Combined with some basic clinical and surgical information, the distances between each patient were measured by a series of calculation formulas. Inspired by structure-mapping theory, the fusion of distances between different dimensions can be modulated by clinical experts. In addition to supporting direct analogical reasoning, a machine learning model can be constructed based on similar patients to provide personalized prediction. A user-operable patient similarity network (PSN) of CHD called CHDmap ResultsUsing 256 CHD cases, CHDmap was evaluated on 2 different types of postoperative prognostic prediction tasks: a binary classification task to predict postoperative complications and a multiple classification task to predict mechanical ventilation duration. A simple poll of the k ConclusionsWithout individual optimization, CHDmap demonstrates competitive performance compared to clinical experts. In addition, CHDmap has the advantage of enabling clinicians to use their superior cognitive abilities in conjunction with it to make decisions that are sometimes even superior to those made using artificial intelligence models. The MBE approach can be embraced in clinical practice, and its full potential can be realized.

IntroductionPeriodontal disease (PD) presents a substantial global health challenge, encompassing conditions from reversible gingivitis to irreversible periodontitis, often culminating in tooth loss. The gut-oral axis has recently emerged as a focal point, with potential gut microbiota dysbiosis exacerbating PD.MethodsIn this study, we employed a double-sample bidirectional Mendelian randomized (MR) approach to investigate the causal relationship between specific gut microbiota and periodontal disease (PD) and bleeding gum (BG) development, while exploring the interplay between periodontal health and the gut microenvironment. We performed genome-wide association studies (GWAS) with two cohorts, totalling 346,731 (PD and control) and 461,113 (BG and control) participants, along with data from 14,306 participants’ intestinal flora GWAS, encompassing 148 traits (31 families and 117 genera). Three MR methods were used to assess causality, with the in-verse-variance-weighted (IVW) measure as the primary outcome. Cochrane’s Q test, MR-Egger, and MR-PRESSO global tests were used to detect heterogeneity and pleiotropy. The leave-one-out method was used to test the stability of the MR results. An F-statistic greater than 10 was accepted for instrument exposure association.Results and conclusionSpecifically, Eubacterium xylanophilum and Lachnoclostridium were associated with reduced gum bleeding risk, whereas Anaerotruncus, Eisenbergiella, and Phascolarctobacterium were linked to reduced PD risk. Conversely, Fusicatenibacter was associated with an elevated risk of PD. No significant heterogeneity or pleiotropy was detected. In conclusion, our MR analysis pinpointed specific gut flora with causal connections to PD, offering potential avenues for oral health interventions.

BackgroundCervical carcinoma is a type of malignant tumor that primarily develops in the cervix, the lower part of the uterus. In recent years, Despite the considerable progress made in immunotherapy research for cervical carcinoma, an important aspect has been largely overlooked - the absence of a comprehensive bibliometric analysis in this field. By employing bibliometric techniques, this study aims to fill this gap and provide a comprehensive overview of the knowledge structure and research hotspots within the realm of immunotherapy in cervical carcinoma.MethodA comprehensive search was conducted on the web of science core collection(WoSCC) database to identify publications related to immunotherapy specifically for the treatment of cervical carcinoma. The search spanned the period from the year 2000 to 2023. Several analytical tools were employed. These included VOSviewers, CiteSpace, and the R package “bibliometrix”.ResultsA total of 654 research articles from 66 different countries have been included in the analysis. The United States and China have emerged as the leading countries in publishing research on immunotherapy in cervical carcinoma. Leiden University and Memorial Sloan-Kettering Cancer Center from the Netherlands and the United States respectively have a close cooperation. Fudan University from China and the German Cancer Research Center are also among the key institutions leading research in this area. Frontiers in Oncology has emerged as the most popular and widely recognized publication in the field of immunotherapy in cervical carcinoma. Journal of Clinical Oncology is frequently cited by researchers in this area. Van Der Burg, Sjoerd H has published the highest number of papers. Tewari, Krishnansu S has been the most co-cited author. Keywords such as PD-L1, chemotherapy, and immune checkpoint inhibitors have gained significant attention in recent years.ConclusionThis is the first bibliometric study that comprehensively summarizes the research trends and developments of immunotherapy in cervical carcinoma. This groundbreaking study not only summarizes the current research trends and developments in immunotherapy for cervical carcinoma but also provides a reference for scholars studying the treatment of cervical cancer.

All-fiber coherent beam combiners based on the self-imaging effect can achieve a near-perfect single laser beam, which can provide a promising way to overcome the power limitation of a single-fiber laser. One of the key points is combining efficiency, which is determined by various mismatches during fabrication. A theoretical model has been built, and the mismatch error is analyzed numerically for the first time. The mismatch errors have been numerically studied with the beam quality and combining efficiency being chosen as the evaluation criteria. The tolerance of each mismatch error for causing 1% loss is calculated to guide the design of the beam combiners. The simulation results are consistent with the experimental results, which show that the mismatch error of the square-core fiber is the main cause of the efficiency loss. The results can provide useful guidance for the fabrication of all-fiber coherent beam combiners.

Hand, foot, and mouth disease (HFMD) caused by a group of enteroviruses is a global public health problem. In recent years, coxsackievirus A6 (CVA6) has emerged as an important HFMD agent. Previous studies have shown that mutations of glycine 64 in RNA-dependent RNA polymerase (3D polymerase), which is central to viral replication, cause phenotypic changes such as ribavirin resistance, increased replication fidelity, and virulence attenuation in poliovirus and enterovirus A71. In this study, we constructed CVA6 mutants with G64R, G64S, and G64T substitutions by site-directed mutagenesis in full-length cDNA of an infectious CVA6 strain cloned in pcDNA3.1. Viral RNA was obtained by in vitro transcription, and the rescued virus strains were propagated in RD cells. Sequencing after six passages revealed that G64S and G64T mutations were stably inherited, whereas G64R was genetically unstable and reversed to the wild type. Comparison of the biological characteristics of the wild-type and mutant CVA6 strains in an in vivo model (one-day-old ICR mice) revealed that the pathogenicity of CVA6-G64S and CVA6-G64T was significantly reduced compared to wild-type CVA6. In vitro experiments indicated the mutant CVA6-G64S and CVA6-G64T strains had increased resistance to 0.8 mM ribavirin and a decreased replication rate in the presence of 0.8 mM guanidine hydrochloride. Our results show that mutation of residue 64 reduces CVA6 susceptibility to ribavirin and increases CVA6 susceptibility to guanidine hydrochloride, together with increased replication fidelity and attenuated viral pathogenicity, thus laying a foundation for the development of safe and effective live attenuated CVA6 vaccine.

This study focuses on a novel clutchless and synchronizer-free drive system designed explicitly for pure electric vehicles. In contrast to the majority of previous research that solely considers internal excitations, this study not only incorporates various non-linear factors such as time-varying friction forces, time-varying mesh stiffness, and damping associated with internal excitations but also places significant emphasis on analyzing the impact of non-linear external excitations, including road surface unevenness and motor torque fluctuations, on the shifting process of the drive system. Subsequently, a non-linear dynamic model of the shifting process is established. In the modeling process, departing from the traditional two-degree-of-freedom quarter vehicle dynamics model, this study adopts an elastic tire-body and elastic tire-tread tire model, enabling the establishment of a highly accurate multi-degree-of-freedom quarter vehicle dynamics model. The simulation results indicate that road surface roughness and motor torque fluctuation significantly impact the gear-shifting process and the impact of road surface roughness increases with the level of roughness. Moreover, the effect of motor torque fluctuation on the gear-shifting process varies depending on different factors and is not simply additive. Consequently, when formulating and optimizing shifting strategies, it becomes imperative to consider various external factors. The research methodology integrates these factors into the dynamic analysis of the shifting process, providing a theoretical basis for developing effective shifting control strategies while considering external excitations.

Perovskite photovoltaic has been attracting intense attention as an emerging technology due to its figure of merits including high power conversion efficiency, low-cost fabrication, and others. A successful commercialization of this type of technology has been significantly retarded by issues of elemental toxicity and device stability which are related to the key component of lead (Pb) in most efficient halide perovskites. Here, we first elucidated the origin of the superior optoelectronic properties of lead halide perovskites and their impact on photovoltaic device performance. We then discussed the promising approaches to solve the toxicity issue of lead hybrid perovskites. We further outlooked the effective solutions for lead hybrid perovskites for solar cell application. This review may provide a guidance for researchers interested in facilitating perovskite solar cells from exploitation to application.

ABSTRACT The gut microbiota develops specialized local communities along the gastrointestinal (GI) tract of the host. Among these microbes, intestinal bacteria and fungi interact closely with the host and play vital roles in their health. However, the gut biogeography of bacteria and fungi has rarely been studied simultaneously, and their correlations have not been reported. In this study, we collected the intestinal luminal contents from different gastrointestinal regions (the ileum, caecum, and colon) of wild-type female cynomolgus monkeys and performed 16S and 18S rRNA gene sequencing to determine the gut biogeography of bacterial and fungal communities. The richness and diversity of bacteria and fungi increased gradually from the small to the large intestine. The bacterial and fungal composition of ileum differed significantly from that of the colon. Specifically, Bacteroidia and Spirochaetia were abundant in the caecum and colon, while Actinobacteria and Cyanobacteria were enriched in the ileum. As for fungal taxa, the genera Aspergillus, Wallemia, and Cryptococcus_f_Tremellaceae were enriched in the colon, while the genus Fusarium was abundant in the caecum. Consequently, the bacterial and fungal functions of the ileum differed from those of the caecum and colon. Notably, we characterized the correlations between intestinal bacteria and fungi at different gastrointestinal regions of cynomolgus monkeys using Spearman correlation analysis. In summary, our results contribute to a more comprehensive understanding of the composition and function of intestinal bacteria and fungi in non-human primates (NHPs) and reveal their correlations along the longitudinal axis of the intestine. IMPORTANCE Gut microbiota varies along the gastrointestinal (GI) tract and exerts profound influences on the host’s physiology, immunity, and nutrition. Given that gut microbes interact with the host closely and the gastrointestinal function differed from the small to the large intestine, it is essential to characterize the gut biogeography of the microbial community. Here, we focused on intestinal bacteria and fungi in cynomolgus monkeys and determined their spatial distribution along the GI tract by performing 16S and 18S rRNA gene sequencing. The composition and function of bacterial and fungal communities differed significantly at different biogeographic sites of the intestine, and the site-specific correlations between intestinal bacteria and fungi were revealed. Thus, our studies characterized the gut biogeography of bacteria and fungi in NHPs and revealed their site-specific correlations along the GI tract.

CrtN has been identified as an appealing target for treatment of pigmented staphylococcus aureus infections. A novel of N-methyl-N-(2,4,6-trimethoxybenzyl)cinnamamide derivatives as CrtN inhibitors based on the structure of naftifine (NTF) were designed and synthesis, and evaluate for their pigment inhibition activities in S.aureus Newman. Out of them, compound 6q represented the potent activity against the pigment and CrtN enzyme with the IC50 value of 23.1 nM and 233.1 nM, respectively, which was superior to that of NTF. Meanwhile, compound 6q could make S. aureus more susceptible to immune clearance. It was indicated that replacement of the naphthalenyl ring in NTF with the phloroglucinol ring is an effective strategy to develop new CrtN inhibitors.

The pressure analysis and flow characteristics during the flight of a high-speed bullet are significant for aerodynamic performance, flight trajectory control, safety and reliability, performance optimization, guidance and navigation. To accurately monitor the pressure variation for a high-speed bullet in the high-altitude flight, a novel local fluid domain method is introduced in current study. This method overcomes the limitations of conventional global fluid domain simulation methods, which often suffer from poor convergence and stability issues. On the basis, the force analysis is conducted and the mathematical model for the theoretical trajectory is established, which is applied to simulate the flight trajectory and construct fluid domain for the high-speed bullet. The findings reveal that monitoring points within the bullet hole are influenced by both cavity flow and the collision of forward airflows during the high-altitude flight. Furthermore, it is observed that the absolute total pressure and reference pressure at these monitoring points within the bullet hole are influenced by altitude variations. Subsequently, the factors affecting the absolute total pressure within the hole are explored, including the hole depth, the hole diameter, the hole position, and the bullet orientation. The results indicate that modifying the bullet structure to incorporate 45° angled hole, as opposed to standard holes, can lead to a 13.6% reduction in absolute total pressure variation. Additionally, mitigating the interaction between the external and internal fluids emerges as a critical factor in reducing absolute total pressure within the hole. This research not only presents a fresh perspective for pressure monitoring within the bullet hole, but also establishes a theoretical foundation for the precise guidance of high-altitude bullets.

Background: Diabetic retinopathy (DR) is a leading cause of blindness characterized by damage to the retinal neurovascular unit, which is caused by hyperglycemia-induced metabolic and inflammatory responses. 5-Bromo-3,4-dihydroxybenzaldehyde (BDB) is a compound derived from marine red algae and known for its anti-inflammatory effects. Methods: This study aimed to investigate the potential protective effects of BDB on DR using primary human retinal vascular endothelial cells and retinal tissue explants. The analysis involved assessing vascular integrity, expression of tight junction protein, hyperglycemia-induced permeability, and retinal ganglion cell (RGC) apoptosis. The protective effect of BDB in maintaining the diabetic retinal neurovascular units was verified using type 1 diabetic mouse models. Additionally, the inhibitory effect of BDB on the levels of inflammatory cytokines TNF-α, IL-1β, and IL-6 were examined. Results: In vitro experiments revealed that BDB promoted vascular integrity, inhibited the transcription of pro-inflammatory factors, and alleviated hyperglycemia-induced permeability. BDB also protected RGC from hyperglycemia-induced apoptosis. In diabetic mice models, BDB treatment maintained the integrity of diabetic retinal neurovascular units and inhibited the secretion of TNF-α, IL-1β, and IL-6. Conclusion: BDB demonstrated a protective effect on DR by inhibiting the secretion of inflammatory factors, suggesting its potential as a therapeutic agent for the treatment of DR. Further research is warranted to validate its safety and efficacy for clinical application.

Net ecosystem productivity (NEP) quantifies magnitude of the terrestrial vegetation carbon sinks. Drought is one of the most important stressors affecting vegetation NEP. At present, the spatiotemporal dynamics of vegetation NEP in drought-prone of Northwest China (NWC) lack discussion under different climatic zones and land cover types, and the response of vegetation NEP to drought remains unclear. Hence, we estimated the vegetation NEP in NWC using ground and remote sensing data and quantified the spatiotemporal differentiation of NEP under different climatic zones and land cover types. The drought fluorescence monitoring index (DFMI) was developed to examine the relationship between vegetation NEP and drought response based on the solar-induced chlorophyll fluorescence (SIF) data. Our results suggested that vegetation carbon sinks increased significantly at 7.09 g C m−2 yr−1 in NWC during 2000–2019, mainly in northern Shaanxi, eastern and southern Gansu, and southern Ningxia. NEP showed increasing trends under different climatic zones and land cover types, but there were differences in carbon sink capacity. The strongest carbon sink capacity was in humid regions and forests, while the weakest was in arid regions and grasslands. The vegetation carbon sinks showed a non-linear relationship with the drought degree reflecting multiple trend differences, especially in forests and grasslands. The response to drought was faster and more significant in semi-arid and semi-humid transition zones and extreme humid regions when vegetation carbon sinks decreased. DFMI was a good indicator to monitor drought conditions in NWC. NEP and DFMI were an 8–20-month periodic positive correlation and showed a high correlation with high–high and low–low clustering spatially. Drought significantly weakened vegetation carbon sinks in NWC. This study emphasizes the demand to rapidly identify climatic conditions that lead to decrease significantly in vegetation carbon sinks and to formulate adaptation strategies aimed at reducing drought risk under global warming.

ABSTRACTEnterovirus 76 (EV-A76) is a serotype of enterovirus A and has been rarely reported. In this paper, we present the genetic characteristics of 15 EV-A76 isolates reported to circulate in the Xinjiang Uighur autonomous region of China in 2011. Sequence analysis revealed that all Chinese EV-A76 isolates had high similarity (> 98.3%) in the VP1 region, and five Chinese EV-A76 isolates were selected for whole genome sequencing based on VP1 nucleotide divergence. Similarity plots and boot-scanning analyses revealed frequent intertypic recombination in the nonstructural region of the EV-A76 isolate, as found with the EV-A89 donor sequence (also isolated in Xinjiang). The breakpoint of recombination is around nucleotide 3960, and the recombinant fragments covered part 2C and all P3 regions. This study increases publicly available EV-A76 nucleotide sequence and further our understanding EV-A76 molecular epidemiology.

Abstract Background Congenital pulmonary airway malformation (CPAM) is the most frequent pulmonary developmental malformation and the pathophysiology remains poorly understood. This study aimed to identify the characteristic gene expression patterns and the marker genes essential to CPAM. Methods Tissues from the cystic area displaying CPAM and the area of normal appearance were obtained during surgery. Bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) were performed for integrating analysis. Iterative weighted gene correlation network analysis (iWGCNA) was used to identify specifically expressed genes to CPAM. Results In total, 2074 genes were significantly differentially expressed between the CPAM and control areas. Of these differentially expressed genes (DEGs), 1675 genes were up-regulated and 399 genes were down-regulated. Gene ontology analysis revealed these DEGs were specifically enriched in ciliated epithelium and involved in immune response. We also identified several CPAM-related modules by iWGCNA, among them, P15_I4_M3 module was the most influential module for distinguishing CPAMs from controls. By combining the analysis of the expression dataset from RNA-seq and scRNA-seq, SPOCK2, STX11, and ZNF331 were highlighted in CPAM. Conclusions Through our analysis of expression datasets from both scRNA-seq and bulk RNA-seq of tissues obtained from patients with CPAM, we identified the characteristic gene expression patterns associated with the condition. Our findings suggest that SPOCK2 could be a potential biomarker gene for the diagnosis and therapeutic target in the development of CPAM, whereas STX11 and ZNF331 might serve as prognostic markers for this condition. Further investigations with larger samples and function studies are necessary to confirm the involvement of these genes in CPAM.