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We investigated the effect of culture and social status on sarcasm interpretation. Two hundred U.K. participants and 200 Chinese participants read scenarios in which the final comment could be either literal or sarcastic criticism and the speaker had equal, higher, or lower social status compared to the recipient. Comments were rated on degree of sarcasm, amusement, politeness, and aggression. Results showed that compared to literal criticism, sarcasm was viewed as being more polite and less aggressive in the United Kingdom but more aggressive in China. When the speaker had higher social status, sarcasm was rated less amusing and marginally more aggressive in the United Kingdom but less aggressive and more polite in China. Results have theoretical implications, in that theories designed to explain the emotional impact of sarcasm (such as the Tinge Hypothesis) need to be modified to take cultural differences into account, as well as practical implications for successful cross-cultural communication.

Abstract Objective The objective of this study was to investigate the potential association between the inflammatory burden index (IBI) and the prevalence of chronic inflammatory airway diseases (CIAD), as well as mortality rates among individuals diagnosed with CIAD. Methods Participants were sourced from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2010. The IBI was calculated using the formula: IBI = C-reactive protein * neutrophils / lymphocytes. CIAD comprised self-reported asthma, chronic bronchitis, and chronic obstructive pulmonary disease (COPD). Mortality outcomes, including all-cause and respiratory disease mortality, were determined through linked data from the National Death Index (NDI) up to December 2019. Results A total of 27,495 adults were included. IBI was divided into quartiles, with the lowest quartile as the reference group. After adjusting for confounding variables, a positive correlation was observed between higher IBI and increased prevalence of total CIAD (OR = 1.383 [1.215–1.575]), asthma (OR = 1.267 [1.096–1.465]), chronic bronchitis (OR = 1.568 [1.263–1.946]), and COPD (OR = 1.907 [1.311–2.774]). Over a median follow-up of 12.33 [9.92-16.00] years, there were 1221 deaths from all causes and 220 deaths from respiratory disease among 4499 patients with CIAD. Following multivariate adjustments, the fourth quartile was significantly associated with increased risk of all-cause mortality (HR = 2.227 [1.714–2.893]) and respiratory disease mortality (HR = 2.748 [1.383–5.459]) compared to the first quartile of IBI in CIAD participants. Moreover, variable importance analysis using a random survival forest model demonstrated the significance of IBI in predicting mortality from both all-cause and respiratory diseases. Conclusion IBI exhibited an association with the prevalence of CIAD, with higher IBI levels correlating with elevated all-cause and respiratory disease mortality among individuals with CIAD.

Abstract With the discovery of the therapeutic activity of peptides, they have emerged as a promising class of anti-cancer agents due to their specific targeting, low toxicity, and potential for high selectivity. In particular, as peptide-drug conjugates enter clinical, the coupling of targeted peptides with traditional chemotherapy drugs or cytotoxic agents will become a new direction in cancer treatment. To facilitate the drug development of cancer therapy peptides, we have constructed DCTPep, a novel, open, and comprehensive database for cancer therapy peptides. In addition to traditional anticancer peptides (ACPs), the peptide library also includes peptides related to cancer therapy. These data were collected manually from published research articles, patents, and other protein or peptide databases. Data on drug library include clinically investigated and/or approved peptide drugs related to cancer therapy, which mainly come from the portal websites of drug regulatory authorities and organisations in different countries and regions. DCTPep has a total of 6214 entries, we believe that DCTPep will contribute to the design and screening of future cancer therapy peptides.

Abstract Background Deubiquitinating enzymes (DUBs) cleave ubiquitin on substrate molecules to maintain protein stability. DUBs reportedly participate in the tumorigenesis and tumour progression of hepatocellular carcinoma (HCC). OTU deubiquitinase 5 (OTUD5), a DUB family member, has been recognized as a critical regulator in bladder cancer, breast cancer and HCC. However, the expression and biological function of OTUD5 in HCC are still controversial. Results We determined that the expression of OTUD5 was significantly upregulated in HCC tissues. High levels of OTUD5 were also detected in most HCC cell lines. TCGA data analysis demonstrated that high OTUD5 expression indicated poorer overall survival in HCC patients. OTUD5 silencing prominently suppressed HCC cell proliferation, while its overexpression markedly enhanced the proliferation of HCC cells. Mass spectrometry analysis revealed solute carrier family 38 member 1 (SLC38A1) as a candidate downstream target protein of OTUD5. Coimmunoprecipitation analysis confirmed the interaction between OTUD5 and SLC38A1. OTUD5 knockdown reduced and OTUD5 overexpression increased SLC38A1 protein levels in HCC cells. However, OTUD5 alteration had no effect on SLC38A1 mRNA expression. OTUD5 maintained SLC38A1 stability by preventing its ubiquitin-mediated proteasomal degradation. SLC38A1 silencing prominently attenuated the OTUD5-induced increase in HCC cell proliferation. Finally, OTUD5 knockdown markedly suppressed the growth of HCC cells in vivo. Conclusions OTUD5 is an oncogene in HCC. OTUD5 contributes to HCC cell proliferation by deubiquitinating and stabilizing SLC38A1. These results may provide a theoretical basis for the development of new anti-HCC drugs.

Using data independent acquisition (DIA) proteomics, the composition and biological functions of differentially expressed proteins in raw milk during cold storage at 4 ℃ for up to 6 days were investigated. A total of 902 proteins were detected. Among them, 70 and 71 differentially expressed proteins were selected during the early (day 0 vs day 3) and late (day 3 vs day 6) stages of refrigeration, respectively. The differentially expressed proteins played an important role in the response to nerve growth factors and the regulation of cells and tissues at the early stage of refrigeration, and were mainly involved in the biological processes of cells. At the late stage of refrigeration, the differentially expressed proteins could regulate the metabolic processes of carbohydrate and RNA, and mainly participated in the sugar metabolic pathways. Protein-protein interaction (PPI) network analysis indicated that cell division control protein 42 homolog (CDC42) was the hub node protein for both refrigeration periods, which was closely related to phagocytosis. These findings revealed the compositional changes and functional diversity of functions in raw milk proteins during refrigeration, which will provide a theoretical basis for the cold storage of raw milk and be of great significance for the quality control of raw milk.

BackgroundPreoperative immune-inflammatory condition influencing the metabolism of malignancies. We sought to investigate the prognostic value of a novel immune-inflammatory metabolic marker, the monocyte-to-high-density lipoprotein ratio (MHR), in patients with locally advanced pancreatic cancer.MethodsA retrospective analysis was conducted on the clinical data of 118 patients with locally advanced pancreatic cancer and obstructive jaundice who underwent allogeneic vascular replacement pancreaticoduodenectomy in our hospital from Apr. 2011 to Dec. 2023. To assess the predictive capacity of immune-inflammatory metabolic marker, we utilized the area under the receiver operating characteristic curve (AUC-ROC) and assessed the predictive potential of MHR in forecasting outcomes through both univariate and multivariate Cox proportional hazard analyses.ResultsThe area under AUC for MHR in predicting 1-year postoperative survival was 0.714, with an optimal cutoff value of 1.184, yielding a sensitivity of 78.9% and specificity of 66.2%. Based on this cutoff value, patients were divided into a low MHR group (MHR ≤1.184, n = 61) and a high MHR group (MHR >1.184, n = 57). The median survival times for the low and high MHR groups were 27.0 months and 12.0 months, respectively (χ2 = 30.575, p < 0.001), and the median DFS were 18.0 months and 8.0 months, respectively (χ2 = 26.330, p < 0.001). Univariate and multivariate analyses indicated that preoperative MHR, preoperative creatinine, operation duration, and TNM stage were independent predictors of postoperative mortality, while preoperative MHR, preoperative creatinine, and TNM stage were independent predictors of postoperative recurrence risk.ConclusionMHR, as an independent immune-inflammatory metabolic predictor of OS and DFS in patients with advanced PC after pancreaticoduodenectomy. Early monitoring and reduction of MHR may be of great significance in improving prognosis.

PurposeTo evaluate the cost-effectiveness of sotorasib versus docetaxel in non-small cell lung cancer (NSCLC) patients with KRASG12C mutation from the China and United States’social perspective.Materials and MethodsA Markov model that included three states (progression-free survival, post-progression survival, and death) was developed. Incremental cost-effectiveness ratio (ICER), quality-adjusted life-year (QALY), and incremental QALY were calculated for the two treatment strategies. One-way sensitivity analysis was used to investigate the factors that had a greater impact on the model results, and tornado diagrams were used to present the results. Probabilistic sensitivity analysis was performed with 1,000 Monte Carlo simulations. Assume distributions based on parameter types and randomly sample all parameter distributions each time., The results were presented as cost-effectiveness acceptable curves.ResultsThis economic evaluation of data from the CodeBreak 200 randomized clinical trial. In China, sotorasib generated 0.44 QAYL with a total cost of $84372.59. Compared with docetaxel, the ICER value of sotorasib was $102701.84/QALY, which was higher than willingness to pay (WTP), so sotorasib had no economic advantage. In the US, sotorasib obtained 0.35 QALY more than docetaxel, ICER was $15,976.50/QALY, which was more than 1 WTP but less than 3 WTP, indicating that the increased cost of sotorasib was acceptable. One-way sensitivity analysis showed that the probability of sotorasib having economic benefits gradually increased when the cost of follow-up examination was reduced in China. And there was no influence on the conclusions within the range of changes in China. When the willingness to pay (WTP) exceeds $102,500, the probability of sotorasib having cost effect increases from 0% to 49%.ConclusionSotorasib had a cost effect from the perspective in the United States. However, sotorasib had no cost effect from the perspective in China, and only when the WTP exceeds $102,500, the probability of sotorasib having cost effect increases from 0% to 49%.

Abstract Background Smoke exposure is a prevalent and well-documented risk factor for various diseases across different organ systems. Serum neurofilament light chain (sNfL) has emerged as a promising biomarker for a multitude of nervous system disorders. However, there is a notable paucity of research exploring the associations between smoke exposure and sNfL levels. Methods We conducted a comprehensive analysis of the National Health and Nutrition Examination Survey (NHANES) cross-sectional data spanning the years 2013 to 2014. Serum cotinine levels were classified into the following three groups: < 0.05, 0.05–2.99, and ≥ 3 ng/ml. Multiple linear regression models were employed to assess the relationships between serum cotinine levels and sNfL levels. Additionally, we utilized restricted cubic spline analyses to elucidate the potential nonlinear relationship between serum cotinine and sNfL levels. Results A total of 2053 participants were included in our present research. Among these individuals, the mean age was 47.04 ± 15.32 years, and males accounted for 48.2% of the total study population. After adjusting the full model, serum cotinine was positively correlated with sNfl in the second group (β = 0.08, 95%CI 0.01–0.15) and in the highest concentration of serum cotinine (β = 0.10, 95%CI 0.01–0.19) compared to the group with the lowest serum cotinine concentrations. Current smokers, in comparison to non-smokers, exhibited a trend toward elevated sNfL levels (β = 0.07, 95%CI 0.01–0.13). Furthermore, subgroup analyses revealed interactions between serum cotinine levels and different age groups (P for interaction = 0.001) and gender stratification (P for interaction = 0.015) on sNfL levels. Conclusion The study suggested that serum cotinine was significantly and positively associated with sNfl levels in adult participants. Furthermore, current smokers tend to exhibit elevated sNfL levels. This research sheds light on the potential implications of smoke exposure on neurological function impairment and underscores the importance of further exploration in this area.

Objective The Holocene climate of the Tibetan Plateau (TP) is mainly controlled by midlatitude westerlies, the East Asian monsoon, and the Indian monsoon. Previous studies have identified different patterns of Holocene climate change in different regions of the TP. Holocene climate reconstructions for the entire TP help us comprehensively understand the internal linkages of different factors influencing the climate change in the TP. Methods In this paper, we study the Holocene climate in the eastern TP based on 14C dating, lithology and various proxies from the glaciolacustrine strata in the Maoyaba Basin in Litang County, western Sichuan Plateau. Results The Early-Middle Holocene glaciolacustrine sediments covered the last glacial moraines, and then the alluvial-proluvial fans were common during the Late Holocene in the Maoyaba Basin. The grain size of all samples mainly shows a bimodal size distribution after sieving out >2 mm particles. The content of the grain size below medium silt (< 32 μm) is more than 80%, which may be produced by glacial abrasion. The magnetic susceptibility increases obviously in the paleosol, and the appearance of < 1 μm particle size components may indicate that the strong magnetic minerals were generated by pedogenesis. However, the magnetic susceptibility decreased significantly in the glaciolacustrine sediments, which may be related to the dissolution of magnetic minerals in the reducing environment. Conclusion Comprehensive analysis of the sedimentary environment, grain size, magnetic susceptibility, total organic carbon (TOC) and color parameters indicates that the Maoyaba Basin was temperate and dry in the Early Holocene, warm and wet in the Middle Holocene, and temperate and dry in the Late Holocene. This pattern is consistent with the general trend of the Holocene climate in the eastern TP. The paleosol dated to~2 700 cal.yr. B.P. in the Maoyaba Basin indicates a relatively wet period against the background of cooling and a dry climate in the Late Holocene.

BackgroundPrevious research has indicated the potential involvement of the microbiota in smoking-related processes. The present study seeks to examine the relationship between dietary live microbes, as well as probiotic or prebiotic consumption, and serum cotinine levels.MethodsThis study used data from the National Health and Nutrition Examination Survey 1999–2018. Dietary intake information and probiotic/prebiotic intake data was collected through self-reported questionnaires. Participants were stratified into low, medium, and high intake groups according to their consumption of foods with varying microbial content. Multiple linear models were applied to explore the relationships of dietary live microbes, probiotic or prebiotic use with the serum cotinine level.ResultsA total of 42,000 eligible participants were included in the final analysis. The weighted median serum cotinine level was 0.05 (0.01, 10.90) ng/ml. Participants with low, medium, and high dietary microbe intake represented 35.4, 43.6, and 21.0% of the cohort, respectively. Furthermore, participants were stratified into three groups based on their overall consumption of foods with variable microbe contents. The association between dietary live microbe intake and serum cotinine levels remained robust across all models, with medium intake as the reference (Model 2: β = −0.14, 95% CI: −0.20, −0.07; High: β = −0.31, 95% CI: −0.39, −0.22). Moreover, both prebiotic and probiotic use exhibited an inverse relationship with serum cotinine levels (Prebiotic: β = −0.19, 95% CI: −0.37, −0.01; Probiotic: β = −0.47, 95% CI: −0.64, −0.30). Subgroup analyses revealed no discernible interactions between dietary live microbe, prebiotic, probiotic use, and serum cotinine levels.ConclusionOur findings suggest a negative correlation between dietary live microbe intake, as well as non-dietary prebiotic/probiotic consumption, and serum cotinine levels.

ObjectivesWe explored the relationship between blood pressure variability (BPV) during craniotomy aneurysm clipping and short-term prognosis in patients with aneurysmal subarachnoid hemorrhage to provide a new method to improve prognosis of these patients.MethodsWe retrospectively analyzed the differences between patient groups with favorable modified Rankin Scale (mRS ≤ 2) and unfavorable (mRS > 2) prognosis, and examined the association between intraoperative BPV and short-term prognosis.ResultsThe intraoperative maximum systolic blood pressure (SBPmax, p = 0.005) and the coefficient of variation of diastolic blood pressure (DBPCV, p = 0.029) were significantly higher in the favorable prognosis group. SBPmax (OR 0.88, 95%CI 0.80–0.98) and Neu% (OR 1.22, 95%CI 1.03–1.46) were independent influence factors on prognosis. Patients with higher standard deviations of SBP (82.7% vs. 56.7%; p = 0.030), DBP (82.7% vs. 56.7%; p = 0.030), and DBPCV (82.7% vs. 56.7%; p = 0.030) had more favorable prognosis.ConclusionHigher SBPmax (≤180 mmHg) during the clipping is an independent protective factor for a 90-day prognosis. These results highlight the importance of blood pressure (BP) control for improved prognosis; higher short-term BPV during clipping may be a precondition for a favorable prognosis.

Background: Globally, cardiovascular disease (CVD) has emerged as a leading cause of mortality. Bisphenol A (BPA), recognized as one of the most prevalent and widely distributed endocrine-disrupting chemicals (EDCs), has been consistently linked to the progression of CVD. This research centers on unraveling the molecular mechanisms responsible for the toxic effects of BPA exposure on CVD. Key targets and pathways involved in action of BPA on CVD were investigated by network toxicology. Binding abilities of BPA to core targets were evaluated by molecular docking. Methods and results: Based on information retrieved from ChEMBL, DrugBank, and OMIM databases, a total of 27 potential targets were found to be associated with the influence of BPA on CVD. Furthermore, the STRING and Cytoscape software were employed to identify three central genes—ESR1, PPARG, and PTGS2—and to construct both the protein-protein interaction network and an interaction diagram of potential targets. Gene ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes, KEGG) pathway enrichment analyses via WebGestalt revealed key biological processes (BP), cellular components (CC), molecular functions (MF), and pathways, such as the calcium signaling pathway, inflammatory mediator regulation of TRP channels, gap junction, adrenergic signaling in cardiomyocytes, cGMP-PKG signaling pathway, and cAMP signaling pathway, predominantly involved in BPA-induced CVD toxicity. By using molecular docking investigations, it proved that BPA binds to ESR1, PPARG, and PTGS2 steadily and strongly. Conclusion: This study not only establishes a theoretical framework for understanding the molecular toxicity mechanism of BPA in cardiovascular disease (CVD) but also introduces an innovative network toxicology approach to methodically investigate the influence of environmental contaminants on CVD. This methodology sets the stage for drug discovery efforts targeting CVD linked to exposure to endocrine-disrupting chemicals (EDCs).

The physical properties of shale oil reservoirs under overburden pressure are of great significance for reservoir prediction and evaluation during exploration and development. Based on core, thin section, and SEM observations, as well as test data such as XRD, TOC, and porosity and permeability under pressure conditions, this study systematically analyzes the variation of physical properties of different lithofacies shales in the Jiyang depression and the influence of rock fabric on the physical variation under pressure. The porosity and permeability of shale samples significantly decrease under pressure. According to the phased reduction in porosity and permeability, the pressurization process is divided into three pressure stages: low pressure (15 MPa). The reduction of porosity is fastest in the low-pressure stage and slowest in the medium-pressure stage. The reduction of permeability is fastest in the low-pressure stage and the slowest in the high-pressure stage. The rock fabric has a significant impact on porosity and permeability under pressure conditions. The permeability of laminated shale and bedded shale is higher than that of massive shale under pressure, and the permeability loss rate is lower than that of massive shales. Especially under lower pressure, the difference can be 10–20 times. In addition, the reduction rate of porosity and permeability under pressure is negatively correlated with felsic minerals content, which is positively correlated with carbonate minerals content and clay minerals content. The contribution of clay minerals to the porosity reduction rate is dominant, followed by carbonate minerals. The contribution of carbonate minerals to the permeability reduction rate is dominant, followed by clay minerals. The TOC content has no significant impact on the porosity and permeability of shales under pressure in the study due to the low maturity.

Abstract Background The death burden attributable to modifiable risk factors is key to colorectal cancer (CRC) prevention. This study aimed to assess the prevalence and regional distribution of attributable CRC death burden worldwide from 1990 to 2019. Methods We extracted data from the Global Burden of Disease Study in 2019 and assessed the mortality, age‐standardized death rate (ASDR), population attributable fractions, and time trend in CRC attributable to risk factors by geography, socio‐demographic index (SDI) quintile, age, and sex. Results Over the past 30 years, from high to low SDI region, the number of deaths increased by 46.56%, 103.55%, 249.64%, 231.89%, 163.11%, and the average annual percentage change (AAPC) for ASDR were −1.06%, −0.01%, 1.32%, 1.19%, and 0.65%, respectively. ASDR in males was 1.88 times than in females in 2019; ASDR in males showed an increasing trend (AAPC 0.07%), whereas ASDR in females showed a decreasing trend (AAPC −0.69%) compared to figures in 1990. In 2019, from high to low SDI region, the 15–49 age group accounted for 3%, 6%, 10%, 11%, and 15% of the total population; dietary and metabolic factors contributed 43.4% and 20.8% to CRC‐attributable death worldwide. From high to low SDI region, ASDRs caused by dietary and metabolic factors increased by −23.4%, −5.5%, 25.8%, 29.1%, 13.5%, and 1.4%, 33.3%, 100.8%, 128.4%, 77.7% respectively, compared to 1990. Conclusions The attributable CRC death burden gradually shifted from higher SDI to lower SDI regions. The limitation in males was more significant, and the gap is expected to be further expanded. In lower SDI regions, the death burden tended to affect younger people. The leading cause of CRC‐attributable deaths was the inadequate control of dietary and metabolic risk factors.

Abstract Biomimetic intelligent polymeric hydrogel actuators with cooperative fluorescence‐color switchable behaviors are expected to find great potential applications in soft robotics, visual detection/display, and camouflage applications. However, it remains challenging to realize the spatial manipulation of synergistic shape/color‐changing behaviors. Herein, we report an interfacial supramolecular assembly (ISA) approach that enables the construction of robust fluorescent polymeric hydrogel actuators with spatially anisotropic structures. On the basis of this ISA approach, diverse 2D/3D soft fluorescent hydrogel actuators, including chameleon‐ and octopi‐shaped ones with spatially anisotropic structures, were facilely assembled from two different fluorescent hydrogel building blocks sharing the same physically cross‐linked agar network. Spatially control over synergistic shape/color‐changing behaviors was then realized in one single anisotropic hydrogel actuator. The proposed ISA approach is universal and expected to open promising avenues for developing powerful bioinspired intelligent soft actuators/robotics with selective spatial shape/color‐changing behaviors.

ABSTRACTPrevious studies have profiled the gut microbiota among psoriatic patients compared to that among healthy individuals. However, a comprehensive understanding of the magnitude, direction, and detailed compositional and functional profiles remains limited. Additionally, research exploring the gut microbiota in the context of both plaque psoriasis (PsO) and psoriatic arthritis (PsA) is lacking. To assess the taxonomic and functional characteristics of the gut microbiota in PsO and PsA patients and investigate potential links between the gut microbiota and disease pathogenesis. We collected fecal samples from 70 psoriatic patients (44 PsO and 26 PsA) and 25 age- and gender-matched healthy controls (HC) and employed deep metagenomic sequencing to characterize their gut microbiota. We noted significant alternations in the gut microbiota compositions of both PsO and PsA patients compared to those of HC. Despite limited effect sizes in alpha diversity (12.3% reduction of microbial richness but unchanged evenness in psoriatic patients) and beta diversity (disease accounts for 3.5% of total variations), we consistently observed substantial reductions of Eubacterium rectale in both PsO and PsA patients, with PsA patients exhibiting even lower levels of E. rectale than PsO patients. Additionally, two Alistipes species were also depleted in psoriatic patients. These microorganisms are known to play crucial roles in carbohydrate metabolism pathways, mainly producing short-chain fatty acids with anti-inflammatory effects. Overall, our observations supplemented the profiling of altered gut microbiota in patients with PsO and PsA at the species level and described a link between the dominant short-chain fatty acid-producing bacterial species and systemic immunity in psoriatic patients.IMPORTANCEIn this observational clinical study with sufficient sample size and metagenomic sequencing to profile the gut microbiota, we identified consistent signals of the depleted abundance of Eubacterium rectale and related functional genes among psoriatic patients, including those with psoriatic arthritis. E. rectale may serve as an ecologically important functional unit in the gut microbiota, holding potential as a diagnostic marker and target for therapeutic interventions to achieve lasting effects. Our findings provide comprehensive gut microbiota profiling in psoriasis, resolving previous contradictions and generating new hypotheses for further investigation. These insights may significantly impact psoriasis management and related conditions.

Hydrogels have emerged as promising biomaterials for nerve regeneration due to their adjustable properties, structural resemblance to the extracellular matrix, and ability to promote cell adhesion and proliferation. This comprehensive review discusses the advantages, challenges, and future directions of various functional hydrogels. Advanced technologies for fabricating Multistructured hydrogel, including injectable hydrogels, hydrogel microspheres, fibrous hydrogels, 3D printing hydrogels, nanogels, stem cell-loaded hydrogels, electrical hydrogels, ultrasound hydrogels, and magnetic hydrogels, have been developed and studied for nerve regeneration. These technologies demonstrate the versatility of hydrogels in neural tissue repair. However, challenges such as biocompatibility, degradation rates, and scaffold design need to be addressed. Interdisciplinary research is necessary to develop innovative hydrogel systems that overcome these challenges and realize the potential of hydrogels for nerve regeneration. This review provides valuable insights into advanced hydrogel technologies and highlights their potential in regenerative medicine, particularly in neural regeneration. Researchers can use this knowledge to refine therapeutic approaches involving hydrogels for enhancing nerve regeneration.

Abstract Acute pulmonary embolism (APE) is a potentially fatal disease. Early risk stratification is essential to determining appropriate treatment. We aimed to investigate the predictive value of the Naples Prognostic Score (NPS) for 30-day all-cause mortality in patients with APE. In this retrospective analysis, 325 hospitalized patients with APE were divided into Groups 0 (n = 131), 1 (n = 153), and 2 (n = 41) according to the NPS. The primary outcome event was all-cause mortality during 30 days of follow-up from the day of admission. The correlation between NPS, clinical features, and outcomes in each group was evaluated. The patients were divided into two groups, survivor (n = 294) and nonsurvivor (n = 31), according to their prognosis. The results of the comparison between the three NPS groups revealed that patients with older age, faster heart rate, lower systolic blood pressure, low albumin and total cholesterol levels, high neutrophil to lymphocyte ratio (NLR), low lymphocyte-to-monocyte ratio (LMR), right heart dilatation, heart failure, malignancy, and lower extremity venous thrombosis had significantly higher 30-day all-cause mortality (P

Abstract Background Circular RNA RHOT1 (circRHOT1) plays crucial roles in tumorigenesis by competing with microRNAs. It is largely abundant in tumor cell-derived exosomes. Meanwhile, cancer-derived exosomes participate in diverse biological processes. However, the expression patterns and functions of exosomal circRHOT1 in breast cancer remain unknown. This study is aimed to investigate and elucidate the exosomal circRHOT1/miR-204-5p/PRMT5 axis in breast cancer. Methods The exosomes derived from serum samples of breast cancer patients and breast cancer cell lines were characterized using transmission electron microscopy and Western blot. MTT, colony formation, wound healing, and transwell assays were utilized to analyze cell proliferation, migration, and invasion of breast cancer cells. Flow cytometry was used for apoptosis analysis. The bioinformatics method was employed to screen differentially expressed novel circRNAs and predict the microRNA targets of circRHOT1. Dual-luciferase reporter gene assays were performed to verify their direct interaction. Finally, Xenograft experiments were used to investigate the effect of exosomal circRHOT1 on tumor growth in vivo. Results CircRHOT1 exhibited significantly high expression in exosomes derived from the serum of breast cancer patients and breast cancer cell lines, which suggested its potential diagnostic value. Breast cancer-derived exosomes promoted the cell proliferation, migration, invasion, and epithelial-mesenchymal transition of breast cancer cells while inhibiting apoptosis. However, exosomes with downregulated circRHOT1 inhibited the growth of co-cultured cells. Mechanistically, circRHOT1 acted as a sponge of miR-204-5p and promoted protein arginine methyltransferase 5 (PRMT5) expression. Moreover, miR-204-5p inhibitor and pcPRMT5 could reverse the tumor suppressive effects mediated by circRHOT1-knockdown. Furthermore, treatment with exosomes derived from breast cancer cells with circRHOT1 knockdown attenuated tumor growth in tumor-bearing nude mice, which was accompanied by a reduction in PRMT5 expression and an enhancement of miR-204-5p expression. Conclusion The exosomal circRHOT1 may promote breast cancer progression by regulating the miR-204-5p/PRMT5 axis. The current study strengthens the role of circRHOT1, miR-204-5p, and PRMT5 in breast cancer development and provides a potential treatment strategy for breast cancer.

Abstract Adding adipose cells to cell-cultured meat can provide a distinctive aroma and juicy texture similar to real meat. However, a significant challenge still exists in obtaining seed cells that can be propagated for long periods, maintain their adipogenic potential, and reduce production costs. In this study, we present a cell strain derived from immortalized porcine preadipocytes that can be subculture for over 40 passages without losing differentiation capacity. This cell strain can be differentiated within 3D bioscaffolds to generate cell-cultured fat using fewer chemicals and less serum. Additionally, it can be expanded and differentiated on microcarriers with upscaled culture to reduce costs and labor. Moreover, it can co-differentiate with muscle precursor cells, producing a pattern similar to real meat. Therefore, our cell strain provides an exceptional model for studying and producing cell-cultured fat.

Abstract Background No consensus currently exists regarding the optimal protocol for repetitive transcranial magnetic stimulation (rTMS) treatment of upper-extremity motor dysfunction after stroke. Studies have shown that combined low- and high-frequency stimulation (LF-HF-rTMS) of the bilateral cerebral hemispheres is more effective than sham stimulation or stimulation of one cerebral hemisphere alone in treating motor dysfunction in the subacute stage of stroke. The efficacy of this protocol in the convalescence phase of stroke has rarely been reported, and its mechanism of action has not been clarified. In this study, we designed a prospective, single-blind, randomized controlled trial to investigate the efficacy and safety of different stimulation regimens for the treatment of upper extremity motor disorders in patients with convalescent stage stroke and aimed to explore the underlying mechanisms based on biomarkers such as brain-derived neurotrophic factor (BDNF). Methods Seventy-six subjects will be randomly divided into combined, low-frequency, high-frequency, and control groups based on the proportion of 1:1:1:1, with 19 cases in each group. All groups will have conventional rehabilitation, on top of which the combined group will receive 1 Hz rTMS in the unaffected hemisphere and 10 Hz rTMS in the affected hemisphere. The low-frequency group will be administered 1 Hz rTMS in the unaffected hemisphere and sham stimulation in the contralateral hemisphere. The high-frequency group will be administered 10 Hz rTMS in the affected hemisphere and contralateral sham stimulation. The control group will receive bilateral sham stimulation. Assessments will be performed at baseline, after 2 weeks of treatment, and at post-treatment follow-up at week 6. The primary outcomes are FMA-UE (Fugl-Meyer assessment-upper extremity), latency, and serum BDNF levels. The secondary outcomes are the National Institute of Health Stroke Scale (NIHSS), Brunnstrom staging (BS), modified Ashworth scale (MAS), Modified Barthel Index (MBI), central motor conduction time (CMCT), precursor proteins of mature BDNF (proBDNF), and matrix metalloproteinase-9 (MMP-9) levels. Adverse events, such as headaches and seizures, will be recorded throughout the study. Discussion The findings of this study will help develop optimal stimulation protocols for motor recovery in stroke patients and identify biomarkers that respond to post-stroke motor rehabilitation, for better guidance of clinical treatment. Trial registration The study protocol was passed by the Medical Research Ethics Committee of the General Hospital of Ningxia Medical University on January 1, 2022 (no. KYLL-2021–1082). It was registered into the Chinese Clinical Trials Registry on May 22, 2022 (no. ChiCTR2200060201). This study is currently in progress. Graphical Abstract

Abstract Xrv proteins are a group of regulators in Xanthomonas spp., belonging to the histone-like nucleoid-structuring (H-NS) proteins of Gram-negative bacteria. The rice bacterial leaf streak pathogen Xanthomonas oryzae pv. oryzicola (Xoc) harbors three Xrv proteins, the XrvA, XrvB, and XrvC. Here, we report that in Xoc, the XrvB but not XrvA and XrvC is involved in negative regulation of the type III secretion system (T3SS) encoded by hrp genes. As with other Xanthomonas spp., the T3SS is an essential virulence determinant of Xoc and the expression of the hrp genes in Xoc is controlled by the HrpG/HrpX regulatory cascade. HrpG positively regulates the expression of HrpX, which in turn activates the transcription of the hrp genes. We provide evidences to demonstrate that the XrvB binds to the promoter region of hrpG and represses its transcription. Furthermore, we found that XrvB production was induced in the Xoc cells cultured in a nutrient-rich medium compared to a hrp-inducing minimal medium. We also found that in Xoc, the hrpG expression level is inversely correlated with the content of XrvB, and XrvB occupancy at hrpG promoter region is positively correlated with XrvB levels. Our data suggest that XrvB is a determinative factor controlling the expression levels of HrpG. In addition, mutation analysis revealed that the Xoc XrvB also plays positive roles in regulating bacterial growth, cell motility, and stress tolerance. Our findings provide important insights into the molecular mechanism of T3SS expression regulation in Xoc.

Abstract Background Heart failure is closely correlated with diabetic cardiomyopathy (DCM) and can lead to mortality. Celastrol has long been utilized for the treatment of immune and inflammatory disorders. However, whether celastrol would exert protective effects on DCM has not been determined. This work aimed to explore the protective actions of celastrol on DCM and unravel the underlying mechanisms involved. Methods A DCM model was constructed in mice by intraperitoneal administration of streptozotocin. ELISA and echocardiography were performed to examine myocardial injury markers and cardiac function, respectively. Morphological changes and fibrosis were assessed using H&E staining and Masson’s staining. Inflammatory cytokines and fibrotic markers were detected by ELISA and RT-PCR. Endothelial nitric oxide synthase, apoptosis, and reactive oxygen species were detected by microscopic staining. Network pharmacology approaches, molecular docking analysis, ELISA, and Western blot were used for mechanism studies. Results Celastrol alleviated diabetes-induced cardiac injury and remodeling. Celastrol also suppressed diabetes-induced production of inflammatory cytokines and reactive oxygen species, as well as cardiomyocyte apoptosis. The cardioprotective effects of celastrol were associated with its inhibition on the angiotensin-converting enzyme / angiotensin II / angiotensin II receptor type 1 signaling pathway. Conclusion Celastrol exhibits significant potential as an effective cardioprotective drug for DCM treatment. The underlying mechanisms can be attributed to the blockage of celastrol on the angiotensin-converting enzyme signaling pathway.

Phosphorus deficiency severely limits crop yields and hinders sustainable agricultural development. Phosphate-solubilizing bacteria (PSB) are beneficial for crop growth because they enhance the uptake and utilization of phosphorus. This study explored the phosphorus-solubilizing, IAA-producing, nitrogen-fixing, potassium-solubilizing, and siderophore-producing abilities of three bacterial strains (Pantoea sp. J-1, Burkholderia cepacia Z-7, and Acinetobacter baumannii B-6) screened from the maize rhizosphere. A pot experiment was also conducted to explore the role of screened PSB in the growth of maize. Finally, the effects of the PSB on the physicochemical properties, enzyme activities, and microbial community structure of maize rhizosphere soil were analyzed. The results showed that strain Z-7 had the strongest abilities phosphorus solubilization, nitrogen fixation, potassium solubilization, and siderophore production, while strain J-1 exhibited the highest yield of IAA. The application of PSB promoted the growth of maize plants to different extents. Among the different treatments, the mixed bacterial treatment (J-1 + Z-7 + B-6) had the most potent growth promotion effect, and the consortium treatment significantly enhanced the activity of soil phosphatase. Soil pH, total phosphorus (TP), total potassium (TK), available phosphorus (AP), NH4+-N, and NO3−-N are key factors for the growth of maize plants. In addition, PSB significantly altered the microbial community structure in the maize rhizosphere soil, and the relative abundance of Proteobacteria increased by 16.07–69.10% compared to the control. These PSB have obvious growth-promoting abilities, with the potential to enhance crop productivity as excellent candidate strains for the development of biological fertilizers.

A-type granites have been the subject of considerable interest due to their distinct anorogenic geological background. The A-type and arc-related granites are crucial in deciphering the evolution of the ocean closure and continental collision in the Tibet Plateau. The demise of the Bangong–Nujiang suture zone (BNSZ) and the Yarlung–Tsangpo suture zone was accompanied by the emplacement of volumes of syn-collisional and post-collisional granites. Controversy has persisted regarding the contribution of the collisional granites within the Lhasa Block to the growth of the Tibetan Plateau. This study provides key evidence about the evolution of the Lhasa Block and Bangong–Nujiang Ocean (BNO) by the newly documented 1200 km long, Early Cretaceous A-type acidic magmatic belt. The resolution was achieved through the utilization of petrology, whole-rock geochemistry, zircon U-Pb geochronology, and in situ zircon Hf isotope analysis of the Burshulaling Granites in the eastern segment and previous existing data in the central and western segment of the Lhasa Block. The Burshulaling Granites are characterized as peraluminous, high-K calc-alkaline series, indicating a post-collision setting with high temperature and low pressure. The zircon grains from two granite samples yield 206Pb/238U ages of 115–113 Ma. In situ zircon Hf analyses with 206Pb/238U ages give εHf(t) of −6.2–0.6, showing prominent characteristics of crust-mantle interaction. Granites from east to west exhibit whole-rock geochemical and geochronological similarities that fall within the well-constrained Early Cretaceous time frame (117–103 Ma) and track post-collisional A-type acidic magmatic belt along BNSZ. We argue that this magmatism resulted from slab break-off or orogenic root detachment, leading to melting and mixing of the lower crust. Meanwhile, this study indicates the existence of the Bangong–Nujiang Ocean southward subduction or a collapse following an Andean-type orogen.

Porcine circovirus type 2 (PCV2) is the etiological agent of PCV2-associated diseases that pose a serious threat to the swine industry. PCV2 capsid (Cap) protein has been shown to interact with DEAD-box RNA helicase 21 (DDX21), an important protein that regulates RNA virus replication. However, whether the interaction between DDX21 and the PCV2 Cap regulates PCV2 replication remains unclear. Herein, by using western blotting, interaction assays, and knockdown analysis, we found that PCV2 infection induced the cytoplasmic relocation of DDX21 from the nucleolus in cultured PK-15 cells. Moreover, the nuclear localization signal (NLS) of PCV2 Cap interacted directly with DDX21. The NLS of PCV2 Cap and 763GSRSNRFQNK772 residues at the C-terminal domain (CTD) of DDX21 were essential for the dual interaction. Upon shRNA-mediated DDX21 depletion in PK-15 cells, we observed impaired PCV2 replication via a lentivirus-delivered system, as evidenced by decreased levels of viral protein expression and virus production. In contrast, the replication of PCV2 increased in transiently DDX21-overexpressing cells. Our results indicate that DDX21 interacts with PCV2 Cap and plays a crucial role in virus replication. These results provide a reference for developing novel potential targets for prevention and control of PCV2 infection.

The new development pattern has identified two key avenues for the sustained advancement of high-quality agricultural and rural development: digitalisation and low-carbon development. The measurement of the digital economy and the agricultural carbon emission performance, and their spatial and temporal heterogeneity, is a crucial step in promoting the spatial coordination and sustainable development of digitalisation and low-carbon agriculture. This paper employs the entropy value method, SBM model, and coupling coordination degree model to investigate the coupling coordination measurement and spatial-temporal heterogeneity of the performance of the digital economy and agricultural carbon emissions. The data used are provincial panel data from 2013 to 2021. The simulation results demonstrate that, between 2013 and 2021, the digital economy of all provinces exhibited varying degrees of growth, yet the development of the digital economy between provinces exhibited a more pronounced tendency to diverge. Concurrently, the agricultural carbon emission efficiency in China exhibited a fluctuating upward trend. The development of the digital economy and the efficiency of agricultural carbon emission were found to be highly coupled. Their coupling and coordination relationship showed a downward trend followed by an upward trend. In general, it is suggested that we should increase investment in digital economy infrastructure and technology, promote digital agricultural applications, strengthen policy guidance and financial support, establish a coupling coordination mechanism and strengthen farmers' digital literacy and environmental awareness.

This study constructed a multidimensional indicator system to evaluate spatio-temporal heterogeneity of China's import and export trade of 31 provinces from 2000 to 2022. This study describes the distribution of China's import and export trade by using location Gini coefficient and exploratory spatial analysis. Additionally, Multiple linear regression was used to ascertain the extent of contribution by various factors on the spatio-temporal heterogeneity of import and export trade. The simulation results show that inter-provincial import and export trade displayed distinct spatio-temporal differentiation characteristics with a prominent east-to-west disparity from 2000 to 2022. The trade links between various regions of the country have gradually strengthened, with a corresponding high correlation to the level of economic development. GDP, financial expenditure, freight transportation volume, technology market turnover, foreign investment, and disposable income of all residents, significantly influence the per capita export and import volume. In general, it is suggested that China and developing countries should take effective measures to promote balanced trade development, strengthen regional cooperation and coordination, and promote green trade and sustainable development.

The pursuit of enhancing NiTi superelasticity through laser powder bed fusion (L-PBF) and [001] texture creation poses a challenge due to increased susceptibility to hot cracking in the resulting microstructure with columnar grains. This limitation restricts NiTi's application and contributes to material waste. To overcome this, we introduce a pioneering approach: utilising spark plasma sintering (SPS) to heal directional cracks in [001] textured L-PBF NiTi shape memory alloy. Diffusion bonding and oxygen utilisation for Ti2NiOx formation was found to successfully heal the cracks. SPS enhances mechanical properties, superelasticity at higher temperatures, and two-way shape memory strain during thermomechanical cycling. This work provides an alternative solution for healing cracks in L-PBF parts, enabling the sustainable reuse of cracked materials. By implementing SPS, this approach effectively addresses hot cracking limitations, expanding the application potential of L-PBF NiTi parts while improving their functional and mechanical properties.

AbstractBackground Occupational-related cancers are a substantial global health issue. The largest proportion of occupational-related cancers is tracheal, bronchus, and lung (TBL) cancer. This study aimed to explore the geographical and temporal trends in occupational carcinogens related to TBL cancer.Methods Data on TBL cancer attributable to occupational carcinogens were collected from the Global Burden of Disease Study 2019. Numbers and age-standardized rates (ASRs) of deaths, disability-adjusted life years (DALYs), and corresponding average annual percentage change (AAPC) were evaluated and stratified by geographic location, socio-demographic index (SDI) quintiles, age, and sex.Results Globally, ASRs of deaths and DALYs in TBL cancer attributable to occupational carcinogens showed a downward trend (AAPC = − 0.69%, − 1.01%) while increases were observed in the low, low-middle, and middle SDI quintiles. Although males accounted for 82.4% and 81.5% of deaths and DALYs in 2019, respectively, it showed an upward trend of ASRs in females (AAPC = 0.33%, 0.02%). Occupational exposure to asbestos, silica and diesel engine exhaust were the top three causes of age-standardized TBL cancer deaths and DALYs. Over the past three decades, the percentage of age-standardized TBL cancer deaths and DALYs attributable to occupational asbestos and silica exposure decreased by 18.24, 6.71 and 20.52%, 4.00% globally, but increased significantly in lower SDI regions, while the burden attributable to occupational diesel engine exhaust exposure increased by 32.76, 37.23% worldwide.Conclusions Occupational exposure remains an important risk factor for TBL cancer. The burden of TBL cancer attributable to occupational carcinogens showed obvious heterogeneity which decreased in higher SDI but increased in lower SDI regions. The burden of males was significantly higher than females, but the females showed an increasing trend. Occupational exposure to asbestos was the main causes of the burden. Therefore, effective prevention and control measures tailored to local conditions are necessary.

Objectives: This paper aims to segment customers in the apparel retail industry using data mining techniques. Methods: First, a customer segmentation model was constructed, and then the K-means algorithm was used to classify customers based on indicators from the model. The classification effectiveness was enhanced by introducing indicator feature weights. A case study was also conducted. Findings: When the value of K was 4, the K-means algorithm achieved the best classification performance. The improved K-means algorithm outperformed the traditional K-means algorithm in terms of classification effectiveness. The improved K-means algorithm categorized customers into premium customers, important customers, regular customers, and churned customers. Different marketing suggestions were proposed to manufacturers. Novelty: The novelty of this article lies in the introduction of feature weights for indicators, which allows for a distinction between their importance and improves classification effectiveness. Doi: 10.28991/HIJ-2023-04-02-05 Full Text: PDF

Abstract Background Irritable bowel syndrome (IBS) is a chronic disorder of the gut-brain axis with significant morbidity. Triptolide, an active compound extracted from Tripterygium wilfordii Hook F (TwHF), has been widely used as a major medicinal herb in the treatment of inflammatory disease. Methods The chronic-acute combined stress (CAS) stimulation was used to establish IBS rat model. The model rats were then gavaged with triptolide. Forced swimming, marble-burying, fecal weight and abdominal withdrawal reflex (AWR) score were recorded. Pathologic changes in the ileal and colonic tissues were validated by hematoxylin and eosin staining. The inflammatory cytokines and Ornithine Decarboxylase-1 (ODC1) in the ileal and colonic tissues were performed by ELISA and WB. Results Triptolide didn’t have antidepressant- and antianxiety- effects in rats caused by CAS, but decreased fecal weight and AWR score. In addition, Triptolide reduced the release of IL-1, IL-6, and TNF-α and the expression of ODC1 in the ileum and colon. Conclusion The therapeutic efficacy of triptolide for IBS induced by CAS was revealed in this study, which may be related to the reduction of ODC1.

Periodically poled lithium niobate on insulator (PPLNOI) offers an admirably promising platform for the advancement of nonlinear photonic integrated circuits (PICs). In this context, domain inversion engineering emerges as a key process to achieve efficient nonlinear conversion. However, periodic poling processing of thin-film lithium niobate has only been realized on the chip level, which significantly limits its applications in large-scale nonlinear photonic systems that necessitate the integration of multiple nonlinear components on a single chip with uniform performances. Here, we demonstrate a wafer-scale periodic poling technique on a 4-inch LNOI wafer with high fidelity. The reversal lengths span from 0.5 to 10.17 mm, encompassing an area of ~1 cm2 with periods ranging from 4.38 to 5.51 μm. Efficient poling was achieved with a single manipulation, benefiting from the targeted grouped electrode pads and adaptable comb line widths in our experiment. As a result, domain inversion is ultimately implemented across the entire wafer with a 100% success rate and 98% high-quality rate on average, showcasing high throughput and stability, which is fundamentally scalable and highly cost-effective in contrast to traditional size-restricted chiplet-level poling. Our study holds significant promise to dramatically promote ultra-high performance to a broad spectrum of applications, including optical communications, photonic neural networks, and quantum photonics.

Abstract Introduction Conventional etiological detection and pathogenic antibody methods make it challenging to identify the atypical pathogens among the community‐acquired pneumonia (CAP). Metagenomic next‐generation sequencing (mNGS) could rapidly detect all potentially infectious diseases and identifies novel or potential pathogens. Methods Eighteen patients diagnosed with atypical CAP were enrolled in this retrospective study, including nine Chlamydia psittaci pneumonia (C. p), four Legionella pneumonia (L. p) and five Mycoplasma pneumonia (M. p). We simultaneously tested bronchoalveolar lavage fluid (BALF) samples for conventional microbiological methods and mNGS, and blood specimens were analysed. We also collected and compared baseline and clinical characteristics and treatment responses. Results Patients with C. p and L. p had similar symptoms, including fever, cough, headache, dyspnoea, asthenia, shivering and headache, compared with M. p, whose symptoms were slight. C. p and L. p usually showed multiple lobar distributions with pleural effusion. Serologic testing indicated that L. p had higher levels of white blood cells (WBCs), neutrophils, C‐reactive protein (CRP), procalcitonin (PCT), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and creatinine compared with M. p and L. p (p

Abstract Background Rhizosphere soil physicochemical, endophytic fungi have an important role in plant growth. A large number of endophytic fungi play an indispensable role in promoting plant growth and development, and they can provide protection for host plants by producing a variety of secondary metabolites to resist and inhibit plant pathogens. Due to the terrain of Gansu province is north–south and longitudinal, different climatic conditions, altitude, terrain and growth environment will affect the growth of Codonopsis pilosula, and the changes in these environmental factors directly affect the quality and yield of C. pilosula in different production areas. However, In C. pilosula, the connection between soil nutrients, spatiotemporal variation and the community structure of endophytic fungi isolated from C. pilosula roots has not been well studied. Results Seven hundred six strains of endophytic fungi were obtained using tissue isolation and the hyphaend-purification method from C. pilosula roots that picked at all seasons and six districts (Huichuan, HC; Longxi, LX; Zhangxian, ZX; Minxian, MX; Weiyuan, WY; and Lintao, LT) in Gansu Province, China. Fusarium sp. (205 strains, 29.04%), Aspergillus sp. (196 strains, 27.76%), Alternaria sp. (73 strains, 10.34%), Penicillium sp. (58 strains, 8.22%) and Plectosphaerella sp. (56 strains, 7.93%) were the dominant genus. The species composition differed from temporal and spatial distribution (Autumn and Winter were higher than Spring and Summer, MX and LT had the highest similarity, HC and LT had the lowest). physical and chemical of soil like Electroconductibility (EC), Total nitrogen (TN), Catalase (CAT), Urease (URE) and Sucrase (SUC) had significant effects on agronomic traits of C. pilosula (P

Abstract Introduction Several factors may lead to increased postoperative pain sensitivity, of which remifentanil-induced hyperalgesia (RIH) is one of the main factors. High-dose remifentanil exposure during anesthesia may induce RIH. Esketamine may prevent RIH by antagonizing N-methyl-d-aspartate (NMDA) receptors, thereby reducing the postoperative pain sensitivity. This study examined the effects of different esketamine doses on pain sensitivity in patients undergoing thyroidectomy and determined the optimal dose. Methods This study included 117 patients who received elective thyroidectomy. They were randomized into four groups: saline group (group C), esketamine 0.2 mg·kg−1 group (group RK1), esketamine 0.4 mg·kg−1 group (group RK2), and esketamine 0.6 mg·kg−1 group (group RK3). Five minutes before anesthesia induction, the same volume of study drugs were injected respectively in groups C, RK1, RK2, and RK3. Remifentanil was pumped at the same rate of 0.3 µg·kg−1·min−1 during surgery to ensure uniformity. This study’s primary outcomes were the mechanical pain thresholds measured before surgery, as well as at 30 min, 6 h, 24 h, and 48 h after surgery. Hyperalgesia, rescue analgesia, numerical rating scale (NRS) score, and adverse reactions were recorded. Results Compared with baseline, the mechanical pain threshold was significantly decreased in group C [(94.67 ± 22.85) versus (112.00 ± 36.62) versus (161.33 ± 53.28) g, P

Synchrotron radiation based dynamic micro-computed tomography (micro-CT) is a powerful technique available at synchrotron light sources for investigating evolving microstructures. Wet granulation is the most widely used method of producing pharmaceutical granules, precursors to products like capsules and tablets. Granule microstructures are known to influence product performance, so this is an area for potential application of dynamic CT. Here, lactose monohydrate (LMH) was used as a representative powder to demonstrate dynamic CT capabilities. Wet granulation of LMH has been observed to occur on the order of several seconds, which is too fast for lab-based CT scanners to capture the changing internal structures. The superior X-ray photon flux from synchrotron light sources makes sub-second data acquisition possible and well suited for analysis of the wet-granulation process. Moreover, synchrotron radiation based imaging is non-destructive, does not require altering the sample in any way, and can enhance image contrast with phase-retrieval algorithms. Dynamic CT can bring insights to wet granulation, an area of research previously only studied via 2D and/or ex situ techniques. Through efficient data-processing strategies, dynamic CT can provide quantitative analysis of how the internal microstructure of an LMH granule evolves during the earliest moments of wet granulation. Here, the results revealed granule consolidation, the evolving porosity, and the influence of aggregates on granule porosity.

Visualization of low-density tissue scaffolds made from hydrogels is important yet challenging in tissue engineering and regenerative medicine (TERM). For this, synchrotron radiation propagation-based imaging computed tomography (SR-PBI-CT) has great potential, but is limited due to the ring artifacts commonly observed in SR-PBI-CT images. To address this issue, this study focuses on the integration of SR-PBI-CT and helical acquisition mode (i.e. SR-PBI-HCT) to visualize hydrogel scaffolds. The influence of key imaging parameters on the image quality of hydrogel scaffolds was investigated, including the helical pitch (p), photon energy (E) and the number of acquisition projections per rotation/revolution (Np), and, on this basis, those parameters were optimized to improve image quality and to reduce noise level and artifacts. The results illustrate that SR-PBI-HCT imaging shows impressive advantages in avoiding ring artifacts with p = 1.5, E = 30 keV and Np = 500 for the visualization of hydrogel scaffolds in vitro. Furthermore, the results also demonstrate that hydrogel scaffolds can be visualized using SR-PBI-HCT with good contrast while at a low radiation dose, i.e. 342 mGy (voxel size of 26 µm, suitable for in vivo imaging). This paper presents a systematic study on hydrogel scaffold imaging using SR-PBI-HCT and the results reveal that SR-PBI-HCT is a powerful tool for visualizing and characterizing low-density scaffolds with a high image quality in vitro. This work represents a significant advance toward the non-invasive in vivo visualization and characterization of hydrogel scaffolds at a suitable radiation dose.

Electrochemical tests and surface analysis measurements were performed to study the corrosion behavior in a 0.9 wt.% NaCl solution at 37 °C of three NiTi shape memory alloys fabricated by laser-powder bed fusion (L-PBF). The passive film characteristics and corrosion resistance of L-PBF NiTi showed different features as a function of their preparation process settings. The passivation rate for L-PBF NiTi surfaces including defects, such as keyhole pores and cracks which showed high electrochemical activity accelerating the passivation reaction process, was higher in the early stages of immersion, but the corrosion resistance provided by such a rapidly formed passive film containing higher defect density is lower than that for an initially defect-free surface. The thickness of the passive film including a higher defect density does not necessarily relate to the corrosion resistance. The L-PBF NiTi prepared at a linear energy density of 0.2 J/m and volumetric energy density of 56 J/mm3 shows the least defects. Also, an outer Ti-rich and inner Ni-rich dense and corrosion protective passive film could be obtained for these L-PBF NiTi samples, which also results in a relatively low Ni ion release rate. A passive film model based on thickness, composition and defect density properties as a function of processing conditions is proposed to explain the difference in corrosion resistance of the various L-PBF NiTi.

Colorectal cancer (CRC) is one of the most common malignancies, and at the initial visit, most patients are diagnosed with metastatic CRC (mCRC). However, immunotherapy is only and highly effective in a very small proportion of patients with mCRC having mismatch repair defect (dMMR)/high microsatellite instability, and the majority of the patients with mCRC having mismatch repair proficient (pMMR)/microsatellite stability (MSS) cannot benefit from it. At present, many clinical studies of immunotherapy combined with tyrosine kinase inhibitors (TKIs) are trying to regulate the immune microenvironment of pMMR/MSS mCRC, transforming a “cold tumor” into a “hot tumor,” which has not only surprising effects but also certain limitations, i.e., the response could not be specific to metastasis. Therefore, regarding the bottleneck encountered by immunotherapy in patients with patients pMMR/MSS mCRC, this study summarized current research and possible mechanisms of immunotherapy combined with local therapy for metastasis, including radiotherapy, ablation, and transcatheter arterial chemoembolization.

The diagnosis of invasive pulmonary aspergillosis (IPA) diseases in non-neutropenic patients remains challenging. It is essential to develop optimal non-invasive or minimally invasive detection methods for the rapid and reliable diagnosis of IPA. Metagenomic next-generation sequencing (mNGS) in bronchoalveolar lavage fluid (BALF) can be a valuable tool for identifying the microorganism. Our study aims to evaluate the performance of mNGS in BALF in suspected IPA patients and compare it with other detection tests, including serum/BALF galactomannan antigen (GM) and traditional microbiological tests (BALF fungal culture and smear and lung biopsy histopathology). Ninety-four patients with suspicion of IPA were finally enrolled in our study. Thirty-nine patients were diagnosed with IPA, and 55 patients were non-IPA. There was significance between the IPA and non-IPA groups, such as BALF GM (P < 0.001), history of glucocorticoid use (P = 0.004), and pulmonary comorbidities (P = 0.002), as well as no significance of the other demographic data including age, sex, BMI, history of cigarette, blood GM assay, T-SPOT.TB, and NEUT#/LYMPH#. The sensitivity of the BALF mNGS was 92.31%, which was higher than that of the traditional tests or the GM assays. The specificity of BALF mNGS was 92.73%, which was relatively similar to that of the traditional tests. The AUC of BALF mNGS was 0.925, which presented an excellent performance compared with other traditional tests or GM assays. Our study demonstrated the important role of BALF detection by the mNGS platform for pathogen identification in IPA patients with non-neutropenic states, which may provide an optimal way to diagnose suspected IPA disease.

Objective: This study was to evaluate the prognostic value of the Naples prognostic score (NPS) in adult patients with asthma. Methods: Data on 44 601 participants from the 1999–2018 National Health and Nutrition Examination Survey (NHANES) were analyzed. The NPS was calculated based on serum albumin, total cholesterol, neutrophil-to-lymphocyte ratio (NLR), and lymphocyte-to-monocyte ratio (LMR), and participants were divided into 3 groups. Self-administered questionnaires were used to collect information on asthma, and mortality was identified using the National Death Index through December 31, 2019. Multiple logistic regressions were used to analyze the relationship between NPS and its components and the prevalence of asthma. Kaplan-Meier survival analysis, Cox proportional regressions, and the random survival forest (RSF) were used to assess the significance of NPS and its components in predicting all-cause and cause-specific (cardiovascular, cancer, and respiratory diseases) mortality in asthma patients. Results: The mean age of the participants was 47.59 ± 0.18 years, and 48.47% were male. The prevalence of asthma was 13.11%. The participants were categorized into 3 groups: 8306 (18.6%) participants were in group 0 (NPS 0), 30 842 (69.2%) were in group 1 (NPS 1 or 2), and 5453 (11.2%) were in group 2 (NPS 3 or 4). Compared to the reference group, participants in group 2 had a higher prevalence of asthma (odds ratio [OR] = 1.40 [1.24–1.56]). Participants with asthma in group 2 had a significantly increased risk of all-cause mortality (hazard ratio [HR] = 2.42 [1.67–3.50]), cardiovascular mortality (HR = 2.68 [1.50–4.79]), cancer mortality (HR = 2.10 [1.00–4.45]), and respiratory disease mortality (HR = 3.00 [1.18–7.65]) compared to those with asthma in group 0. The RSF showed that NPS had the highest value in predicting all-cause mortality in adults with asthma, compared to its components. Conclusions: The results of this study indicate that the NPS is a powerful prognostic indicator for outcomes in asthma patients.

Abstract Fiber components form the standard not only in modern telecommunication but also for future quantum information technology. For high-performance single-photon detection, superconducting nanowire single-photon detectors (SPDs) are typically fabricated on a silicon chip and fiber-coupled for easy handling and usage. The fiber-to-chip interface hinders the SPD from being an all-fiber device for full utilization of its excellent performance. Here, we report a scheme of SPD that is directly fabricated on the fiber tip. A bury-and-planar fabrication technique is developed to improve the roughness of the substrate for all-fiber detectors’ performance for single-photon detection with amorphous molybdenum silicide (MoSi) nanowires. The low material selectivity and universal planar process enable fabrication and packaging on a large scale. Such a detector responds to a broad wavelength range from 405 nm to 1550 nm at a dark count rate of 100 cps. The relaxation time of the response pulse is ~ 15 ns, which is comparable to that of on-chip SPDs. Therefore, this device is free from fiber-to-chip coupling and easy packaging for all-fiber quantum information systems.

Background: Nontuberculous mycobacterial (NTM) pulmonary disease (PD) has rapidly increased globally. The characteristics and comparison of rapidly growing mycobacteria PD (RGM-PD) and slowly growing mycobacteria PD (SGM-PD) are still unclear. Methods: Our study enrolled 31 NTM-PD patients. Clinical data, including baseline, symptoms, underlying disease, laboratory tests, metagenomic next-generation sequencing (mNGS) results, radiological images, treatment, and outcome were recorded and analyzed. Results: Of the 31 patients with NTM-PD, 22 patients were female and 9 were male. It included 11 RGM-PD and 20 SGM-PD. There was no difference in age (P = 0.425) and body mass index (P = 0.152) between the two groups. The common respiratory diseases in prevalence included bronchiectasis and chronic obstructive pulmonary disease. Three patients had positive results of T-SPOT tuberculosis (TB), and none had positive Xpert-Mycobacterium tuberculosis/rifampin results. On admission, patients were symptomatic and included cough/sputum production, fever, weight loss, fatigue, and hemoptysis. In comparison to RGM-PD, patients with SGM-PD had a greater chance of experiencing fatigue (P = 0.012). No significance was found in serum biomarkers between RGM and SGM-PD, including CD4/CD8 ratio, white blood cells, neutrophils, lymphocytes, procalcitonin, ferritin, C-reactive protein, and erythrocyte sedimentation rate. No liver or kidney impairment was found. Patients with RGM-PD were more likely to have right lower lobe (RLL) impairment (P = 0.021) and a cavity characteristic (P = 0.012). All 31 cases had positive mNGS results. The duration of mNGS was shorter than conventional methods (3.4 ± 0.7 vs. 26.4 ± 20.9, P < 0.001). Conclusions: Patients with SGM-PD were more likely to experience fatigue. The cavity and RLL involvement were more frequent in the RGM-PD. mNGS increases the identification of NTM specimens and complements the capabilities of conventional methods.