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The prevalence of metabolic dysfunction–associated steatotic liver disease (MASLD), which is increasingly being recognized as a leading cause of chronic liver pathology globally, is increasing. The pathophysiological underpinnings of its progression, which is currently under active investigation, involve oxidative stress. Human adipose tissue, an integral endocrine organ, secretes an array of adipokines that are modulated by dietary patterns and lifestyle choices. These adipokines intricately orchestrate regulatory pathways that impact glucose and lipid metabolism, oxidative stress, and mitochondrial function, thereby influencing the evolution of hepatic steatosis and progression to metabolic dysfunction–associated steatohepatitis (MASH). This review examines recent data, underscoring the critical interplay of oxidative stress, reactive oxygen species, and redox signaling in adipokine-mediated mechanisms. The role of various adipokines in regulating the onset and progression of MASLD/MASH through mitochondrial dysfunction and endoplasmic reticulum stress and the underlying mechanisms are discussed. Due to the emerging correlation between adipokines and the development of MASLD positions, these adipokines are potential targets for the development of innovative therapeutic interventions for MASLD management. A comprehensive understanding of the pathogenesis of MASLD/MASH is instrumental for identifying therapies for MASH.

Background: Collecting and standardizing clinical research data is a very tedious task. This study is to develop an intelligent data collection tool, named CHB-EDC, for real-world cohort studies of chronic hepatitis B (CHB), which can assist in standardized and efficient data collection. Methods: CHB_EDC is capable of automatically processing various formats of data, including raw data in image format, using internationally recognized data standards, OCR, and NLP models. It can automatically populate the data into eCRFs designed in the REDCap system, supporting the integration of patient data from electronic medical record systems through commonly used web application interfaces. This tool enables intelligent extraction and aggregation of data, as well as secure and anonymous data sharing. Results: For non-electronic data collection, the average accuracy of manual collection was 98.65 %, with an average time of 63.64 min to collect information for one patient. The average accuracy CHB-EDC was 98.66 %, with an average time of 3.57 min to collect information for one patient. In the same data collection task, CHB-EDC achieved a comparable average accuracy to manual collection. However, in terms of time, CHB-EDC significantly outperformed manual collection (p

Background As an important part in medical training in graduate school, 33-month medical residency training could be a stressful period inducing burnout (i.e. emotional exhaustion, depersonalization, and low personal accomplishment). Despite that existing literature has found that sense of belonging may have merits for residents’ well-being, it has remained unclear how sense of school belonging affects burnout and the potential moderators. To address this question, a cross-sectional survey has been conducted among the residents of the physicians standardized residency training program in China.Methods Seven hundred (N = 700) resident physicians from different majors (i.e. clinical medicine, clinical Stomatology, and Chinese medicine) and grades have participated in the survey. Resident’s sense of school belonging was assessed with the psychological sense of school membership scale (PSSM, mean = 45.12, SD = 11.14). Burnout was measured by the 22-item Maslach Burnout Inventory (MBI-HSS, mean = 65.80, SD = 15.89), including three subscales of emotional exhaustion, depersonalization, and personal accomplishment.Results The results showed that over 80% of the residents reported moderate or high level of emotional exhaustion and reduced personal accomplishment during residency training. Meanwhile, higher level of sense of school belonging was associated with lower overall burnout (B = −0.722, p

BackgroundArsenic, cobalt, barium, and other individual metal exposure have been confirmed to be associated with the incidence of kidney stones. However, there are few studies on the association between mixed metal exposure and kidney stones, especially in occupational groups. ObjectiveTo investigate the association between mixed metal exposure and kidney stones in an occupational population from a metal smelting plant. MethodsA questionnaire survey was conducted to collect sociodemographic characteristics, medical history, and lifestyle information of 1158 mixed metal-exposed workers in a metal smelting plant in Guangdong Province from July 2021 to January 2022. Midstream morning urine samples were collected from the workers, the concentrations of 18 metals including lithium, vanadium, chromium, manganese, cobalt, nickel, copper, zinc, arsenic, selenium, strontium, molybdenum, cadmium, cesium, barium, tungsten, titanium, and lead were measured by inductively coupled plasma mass spectrometry, and the urinary mercury levels were measured by cold atomic absorption spectroscopy. Based on predetermined inclusion criteria, a total of 919 mixed metal-exposed workers were included in the study, including 117 workers in the kidney stone group and 802 workers in the non-kidney stone group. With a detection rate of urinary metals greater than 80% as entry criterion, 16 eligible metals were finally included for further analysis. Parametric or non-parametric methods were used to compare the differences between continuous or categorical variables of the non-kidney stone group and the kidney stone group. Logistic regression models were constructed to explore the association between individual metal exposures and kidney stones. Weighted quantile sum (WQS) regression models were used to evaluate the association between mixed metal exposure and kidney stones, as well as the weights of each metal on kidney stones. Then Bayesian kernel machine regression (BKMR) models were used to explore the overall effect of mixed metal exposure on renal calculi and the potential interactions between metals. ResultsWe found that there were significant differences in sex, age, length of service, and body mass Index (BMI) between the non-kidney stone group and the kidney stone group (P

Abstract Background Despite emerging evidence linking blood cell indices (BCIs) to sepsis mortality, the inconsistency of observational studies obscures the clarity of these associations. This study aims to clarify the causal influence of BCIs on 28-day mortality rates in sepsis patients. Methods Utilizing univariable and multivariable Mendelian randomization (MR) analyses, we examined the impact of BCIs on sepsis mortality by analyzing data from extensive genome-wide association studies. The inverse-variance weighted (IVW) method was our primary analytic tool, complemented by several robustness checks to mitigate pleiotropy, including weighted median, mode-based estimates, MR-Egger regression, and MR-PRESSO. Subsequently, we conducted a retrospective study to further explore the correlation between platelet indices and 28-day mortality of sepsis using real-world data. Results Our findings highlight a significant causal relationship between platelet distribution width (PDW) and 28-day mortality in sepsis, with the univariable Mendelian randomization approach yielding an odds ratio of 1.12 (95% CI, 1.06–1.26; P

Abstract A facile and environmentally friendly ion exchange-assisted surface passivation (IASP) strategy is presented for synthesizing red emitting Mn4+-activated fluoride phosphors. A substantial, pristine Mn4+-free shell layer, applied as a coating to Mn4+ doped potassium fluorosilicate K2SiF6:Mn4+ (KSFM) phosphors, enhances both water resistance and luminescence efficiency. The stability test of fluoride in water at ambient temperature and boiling water demonstrates that IASP-treated KSFM phosphors are highly water resistant. Furthermore, both the negative thermal temperature (NTQ) fitting results and the photoluminescence (PL) decay confirm that the IASP process effectively passivates surface defects, leading to enhanced luminescence performance. The maximum internal quantum yield (QYi) of the IASP-KSFM phosphor is 94.24%. A white LED realized a high color rendering index (CRI) of 93.09 and luminous efficiency (LE) of 149.48 lm/W. This work presented a novel technique for the development of stable fluoride phosphors and has the potential to increase the use of KSFM phosphors in plant supplementary lighting systems and white light-emitting diodes.

IntroductionThe cartilage endplate (CEP) plays a crucial role as both a mechanical barrier and nutrient channel for the intervertebral disc, but it is vulnerable to excessive axial loading. We modified the Ilizarov external fixator and applied it to the CEP of the rat tail to impose diurnal, controllable excess axial loading. The objective was to measure morphological changes in the CEP when subjected to loading during the aging process.MethodsTwo Kirschner wires were, respectively, inserted into the center of the eighth and ninth coccygeal vertebrae (Co8/9) of rat (n = 54) to apply axial loading to the CEP. A remote control device was used to establish the diurnal loading schedule. At the end of 4, 8, and 12-week periods, the Co8/9 CEPs in each group were analyzed using MRI, histological staining, and immunohistochemical staining techniques.ResultsThe novel Ilizarov model that we modified successfully induced degeneration of the rat coccygeal CEP. MRI analysis revealed significant degenerative changes in the loaded Co8/9 CEP, including decreased signal intensity and the formation of Schmorl’s nodes at 8 and 12 weeks. Histological examination showed progressive CEP degeneration (CEPD), characterized by decreased microporosity, thinning, and structural irregularities. Immunohistochemical analysis demonstrated a significant reduction in Aggrecan and Collagen II expression in the CEP and nucleus pulposus over time. Control and sham groups maintained normal CEP structure and composition throughout the study period.ConclusionExcessive axial loading induced CEPD in the rat tail, primarily characterized by the formation of Schmorl’s nodes and a reduction in CEP microporosity in this study. Our modified Ilizarov rat tail compression model, featuring stable and controllable axial loading capabilities, provided an alternative experimental paradigm for further investigation into CEPD.

Abstract Background In regional wheat trials, when short-stem wheat varieties and high-stem wheat varieties are planted adjacent to each other in small plots, changes in their marginal plot environment can lead to bias in yield evaluation. Currently, there is no relevant research revealing the degree of their mutual influence. Results In a regional wheat experiment, when high-stem wheat varieties and short-stem wheat varieties were planted adjacent to one another, there was no significant change in soil temperature or humidity in the high-stem wheat variety experimental plot from November to May compared to the control plot, while the soil humidity in the short-stem wheat variety experimental plot was greater than that in the control plot. In May, the soil temperature of the short-stem wheat varieties in the experimental plot was lower than that in the control plot. Illumination of the wheat canopy in the high-stem wheat variety experimental plot had a significant positive effect in April and May, while illumination of the wheat canopy in the short-stem wheat variety experimental plot had a negative effect. The chlorophyll fluorescence parameters of flag leaves in the high-stem wheat variety experimental plots showed an overall increasing trend, while the chlorophyll fluorescence parameters of flag leaves in the experimental plots of short-stem wheat varieties showed a decreasing trend. The analysis of the economic yield, biological yield, and yield factors in each experimental plot revealed that the marginal effects of the economic yield and 1000-grain weight were particularly significant and manifested as positive effects in the high-stem wheat variety experimental plot and as negative effects in the short-stem wheat variety experimental plot. The economic yield of the high-stem wheat variety experimental plot was significantly greater than that of the control plot, the economic yield of the short-stem wheat variety experimental plot was significantly lower than that of the control plot, and the economic yield of the high-stem experimental plot was significantly greater than that of the short-stem experimental plot. When the yield of the control plot of the high-stem wheat varieties was compared to that of the control plot of the short-stem wheat varieties, the yield of the control plot of the short-stem wheat varieties was significantly greater than that of the control plot of the high-stem wheat varieties. Conclusions Based on these findings, it is concluded that plots with high-stem and short-stem wheat varieties are adjacent in regional wheat trials, the plots of high-stem wheat varieties are subject to marginal positive effects, resulting in a significant increase in economic yield; the plots of short-stem wheat varieties are subject to marginal negative effects, resulting in a decrease in economic yield. This study reveals the mutual influence mechanism of environment and yield with adjacent planting of high-stem and short-stem wheat varieties in regional wheat trials, providing a useful reference and guidance for optimizing the layout of regional wheat trials.

Objective: To evaluate the accuracy and safety of the LANCET robotic system, a robot arm assisted operation system for total hip arthroplasty via a multicenter clinical randomized controlled trial. Methods: A total of 116 patients were randomized into two groups: LANCET robotic arm assisted THA group (N = 58) and the conventional THA group (N = 58). General information about the patients was collected preoperatively. Operational time and bleeding were recorded during the surgery. The position of the acetabular prosthesis was evaluated by radiographs one week after surgery and compared with preoperative planning. Harris score, hip mobility, prosthesis position and angle and complications were compared between the two groups at three months postoperatively. Results: None of the 111 patients who ultimately completed the 3-month follow-up experienced adverse events such as hip dislocation and infection during follow-up. In the RAA group, 52 (92.9 %) patients were located in the Lewinnek safe zone and 49 (87.5 %) patients were located in the Callanan safe zone. In the control group were 47 (85.5 %) and 44 (80.0 %) patients, respectively. In the RAA group, 53 (94.6 %) patients had a postoperative acetabular inclination angle and 51 (91.1 %) patients had an acetabular version angle within a deviation of 5° from the preoperative plan. These numbers were significantly higher than those of the control group, which consisted of 42 (76.4 %) and 34 (61.8 %) patients respectively. There were no significant differences between the two groups of subjects in terms of general condition, intraoperative bleeding, hip mobility, and adverse complications. Conclusion: The results of this prospective randomized, multicenter, parallel-controlled clinical study demonstrated that the LANCET robotic system leads conventional THA surgery in accuracy of acetabular cup placement and does not differ from conventional THA surgery in terms of postoperative hip functional recovery and complications. The translational potential of this article: In the past, the success rate of total hip arthroplasty (THA) relied heavily on the surgeon's experience. As a result, junior doctors needed extensive training to become proficient in this technique. However, the introduction of surgical robots has significantly improved this situation. By utilizing robotic assistance, both junior and senior doctors can perform THA quickly and efficiently. This advancement is crucial for the widespread adoption of THA, as patients can now receive surgical treatment in local facilities instead of overwhelming larger hospitals and straining medical resources. Moreover, the development of surgical robots with fully independent intellectual property rights holds immense value in overcoming the limitations of high-end medical equipment. This aligns with the objectives outlined in the 14th Five Year Plan for National Science and Technology Strategy.

Standards of basic dataset of chronic and noncommunicable diseases behavior risk factors surveillance in adults (T/CPMA 033 — 2023) was published and officially implemented by Chinese Preventive Medicine Association on October 20th, 2023. The standard specifies the metadata attributes and data element attributes of the adult chronic and noncommunicable disease behavioral risk factors.It is suitable for the collection of data related to the monitoring, investigation, intervention and evaluation of chronic disease behavior risk factors conducted by health administrative departments, disease prevention and control institutions, primary-level medical and health care institutions, health examination and management institutions and scientific research institutes. The article interprets the key points of the standard, and provides guidance for medical and health institutions and professionals to deeply understand and promote the application of the standard.

Despite their numerous excellent properties, metal sulfides are not particularly efficient at converting energy and purifying the environment, which limits their further applications. Fortunately, the energy conversion and environmental purification efficiencies of these materials have experienced notable advancements in recent years, accompanied by an improved understanding of their underlying mechanisms. Herein, progress in experimental researches in recent years on the engineering of single component metal sulfides by controlling morphology, construction of heterojunctions, and incorporating elements is reviewed. Methods to design and prepare metal sulfide‐based composites by building binary or ternary heterojunctions of metal sulfide/semiconductor/conductor are also discussed in detail. These materials are used in energy conversion and environmental purification systems, where they act as photocatalytic materials not only to split water, reduce carbon dioxide or nitrogen, but also to degrade pollutants (organic and inorganic) in water and gas. Finally, it is concluded by summarizing the research frontiers of metal sulfide nanomaterials in energy and environmental applications, as well as proposing potential challenges and future research directions. This work may contribute to a better understanding of metal sulfide nanocomposites and provide clues for the fabrication of more efficient metal sulfide‐based nanostructures for clean energy production and environmental remediation.

BackgroundOccupational exposure to lead, cadmium, or arsenic is a potential risk factor for blood pressure elevation. Current studies mainly focus on the relationship between a single metal and blood pressure. However, mixed metal exposure often exists in the actual working environment, and the interactive effects of polymetallic interactions on blood pressure and the dose-effect relationship remain unclear yet. ObjectiveTo explore the influence proportion of occupational exposure to lead, cadmium, or arsenic on blood pressure and their interactive effects. MethodsFrom January to December 2021, workers from a smelter in southern China were selected. Demographic characteristics, height, weight, and blood pressure of workers were collected through questionnaire and physical examination. At the same time, their urine samples were collected and the levels of urinary lead, urinary cadmium, and urinary arsenic were detected by inductively coupled plasma mass spectrometry, and corrected by urinary creatinine (Cr). Linear regression and logistic regression were used to analyze the relationship between urinary lead, cadmium, and arsenic and blood pressure. Weighted quantile sum (WQS) regression was applied to evaluate the dose-effect relationship between urinary lead, cadmium, and arsenic exposures and blood pressure and the effect weight of each metal on blood pressure. Generalized linear regression and additive/multiplicative scaling were used to identify interactive effects of the three metals on blood pressure. ResultsA total of 1075 workers were included in this study, with a mean age of (44.68±5.11) years and mean working seniority of (24.66±5.23) years. There were 891 males (88.9%) and 184 were females (17.1%); 24.7% workers were drinkers and 45.7% workers were smokers; 302 workers (28.1%) reported hypertension and 37 of them were taking antihypertensive drugs. The P50 (P25, P75) levels of urinary lead, urinary cadmium, and urinary arsenic were 6.11 (3.71, 11.08), 3.88 (2.68, 5.44), and 26.04 (19.99, 35.11) μg·g−1, respectively. After adjusting for gender, age, working seniority, body mass index, smoking, drinking, and the usage of antihypertensive drugs, systolic and diastolic blood pressure increased by 0.772 and 0.418 mmHg respectively for 10% increase in lead, cadmium, and arsenic mixed exposure. Urinary cadmium, among the three single exposures, had the greatest effect on systolic and diastolic blood pressure, weight (w)=0.523 and 0.551 respectively. The interaction of urinary lead and urinary cadmium was positively correlated with the occurrence of hypertension, multiplicative interaction OR (ORint)=1.88 (95%CI: 1.09, 3.63), attributable proportion due to interaction (AP)=1.19 (95%CI: 0.40, 8.18). ConclusionThis study shows that mixed exposure to lead, cadmium, and arsenic has a positive relationship with blood pressure, in which cadmium plays a major role. Co-exposure to lead and cadmium has a positive interactive effect on hypertension development and systolic blood pressure elevation.

BackgroundThe systemic immune-inflammation index (SII),as measured by lymphocyte, neutrophil and platelet counts in peripheral blood, is regarded as a favorable indicator of both inflammatory state and immune response. Psoriasis is an immune-mediated disease notable for its chronic inflammation of the entire system. Our research sought to explore the latent link between psoriasis and SII.MethodsWe performed a cross-sectional investigation utilizing data extracted from the National Health and Nutrition Examination Survey (NHANES, 2009-2014). Employing multivariate linear regression models and subgroup analysis, we sought to uncover the association between SII and psoriasis.ResultsThis study enrolled a total of 17,913 participants as part of its research cohort. Our multivariate linear regression analysis revealed a notable and positive correlation between SII and psoriasis [1.013 (1.000, 1.026)]. As SII tertiles increased, the risk of psoriasis demonstrated an upward trend. The significant dependence on this positive association were maintained in women, BMI(≥ 30 kg/m2),non-stroke and non-cancer subjects in subgroup analysis and interaction tests. Furthermore, we identified a significant association between SII and psoriasis, characterized by two consecutive inverted U-shaped patterns. Notably, the analysis revealed the most prominent inflection point at a specific value of 797.067.ConclusionsThe results indicate a significant correlation between elevated SII levels and the presence of psoriasis. However, to corroborate and strengthen these results, additional large-scale prospective studies are required.

BackgroundPrevious studies have suggested the potential of PD-1/PD-L1 inhibitors in the treatment of chronic HBV infection. However, since phase III clinical trials have not yet been announced, additional clinical insights may be obtained by observing changes in serum hepatitis B surface antigen (HBsAg) and HBV-DNA levels in cancer patients undergoing PD-1 inhibitor therapy.ObjectiveTo explore the effects of PD-1 inhibitor combinational therapy on serum HBsAg and HBV-DNA levels, investigate the incidence of HBsAg loss, HBV reactivation (HBVr), and immune-related adverse events (irAEs), and identify the risk factors associated with significant HBsAg fluctuations and HBVr. MethodsA retrospective study including 1195 HBsAg-positive cancer patients who received PD-1 inhibitors between July 2019 and June 2023 was conducted, and 180 patients were enrolled in this study. Serum HBsAg levels before and after PD-1 inhibitor administration were compared across different subgroups. The Pearson χ2 or Fisher exact test was performed to investigate the relationships between categorical variables. Univariable and multivariable analysis were performed to identify the risk factors associated with significant HBsAg fluctuations and HBVr. ResultsWith the concurrent use of antiviral agents, serum HBsAg levels decreased (Z=-3.966, P < 0.0001) in 129 patients and increased (t=-2.047, P=0.043) in 51 patients. Additionally, 7 patients (3.89%) achieved serum HBsAg loss. Virus replication was suppressed in most of the enrolled patients. When divided patients into different subgroups, significant HBsAg decreases after PD-1 inhibitor administration were discovered in lower baseline HBsAg group (Z=-2.277, P=0.023), HBeAg-seronegative group (Z=-2.200, P=0.028), non-irAEs occurrence group (Z=-2.007, P=0.045) and liver cancer group (Z=-1.987, P=0.047). Of note, 11 patients and 36 patients experienced HBVr (6.11%) and irAEs (20%), respectively, which could lead to discontinuation or delayed use of PD-1 inhibitors. After multivariable analysis, HBeAg-seropositive (OR, 7.236 [95% CI, 1.757-29.793], P=0.01) and the occurrence of irAEs (OR, 4.077 [95% CI, 1.252-13.273], P=0.02) were identified as the independent risk factors for significant HBsAg increase, the occurrence of irAEs (OR, 5.560 [95% CI, 1.252-13.273], P=0.01) was identified as the only independent risk factor for HBVr. ConclusionPD-1 inhibitors combined with nucleos(t)ide analogues (NAs) may exert therapeutic potential for chronic HBV infection in cancer patients. However, attention also should be paid to the risk of significant elevation in HBsAg levels, HBVr, and irAEs associated with PD-1 inhibitor combinational therapy.

Abstract Systemic administration of platinum-based drugs has obvious limitations in the treatment of advanced bladder cancer (BC) owing to lower tumor accumulation and uncontrolled release of chemotherapeutics. There is an urgent need for advanced strategies to overcome the current limitations of platinum-based chemotherapy, to achieve maximal therapeutic outcomes with reduced side effects. In this study, self-polymerized platinum (II)-polydopamine nanocomplexes (PtPDs) were tailored for efficient chemo-photoimmunotherapy of BC. PtPDs with high Pt loading content (11.3%) were degradable under the combination of a reductive tumor microenvironment and near-infrared (NIR) light irradiation, thus controlling the release of Pt ions to achieve efficient chemotherapy. In addition, polydopamine promoted stronger photothermal effects to supplement platinum-based chemotherapy. Consequently, PtPDs provided effective chemo-photothermal therapy of MB49 BC in vitro and in vivo, strengthening the immunogenic cell death (ICD) effect and robust anti-tumoral immunity response. When combined with a PD-1 checkpoint blockade, PtPD-based photochemotherapy evoked systemic immune responses that completely suppressed primary and distant tumor growth without inducing systemic toxicities. Our work provides a highly versatile approach through metal-dopamine self-polymerization for the precise delivery of metal-based chemotherapeutic drugs, and may serve as a promising nanomedicine for efficient and safe platinum-based chemotherapy for BC.

Liver failure is a group of clinical syndromes with a mortality rate of >50%. The accurate evaluation of severity in patients with liver failure has been a meaningful and hot topic in clinical research and an important guide for liver transplantation. Numerous prognosis studies have emerged in recent years with high accuracy and adequate validity. Nonetheless, different models utilize distinct parameters and have unequal efficiencies, leading to a specific value and unique application situations for each model. This review focused on the progress in recent prognostic studies including the model for end-stage liver disease, sequential organ failure assessment and its derivative models, the Chinese Group on the Study of Severe Hepatitis B Acute-on-Chronic Liver Failure, the Tongji prognostic predictor model, and other emerging prognostic models and predictors. This review aims to assist clinicians understand the framework of recent models and choose the appropriate model and treatment.

Abstract Objective and background The deficiency of ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1) causes the phenotype similar to knee osteoarthritis (OA). However, the molecular mechanism is poorly understood. Method The global deletion of Enpp1 (Enpp1−/−) mice was created to analyze the role of Enpp1 in the progress of knee OA. The apoptosis, proliferation and chondrogenic differentiation ability of chondrocytes from wild-type (WT) and Enpp1−/− joints were compared. According to the results of high-throughput quantitative molecular measurements, the proteins of chondrocytes from WT and Enpp1−/− mice were used to explore the mechanism of Enpp1 deficiency-associated knee OA. Result In Enpp1−/− knee joints, we found significant chondrocyte apoptosis and proteomic results showed that abnormal expression of AMP-activated protein kinase (AMPK) signaling pathway may contribute to this phenotype. In primary chondrocyte cultures in vitro, Enpp1 deletion dramatically enhancing chondrocyte apoptosis. Meanwhile, we found Enpp1 deletion inhibits the phosphorylation of AMPK (P-AMPK). We also found that decreased level of P-AMPK and chondrocyte apoptosis, which are caused by Enpp1 deficiency, can be reversed by Acadesine (AICAR), the activator of AMPK. Conclusion Consequently, Enpp1 deficiency plays an essential role in knee OA by regulating AMPK signaling pathway.

Background and aims: There is currently no single model for predicting Wilson's disease (WD). We aimed to create a nomogram using daily clinical parameters to improve the accuracy of WD diagnosis in patients with abnormal liver function. Methods: Between July 2016 and December 2020, we identified 90 WD patients with abnormal liver function who had homozygous or compound heterozygous mutations in the ATP7B gene. The control group included 128 patients with similar liver function but no WD during the same time period. To create a nomogram, we screened potential predictive variables using the least absolute shrinkage and selection operator model and multivariate logistic regression. Results: We developed a nomogram for screening for WD based on six predictive factors: serum copper, direct bilirubin, uric acid, cholinesterase, prealbumin, and reticulocyte percentage. In the training cohort, the area under curve (AUC) of the nomogram reached 0.967 (95% confidence interval (CI) 0.946–0.988), while the area under the precision-recall curve was 0.961. Based on the optimal cutpoint of 213.55, our nomogram performed well, with a sensitivity of 96% and a specificity of 87%. In the validation cohort, the AUC of the nomogram was as high as 0.991 (95% CI 0.970–1.000). Conclusions: We developed a nomogram that can predict the risk of WD prior to the detection of serum ceruloplasmin or urinary copper, greatly increasing screening efficiency for patients with abnormal liver function.

Islamic floral patterns warrant further research and analysis as they are an important aspect of the cultural heritage of Islamic patterns. These floral patterns are aesthetically inspired by flowers, leaves, vines, and stems and feature characteristics such as symmetry, interlacing, and pattern repetition. This study analysed a five-pointed rose pattern (peony flower) and its elements, such as the curved lines that make up the leaves and flowers. A new floral pattern featuring a botanical motif and curved lines was designed and distributed using kite and dart tiling. The floral pattern was designed using the pentagram reflection of the Penrose tiling method to suit modern design requirements of looking like a Shamsah. The results of the floral ornament and newly designed patterns were then reviewed in order to facilitate the generation of new patterns accurately and quickly through computer design software. Thus, the problem of time and effort in designing Islamic floral patterns was solved. This study also provides suggestions for future studies on Islamic floral patterns.

Dynamic changes of the paired heavy and light chain B cell receptor (BCR) repertoire provide an essential insight into understanding the humoral immune response post-SARS-CoV-2 infection and vaccination. However, differences between the endogenous paired BCR repertoire kinetics in SARS-CoV-2 infection and previously recovered/naïve subjects treated with the inactivated vaccine remain largely unknown. We performed single-cell V(D)J sequencing of B cells from six healthy donors with three shots of inactivated SARS-CoV-2 vaccine (BBIBP-CorV), five people who received the BBIBP-CorV vaccine after having recovered from COVID-19, five unvaccinated COVID-19 recovered patients and then integrated with public data of B cells from four SARS-CoV-2-infected subjects. We discovered that BCR variable (V) genes were more prominently used in the SARS-CoV-2 exposed groups (both in the group with active infection and in the group that had recovered) than in the vaccinated groups. The VH gene that expanded the most after SARS-CoV-2 infection was IGHV3-33, while IGHV3-23 in the vaccinated groups. SARS-CoV-2-infected group enhanced more BCR clonal expansion and somatic hypermutation than the vaccinated healthy group. A small proportion of public clonotypes were shared between the SARS-CoV-2 infected, vaccinated healthy, and recovered groups. Moreover, several public antibodies had been identified against SARS-CoV-2 spike protein. We comprehensively characterize the paired heavy and light chain BCR repertoire from SARS-CoV-2 infection to vaccination, providing further guidance for the development of the next-generation precision vaccine.

Background: The pathogenic genes of colorectal cancer (CRC) have not yet been fully elucidated, and there is currently a lack of effective therapeutic targets. This study used bioinformatics methods to explore and experimentally validate the most valuable biomarkers for colorectal cancer and further investigate their potential as targets.Methods: We analyzed differentially expressed genes (DEGs) based on the Gene Expression Omnibus (GEO) dataset and screened out hub genes. ROC curve and univariate Cox analysis of The Cancer Genome Atlas (TCGA) dataset revealed the most diagnostically and prognostically valuable genes. Immunohistochemistry (IHC) experiments were then conducted to validate the expression level of these selected genes in colorectal cancer. Gene set enrichment analysis (GSEA) was performed to evaluate the enriched signaling pathways associated with the gene. Using the CIBERSORT algorithm in R software, we analyzed the immune infiltrating cell abundance in both high and low gene expression groups and examined the gene’s correlation with immune cells and immune checkpoints. Additionally, we performed drug sensitivity analysis utilizing the DepMap database, and explored the correlation between gene expression levels and ferroptosis based on the The Cancer Genome Atlas dataset.Results: The study identified a total of 159 DEGs, including 7 hub genes: SPP1, MMP1, CXCL8, CXCL1, TIMP1, MMP3, and CXCL10. Further analysis revealed TIMP1 as the most valuable diagnostic and prognostic biomarker for colorectal cancer, with IHC experiments verifying its high expression. Additionally, GSEA results showed that the high TIMP1 expression group was involved in many cancer signaling pathways. Analysis of the TCGA database revealed a positive correlation between TIMP1 expression and infiltration of macrophages (M0, M1, M2) and neutrophils, as well as the expression of immune checkpoint genes, including CTLA-4 and HAVCR2. Drug sensitivity analysis, conducted using the DepMap database, revealed that colorectal cancer cell lines exhibiting elevated levels of TIMP1 expression were more responsive to certain drugs, such as CC-90003, Pitavastatin, Atuveciclib, and CT7001, compared to those with low levels of TIMP1. Furthermore, TIMP1 expression was positively correlated with that of ferroptosis-related genes, such as GPX4 and HSPA5.Conclusion: TIMP1 can be used as a biomarker for colorectal cancer and is associated with the immunological microenvironment, drug sensitivity, and ferroptosis inhibition in this disease.

Ad-sig-hMUC1/ecdCD40L is a recombinant adenovirus vaccine comprising human MUC1 antigen fused to the extracellular domain of the CD40 ligand. Here the authors report the result of a phase I clinical trial of Ad-sig-hMUC1/ecdCD40L in patients with advanced adenocarcinoma.

Background and aim: Some previous studies supported that rifampicin was an effective treatment for benign intrahepatic cholestasis. However, the efficacy and safety of rifampicin remain unclear. Therefore, this study aimed to evaluate its efficacy and safety on benign intrahepatic cholestasis. Methods: A retrospective, single-center, observational study was conducted on patients diagnosed with benign intrahepatic cholestasis between 2019 and 2021, who were administered 150 mg of rifampicin orally once a day. We collected and analyzed the data at baseline and post-treatment, including total bilirubin (TBIL), direct bilirubin (DBIL), total bile acid (TBA), gamma-glutamyl transferase (GGT), alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase levels. Statistical analysis was performed using appropriate tests. Results: A total of 17 rifampicin-treated patients were enrolled in the study from January 2019 to January 2021. Among them, 14 patients (82%) improved, with significantly decreased TBIL, DBIL, and TBA levels after 3 weeks of treatment (all P

BackgroundDespite accumulating evidence revealing that Glucose-6-phosphate dehydrogenase (G6PD) is highly expressed in many tumor tissues and plays a remarkable role in cancer tumorigenesis and progression, there is still a lack of G6PD pan-cancer analysis. This study was designed to analyze the expression status and prognostic significance of G6PD in pan-cancer.MethodsG6PD expression data were obtained from multiple data resources including the Genotype-Tissue Expression, the Cancer Genome Atlas, and the Tumor Immunity Estimation Resource. These data were used to assess the G6PD expression, prognostic value, and clinical characteristics. The ESTIMATE algorithms were used to analyze the association between G6PD expression and immune-infiltrating cells and the tumor microenvironment. The functional enrichment analysis was also performed across pan-cancer. In addition, the GDSC1 database containing 403 drugs was utilized to explore the relationship between drug sensitivity and G6PD expression levels. Furthermore, we also performed clinical validation and in vitro experiments to further validate the role of G6PD in hepatocellular carcinoma (HCC) cells and its correlation with prognosis. The R software was used for statistical analysis and data visualization.ResultsG6PD expression was upregulated in most cancers compared to their normal counterparts. The study also revealed that G6PD expression was a prognostic indicator and high levels of G6PD expression were correlated with worse clinical prognosis including overall survival, disease-specific survival, and progression-free interval in multiple cancers. Furthermore, the G6PD level was also related to cancer immunity infiltration in most of the cancers, especially in KIRC, LGG, and LIHC. In addition to this, G6PD expression was positively related to pathological stages of KIRP, BRCA, KIRC, and LIHC. Functional analysis and protein-protein interactions network results revealed that G6PD was involved in metabolism-related activities, immune responses, proliferation, and apoptosis. Drug sensitivity analysis showed that IC50 values of most identified anti-cancer drugs were positively correlated with the G6PD expression. Notably, in vitro functional validation showed that G6PD knockdown attenuated the phenotypes of proliferation in HCC.ConclusionG6PD may serve as a potential prognostic biomarker for cancers and may be a potential therapeutic target gene for tumor therapy.

Background and aimsDetermining the transcriptomes and molecular mechanism underlying human degenerative nucleus pulposus (NP) is of critical importance for treating intervertebral disc degeneration (IDD). Here, we aimed to elucidate the detailed molecular mechanism of NP ossification and IDD using single-cell RNA sequencing.MethodsSingle-cell RNA-seq and bioinformatic analysis were performed to identify NP cell populations with gene signatures, biological processes and pathways, and subpopulation analysis, RNA velocity analysis, and cell-to-cell communication analysis were performed in four IDD patients. We also verified the effects of immune cells on NP ossification using cultured NP cells and a well-established rat IDD model.ResultsWe identified five cell populations with gene expression profiles in degenerative NP at single-cell resolution. GO database analysis showed that degenerative NP-associated genes were mainly enriched in extracellular matrix organization, immune response, and ossification. Gene set enrichment analysis showed that rheumatoid arthritis signaling, antigen processing and presentation signaling were activated in the blood cell cluster. We revealed that stromal cells, which are progenitor cells, differentiated toward an ossification phenotype and delineated interactions between immune cells (macrophages and T cells) and stromal cells. Immune factors such as TNF-α, CD74 and CCL-3 promoted the differentiation of stromal cells toward an ossification phenotype in vitro. Blocking TNF-α with a specific inhibitor successfully reversed NP ossification and modified NP morphology in vivo.ConclusionOur study revealed an increase in macrophages and T cells in degenerative NP, which induced stromal cell differentiation toward an ossification phenotype, and contributed to the identification of a novel therapeutic target to delay IDD.

Abstract Objectives Graduated compression stocking (GCS) is one of the mechanical prophylaxes commonly used for deep vein thrombosis (DVT). The present study was designed to observe the effects of graduated compression stockings on the vein deformation and hemodynamics of lower limbs in patients awaiting total hip arthroplasty (THA). Methods The lower extremity veins of 22 patients awaiting THA were examined by ultrasound, when they rested in supine position with or without thigh-length GCS. The deformation parameters we measured included antero-posterior (AP) diameters, latero-medial (LM) diameters, and cross-sectional area (CSA) of great saphenous vein (GSV), posterior tibial vein (PTV), popliteal vein (PV), gastrocnemius vein (GV), and superficial femoral vein (SFV). We measured peak velocity and mean velocity of GSV, common femoral vein (CFV), junction of GSV and CFV to represent for hemodynamics of veins. Results Significant compression was observed in almost all measured veins with the use of thigh-length GCS, while it was unable to significantly compress GSV in latero-medial diameter. The mean latero-medial diameter reductions for GSV, PTV, GV, PV and SFV were 19.4, 30.2, 43.2, 29.7 and 20.4%, respectively. GCS significantly compressed antero-posterior diameter of GSV, PTV, GV, PV and SFV by 43.4, 33.3, 42.1, 37.5, and 27.8%, respectively. The mean reduction of cross-section area was 44.8% for GSV, 49.6% for PTV, 60.0% for GV, 57.4% for PV, and 36.2% for FV. No significant changes were observed in the mean blood velocity of GSV, CFV, and junction. GCS was able to significantly reduce peak velocity of CFV (17.6 ± 5.6 cm/s to 16.1 ± 6.0 cm/s) and junction (23.3 ± 9.5 cm/s to 21.3 ± 9.7 cm/s), while it did not change the peak velocity of GSV. Conclusion Thigh-length GCS is sufficient to compress lower extremity veins in patients awaiting THA in supine position with the greatest compression in GV, while it was unable to significantly increase blood velocity of common femoral vein or GSV. GCS may prevent DVT through more than simply increasing blood flow. Further studies are needed to determine the specific effects of GCS.

Abstract Background Medulloblastoma (MB) is the most common malignant brain tumor in children. Approximately one-third of MB patients remain incurable. Understanding the molecular mechanism of MB tumorigenesis is, therefore, critical for developing specific and effective treatment strategies. Our previous work demonstrated that astrocytes constitute the tumor microenvironment (TME) of MB and play an indispensable role in MB progression. However, the underlying mechanisms by which astrocytes are regulated and activated to promote MB remain elusive. Methods By taking advantage of Math1-Cre/Ptch1 loxp/loxp mice, which spontaneously develop MB, primary MB cells and astrocytes were isolated and then subjected to administration and coculture in vitro. Immunohistochemistry was utilized to determine the presence of C3a in MB sections. MB cell proliferation was evaluated by immunofluorescent staining. GFAP and cytokine expression levels in C3a-stimulated astrocytes were assessed by immunofluorescent staining, western blotting, q-PCR and ELISA. C3a receptor and TNF-α receptor expression was determined by PCR and immunofluorescent staining. p38 MAPK pathway activation was detected by western blotting. Transplanted MB mice were treated with a C3a receptor antagonist or TNF-α receptor antagonist to investigate their role in MB progression in vivo. Results We found that complement C3a, a fragment released from intact complement C3 following complement activation, was enriched in both human and murine MB tumor tissue, and its receptor was highly expressed on tumor-associated astrocytes (TAAs). We demonstrated that C3a activated astrocytes and promoted MB cell proliferation via the p38 MAPK pathway. Moreover, we discovered that C3a upregulated the production of proinflammatory cytokines, such as IL-6 and TNF-α in astrocytes. Application of the conditioned medium of C3a-stimulated astrocytes promoted MB cell proliferation, which was abolished by preincubation with a TNF-α receptor antagonist, indicating a TNF-α-dependent event. Indeed, we further demonstrated that administration of a selective C3a receptor or TNF-α receptor antagonist to mice subcutaneously transplanted with MB suppressed tumor progression in vivo. Conclusions C3a was released during MB development. C3a triggered astrocyte activation and TNF-α production via the p38 pathway, which promoted MB cell proliferation. Our findings revealed the novel role of C3a-mediated TNF-α production by astrocytes in MB progression. These findings imply that targeting C3a and TNF-α may represent a potential novel therapeutic approach for human MB.

Erythropoietic protoporphyria (EPP) is a rare inherited disease caused by partial deficiency activity of the enzyme ferrochelatase (FECH), resulting in excessive accumulation of protoporphyrin IX in erythrocyte and tissues. Here, we report a patient with photosensitive dermatitis and acute icteric hepatitis caused by EPP, whose clinical and biochemical results successfully improved following 2-month treatment with glucose load, ursodeoxycholic acid capsules, and cholestyramine powder. This case provides a reference for a combination therapy strategy for patients with liver and skin injury caused by EPP.

Abstract Type II collagen-positive (Col2+) cells have been reported as skeletal stem cells (SSCs), but the contribution of Col2+ progenitors to skeletal development both prenatally and postnatally during aging remains unclear. To address this question, we generated new mouse models with ablation of Col2+ cells at either the embryonic or postnatal stages. The embryonic ablation of Col2+ progenitors resulted in the death of newborn mice due to a decrease in skeletal blood vessels, loss of all vertebral bones and absence of most other bones except part of the craniofacial bone, the clavicle bone and a small piece of the long bone and ribs, which suggested that intramembranous ossification is involved in long bone development but does not participate in spine development. The postnatal ablation of Col2+ cells resulted in mouse growth retardation and a collagenopathy phenotype. Lineage tracing experiments with embryonic or postnatal mice revealed that Col2+ progenitors occurred predominantly in the growth plate (GP) and articular cartilage, but a limited number of Col2+ cells were detected in the bone marrow. Moreover, the number and differentiation ability of Col2+ progenitors in the long bone and knee joints decreased with increasing age. The fate-mapping study further revealed Col2+ lineage cells contributed to, in addition to osteoblasts and chondrocytes, CD31+ blood vessels in both the calvarial bone and long bone. Specifically, almost all blood vessels in calvarial bone and 25.4% of blood vessels in long bone were Col2+ lineage cells. However, during fracture healing, 95.5% of CD31+ blood vessels in long bone were Col2+ lineage cells. In vitro studies further confirmed that Col2+ progenitors from calvarial bone and GP could form CD31+ vascular lumens. Thus, this study provides the first demonstration that intramembranous ossification is involved in long bone and rib development but not spine development. Col2+ progenitors contribute to CD31+ skeletal blood vessel formation, but the percentage differs between long bone and skull bone. The number and differentiation ability of Col2+ progenitors decreases with increasing age.

Abstract Objectives To analyze the changes of lower limb hemodynamics parameters before and after wearing graduated compression stockings (GCS) during ankle pump exercise in patients preparing for arthroplastic surgery. Method The leg veins of 16 patients awaiting arthroplasty were analyzed using a Sonosite M-Turbo ultrasound system during ankle pump exercise with or without GCS. The age of them was 70 ± 7 years (mean ± SD) (range 56—82 years) and body mass index was 25.8 ± 3.0 kg/m2 (range 18.0—30.5 kg/m2). Measured data including the cross-sectional area (CSA), anteroposterior (AP) diameter and lateromedial (LM) diameter of the soleus vein (SV), posterior tibial vein (PTV) and great saphenous vein (GSV). Additionally, the peak velocities of femoral vein (FV) were also measured. Results GCS could significantly decrease the cross-sectional area of SV, PTV and GSV in supine position at rest and maximum ankle plantar flexion. But the compression effect of GCS to SV and GSV was not observed during maximum ankle dorsiflexion. It was found that GCS application reduced the peak flow velocity of the femoral vein from 61.85 cm/s (95% CI = 50.94–72.75 cm/s) to 38.01 cm/s (95% CI = 28.42–47.59 cm/s) (P

Abstract Objectives To evaluate the effect of prior exposure to simulation-based training on medical students’ performance in simulation-based training in asthma exacerbation. Methods Third-year novice medical students, who had no prior experience in simulation education and completed diagnostics and internal medicine courses, were recruited in this prospective observational study and divided into the pre-exposure and unexposed groups. Each group received a four-hour asthma exacerbation simulation-based training. The pre-exposure group was exposed to a myocardial infarction simulation training two weeks prior to the asthma simulation training. The main outcome was the performance scores in clinical skills and abilities. Performance and task checklist completion were recorded during the training. In addition, the knowledge level was tested before and after the simulation training. Students’ satisfaction was evaluated using a feedback questionnaire. Results In a class of 203 third-year novice medical students, 101 (49.8%) and 102 (50.2%) were assigned to the unexposed and pre-exposure groups, respectively. Scores were higher in the post-simulation test compared with the pre-simulation test. Checklist completion was greater in the pre-exposure group compared with the unexposed group (p 0.001). Totally 73.21% and 26.13% of students strongly agreed and agreed, respectively, that asthma exacerbation simulation-based training was necessary and valuable. Conclusions Prior exposure to simulation training can improve performance in medical students, including communication skills, medical humanistic care and checklist completion in subsequent asthma exacerbation simulation-based training.

In order to realize simultaneous and rapid nondestructive detection of wheat quality (dry matter, weight), 35 wheat varieties samples were subjected to near-infrared (NIR) system scanning, and the spectral information were acquired and pretreated by three methods including Gaussian filtering smoothing (GFS), normalize (N) and baseline correction (BC), respectively. Partial least squares (PLS) algorithm was adopted to build a quantitative relationship between spectra and reference value of dry matter and weight, respectively. Two methods such as regression coefficients (RC) and successive projections algorithm (SPA) were applied to select optimal wavelengths from the full 900~1700 nm range for PLS model optimization. Based on the selected optimal wavelengths, PLS and multiple linear regression (MLR) prediction models were built respectively. The results indicated that the RC-RAW-PLS models based on 20 optimal wavelengths selected from RAW spectra by RC method had better performance in dry matter prediction, with rP of 0.93 and RMSEP of 0.03%. The SPA-RAW-MLR model built with 12 optimal wavelengths selected from RAW spectra by SPA method had better performance in weight prediction, with rP of 0.89 and RMSEP of 0.32 g. In conclusion, NIR spectroscopy combined with PLS and MLR algorithm could be used for rapid prediction of dry matter and weight in wheat grain.

Inactivation mutations in the Indian hedgehog (Ihh) gene in humans cause numerous skeletal chondrodysplasias, including acrocapitofemoral dysplasia, brachydactyly type A1, and human short stature. The lack of an appropriate human-relevant model to accurately represent these chondrodysplasias has hampered the identification of clinically effective treatments. Here, we established a mouse model of human skeletal dysplasia induced by Ihh gene mutations via ablation of Ihh in Aggrecan-positive (Acan+) cells using Aggrecan (Acan)-creERT transgenic mice. Smoothen agonist (SAG) promoted Hh activity and rescued chondrocyte proliferation and differentiation by stimulating smoothened trafficking to the cilium in Ihh-silenced cells. SAG treatment corrected mouse stature and significantly decreased mortality without evidence of toxicity. Moreover, Ihh ablation in Acan+ cells produced enchondroma-like tissues near the growth plates that were significantly reduced by SAG treatment. These results demonstrated that SAG effectively treats skeletal dysplasia caused by Ihh gene mutations in a mouse model, suggesting that SAG may represent a potential drug for the treatment of these diseases and/or enchondromas.

Spinal cord injury (SCI) is a serious disease of the central nervous system that is associated with a poor prognosis; furthermore, existing clinical treatments cannot restore nerve function in an effective manner. Inflammatory responses and the increased production of reactive oxygen species (ROS) in the microenvironment of the lesion are major obstacles that inhibit the recovery of SCI. Small extracellular vesicles (sEVs), derived from mesenchymal stem cells, are suitable options for cell-free therapy and have been shown to exert therapeutic effects in SCI, thus providing a potential strategy for microenvironment regulation. However, the effective retention, controlled release, and integration of small extracellular vesicles into injured spinal cord tissue are still a major challenge. Herein, we fabricated an N-acryloyl glycinamide/gelatin methacrylate/Laponite/Tannic acid (NAGA/GelMA/LPN/TA, NGL/T) hydrogel with sustainable sEV release (sEVs-NGL/T) to promote the recovery of motor function after SCI. The newly developed functional sEVs-NGL/T hydrogel exhibited excellent antioxidant properties in an H2O2-simulated peroxidative microenvironment in vitro. Implantation of the functional sEVs-NGL/T hydrogel in vivo could encapsulate sEVs, exhibiting efficient retention and the sustained release of sEVs, thereby synergistically inducing significant restoration of motor function and urinary tissue preservation. These positive effects can be attributed to the effective mitigation of the inflammatory and ROS microenvironment. Therefore, sEVs-NGL/T therapy provides a promising strategy for the sEV-based therapy in the treatment of SCI by comprehensively regulating the pathological microenvironment.

Abstract Basic mechanism of spine development is poorly understood. Type II collagen positive (Col2+) cells have been reported to encompass early mesenchymal progenitors that continue to become chondrocytes, osteoblasts, stromal cells, and adipocytes in long bone. However, the function of Col2+ cells in spine and intervertebral disc (IVD) development is largely unknown. To further elucidate the function of Col2+ progenitors in spine, we generated the mice with ablation of Col2+ cells either at embryonic or at postnatal stage. Embryonic ablation of Col2+ progenitors caused the mouse die at newborn with the absence of all spine and IVD. Moreover, postnatal deletion Col2+ cells in spine resulted in a shorter growth plate and endplate cartilage, defected inner annulus fibrosus, a less compact and markedly decreased gel‐like matrix in the nucleus pulposus and disorganized cell alignment in each compartment of IVD. Genetic lineage tracing IVD cell populations by using inducible Col2‐creERT;tdTomato reporter mice and non‐inducible Col2‐cre;tdTomato reporter mice revealed that the numbers and differentiation ability of Col2+ progenitors decreased with age. Moreover, immunofluorescence staining showed type II collagen expression changed from extracellular matrix to cytoplasm in nucleus pulposus between 6 month and 1‐year‐old mice. Finally, fate‐mapping studies revealed that Col2+ progenitors are essential for IVD repair in IVD injured model. In summary, embryonic Col2+ cells are the major source of spine development and Col2+ progenitors are the important contributors for IVD repair and regeneration.

Insufficient oxygen supply at the tumor site and hypoxia caused during tumor treatment lead to a poor therapeutic effect and poor prognosis. Therefore, effectively overcoming the problem of hypoxia in tumors and avoiding hypoxia that compromises the efficacy of the treatment could improve the anti-tumor therapeutic effect. Thus, this study reports the ability of W18O49@EP nanoparticles to release reactive oxygen species (ROS) during the combined tumor radiotherapy (RT) and photodynamic therapy (PDT). The release of ROS by the nanoparticles during near infrared light (NIR) irradiation was demonstrated by in vitro and in vivo experiments, realizing an effective PDT without inducing hypoxia. Indeed, the ROS did not derive from the oxygen in the tumor microenvironment but they were released by the nanoparticles. Thus, ROS could improve the therapeutic effect of RT avoiding the problem of hypoxia after RT. Hence, W18O49@EP nanoparticles greatly improved the anti-tumor effect due to their effectiveness despite the insufficient oxygen supply and hypoxia caused by traditional RT and PDT.

IntroductionMannitol is the most widely used hyperosmolar agent during neurosurgical procedures. However, its use can lead to serious hyperkalemia with altered cardiac conduction.Case presentationHere we report a case in which a 40-min cardiac arrest was caused by mannitol-induced hyperkalemia during craniotomy. In addition, we conducted a literature review through a PubMed (MEDLINE) search of the relevant literature published so far. Details of all cases are presented and discussed. The results suggest that male patients or patients with uncontrolled diabetes might be at higher risk to develop this phenomenon. The results also suggest that the high dose and rapid rate of infusion of mannitol might contribute to mannitol-induced hyperkalemia.ConclusionPhysicians should be aware of the existence of mannitol-induced hyperkalemia. Although the mechanism of this complication is not well established, it is prudent to administer mannitol cautiously, especially in patients with uncontrolled diabetes. Continuous electrocardiogram monitoring and frequent measurements of serum electrolytes can help to detect and treat possible life-threatening events induced by mannitol-induced hyperkalemia early.

Abstract Codes of Open Source Software (OSS) are widely reused during software development nowadays. However, reusing some specific versions of OSS introduces 1-day vulnerabilities of which details are publicly available, which may be exploited and lead to serious security issues. Existing state-of-the-art OSS reuse detection work can not identify the specific versions of reused OSS well. The features they selected are not distinguishable enough for version detection and the matching scores are only based on similarity.This paper presents B2SMatcher, a fine-grained version identification tool for OSS in commercial off-the-shelf (COTS) software. We first discuss five kinds of version-sensitive code features that are trackable in both binary and source code. We categorize these features into program-level features and function-level features and propose a two-stage version identification approach based on the two levels of code features. B2SMatcher also identifies different types of OSS version reuse based on matching scores and matched feature instances. In order to extract source code features as accurately as possible, B2SMatcher innovatively uses machine learning methods to obtain the source files involved in the compilation and uses function abstraction and normalization methods to eliminate the comparison costs on redundant functions across versions. We have evaluated B2SMatcher using 6351 candidate OSS versions and 585 binaries. The result shows that B2SMatcher achieves a high precision up to 89.2% and outperforms state-of-the-art tools. Finally, we show how B2SMatcher can be used to evaluate real-world software and find some security risks in practice.

Abstract Study design This was a cross-sectional frequency-matched case–control study. Background and aim The serum lipid profile of lipoprotein(a) [Lp(a)] level and apolipoprotein B/apolipoprotein A1 ratio (Apo B/Apo A1) ratio were found to be more representative for serum lipid level and were recognized as the independent risk factors for various diseases. Although the blood levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were found to be associated with symptomatic intervertebral disk herniation (IDH), no studies to date have evaluated the association of Apo AI, Apo B, Lp(a), and Apo B/Apo AI levels with symptomatic IDH. This study aimed to assess the link between blood lipid levels and symptomatic IDH. Method The study included 1839 Chinese patients. Of these, 918 patients were diagnosed with IDH and enrolled in the experimental group. A control group of 921 patients underwent a physical examination during the same period. The serum lipid levels of TC, TG, LDL-C, HDL-C, Lp(a), Apo B, and Apo B/Apo AI were examined and analyzed. The control group comprised randomly selected patients who met the baseline levels of the aforementioned lipid molecules. Results Patients with IDH exhibited significantly higher TC, TG, LDL, Apo B, and Lp(a) levels than controls. The percentage of high TC, high TG, high LDL, high Apo B, and high Lp(a) were obviously higher in the IDH group than in the control group. However, hyperlipidemia had no relationship with the degenerated segment of the IDH (P = 0.201). The odds ratio (OR) for the incidence of IDH with elevated levels of LDL-C, TC, TG, Lp(a), Apo B, and Apo B/Apo AI was 1.583, 1.74, 1.62, 1.58, 1.49, and 1.39, respectively. The correlation analysis revealed the correlation between elevated LDL-C, TC, TG, Apo B, Lp(a), and incidence of IDH was significant (R 2 LDL = 0.017; R 2 TC = 0.004; R 2 TG = 0.015; R 2 Apo B = 0.004; R 2 Lp(a) = 0.021) (P

Background: Krüppel like factor 10 (KLF10), which is also known as TGF-β Inducible Early Gene-1 (TIEG1), plays a crucial role in regulating cell proliferation, cell apoptosis and inflammatory reaction in human carcinoma cells. Moreover, KLF10 knockout in mice leads to severe defects associated with muscle, skeleton and heart etc. However, the function of KLF10 in intervertebral disc degeneration (IVDD) has not been reported yet. Methods: The relationship between KLF10 and IVDD were investigated in nucleus pulposus (NP) tissues from human and rats. The role of KLF10 in NP cells was explored via loss or gain of function experiments. IVDD rat models were constructed through needle puncture and the effects of KLF10 in IVDD model of rats were investigated via intradiscal injection of KLF10. Results: We first found that KLF10 was lowly expressed in degenerative NP tissues and the level of KLF10 showed negative correlation with the disc grades of IVDD patients. Loss or gain of function experiments demonstrated that KLF10 could inhibit apoptosis and enhance migration and proliferation of IL-1β induced NP cells. And KLF10 overexpression reduced extracellular matrix (ECM) degeneration and enhanced ECM synthesis, whereas knockdown of KLF10 resulted in adverse effects. These positive effects of KLF10 could be reversed by the inhibition of TGF-β signaling pathway. In vivo, KLF10 overexpression alleviated IVDD. Conclusions: This is the first study to reveal that KLF10 was dysregulated in IVDD and overexpressed KLF10 could alleviate IVDD by regulating TGF-β signaling pathway both in vitro and in vivo, which were involved in prohibiting apoptosis, promoting proliferation and migration of NP cells.The translational potential of this article: Overexpression of KLF10 might be an effective therapeutic strategy in the treatment of IVDD.

To ensure the safety of construction site personnel and to improve the efficiency of emergency safety evacuation of site personnel, this study analyzes the risk reasons for fire accidents and the characteristics of combustion fires on construction sites. Based on a refined BIM model, a numerical simulation of the fire situation is performed using PyroSim (2019 version) software on a construction site. In the Pyrosim fire simulation model, fire scenarios with distinct construction stages and fire source locations are set up to simulate, compare, and analyze the varying pattern of each fire product in various fire scenarios. Using this information with the Pathfinder (2019 version) simulation model, a coupled simulation test of fire evacuation is conducted to assess the safety of evacuating individuals in each fire scenario. The results show that flammable materials in open spaces are more risky to burn than in confined spaces. After optimizing the utilization of safety exits and the density of people in the second simulation, it was found that the required safety evacuation time was reduced to 267 s, which is lower than the available safety evacuation time of 318.5 s for each scenario. All fire scenarios meet the safe evacuation criteria. The study results can provide a theoretical basis for developing fire response strategies for construction units and contribute to site safety management.

Abstract Background Hepatocellular carcinoma (HCC) is a common cancer and the leading cause is persistent hepatitis B virus (HBV) infection. We aimed to identify some core genes and pathways for HBV-related HCC. Methods Gene expression profiles of GSE62232, GSE121248, and GSE94660 were available from Gene Expression Omnibus (GEO). The GSE62232 and GSE121248 profiles were the analysis datasets and GSE94660 was the validation dataset. The GEO2R online tool and Venn diagram software were applied to analyze commonly differentially expressed genes between HBV-related HCC tissues and normal tissues. Then, functional enrichment analysis using Gene Ontology (GO) and the Kyoto Encyclopedia of Gene and Genome (KEGG) as well as the protein-protein interaction (PPI) network was conducted. The overall survival rates and the expression levels were detected by Kaplan-Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA). Next, gene set enrichment analysis (GSEA) was performed to verify the KEGG pathway analysis. Furthermore, quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to validate the levels of these three core genes in tumor tissues and adjacent non-tumor liver tissues from 12 HBV related HCC patients, HBV-associated liver cancer cell lines and normal liver cell lines, and HepG2 with p53 knockdown or deletion, respectively. Results Fifteen highly expressed genes associated with significantly worse prognoses were selected and CCNB1, CDK1, and RRM2 in the p53 signaling pathway were identified as core genes. GSEA results showed that samples highly expressing three core genes were all enriched in the p53 signaling pathway in a validation dataset (P < 0.0001). The expression of these three core genes in tumor tissue samples was higher than that in relevant adjacent non-tumor liver tissues (P < 0.0001). Furthermore, we also found that the above genes were highly expressed in liver cancer cell lines compared with normal liver cells. In addition, we found that the expression of these three core genes in p53 knockdown or knockout HCC cell lines was lower than that in negative control HCC cell lines (P < 0.05). Conclusions CCNB1, CDK1, and RRM2 were enriched in the p53 signaling pathway and could be potential biomarkers and therapeutic targets for HBV-related HCC.

A new dysprosium (III) coordination polymer [Dy(Hm-dobdc) (H2O)2]·H2O (Dy-CP), was hydrothermal synthesized based on 4,6-dioxido-1,3-benzenedicarboxylate (H4m-dobdc) ligand containing carboxyl and phenolic hydroxyl groups. The Dy(III) center adopts an octa-coordinated [DyO8] geometry, which can be described as a twisted square antiprism (D4d symmetry). Neighboring Dy(III) ions are interconnected by deprotonated Hm-dobdc3− ligand to form the two-dimensional infinite layers, which are further linked to generate three-dimensional structure through abundant hydrogen bonds mediated primarily by coordinated and lattice H2O molecules. Magnetic studies demonstrates that Dy-CP shows the field-induced slow relaxation of magnetization and the energy barrier Ueff/kB and relaxation time τ0 are 35.3 K and 1.31 × 10–6 s, respectively. Following the vehicular mechanism, Dy-CP displays proton conductivity with σ equal to 7.77 × 10–8 S cm−1 at 353 K and 30%RH. Moreover, luminescence spectra reveal that H4m-dobdc can sensitize characteristic luminescence of Dy(III) ion. Herein, good magnetism, proton conduction, and luminescence are simultaneously achieved, and thus, Dy-CP is a potential multifunctional coordination polymer material.

BackgroundTobacco smoking is a leading cause of premature death in China, especially among adult men. Since the implementation of the Framework Convention on Tobacco Control in 2005, nationwide tobacco control has been strengthened, but its long-term impact on smoking prevalence is unclear.Methods and findingsFive nationally representative surveys of the China Chronic Disease and Risk Factor Surveillance (CCDRFS) were conducted in 2007, 2010, 2013, 2015, and 2018. A total of 624,568 adults (278,605 men and 345,963 women) aged 18 to 69 years were randomly selected from 31 provinces (or equivalent) in China. Temporal changes in smoking prevalence and patterns (e.g., percentages of those smoking manufactured cigarettes, amount smoked, and age at smoking initiation) were analyzed, overall and by sex, urban or rural residence, year of birth, education and occupation, using linear regression methods. Among men, the standardized prevalence of current smoking decreased from 58.4% (95% confidence interval [CI]: 56.1 to 60.7) to 50.8% (95% CI: 49.1 to 52.5, p < 0.001) between 2007 and 2018, with annual decrease more pronounced in urban (55.7% [95% CI: 51.2 to 60.3] to 46.3% [95% CI: 43.7 to 49.0], p < 0.001) than rural men (59.9% [95% CI: 57.5 to 62.4] to 54.6% [95% CI: 52.6 to 56.6], p = 0.05) and in those born before than after 1980. Among rural men born after 1990, however, the prevalence increased from 40.2% [95% CI: 34.0 to 46.4] to 52.1% ([95% CI: 45.7 to 58.5], p = 0.007), with the increase taking place mainly before 2015. Among women, smoking prevalence remained extremely low at around 2% during 2007 to 2018. No significant changes of current smoking prevalence (53.9% to 50.8%, p = 0.22) were observed in male patients with at least 1 of major chronic diseases (e.g., hypertension, diabetes, myocardial infarction, stroke, chronic obstructive pulmonary disease (COPD)). In 2018, 25.6% of adults aged ≥18 years smoked, translating into an estimated 282 million smokers (271 million men and 11 million women) in China. Across 31 provinces, smoking prevalence varied greatly. The 3 provinces (Yunnan, Guizhou, and Hunan) with highest per capita tobacco production had highest smoking prevalence in men (68.0%, 63.4%, and 61.5%, respectively), while lowest prevalence was observed in Shanghai (34.8%). Since the children and teenage groups were not included in the surveys, we could not assess the smoking trends among youths. Furthermore, since the smoking behavior was self-reported, the smoking prevalence could be underestimated due to reporting bias.ConclusionsIn this study, we observed that the smoking prevalence has decreased steadily in recent decades in China, but there were diverging trends between urban and rural areas, especially among men born after 1980. Future tobacco control strategies should target rural young men, regions with high tobacco production, and patients suffering from chronic diseases.

Abstract Seed germination and uniform plant stand in the field are the most critical crop growth stages determining the final yield. Pea (Pisum sativum L.) seeds production is often hampered due to the seed dormancy caused by the hard seed coat. Such effect is mainly attributed to poor or uneven germination and unsynchronised seedling emergence. Understanding the time course of water intake and several critical germination indicators can reveal many features of seed germination such as rate and uniformity. This paper used optical coherence tomography (OCT), a noninvasive and cross‐sectional imaging technique, to monitor the inner structural changes throughout the germination process. A sequence of cross‐sectional OCT images of pea (P. sativum L.) seeds, together with additional microscopic optical images, was recorded continuously and in situ for over 40 h. OCT and microscopic images revealed the changes in the internal structure and the external shape of the pea seeds during germination, respectively. It was found that the cross‐sectional OCT images helped to identify the critical indicators distinguishing the different phases of germination pea seeds. Therefore, the presented OCT approach offers a fast and nondestructive way to precisely measure the structural indicators in different germination phases.

In recent decades, environmental problems have enforced designers to estimate the level of environmental emission of building design and reduce their environmental impact. On the premise of ensuring indoor comfort, the cost-effectiveness of solutions for reducing the building’s greenhouse gas has become a critical issue. Based on the Life Cycle Assessment (LCA), this paper establishes a building performance trade-off framework for indoor thermal comfort, economics, and environmental implication. This framework consists of four parts: the establishment of the optimization model; sensitivity analysis; obtain of Pareto frontier solutions, and decision-making analysis. Optimization variables involve envelope type and some envelope physical parameters. The “design variables-building performances” database is obtained by using building simulation software combined with the Latin hypercube sampling algorithm. Sensitivity analysis is used to extract the key factors affecting building performance. The designer can prioritize these key factors and it can reduce the uncertainty of building performance. A multi-objective optimization method coupling Gradient Boosted Decision Tree (GBDT) and non-dominated sorting genetic (NSGA-II) algorithm is proposed to seek the trade-off between three performances (obtain Pareto frontier solutions). The Pareto solution provides a more comprehensive reference for the preferences of different stakeholders, and the set of alternative solutions is further shrunk. Finally, take a specific residential building in China’s cold climate zone as a showcase of the trade-off framework. According to the obtained Pareto frontier solution, the solution set is shrunk to a certain range, and the distribution ranges of Life Cycle Costs, the greenhouse gas emissions, and the annual thermal discomfort hour ratio are 122.3–137.1 USD/m2, 15.6–44.8 kg CO2/m2, and 19.1–25.2%, respectively. The trade-off framework adopts the order of objective Pareto optimal and then subjective preference selection, narrowing the scope of alternatives for designers and saving time-cost of decision-making.

Objective: In the context of China’s “two-child” policy, this study aims to compare socio-demographic characteristics and attitudes towards the desired number of children among couples of different family size. We describe the major reasons for and against couples raising a (further) child based on the theory of planned behavior. Material and Methods: An interview-based survey was conducted in Inner Mongolia among couples visiting marital registration offices, antenatal care clinics, kindergartens, and primary schools. Using prevalence ratios and 95% confidence intervals estimated from multivariate log-binomial regression models, socio-demographic characteristics and attitudes towards the two-child policy were compared between three types of couples: those without children, those with one child, and those with multiple children. Results: The sample consisted of 2,013 women aged 20-49 years and their partners. The top difficulty in raising a child was “increased economic burden”. Factors significantly associated with a reduced prevalence of raising children included the woman’s marital age and the couple’s educational achievement, employment status, and monthly income. Factors associated with an increased prevalence of raising children included a lack of inter-couple communication, having a perception of the strong influence of the two-child policy, and Han ethnicity. Conclusion: Significant socio-demographic differences were seen between couples with and without children in China. Childless couples were more affluent than single- or multi-child couples and they perceived the two-child policy to be less influential on their decision to raise children.

Abstract Background Cold, an environmental factor, induces many reproductive diseases. It is known that endothelin (ET) is a potent vasoconstrictor, and cold stress can increase the expression of ET and its receptors. The cold stress rat model was developed to examine two parameters: (1) the effects of cold stress on ovarian and uterine morphology, function, and microvascular circulation and (2) possible mechanisms of ET and its receptors involved in cold stress-induced menstruation disorders. Methods The rat cold stress model was prepared with an ice water bath. The estrous cycle was observed by methylene blue and hematoxylin and eosin (H&E) staining. Serum estradiol 2 (E2), testosterone (T), progesterone (P) were detected by radioimmunoassay. Hemorheology indices were measured. The real-time blood flow of auricle and uterine surfaces was measured. Expressions of CD34 and α-SMA in ovarian and uterine tissues were detected by immunohistochemistry. ET-1 contents in serum were tested, and expressions of ET-receptor types A and B (ET-AR and ET-BR) in ovarian tissues were detected via Western blotting. Results Cold stress extended the estrous cycle, thereby causing reproductive hormone disorder, imbalance of local endothelin/nitric oxide expression, and microcirculation disturbance. Cold-stress led to up-regulation of ET-AR expression and protein and down-regulation of ET-BR expression in rats. Conclusions This study suggests that the reason for cold stress-induced dysfunction in reproductive organs may be closely related to the imbalance of ET-1 and its receptor expressions, leading to microvascular circulation disorders in local tissues.

Primary cilia are highly conserved microtubule-based organelles that project from the cell surface into the extracellular environment and play important roles in mechanosensation, mechanotransduction, polarity maintenance, and cell behaviors during organ development and pathological changes. Intraflagellar transport (IFT) proteins are essential for cilium formation and function. The skeletal system consists of bones and connective tissue, including cartilage, tendons, and ligaments, providing support, stability, and movement to the body. Great progress has been achieved in primary cilia and skeletal disorders in recent decades. Increasing evidence suggests that cells with cilium defects in the skeletal system can cause numerous human diseases. Moreover, specific deletion of ciliary proteins in skeletal tissues with different Cre mice resulted in diverse malformations, suggesting that primary cilia are involved in the development of skeletal diseases. In addition, the intact of primary cilium is essential to osteogenic/chondrogenic induction of mesenchymal stem cells, regarded as a promising target for clinical intervention for skeletal disorders. In this review, we summarized the role of primary cilia and ciliary proteins in the pathogenesis of skeletal diseases, including osteoporosis, bone/cartilage tumor, osteoarthritis, intervertebral disc degeneration, spine scoliosis, and other cilium-related skeletal diseases, and highlighted their promising treatment methods, including using mesenchymal stem cells. Our review tries to present evidence for primary cilium as a promising target for clinical intervention for skeletal diseases.