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Abstract Background To investigate the relationship between estimated glucose disposal rate (eGDR), a surrogate indicator of insulin resistance, and atherosclerotic cardiovascular diseases (ASCVD) incidence risk. Methods This prospective cohort study utilized data from the 6026 participants from the Multi-Ethnic Study of Atherosclerosis. The eGDR (mg/kg/min) was computed as 21.158 − (0.09 × waist circumference [cm]) − (3.407 × hypertension [yes/no]) − (0.551 × HbA1c [%]). The population was categorized into four subgroups according to the quartiles (Q) of eGDR. Cox proportional hazard models were applied to assess the associations between eGDR and ASCVD incidence, and restricted cubic spine (RCS) was employed to examine the dose–response relationship. Results The mean age of participants was 63.6 ± 10.1 years, comprising 3163 (52.5%) women. Over a median follow-up duration of 14.1 years, 565 (9.4%) developed ASCVD, including 256 (4.2%) myocardial infarctions, 234 (3.9%) strokes, and 358 (5.9%) fatal coronary heart disease. Compared to the lowest quartile, the adjusted hazard ratios (95% confidence intervals) for incident ASCVD for Q2–Q4 were 0.87 (0.68−1.10), 0.63 (0.47−0.84), and 0.43 (0.30−0.64), respectively. Per 1 standard deviation increase in eGDR was associated with a 30% (HR: 0.70, 95% CI 0.60−0.80) risk reduction of ASCVD, with the subgroup analyses indicating that age and hypertension modified the association (P for interaction

BackgroundAfter working in a harsh occupational hazard environment for a long time, open-pit coal mine workers are under tremendous physical and mental pressure, which is prone to presenteeism behavior. objectiveTo identify the relationships between presenteeism, job burnout, and social support of open-pit coal miners, and verify potential mediating effect of job burnout between social support and presenteeism. MethodsIn 2020—2021, a questionnaire survey was conducted among employees of 6 open-pit coal mining enterprises in Xinjiang by stratified cluster random sampling. Job Burnout Questionnaire, Job Content Questionnaire, and Presenteeism Behavior Scale were used to evaluate burnout, social support, and presenteeism behavior in the study subjects. SPSS 26.0 software was used for t test, F test, correlation analysis, and mediating effect test. ResultsA total of 1199 questionnaires were distributed and 1083 valid questionnaires were recovered, with an effective recovery rate of 90.3%. The M (P25, P75) scores of presenteeism behavior, social support, and job burnout were 2.0 (2.0, 5.0), 24.0 (23.0, 26.0), and 45.0 (34.0, 51.0), respectively. The Spearman correlation analysis results showed that there was a significant negative correlation between social support and job burnout (\begin{document}$ r $\end{document}=−0.200, P

PurposePatients with colorectal cancer (CRC) frequently present with anemia and signs of infection. However, the relationships between these factors remain unclear. This study investigated the potential association between anemia, inflammatory indices, and CRC.MethodsWe analyzed data from the 2011–2018 National Health and Nutrition Examination Survey to investigate links between anemia, inflammation, and CRC. Inflammatory indices, including the neutrophil-percentage-to-albumin ratio, neutrophil-to-lymphocyte ratio, and eosinophil-to-lymphocyte ratio, were analyzed. Following rigorous inclusion criteria, 14,114 participants were included. Statistical methods such as logistic regression and subgroup analyses were employed. Moreover, survival analysis was performed.ResultsAmong the 14,114 participants, 0.6% had CRC and 11.0% were diagnosed with anemia. Anemia and inflammatory indices were associated with CRC, suggesting an increased risk (OR range: 2.03-2.50, P

Purpose: To investigate the effects of accommodation on the geometrical parameters of human lens. Methods: Eight databases from inception to November 2023 were used for the literature search: CNKI, CBM, VIP, Wan-Fang, PubMed, Web of Science, EMBASE, and the Cochrane Library. The Methodological Index for Non-randomized Studies was used to assess the risk of bias. The PRISMA were followed and the following outcomes were taken into consideration: lens diameter (LD), lens thickness (LT), anterior curvature radius (ACR), posterior curvature radius (PCR), lens center position (LCP), and total cross-sectional area (TCSA). This systematic review was registered on an international platform for registered systematic reviews and meta-analysis (INPLASY202260085). Results: A total of 19 studies were included. LT increased by 0.04 mm/D (18 studies; 95% confidence interval [CI], 0.03–0.06; I2 = 96.6%; P

The retinal pigment epithelium (RPE) and choroid are located behind the human retina and have multiple functions in the human visual system. Knowledge of the RPE and choroid cells and their gene expression profiles are fundamental for understanding retinal disease mechanisms and therapeutic strategies. Here, we sequenced the RNA of about 0.3 million single cells from human RPE and choroids across two regions and seven ages, revealing regional and age differences within the human RPE and choroid. Cell–cell interactions highlight the broad connectivity networks between the RPE and different choroid cell types. Moreover, the transcription factors and their target genes change during aging. The coding of somatic variations increases during aging in the human RPE and choroid at the single-cell level. Moreover, we identified ELN as a candidate for improving RPE degeneration and choroidal structure during aging. The mapping of the molecular architecture of the human RPE and choroid improves our understanding of the human vision support system and offers potential insights into the intervention targets for retinal diseases.

Abstract Background Intestinal ischemia-reperfusion injury occurs in acute intestinal obstruction, intussusception, acute mesenteric artery embolism, and other diseases and can lead to local intestinal necrosis, distant organ involvement, or systemic reactions, with high morbidity and mortality. Ferroptosis plays a crucial role in intestinal ischemia-reperfusion injury, and inhibition of ferroptosis may provide new approaches for treating the disease. SIRT3 protects cells from oxidative stress and may be involved in the process of ferroptosis. We hypothesized that resveratrol, an agonist of SIRT3, could ameliorate intestinal ischemia-reperfusion injury by compensating the GSH/GPX4 pathway. Methods Intestinal ischemia-reperfusion (I/R) and Caco-2 hypoxia-reoxygenation models were established. Transmission electron microscopy was used to assess mitochondrial function; the Chiu’s score was used to evaluate the degree of intestinal mucosal injury based on HE staining; and Western blot was used to detect the SIRT3/FoxO3a pathway, tight junction proteins and ferroptosis-related protein expression. Sirt3 -/- C57, shSIRT3-Caco-2 cells and siFoxO3a-Caco-2 cells were established. C11-BODIPY was used to detect lipid peroxide in cells; FD4 and IFABP were used to detect intestinal permeability; MitoSOX was used to detect ROS levels; and MitoTracker and immunofluorescence colocalization were used to detect SIRT3 levels. Results In the intestinal I/R model, I/R injury occurs mainly during the reperfusion period and leads to ferroptosis through the GSH/GPX4 pathway. Resveratrol could reduce ferroptosis and ameliorate I/R injury by activating SIRT3. In Sirt3-/- mice, more intestinal mucosal cells underwent ferroptosis, I/R injury was more severe, and resveratrol lost the ability to ameliorate I/R injury. In addition, hypoxia-reoxygenation increased RSL3-induced ferroptosis sensitivity in Caco-2 cells in vitro. In the presence of shSIRT3 or RSL3 alone, resveratrol could ameliorate Caco-2 ferroptosis, but not RSL3-induced shSIRT3-Caco-2 ferroptosis. Furthermore, resveratrol might activate the SIRT3/FoxO3a pathway, increase the expression of SOD2 and catalase, and inhibit ROS generation, thus reducing lipid peroxidation and ferroptosis. Conclusion To date, this is the first study to show that resveratrol ameliorates intestinal ischemia-reperfusion injury by activating SIRT3 and reducing ferroptosis. Resveratrol can reduce intestinal ischemia-reperfusion injury by activating the SIRT3/FoxO3a pathway, increasing the expression of SOD2 and catalase, reducing ROS and LPO production, compensating for the GSH/GPX4 pathway and inhibiting ferroptosis. Graphical abstract Resveratrol increases the expression of SOD2 and catalase, reduces the production of ROS and LPO, compensates for the GSH/GPX4 pathway and inhibits ferroptosis by activating the SIRT3/FoxO3a pathway

ObjectivesTo investigate the current situation regarding occupational burnout among coal miners, explore the relationship between NR3C2 gene polymorphism and occupational burnout, and analyze the influence of the interaction between environment and gene on occupational burnout. This study provides a scientific basis for formulating health strategies to combat job burnout.MethodsA total of 1,500 first-line coal mine workers were selected by cluster random sampling, and the job burnout scale, job content questionnaire (JCQ), and simplified coping style questionnaire (SCSQ) were used for the questionnaire survey. A total of 150 workers were randomly selected from the high burnout group and the low burnout group, and a total of 300 workers were selected as the research objects to examine the relationship between gene polymorphism, environment-gene interactions and burnout. This study employed iMLDRTM genotyping technology for NR3C2 gene (rs5522, rs2070950) polymorphism analysis. The relationship between the occurrence of job burnout, occupational stress, coping styles and the NR3C2 gene was analyzed.ResultsFinally, a total of 1,282 valid questionnaires were retrieved, with an effective recovery rate of 85.5%. The study included 128 participants (10%) with zero burnout, 400 (31.2%) with mild burnout, 649 (50.6%) with moderate burnout and 105 (8.2%) with severe burnout. There were significant differences in the rate of burnout among miners with respect to sex, age, working years, educational level, shifts, and marital status (P < 0.05). The difference in occupational stress between the different job burnout groups was statistically significant (P < 0.05). Compared with the GG genotype of rs2070950 of the NR3C2 gene, the CC genotype was identified as a susceptibility gene for occupational burnout (P < 0.05). In respect to rs5522, rs2070950, occupational stress, positive coping, and negative coping, the low-risk group was unlikely to suffer from job burnout compared with the high-risk group (OR = 0.103, 95%CI: 0.058–0.182).ConclusionIn addition to demographic characteristics, occupational stress and negative coping styles were also identified as risk factors for job burnout. The interaction between locus rs5522, locus rs2070950, occupational stress, positive response, and negative response were found to affect the incidence of occupational burnout.

Quartz sand (SiO2) is a prevalent filtration medium, boasting wide accessibility, superior stability, and cost-effectiveness. However, its utility is often curtailed by its sleek surface, limited active sites, and swift saturation of adsorption sites. This review outlines the prevalent strategies and agents for quartz sand surface modification and provides a comprehensive analysis of the various modification reagents and their operative mechanisms. It delves into the mechanism and utility of surface-modified quartz sand for adsorbing heavy metal ions (HMIs). It is found that the reported modifiers usually form connections with the surface of quartz sand through electrostatic forces, van der Waals forces, pore filling, chemical bonding, and/or molecular entanglement. The literature suggests that these modifications effectively address issues inherent to natural quartz sand, such as its low superficial coarseness, rapid adsorption site saturation, and limited adsorption capacity. Regrettably, comprehensive investigations into the particle size, regenerative capabilities, and application costs of surface-modified quartz sand and the critical factors for its wider adoption are lacking in most reports. The adsorption mechanisms indicate that surface-modified quartz sand primarily removes HMIs from aqueous solutions through surface complexation, ion exchange, and electrostatic and gravitational forces. However, these findings were derived under controlled laboratory conditions, and practical applications for treating real wastewater necessitate overcoming further laboratory-scale obstacles. Finally, this review outlines the limitations of partially surface modified quartz sand and suggests potential venues for future developments, providing a valuable reference for the advancement of cost-effective, HMI-absorbing, surface-modified quartz sand filter media.

Abstract Objective The purpose of this study is to verify the correlation between medium and low radiation doses of the pelvic-bone marrow and the incidence of lymphocytic toxicity during concurrent chemoradiotherapy for cervical cancer. Materials and methods This research included 117 cervical cancer patients, who received concurrent chemoradiotherapy. Radiotherapy included external-beam radiation therapy and brachytherapy. The dosimetry parameters include the Volume receiving 5 Gy (V5), 10 Gy (V10), 20 Gy (V20), 30 Gy (V30), 40 Gy (V40), 50 Gy (V50), and the mean dose (D mean) of the bone marrow. Lymphocytic toxicity was calculated from lowest lymphocytic count after two cycles of concurrent chemotherapy. Results During concurrent chemoradiotherapy, the incidence of lymphocytic toxicity is 94.88%. The incidence of grade 3–4 toxicity is 68.38%. Multivariate analysis findings show that the dosimetry parameters V5, V10, V20, and V30 are significantly correlated with lymphocytic toxicity. The patients are divided into small-volume subgroups and large-volume subgroups based on the cutoff values. The relative risk of both grade 1–4 and grade 3–4 lymphocytic toxicity is significantly lower in the small-volume subgroups than in the large-volume subgroups (P

Introduction In the Chinese healthcare system, where there is overcrowding in hospitals, especially in tertiary care centres, adoption of same-day discharge (SDD) post-percutaneous coronary intervention (PCI) could potentially lead to significant savings of healthcare resources and costs. This study is a non-inferiority trial examining whether post-PCI SDD is feasible in China. The primary hypothesis is that patient outcomes in post-urgent PCI SDD patients are non-inferior to regular discharge patients.Methods and analysis Post-Urgent PCI Same-DaY is an investigator-initiated multicentre randomised unblinded clinical non-inferiority trial, with 1:1 centralised randomisation to the SDD or usual care (UC) group. Based on sample size calculations, 1296 patients from at least three hospitals, with mild to moderate myocardial infarction, will be included, and acute coronary syndrome patients will be excluded. All patients will receive UC while patients assigned to the SDD group will be discharged on the same day or within 12 hours post-PCI. The primary outcome is major adverse cardiovascular and cerebrovascular events 30 days after discharge. The secondary outcomes are all-cause mortality, bleeding and access site complications. The outcome rates will be compared between groups with the absolute risk difference with a 95% CI.Ethics and dissemination The study protocol V.2.0 has been approved on 21 January 2022 by the Ethics Committee of Beijing Anzhen Hospital, Capital Medical University (approval number: 2021 KLSD No. 23). The outcomes of this study will be disseminated through a peer-reviewed journal and presented at international conferences.Trial registration number ChiCTR 2200057065; China Clinical Trial Registration.

Corneal disease threatens vision globally. Among corneal diseases, calcific band keratopathy has severe effects on vision owing to its unique location. Currently, ethylene diamine tetraacetic acid (EDTA) chelation remains the most important treatment. However, only the safety of low-dose topical EDTA eye drops is well established in humans. Therefore, the purpose of this study was to determine the safe dose range of EDTA for calcific band keratopathy surgery and its toxic effects on rabbit eyes. Rabbits were administered different doses of EDTA solutions (0.50, 0.20, 0.10, 0.05, and 0.01 M) for twenty minutes. In day seven, the rabbits were euthanized and pathological examination was performed for cornea. We found severe corneal edema in 0.50 M group, while milder edema in lower-concentration treated groups. Followed by corneal thickness measurement, the measured values increase to the peak in post-operative three day (0.20 M group) or one day (lower-concentration groups), then decreased. Groups comparison shown significant difference between BSS control group and higher concentration groups (0.20 M and 0.10 M) (P 0.05). Confocal microscopy examination suggested, the number of corneal endothelial cells significantly decreased from 3428.6 ± 180.3 cells/mm2 to 2808 ± 80.6 cells/mm2 in the 0.50 M group, while the lower-concentration groups showed lesser toxic effects on corneal endothelial cells. Finally, our histological examination demonstrated inflammation in each experimental group and dose-dependent, compared with control group. Our study found 0.05 M and 0.01 M EDTA solutions had no obvious toxic effect on the corneal endothelium compared with higher concentration. However, further study of EDTA side effect by clinical trials, and therapeutic effect observation with different concentration are necessary.

The supervised super-resolution (SR) methods based on simple degradation assumptions (e.g., bicubic downsampling) have unsatisfactory generalization ability on real-world thermal images. To enhance the SR effect of real-world sceneries, we introduce an unsupervised SR framework for thermal images, incorporating degradation modeling and corresponding SR. Inspired by the physical prior that high frequency affects details and low frequency affects thermal contrast, we propose a frequency-aware degradation model, named TFADGAN. The model achieves image quality migration between thermal detectors of different resolutions by degrading different frequency components of the image from high-resolution (HR) to low-resolution (LR). Specifically, by adversarial learning with unpaired LR thermal images, the complex degradation processes of HR thermal images at low and high frequencies are modeled separately. Benefiting from the thermal characteristics mined from real-world images, the degraded images generated by TFADGAN are similar to LR thermal ones in terms of detail and contrast. Then, the SR model is trained based on the pseudo-paired data consisting of degraded images and HR images. Extensive experimental results demonstrate that the degraded images generated by TFADGAN provide reliable alternatives to real-world LR thermal images. In real-world thermal image experiments, the proposed SR framework can improve the peak signal-to-noise ratio (PSNR) and structural similarity degree (SSIM) by 1.28 dB and 0.02, respectively.

Blood contact materials require strong anti-fouling capabilities to avoid thrombus formation. Recently, TiO2-based photocatalytic antithrombotic treatment has gained focus. Nevertheless, this method is restricted to titanium materials with photocatalytic abilities. This study offers an alternative solution that can be applied to a broader range of materials: piranha solution treatment. Our findings revealed that the free radicals generated by the treatment effectively altered the surface physicochemical properties of various inorganic materials, enhancing their surface hydrophilicity and oxidizing organic contaminants, thus improving their antithrombotic properties. Additionally, the treatment resulted in contrasting effects on the cellular affinity of SS and TiO2. While it significantly reduced the adhesion and proliferation of SMCs on SS surfaces, it significantly enhanced these on TiO2 surfaces. These observations suggested that the impact of the piranha solution treatment on the cellular affinity of biomaterials was closely tied to the intrinsic properties of the materials. Thus, materials suitable for piranha solution treatment could be selected based on the functional requirements of implantable medical devices. In conclusion, the broad applicability of piranha solution surface modification technology in both blood-contact and bone implant materials highlights its promising prospects.

Age-related macular degeneration (AMD) is a complex eye disorder and is the leading cause of incurable blindness worldwide in the elderly. Clinically, AMD initially affects the central area of retina known as the macula and it is classified as early stage to late stage (advanced AMD). The advanced AMD is classified into the nonexudative or atrophic form (dry AMD) and the exudative or neovascular form (wet AMD). More severe vision loss is typically associated with the wet form. Multiple genetic factors, lipid metabolism, oxidative stress and aging, play a role in the etiology of AMD. Dysregulation in genetic to AMD is established to 46%–71% of disease contribution, with CFH and ARMS2/HTRA1 to be the two most notable risk loci among the 103 identified AMD associated loci so far. Chronic cigarette smoking is the most proven consistently risk living habits for AMD. Deep learning algorithm has been developed based on image recognition to distinguish wet AMD and normal macula with high accuracy. Currently, anti-vascular endothelial growth factor (VEGF) therapy is highly effective at treating wet AMD. Several new generation AMD drugs and iPSC-derived RPE cell therapy are in the clinical trial stage and are promising to improve AMD treatment in the near future.

Background and objectiveGastric cancer (GC) represents a major factor inducing global cancer-associated deaths, but specific biomarkers and therapeutic targets for GC are lacking at present. Therefore, the present work focused on developing an immune-related genetic signature at the single-cell level for categorizing GC cases and predicting patient prognostic outcome, immune status as well as treatment response.MethodsSingle-cell RNA-sequencing (scRNA-seq) data were combined with bulk RNA-seq data in GC patients for subsequent analyses. Differences in overall survival (OS), genomic alterations, immune status, together with estimated immunotherapeutic outcomes were measured between different groups.ResultsNine cell types were identified by analyzing scRNA-seq data from GC patients, and marker genes of immune cells were also selected for subsequent analysis. In addition, an immune-related signature was established to predict OS while validating the prediction power for GC patients. Afterwards, a nomogram with high accuracy was constructed for improving our constructed signature’s clinical utility. The low-risk group was featured by high tumor mutation burden (TMB), increased immune activation, and microsatellite instability-high (MSI-H), which were related to the prolonged OS and used in immunotherapy. By contrast, high-risk group was associated with microsatellite stability (MSS), low TMB and immunosuppression, which might be more suitable for targeted therapy. Meanwhile, the risk score generated by our signature was markedly related to the cancer stem cell (CSC) index. In addition, the immunotherapeutic response prediction accuracy of our signature was validated in an external dataset IMvigor210 cohort.ConclusionA signature was constructed according to scRNA-seq data analysis. The signature-screened low- and high-risk patients had different prognoses, immune statuses and enriched functions and pathways. Such results shed more lights on immune status of GC, prognosis assessment, and development of efficient immunotherapeutic treatments.

Soil organic carbon (SOC) is a crucial component of the soil carbon pool that regulates fundamental soil properties and water status. In the global context of restoring vegetation, the soil carbon-water coupling relationship has gained attention. In particular, the regulatory mechanism of SOC on soil moisture requires further research. In this study, three typical forests in subtropical China were chosen as restoration sequences to investigate the changes in SOC and soil moisture during subtropical forest restoration and its regulation mechanisms: broadleaf-conifer mixed forest (EF), broad-leaved forest (MF), and old-growth forest (LF). The soil water content (35.71 ± 1.52%), maximum water holding capacity (47.74 ± 1.91%), capillary water holding capacity (43.92 ± 1.43%), and field water holding capacity (41.07 ± 1.65%) in LF were significantly higher than those in EF (p < 0.01). As forest restoration progressed, the amount of litter returning to the soil increased gradually, and the SOC content (0–100 cm) increased from 9.51 ± 1.42 g/kg (EF) to 15.60 ± 2.30 g/kg (LF). The SOC storage increased from 29.49 ± 3.59 to 42.62 ± 5.78 Mg/ha. On one hand, forest restoration led to a change in SOC content, which optimizes the soil structure and enhances soil porosity (path coefficient of 0.537, p < 0.01), further leading to a change in soil water content (path coefficient of 0.940, p < 0.01). On the other hand, the increase in SOC influenced the change in soil nutrient content, i.e., total nitrogen (TN) and total phosphorus (TP) (path coefficient of 0.842, p < 0.01). Changes in SOC and soil nutrients stimulated changes in the stoichiometric ratio, i.e., C:P and N:P (path coefficients of 0.988 and –0.968, respectively, p < 0.01), and the biological activity in soil changed appropriately, which eventually led to a change in soil water content (path coefficient of –0.257, p < 0.01). These results highlight the changes in SOC and soil water content (SWC), as well as the mechanism of SOC controlling SWC as a result of vegetation restoration, which is of tremendous importance for advancing our understanding of the eco-hydrological process of subtropical forest restoration.

Background: Hepatocellular carcinoma (HCC) refers to the malignant tumor associated with a high mortality rate. This work focused on identifying a robust tumor glycolysis-immune-related gene signature to facilitate the prognosis prediction of HCC cases.Methods: This work adopted t-SNE algorithms for predicting glycolysis status in accordance with The Cancer Genome Atlas (TCGA)-derived cohort transcriptome profiles. In addition, the Cox regression model was utilized together with LASSO to identify prognosis-related genes (PRGs). In addition, the results were externally validated with the International Cancer Genome Consortium (ICGC) cohort.Results: Accordingly, the glycolysis-immune-related gene signature, which consisted of seven genes, PSRC1, CHORDC1, KPNA2, CDCA8, G6PD, NEIL3, and EZH2, was constructed based on TCGA-HCC patients. Under a range of circumstances, low-risk patients had extended overall survival (OS) compared with high-risk patients. Additionally, the developed gene signature acted as the independent factor, which was significantly associated with clinical stage, grade, portal vein invasion, and intrahepatic vein invasion among HCC cases. In addition, as revealed by the receiver operating characteristic (ROC) curve, the model showed high efficiency. Moreover, the different glycolysis and immune statuses between the two groups were further revealed by functional analysis.Conclusion: Our as-constructed prognosis prediction model contributes to HCC risk stratification.

Abstract Zinc-finger of the cerebellum 2 (Zic2) is widely implicated in cancers, but the role of Zic2 in tumorigenesis is bilateral. A recent study indicated that Zic2 could render colon cancer cells more resistant to low glucose-induced apoptosis. However, the functional roles of Zic2 in colon cancer and the underlying molecular mechanism remain elusive. Herein, we demonstrated that Zic2 was highly expressed in colon cancer tissues and correlated with poor survival. Knockdown of Zic2 inhibited colon cancer cell growth, arrested the cell cycle transition from G0/G1 to S phase, and suppressed tumor sphere formation in vitro; in addition, silencing Zic2 retarded xenograft tumor formation in vivo. Consistently, ectopic expression of Zic2 had the opposite effects. Mechanistically, Zic2 executed its oncogenic role in colon cancer by enhancing Wnt/β-catenin signaling. Zic2 directly binds to the promoter of Axin2 and transcriptionally represses Axin2 expression and subsequently promotes the accumulation and nuclear translocation of β-catenin. Meanwhile, Zic2 could activate Wnt signaling by interacting with β-catenin. Intriguingly, in HCT116 cells with intrinsic Ser45 mutation of β-catenin, which blocks the degradation-related phosphorylation of β-catenin by CK1, modified Zic2 expression did not affect the protein level of β-catenin. Altogether, our findings uncover a novel multilevel mechanism for the oncogenic activity of Zic2 in colon cancer and suggest Zic2 as a potential therapeutic target for colon cancer patients.

Vegetation succession can change the function and quality of the soil. Exploring the changes in soil properties during secondary forest restoration is of great significance to promote forest restoration and improve the ecological service function of subtropical ecosystems in South China. In this study, we chose three typical forests in subtropical China as restoration sequences, broadleaf–conifer mixed forest (EF), broad-leaved forest (MF), and old-growth forest (LF), to study the changes in soil physico-chemical and biological properties and the changes of soil comprehensive quality during the secondary succession of subtropical forest. The results showed that the soil physical structure was optimized with the progress of forest succession. The soil bulk density decreased gradually with the progress of forest restoration, which was significantly affected by soil organic carbon (p

Abstract Background Kaempferol, a natural flavonoid, exhibits anticancer properties by scavenging reactive oxygen species (ROS). However, increasing evidence has demonstrated that, under certain conditions, kaempferol can inhibit tumor growth by upregulating ROS levels. In this study, we aimed to investigate whether kaempferol effectively suppresses pancreatic cancer through upregulation of ROS, and to explore the underlying molecular mechanism. Methods PANC-1 and Mia PaCa-2 cells were exposed to different concentrations of kaempferol. Cell proliferation and colony formation were evaluated by CCK-8 and colony formation assays. Flow cytometry was performed to assess the ROS levels and cell apoptosis. The mRNA sequencing and KEGG enrichment analysis were performed to identify differentially expressed genes and to reveal significantly enriched signaling pathways in response to kaempferol treatment. Based on biological analysis, we hypothesized that tissue transglutaminase (TGM2) gene was an essential target for kaempferol to induce ROS-related apoptosis in pancreatic cancer. TGM2 was overexpressed by lentivirus vector to verify the effect of TGM2 on the ROS-associated apoptotic signaling pathway. Western blot and qRT-PCR were used to determine the protein and mRNA levels, respectively. The prognostic value of TGM2 was analyzed by Gene Expression Profiling Interactive Analysis (GEPIA) tools based on public data from the TCGA database. Results Kaempferol effectively suppressed pancreatic cancer in vitro and in vivo. Kaempferol promoted apoptosis in vitro by increasing ROS generation, which was involved in Akt/mTOR signaling. TGM2 levels were significantly increased in PDAC tissues compared with normal tissues, and high TGM2 expression was positively correlated with poor prognosis in pancreatic cancer patients. Decreased TGM2 mRNA and protein levels were observed in the cells after treatment with kaempferol. Additionally, TGM2 overexpression downregulated ROS production and inhibited the abovementioned apoptotic signaling pathway. Conclusions Kaempferol induces ROS-dependent apoptosis in pancreatic cancer cells via TGM2-mediated Akt/mTOR signaling, and TGM2 may represent a promising prognostic biomarker for pancreatic cancer.

Yeasts are one of the predominant microbial groups in fermented meats. In this study, yeast communities of Chinese Dong fermented pork (Nanx Wudl) were investigated and the technological properties of 73 yeast isolates were evaluated. Through culture-dependent and high-throughput sequencing methods, the main yeast species identified included Pichia membranifaciens, Kazachstania bulderi, Millerozyma farinosa, Candida zeylanoides, Kazachstania exigua, Candida parapsilosis and Saccharomyces cerevisiae. Among these yeasts, P. membranifaciens, M. farinosa, K. exigua and K. bulderi were detected in fermented meats for the first time. A total of 73 yeast isolates was investigated for their lipolytic and proteolytic activities. All yeast species showed lipolytic activity, while proteolytic activity against meat protein was only detected in S. cerevisiae. Assay of aroma-producing potential was performed in a model simulating fermented sausage condition. Inoculation of yeast strains increased volatiles production, especially esters and alcohols. The highest ester production was observed in S. cerevisiae Y70 strain, followed by K. exigua Y12 and K. bulderi Y19. C. zeylanoides Y10 and S. cerevisiae Y70 were the highest producers of benzeneethanol and 3-methyl-1-butanol. S. cerevisiae Y70 with its highest production of branched alcohols and esters could be a promising candidate as aroma enhancer in the manufacture of fermented sausages.

Background: Inflammation is essential in cardiovascular disease (CVD) development and progression. A novel inflammatory parameter, the systemic inflammation response index (SIRI), has been proven to predict cancer prognosis strongly. Little is known about the relationship between SIRI and outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Methods: 1312 STEMI patients who underwent percutaneous coronary intervention (PCI) in Beijing Anzhen hospital from January 2019 to December 2021 were analyzed. SIRI was calculated as neutrophils × monocytes/lymphocytes. Our primary outcome was a 30-day major adverse event (MACE), including all-cause mortality, non-fatal myocardial infarction (MI), stroke, incident heart failure (HF), cardiogenic shock, and cardiac arrest. Results: Patients were stratified into four groups according to quartiles of SIRI: SIRI 0.05). Conclusions: In patients with STEMI, higher SIRI indicated a higher incidence of 30-day MACE, except for those with very high inflammatory indicators. In most STEMI patients, SIRI might be a trustworthy indicator of short-term prognosis.

The unique processing technology of dry-cured meat products leads to strong proteolysis, which produces numerous peptides. The purpose of this investigation was the systematic isolation, purification, and identification of potentially cardioprotective bioactive peptides from dry-cured pork coppa during processing. According to the results of anti-platelet-activating factor acetyl hydrolase activity and radical scavenging ability in vitro, the inhibitory effect of M1F2 in purified fractions on cardiovascular inflammation was higher than that of M2F2. The peptide of M1F2 was identified by nano-liquid chromatography–tandem mass spectrometry. A total of 30 peptides were identified. Based on bioinformatics methods, including in silico analysis and molecular docking, LTDKPFL, VEAPPAKVP, KVPVPAPK, IPVPKK, and PIKRSP were identified as the most promising potential platelet-activating factor acetyl hydrolase inhibitory peptides. Overall, bioactive peptides produced during dry-cured pork coppa processing demonstrate positive effects on human health.

The effect of a proteolytic starter culture isolated from Nanx Wudl, on microbiological, biochemical and organoleptic attributes of dry fermented sausages was investigated during processing. Based on preliminary screening, the combination of Staphylococcus xylosus SX16 and Lactobacillus plantarum CMRC6, showing excellent proteolytic activity in vitro, was selected as the multi-strain starter (starter LS). For comparison, the single-strain starter culture of L. plantarum CMRC6 (starter LB) and non-inoculated control were also tested. During fermentation, lactic acid bacteria and staphylococci dominated the microbiota and suppressed the Enterobacteriaceae growth in LS-inoculated sausages. The addition of LS starter accelerated acidification and proteolysis during ripening, improving the contents of total free amino acids and several essential free amino acids (Phe, Ile and Leu). Volatile compounds analysis revealed that LS-fermented sausage showed the highest abundance of 3-methyl-1-butanol, probably due to the inoculated S. xylosus. The inoculation of LS starter improved the sensory properties of sausages, especially the flavor attribute. Therefore, S. xylosus SX16 and L. plantarum CMRC6 are promising candidates for inclusion as multi-strain starters in the manufacture of gourmet fermented dry sausage.

AIM: To investigate the effect of IOP of emmetropes and different types of myopia induced by accommodation.METHODS: A descriptive study. A total of 88 volunteers were included from January to April 2018. Among them, 28(28 eyes)were in the emmetropia group, 60(60 eyes)were in the myopia group, and the myopia group was divided into stable myopia group(myopia progression is less than or equal to 0.50D per year in the past two years)and progressive myopia group(myopia progression is greater than 0.50D per year in the past two years)according to the refractive stability. Meanwhile, the myopia group was also divided into three groups according to the degree of myopia: low myopia group(-0.5D≤SERESULTS: There was no significant difference in IOPs among emmetropia group(16.54±2.12mmHg), stable myopia group(17.15±2.23mmHg)and progressive myopia group(16.88±2.37mmHg)when relaxed(P>0.05), so did the emmetropia group, low myopia group(16.41±2.21mmHg), moderate myopia group(17.11±2.27mmHg)and high myopia group(17.60±2.35mmHg)(P>0.05). The IOPs of progressive myopia group and high myopia group were significantly increased with 3D accommodation(PP>0.05).CONCLUSION: Accommodation could increase the IOPs of progressing myopes and high myopes, and it suggested that the increase of IOP was related to the progression of adult myopia.

Corneal injury inevitably leads to disruption of the ocular surface microenvironment, which is closely associated with delayed epithelial cell repair and the development of infection. Recently, drug-loaded therapeutic contact lenses have emerged as a new approach to treating corneal injury due to their advantages of relieving pain, promoting corneal repair, and preventing infection. However, few therapeutic contact lenses could modulate the ocular surface’s inflammation and oxidative stress microenvironment. To address this, in this study, we covalently immobilized multifunctional baicalin (BCL), a flavon molecular with anti-inflammatory, anti-oxidative stress, and antibacterial capabilities, onto the surface of the contact lens. The BCL-modified contact lens showed excellent optical properties, powerful antibacterial properties, and non-toxicity to endothelial cells. Furthermore, the BCL-modified contact lens could significantly modulate the ocular surface microenvironment, including inhibition of macrophage aggregation and resistance to epithelium damage caused by oxidative stress. In animal models, BCL-modified corneal contact lens effectively promoted corneal epithelial cells repair. These excellent properties suggested that multifunctional BCL molecules had great application potential in the surface engineering of ophthalmic medical materials.

AimsAcute decompensated right heart failure (RHF) in chronic precapillary pulmonary hypertension is often typified by a swiftly progressive syndrome involving systemic congestion. This results from the impairment of the right ventricular filling and/or a reduction in the flow output of the right ventricle, which has been linked to a dismal prognosis of short duration. Despite this, there are limited therapeutic data regarding these acute incidents. This study examined the effect of levosimendan on acute decompensated RHF in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH).MethodsThis retrospective study included 87 patients with confirmed CTD-PAH complicated acute decompensated RHF between November 2015 and April 2021. We collected biological, clinical, and demographic data, as well as therapy data, from patients with acute decompensated RHF who required levosimendan treatment in the cardiac care unit (CCU) for CTD-PAH. The patients were divided into two groups according to the levosimendan treatment. Patient information between the two groups was systematically compared in hospital and at follow-up.ResultsOxygen saturation of mixed venose blood (SvO2), estimated glomerular filtration rate (eGFR), 24-h urine output, and tricuspid annular plane systolic excursion (TAPSE) were found to be considerably elevated in the levosimendan cohort compared with the control cohort. Patients in the levosimendan cohort exhibited considerably reduced levels of C-reactive protein (CRP), white blood cell (WBC), troponin I, creatinine, NT-proBNP, and RV diameter compared with those in the control cohort. A higher survival rate was observed in the levosimendan cohort.ConclusionsLevosimendan treatment could effectively improve acute decompensated RHF and systemic hemodynamics in CTD-PAH patients, with positive effects on survival in hospital and can, therefore, be considered as an alternative treatment option for improving clinical short-term outcomes.

AIM: To explore the protective effect of dexamethasone combined with hypertonic solution on corneal endothelial cells of rabbit eyes. METHODS: We made four groups of rabbits for different treatments with dexamethasone and hypertonic solution. All groups were treated with low-permeability solution for 10min to maintain anterior chamber perfusion. Group A was treated with 0.2mL dexamethasone subconjunctival injection, and hypertonic glucose eye drop immediately after surgery. Group B(control group)was subjected to 0.2mL of 0.9% saline subconjunctival injection, and balanced salt solution eye drop immediately after surgery. In group C, 0.2mL dexamethasone subconjunctival injection, and hypertonic glucose eye drop were given on the second day of surgery and in group D(control group), 0.2mL of 0.9% saline through subconjunctival injection and balanced salt solution eye drop were given on the second day of the surgery. The edema degree of cornea was observed with slit lamp before the operation and on the 1, 3, 5 and 7d after operation. The cornea were also examined by anterior segment OCT, and the corneal thickness was measured by A-scan ultrasonography.RESULTS: In group A, during the entire experimental observation period, the cornea had no edema or only mild edema, the thickness of the central cornea hardly increased, and the number of corneal endothelial cells did not change significantly. There was no significant difference compared with(control group B)before modeling(P>0.05). In groups B, C, and D, corneal edema and corneal thickness increased after the rabbit eyes were modeled. There was a significant difference compared with group A(PPCONCLUSION: Dexamethasone combined with hypertonic glucose solution has a good protective effect on rabbit corneal endothelial cells. And early application can effectively prevent rabbit corneal edema and this method can also prevent the progression of corneal endothelial decompensation.

The water inrush and large surface settlement encountered by EPB shield crossing water-rich gravel layer have attracted much attention. Based on the section tunnel engineering of the Inner Mongolia University South Campus Station-Xilin Park Station of line 2 of Hohhot Rail Transit, the optimum mix proportion of bentonite slurry and foam diluent for forming slurry membrane in water-rich gravel stratum was studied in this study at first. The characteristics of conditioned soil were analyzed in combination with slag soil. The water plugging effect and surface settlement with or without slurry membrane were investigated with numerical simulation. The numerical model has been effectively verified by comparing the field monitoring and numerical simulation of surface settlement value. Further, the water shutoff mechanism of the slurry membrane is revealed. The setting of the slurry membrane exhibited a good water plugging effect and effectively decreased the surface settlement. The construction method of “water plugging with a slurry membrane” proposed in this study could powerfully combine the respective advantages of EPB shield and slurry balance shield, ensuring the safety, high quality, and high efficiency of tunnel construction.

Inflammatory bowel disease (IBD) is an intestinal chronic inflammatory disease, and is related to imbalance of CD4+T subsets. However, the current treatments of chronic colitis are not ideal and have potential side effects. Therefore, more effective and safer biologically active substances which are extracted from natural plants have been widely concerned. In this study, it was found that Inonotus obliquus polysaccharides (IOP), the main bioactive constituent of Inonotus obliquus, can alleviate dextran sodium sulfate-induced chronic murine intestinal inflammation. Oral administration of IOP (100, 200, 300 mg/kg) can significantly reduce the disease active index and alleviate the pathological changes in colitis mice, where the tight junction proteins Occludin and ZO-1 losses in colon tissues were reduced. It can also regulate imbalanced Th1/Th2 and Th17/Treg in colon tissues, mesenteric lymph nodes and spleen using Reverse Transcription-Polymerase Chain Reaction detection and flow cytometry. Immunohistochemistry and western blot assays further revealed the modulatory effect of IOP on the p-STAT1, p-STAT6, p-STAT3 expression, which promoted the balance of Th1/Th2, Th17/Treg in the colon of chronic colitis mice. In short, these results indicated that IOP was potentially effective therapeutic agent for IBD.

Introduction: It has been reported that sex has well-established relationships with the prevalence of coronary artery disease (CAD) and the major adverse cardiovascular events. Compared with men, the difference of coronary artery and myocardial characteristics in women has effects on anatomical and functional evaluations. Quantitative flow ratio (QFR) has been shown to be effective in assessing the hemodynamic relevance of lesions in stable coronary disease. However, its suitability in acute myocardial infarction patients is unknown. This study aimed to evaluate the sex differences in the non-infarct-related artery (NIRA)-based QFR in patients with ST-elevation myocardial infarction (STEMI).Methods: In this study, 353 patients with STEMI who underwent angiographic cQFR assessment and interventional therapy were included. According to contrast-flow QFR (cQFR) standard operating procedures: reliable software was used to modeling the hyperemic flow velocity derived from coronary angiography in the absence of pharmacologically induced hyperemia. 353 patients were divided into two groups according to sex. A cQFR ≤0.80 was considered hemodynamically significant, whereas invasive coronary angiography (ICA) luminal stenosis ≥50% was considered obstructive. Demographics, clinical data, NIRA-related anatomy, and functional cQFR values were recorded. Clinical outcomes included the NIRA reclassification rate between men and women, according to the ICA and cQFR assessments.Results: Women were older and had a higher body mass index (BMI) than men. The levels of diastolic blood pressure, troponin I, peak creatine kinase-MB, low-density lipoprotein cholesterol, N terminal pro B-type natriuretic peptide, stent diameter, and current smoking rate were found to be significantly lower in the female group than in the male group. Women had a lower likelihood of a positive cQFR ≤0.80 for the same degree of stenosis and a lower rate of NIRA revascularization. Independent predictors of positive cQFR included male sex and diameter stenosis (DS) >70%.Conclusions: cQFR values differ between the sexes, as women have a higher cQFR value for the same degree of stenosis. The findings suggest that QFR variations by sex require specific interpretation, as these differences may affect therapeutic decision-making and clinical outcomes.

Refractory organic wastewater mainly includes wastewater from papermaking, textile, printing and dyeing, petrochemical, coking, pharmaceutical and other industries, as well as landfill leachate and its membrane-treated concentrate. The traditional biochemical method is difficult to adapt to its harsh conditions such as high toxicity, high organic load and high salinity. Compared to other methods, the electro-oxidation (EO) process owns the attractive characteristics of being clean and eco-friendly, highly efficient and producing no secondary pollution. EO systems mainly include electrodes, a reactor, a power supply and other basic units. The design of reactors with different electrodes was the key link in the application of EO technology. This paper mainly reported the different configurations of electrochemical reactors (ECRs) for refractory organic wastewater treatment, and summarized the advantages and disadvantages of them, including reactor structure, flow mode, operation mode and electrode construction. Compared with traditional reactors, the improved reactors such as 3D-ECR achieve higher mass transfer efficiency by increasing the contact area between the electrode and the fluid. Additionally, it has a higher removal rate of organics and a lower energy consumption. Finally, the future perspectives of the treatment of refractory organic wastewater by ECRs is discussed. This paper is expected to provide a reliable scientific basis for the real application of EO technology in refractory organic wastewater treatment.

Background: Acute systolic heart failure (ASHF) is one of the most serious complications of the acute coronary syndrome (ACS), and increases the likelihood of adverse clinical outcomes. It remains unclear whether the use of non-invasive ventilation (NIV) could improve symptoms and reduce mortality in patients with ASHF derived from ACS. Methods: Data on biological, clinical, and demographic factors, as well as therapy data, were collected from patients with ASHF in the cardiac department. A total of 1257 ACS patients with ASHF were included in the study. Patients were divided into two groups. The control group received standard oxygen therapy. The comparison group consisted of those who underwent NIV as part of their immediate care. During hospitalization and at follow-up, information on both groups was systematically compared. Results: In comparison with the control group, mean 24-hour urine output was found to be significantly higher in the NIV group. A significant reduction in the duration of symptoms was observed among patients in the NIV group from the time of admission until relief of dyspnea. Heart rate, C-reactive protein, estimated glomerular filtration rate, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) was also improved, compared with those in the control group. The NIV group was found to have a higher survival rate. NIV was independently related to all-cause mortality in 1-year follow-up (hazard ratio, 0.674; p = 0.045). Conclusions: Our study shows that NIV, as compared with standard oxygen therapy, has a beneficial impact on heart rate, metabolic balance, and relief of dyspnea in ACS patients with ASHF which results in reduced intubation rate, duration of in-hospital stay, and 1-year mortality.

Abstract Background Chronic hepatitis B virus (HBV) infection is a major risk factor for the occurrence and development of cirrhosis and hepatocellular carcinoma (HCC). Microvascular invasion (MVI) of HCC is closely related to postoperative recurrence. We aimed to investigate the effect of HBV DNA replication levels and anti-HBV treatment on the occurrence of MVI in HCC. Methods A retrospective analysis of the clinical and pathological data of 660 patients undergoing hepatectomy for hepatocellular carcinoma at the Affiliated Hospital of Qingdao University from January 2015 to December 2017 is included in this study. Results This study involved a total of 660 patients with an MVI incidence rate of 46.8% (309/660). Univariate analysis revealed that positive HBV surface antigen (HBsAg), detectable HBV DNA load, and administration of antiviral treatment were significantly associated with the formation of MVI. Multivariable logistic regression analysis in patients with positive seral HBsAg showed that detectable HBV DNA load (OR = 5.33, P 100 IU/ml) rate (P

Background/Aims: Open resection/laparoscopic resection (LR) is the traditional treatment of gastric submucosal tumor (G-SMT). The endoscopic resection (ER) technology provides good results for G-SMT treatment but lacks sufficient evidence-based evidence. This retrospective study aimed to compare the clinical efficacy of ER [endoscopic submucosal dissection (ESD), endoscopic submucosal excavation (ESE), and endoscopic full-thickness resection (EFR)] and LR [laparoscopic wedge resection (LWR) and laparoscopic subtotal gastrectomy (LSG)] for G-SMT. Patients and Methods: From January 2013 to January 2017, data of patients with G-SMT with tumor diameter 0.05). The ER group had a significantly higher percentage of intraluminal tumor (94.1% vs 62.4%) and smaller tumor size (1.8 ± 0.8 vs 3.4 ± 1.2 cm) than the LR group. The ER group had less muscular tumors than the LR group (54.6% vs 70.7%). The ER group had no serosal tumor. The ER group had shorter hospitalization time, postoperative hospital stay and diet recovery time. The LR group had shorter operation time, less cost and less blood loss. Conclusion: ER and LR are safe and effective treatments for SMT. For small intraluminally growing SMT, ER is better than LR.

Abstract. Retinitis pigmentosa (RP), a major cause of inherited blindness worldwide, is highly heterogeneous. This study aimed to identify mutations in a Chinese cohort of sporadic probands with presumptive RP. Whole exome sequencing represents a considerable advancement in the identification of mutations associated with Mendelian diseases, such as RP. In this study, whole exome sequencing analysis was performed in a Chinese cohort of 95 sporadic probands who were initially diagnosed with RP, in order to identify disease mutations. All detected variations were confirmed by direct Sanger sequencing, and potential pathogenicity was assessed by predictions of the mutations’ functions. The overall mutation rate of presumptive RP genes for this cohort was 30.5% (n = 29 of 95 probands). Forty-four mutations were identified in 19 RP genes, among which 40 mutations were novel. Eleven probands carried mutations in autosomal dominant genes (38.0%), 16 probands carried mutations in autosomal recessive genes (55.2%), and 2 probands carried mutations in X-linked genes (6.9%). Twenty-eight mutations in 18 genes linked to other retinal diseases in 23 probands were also identified. Overall, mutations were detected in 52 probands (54.7%). The recurrent and novel mutations reported here will expand potential understanding of the pathogenesis of RP and other retinal diseases.

Inonotus obliquus polysaccharide (IOP), the primary constituent of the parasitic fungus Inonotus obliquus, has anti-tumor, anti-inflammatory, anti-oxidation effects. However, the roles of IOP on colitis-associated cancer (CAC) are still unclear. Herein, we tested the efficacy of IOP using a mouse model of CAC induced by azoxymethane and dextran sulfate sodium (AOM/DSS). We confirmed that intragastric administration of IOP decreased CAC-induced body weight loss, colon tissue damage, colon shortening, and expression of proinflammatory mediators. Meanwhile, IOP treatment increased in expression of the NLRP3 inflammasome, IL-1β, and IL-18 in the colon of CAC mice. Moreover, in vitro, IOP inhibited the proliferation of SW620 colorectal cancer cells. Finally, overexpression of NLRP3 with plasmid transfection could further enhance the activation of NLRP3 inflammasome by IOP. Taken together, these results suggest that IOP suppresses the development of CAC, possibly by activation of the NLRP3 inflammasome, and reveal that IOP may be a therapeutic drug candidate for CAC.

BackgroundMicroRNAs (miRNAs) have been discovered to dictate the development of various tumors. However, studies on the roles of miRNAs in the progression of gastric cancer (GC) are still lacking.MethodsHerein, by analyzing GC cell lines and patients samples, we observed that miR-148b-5p was significantly downregulated in GC. We also confirmed that miR-148b-5p overexpression significantly inhibited GC cell proliferation and invasion in vitro and in vivo.ResultsOverexpression of miR-148b-5p not only reprogrammed the metabolic properties of GC but also regulated the immune microenvironment by shifting lymphocyte and myeloid populations. Mechanistically, ATPIF1, an important glycolysis-associated gene, was identified as a direct target of miR-148b-5p and mediated the effect of miR-148b-5p. Notably, the low level of miR-148b-5p was significantly related with poor prognosis of GC patients (P < 0.001). Importantly, the levels of miR-148b-5p significantly changed the sensitivity of GC cells to several anti-cancer drugs (Doxorubicin, P < 0.05, Paclitaxel, P < 0.01, Docetaxel, P < 0.05).ConclusionsTargeting miR-148b-5p inhibits immunity microenvironment and gastric cancer progression.

Radiation-induced fibrosis (RIF) is a severe long-term complication of the normal tissue following radiotherapy. Its prototypical characteristic is the persistent activation of myofibroblasts, resulting in proportion disorder and hyperplasia remodeling of the extracellular matrix comprising collagen. The continuous progress of RIF may contribute to multiple clinical manifestations such as hollow organ stenosis, impaired gaseous diffusion, and loss of tissue compliance significantly affecting the overall quality of daily life in patients with irradiated cancer. Traditionally, the potential mechanism of myofibroblast activation and differentiation has not been elucidated, and the process has been considered as static and irreversible. Recent studies have shown that RIF is a dynamic, multi-step process mediated by many regulated chemokines and cytokines. The RIF process includes release of reactive oxygen species (ROS), microvascular injury, recruitment of inflammatory cells, and activation of myofibroblasts. Numerous signaling pathways are involved in the initiation and progression of RIF, of which SMAD-regulated CTGF expression mediated by TGF-β1 is referred as the main axis. Current management strategies applied in clinical practice for patients with RIF are only supportive treatments, such as anti-inflammatory therapy using steroids; however, the efficacies achieved by these interventions are limited and unsatisfactory. Therefore, this review explores advances in RIF pathogenesis and anti-fibrosis therapy. We hope to provide clinicians with improved awareness and enormous promise in the management of RIF.

Retinal microaneurysm (MA) is the initial symptom of diabetic retinopathy (DR). The automatic detection of MA is helpful to assist doctors in diagnosis and treatment. Previous algorithms focused on the features of the target itself; however, the local structural features of the target and background are also worth exploring. To achieve MA detection, an efficient local structure awareness-based retinal MA detection with the multi-feature combination (LSAMFC) is proposed in this paper. We propose a novel local structure feature called a ring gradient descriptor (RGD) to describe the structural differences between an object and its surrounding area. Then, a combination of RGD with the salience and texture features is used by a Gradient Boosting Decision Tree (GBDT) for candidate classification. We evaluate our algorithm on two public datasets, i.e., the e-ophtha MA dataset and retinopathy online challenge (ROC) dataset. The experimental results show that the performance of the trained model significantly improved after combining traditional features with RGD, and the area under the receiver operating characteristic curve (AUC) values in the test results of the datasets e-ophtha MA and ROC increased from 0.9615 to 0.9751 and from 0.9066 to 0.9409, respectively.

Performance of a collaborative task is mostly dependent on the collective effort from participants. To accomplish a participatory task effectively and efficiently, the team formation problem (TFP) outweighs all other considerations. It is even more complicated when social connections among candidates is taken into account. As we can imagine, a large number of tasks require members of the team to be socially close. On the contrary, a portion of tasks, e.g., proposal review, pay more attention to a multidimensional view, and team members should be selected from a variety of cliques. Due to the nature of tasks, it is challenging to find a subset that meets the skill requirement of the task as well as socially diversity demand of team members from a pool of candidates. In this paper, we explore the TFP in a social network. Based on different task objectives, we first formulate the TFP as TFP with strong ties (TFP-ST) and TFP with weak ties (TFP-WT), respectively. Both TFP-ST and TFP-WT are proven to be NP-hard, and we then design corresponding heuristic algorithms to solve the two problems. Through extensive simulations, we show that the solution to TFP-ST can achieve significant improvement in terms of collaboration cost, team size, as well as running time, and the solution to TFP-WT can provide better performance than existing approaches at the same time.

Abstract The NLRP3 inflammasome senses a variety of signals referred to as danger associated molecular patterns (DAMPs), including those triggered by crystalline particulates or degradation products of extracellular matrix. Since some DAMPs confer tissue-specific activation of the inflammasomes, we tested the hypothesis that bone matrix components function as DAMPs for the NLRP3 inflammasome and regulate osteoclast differentiation. Indeed, bone particles cause exuberant osteoclastogenesis in the presence of RANKL, a response that correlates with NLRP3 abundance and the state of inflammasome activation. To determine the relevance of these findings to bone homeostasis, we studied the impact of Nlrp3 deficiency on bone using pre-clinical mouse models of high bone turnover, including estrogen deficiency and sustained exposure to parathyroid hormone or RANKL. Despite comparable baseline indices of bone mass, bone loss caused by hormonal or RANKL perturbations is significantly reduced in Nlrp3 deficient than in wild type mice. Consistent with the notion that osteolysis releases DAMPs from bone matrix, pharmacologic inhibition of bone resorption by zoledronate attenuates inflammasome activation in mice. Thus, signals originating from bone matrix activate the NLRP3 inflammasome in the osteoclast lineage, and may represent a bone-restricted positive feedback mechanism that amplifies bone resorption in pathologic conditions of accelerated bone turnover.

Abstract Skeletal complications are common features of neonatal-onset multisystem inflammatory disease (NOMID), a disorder caused by NLRP3-activating mutations. NOMID mice in which NLRP3 is activated globally exhibit several characteristics of the human disease, including systemic inflammation and cartilage dysplasia, but the mechanisms of skeletal manifestations remain unknown. In this study, we find that activation of NLRP3 in myeloid cells, but not mesenchymal cells triggers chronic inflammation, which ultimately, causes growth plate and epiphyseal dysplasia in mice. These responses are IL-1 signaling-dependent, but independent of PARP1, which also functions downstream of NLRP3 and regulates skeletal homeostasis. Mechanistically, inflammation causes severe anemia and hypoxia in the bone environment, yet down-regulates the HIF-1α pathway in chondrocytes, thereby promoting the demise of these cells. Thus, activation of NLRP3 in hematopoietic cells initiates IL-1β-driven paracrine cascades, which promote abnormal growth plate development in NOMID mice.

Abstract Retinitis pigmentosa (RP) is highly heterogeneous in both clinical and genetic fields. Accurate mutation screening is very beneficial in improving clinical diagnosis and gene-specific treatment of RP patients. The reason for the difficulties in genetic diagnosis of RP is that the ethnic-specific mutation databases that contain both clinical and genetic information are largely insufficient. In this study, we recruited 98 small Han Chinese families clinically diagnosed as RP, including of 22 dominant, 19 recessive, 52 sporadic, and five X-linked. We then used whole exome sequencing (WES) analysis to detect mutations in the genes known for RP in 101 samples from these 98 families. In total, we identified 57 potential pathogenic mutations in 40 of the 98 (41%) families in 22 known RP genes, including 45 novel mutations. We detected mutations in 13 of the 22 (59%) typical autosomal dominant families, 8 of the 19 (42%) typical autosomal recessive families, 16 of the 52 (31%) sporadic small families, and four of the five (80%) X-linked families. Our results extended the mutation spectrum of known RP genes in Han Chinese, thus making a contribution to RP gene diagnosis and the pathogenetic study of RP genes.

Pancreatic ductal adenocarcinoma is characterized by an extensive stromal response called desmoplasia. Within the tumor stroma, cancer-associated fibroblasts (CAFs) are the primary cell type. CAFs have been shown to play a role in pancreatic cancer progression; they secrete growth factors, inflammatory cytokines, and chemokines that stimulate signaling pathways in cancer cells and modulate the cancer biology toward increased aggressiveness. Therefore, targeting CAFs may serve as a powerful weapon against pancreatic cancer and improve therapeutic effects. However, a previous study aiming to deplete CAFs by inhibiting sonic Hedgehog signaling failed to show any benefit in survival time of pancreatic cancer patients. We reported that the natural product curcumin reeducated CAFs in pancreatic cancer treatment. A low concentration of curcumin reversed the activation of fibroblasts without exhibiting growth suppression effects. In addition, curcumin suppressed CAF-induced pancreatic cancer cell migration and invasion in vitro and lung metastasis in vivo. The results of our study suggest that active CAFs can be inactivated by certain natural products such as curcumin. Reeducation of CAFs back to their normal state, rather than their indiscriminate depletion, may broaden our view in the development of therapeutic options for the treatment of pancreatic cancer.

Xuanwei ham is especially rich in a large amount of peptides and free amino acids under the action of protein degradation. Some of these peptides can potentially exert bioactivities of interest for human health. Traditionally, Xuanwei ham should undergo Chinese household cooking treatments before eating. However, it has not been known how its bioactivity changes after cooking and gastrointestinal digestion. Herein, Xuanwei ham is analysed before and after cooking, as well as gastrointestinal digestion being simulated so as to evaluate and compare its effect on antioxidant and angiotensin I-converting enzyme (ACE) inhibitory activities. The antioxidant activity is analysed using five different methods, and results demonstrate that cooking has some negative effects on antioxidative capacity when determined using different antioxidant methods except for a significant increment in 1,1'-diphenyl-2-picrylhydrazyl radical-scavenging activity, while ACE inhibitory activity increases significantly after cooking compared with control samples. After gastrointestinal digestion of samples, there is a significant increment of the antioxidant and ACE inhibitory activities in comparison with control and cooked samples. Particularly, after gastrointestinal digestion, free thiols content and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical-cation-scavenging activity of Xuanwei ham, respectively, increase about twice and fourfold, while ACE inhibitory activity increases about twice compared to cooked samples, reaching the value of 83.73%. Therefore, through cooking the antioxidant activity and ACE inhibitory activity of Xuanwei ham are not completely lost and a part of them is still maintained, while gastrointestinal digestion produces a significant enhancement in both bioactivities, highlighting a greater potential for a beneficial physiological effect on human health after eating it.

In electrical discharge machining (EDM), workpiece is machined using heat of the arc-plasma generated in the discharge gap after dielectric breakdown. The characteristics and behavior of the arc-plasma during a single discharge have a great influence on the formation of the discharge crater. In order to improve the machining accuracy and surface roughness of the workpiece, it is quite necessary to research on plasma behavior and its characteristics. In this study, light intensities radiated from the plasma which are considered to reflect the material removal behavior were measured using a spectrometer under different machining conditions. It was found that the starting moment when light intensity was detected had a time delay after the dielectric breakdown. It is because of the time needed for the material to be evaporated before its temperature reaches the boiling point. Besides, the time delay increases accordingly by slowing down the rise speed of the discharge current because of lower heat flux flowing into the surface of the workpiece. In addition, heat conduction analysis was conducted to compare the time delay calculated with the experimental ones. It was found that plasma expanded in a rapid speed within about 180ns right after dielectric breakdown and remained constant with the diameter of about 20µm after that under a roughing condition of micro EDM.

With the fast development and expansion of the Internet of Things (IoT), billions of smart devices are being continuously connected, and smart homes, as a typical IoT application, are providing people with various convenient applications, but face security and privacy issues. The idea of Blockchain (BC) theory has brought about a potential solution to the IoT security problem. The emergence of blockchain technology has brought about a change of decentralized management, providing an effective solution for the protection of network security and privacy. On the other hand, the smart devices in IoT are always lightweight and have less energy and memory. This makes the application of blockchain difficult. Against this background, this paper proposes a blockchain model based on hypergraphs. The aims of this model are to reduce the storage consumption and to solve the additional security issues. In the model, we use the hyperedge as the organization of storage nodes and convert the entire networked data storage into part network storage. We discuss the design of the model and security strategy in detail, introducing some use cases in a smart home network and evaluating the storage performance of the model through simulation experiments and an evaluation of the network.

Background: Previous studies showed that Chromobox protein homolog 3 (CBX3) was overexpressed in several types of human cancers, however its pattern and role in pancreatic adenocarcinoma (PAAD) has not yet been understood. The aim of this study was to identify the expression and function of CBX3 in PAAD. Methods: Data of transcriptomic and protein expression of CBX3 in PAAD were collected from different databases and analyzed. The in vitro and in vivo role of CBX3 in PAAD was examined. Results: CBX3 was overexpressed in human PAAD tissues, which was associated with poor prognosis of overall and disease-free survival of the patients. Overexpression of CBX3 induced the in vitro proliferation, anchorage-free growth, migration and invasion of the PAAD cells, and led to in vivo growth of orthotoptic PAAD tumors in mice. GO and KEGG pathway analysis, as well as experimental observation showed that CBX3 may be associated with cell cycle transition of PAAD cells, and cyclin-dependent kinase 1 (CDK1) and proliferating cell nuclear antigen (PCNA) may mediate the tumor-promoting action of CBX3. CDK1 knockdown attenuated the cell cycle transition, proliferation and invasion of CBX3-overexpressing PAAD cells. Conclusion: Our findings suggest the tumor-promoting role of CBX3 in PAAD to be targeted by novel therapeutic strategies.