L.acidophilus HSCC LA042 and HKL suspension ameliorate DSS-induced ulcerative colitis in mice by improving the intestinal barrier inhibiting the NLRP3 inflammasome and pathogenic bacteria.

Ulcerative Colitis(UC) is a chronic intestinal inflammation affecting the intestines, yet its underlying causes remain unclear. In recent decades, the global prevalence of UC has been on the rise, leading to an increasing demand for therapeutic drugs with minimal side effects. Huan Kui Le (HKL), a traditional Chinese medicine compound, has demonstrated promising efficacy when combined with Lactobacillus acidophilus (Lac.) for UC intervention. However, the precise therapeutic mechanism of this combination remains unknown. The study focused on understanding the mechanisms of UC by examining the effects of Lac. and HKL (LH) treatment. The outcomes discovered that the disruption of gut microbiota, triggered by the activation of the NLRP3 inflammasome, plays a crucial role in UC development. This disruption exacerbates UC symptoms by causing disturbances in inflammatory cytokines and mucosal permeability. We investigated the dynamic changes following the application of this treatment using 16S rRNA sequencing, HE, WB, IHC, and ELISA. Compared with the UC group, LH treatment reduced colon pathological injury, improved colon length, and decreased IL-1 ß serum levels. Furthermore, it restored the expression of TJs and preserved mucosal barrier integrity. LH treatment also mitigated colon injury by attenuating the expression of pyroptosis-related genes and proteins, such as NLRP3 and Caspase-1. Additionally, LH treatment altered the gut microbiota's microecology, characterized by a reduction in pathogenic bacteria abundance like Escherichia-shigella and an increase in beneficial bacteria abundance like Akkermansia and Erysipelatoclostridium. Overall, our findings indicate that LH therapy may be associated with intestinal barrier repair, inflammasome inhibition, and gut microbiota regulation, suggesting its potential as a UC treatment.

Association between metabolic dysfunction-associated steatotic liver disease and risk of colorectal cancer or colorectal adenoma: an updated meta-analysis of cohort studies.

Background and aims: In recent years, the relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and colorectal cancer (CRC) or colorectal adenoma (CRA) has gained widespread attention. Previous meta-analyses on this subject either incorporated numerous cross-sectional studies, which were susceptible to bias, or concentrated solely on a restricted number of cohort studies. Moreover, with the release of a substantial number of high-quality cohort studies on this subject in the past two years, the findings continue to be debated and contradictory. Therefore, we conducted an updated systematic review and meta-analysis of cohort studies to quantitatively evaluate the magnitude of the association between them. Methods: Comprehensive searches of PubMed, Web of Science, and Embase were conducted without language restrictions from the time of their creation up to December, 2023. The pooled hazard ratios (HRs) with 95% confidence interval (CIs) were calculated by the generic inverse variance based on the random-effects model. Moreover, subgroup and sensitivity analyses were performed. Results: A total of 15 cohort studies were analyzed in this meta-analysis, which included 9,958,412 participants. The meta-analysis of 13 cohort studies showed that MASLD was linked to a higher risk of CRC (HR=1.25, 95% CI: 1.15-1.36, P < 0.00001). Additionally, further subgroup analysis indicated that the combined HR remained consistent regardless of the study location, nomenclature of fatty liver disease (FLD), confirmation methods for FLD, sample size, follow-up time, and study quality. Furthermore, the meta-analysis of four cohort studies demonstrated that MASLD was correlated with an increased risk of CRA (HR=1.38, 95% CI: 1.17-1.64, P = 0.0002). The sensitivity analysis results further validated the robustness of the aboved findings. Conclusion: The results of our meta-analysis indicated that MASLD was associated with an increased risk of incident CRC/CRA. In the future, it is necessary to conduct more prospective cohort studies to thoroughly assess potential confounding factors, particularly in individuals from Europe and North America. Furthermore, related mechanism studies should be conducted to enhance our understanding of the link between MASLD and CRC/CRA. Systematic review registration: Open Science Framework registries (https://osf.io/m3p9k).

miR-199a-5p modulates choroidal neovascularization by regulating Wnt7b/Wnt/ß-catenin signaling pathway.

Choroidal neovascularization (CNV) can be seen in many fundus diseases, and lead to fundus exudation, bleeding, or vision loss. miRNAs are vital regulator in CNV. miR-199a-5p has been proved to be involved in regulating vascular formation of endothelial cells, but its role in CNV remains unclear. This study aims to study the role of miR-199a-5p in CNV. Laser irradiation was used to induce CNV model. The lesion area of CNV was calculated by high-resolution angiography with fluorescein isothiocyanate-dextran. Wnt family member 7b (Wnt7b), ß-catenin, and Wnt pathway proteins was measured by western blot. Immunofluorescence was performed to test Wnt7b, ß-catenin, CD31, and p-p65. miR-199a-5p and Wnt7b mRNA were tested by reverse transcription real-time polymerase chain reaction. Cell count kit-8, wound healing, Transwell, tube formation, and flow cytometry were used to detect the function of miR-199a-5p and Wnt7b on human retinal microvascular endothelial cells (HRMEC). TargetScan database and dual-luciferase reporter assay verified the interaction between miR-199a-5p and Wnt7b. The results revealed that Wnt7b increased in CNV rats. Knocking down Wnt7b repressed cell proliferation, migration, invasion, and angiogenesis, and accelerated cell apoptosis of HRMEC. Dual-luciferase reporter assay verified that miR-199a-5p targeted Wnt7b. Overexpression of miR-199a-5p inhibited the angiogenesis of HRMEC and promoted cell apoptosis by inhibiting Wbt7b. In vivo experiment found that Wnt7b rescued the promotion of miR-199a-5p inhibition on CNV lesion of rats. In addition, Wnt7b positively regulated Wnt/ß-catenin signaling pathway and promoted the angiogenesis of HRMEC. In conclusion, overexpression of miR-199a-5p inhibited the angiogenesis of HRMEC by regulating Wnt7b/Wnt/ß-catenin signaling pathway, which may serve as a promising therapy target of CNV.

Cardiac commitment driven by MyoD expression in pericardial stem cells.

Cellular therapy holds immense promise to remuscularize the damaged myocardium but is practically hindered by limited allogeneic sources of cardiac-committed cells that engraft stably in the recipient heart after transplantation. Here, we demonstrate that the pericardial tissue harbors myogenic stem cells (pSCs) that are activated in response to inflammatory signaling after myocardial infarction (MI). The pSCs derived from the MI rats (MI-pSCs) show in vivo and in vitro cardiac commitment characterized by cardiac-specific Tnnt2 expression and formation of rhythmic contraction in culture. Bulk RNA-seq analysis reveals significant upregulation of a panel of genes related to cardiac/myogenic differentiation, paracrine factors, and extracellular matrix in the activated pSCs compared to the control pSCs (Sham-pSCs). Notably, we define MyoD as a key factor that governs the process of cardiac commitment, as siRNA-mediated MyoD gene silencing results in a significant reduction of myogenic potential. Injection of the cardiac-committed cells into the infarcted rat heart leads to long-term survival and stable engraftment in the recipient myocardium. Therefore, these findings point to pericardial myogenic progenitors as an attractive candidate for cardiac cell-based therapy to remuscularize the damaged myocardium.

On-road evaluation and regulatory recommendations for NOx and particle number emissions of China VI heavy-duty diesel trucks: A case study in Shenzhen.

This research analyzed the real-world NOx and particle number (PN) emissions of 21 China VI heavy-duty diesel trucks (HDDTs). On-road emission conformity was first evaluated with portable emission measurement system (PEMS). Only 76.19 %, 71.43 % and 61.90 % of the vehicles passed the NOx test, PN test and both tests, respectively. The impacts of vehicle features including exhaust gas recirculation (EGR) equipment, mileage and tractive tonnage were then assessed. Results demonstrated that EGR helped reducing NOx emission factors (EFs) while increased PN EFs. Larger mileages and tractive tonnages corresponded to higher NOx and PN EFs, respectively. In-depth analyses regarding the influences of operating conditions on emissions were conducted with both numerical comparisons and statistical tests. Results proved that HDDTs generated higher NOx EFs under low speeds or large vehicle specific powers (VSPs), and higher PN EFs under high speeds or small VSPs in general. In addition, unqualified vehicles generated significantly higher NOx EFs than qualified vehicles on freeways or under speed≥40 km/h, while significant higher PN EFs were generated on suburban roads, freeways or under operating modes with positive VSPs by unqualified vehicles. The reliability and accuracy of on-board diagnostic (OBD) NOx data were finally investigated. Results revealed that 43 % of the test vehicles did not report reliable OBD data. Correlation analyses between OBD NOx and PEMS measurements further demonstrated that the consistency of instantaneous concentrations were generally low. However, sliding window averaged concentrations show better correlations, e.g., the Pearson correlation coefficients on 20s-window averaged concentrations exceeded 0.85 for most vehicles. The research results provide valuable insights into emission regulation, e.g., focusing more on medium- to high-speed operations to identify unqualified vehicles, setting higher standards to improve the quality of OBD data, and adopting window averaged OBD NOx concentrations in evaluating vehicle emission performance.

A closed-loop process for spent washing solution from multi-metal contaminated soil: EDTA reclamation and recycling.

The proper disposal of spent soil washing solution is a great challenge to ethylenediamine tetraacetate (EDTA)-base soil washing technologies, particularly when the solution contains multi-metals. In this paper, we proposed an environmentally friendly disposal of multi-metal spent washing solution, in which the multi-metals were concentrated as hazardous precipitates for further safe disposal, and EDTA was reclaimed and recycled to further wash contaminated soil together with the cleansed process water. The results showed that Cr3+ was poorly removed by sole heavy-metal-capturing agent (HMCA) chelation because of the high solubility of HMCA-Cr, which also yielded a low percentage of EDTA reclamation in the multi-metal spent washing solution. We established a closed-loop process for the disposal of multi-metal spent washing solution by combining coagulation-flocculation-sedimentation and HMCA chelation. The novel recycling process was able to remove 99.67% Cu, 99.62% Pb, 92.48% Cd, 88.19% Sb, 84.38% As, and 82.39% Cr as precipitates from the real spent washing solution, and up to 95.64% of EDTA was reclaimed in the cleansed process water. On the average, the overall efficiency of the reclaimed EDTA solution could reach 65% of the fresh EDTA solution in extracting various HMs from contaminated soil. The recycling method provides an efficient and promising alternative for spent soil washing solution with both EDTA and process water reusage in a closed-loop process.

3D printed barium titanate/calcium silicate composite biological scaffold combined with structural and material properties.

In the case of a large bone defect, the human endogenous electrical field is no longer sufficient. Therefore, it is necessary to support structural electrical bone scaffolds. Barium titanate (BT) has received much attention in bone tissue engineering applications due to its biocompatibility and ability to maintain charged surfaces. However, its processability is poor and it does not have the biological activity to promote mineralization, which limits its use in bone repair. In this paper, a composite bone scaffold with excellent piezoelectric properties was prepared by combining 20 wt% calcium silicate. The influence of the light curing process on the properties of the piezoelectric biological scaffold was investigated by comparing it with the traditional piezoelectric ceramic molding method (dry pressing). Despite the structural features of 3D printing (layered structure, pore features), the piezoelectric and mechanical properties of the scaffold are weakened. However, 3D-printed scaffolds can combine structural and piezoelectric properties, which makes the 3D-printed scaffold more effective in terms of degradation and antibacterial performance. In terms of cell activity, piezoelectric properties attract proteins and nutrients into the scaffold, promoting cell growth and differentiation. Besides, it is undeniable that the pore structure of the scaffolds plays an important role in the biological properties. Finally, the 3D printed scaffolds have excellent antimicrobial properties due to the redox reaction under piezoelectric effect as well as structural characterization.

The association between statin use and depression in diabetes.

BACKGROUND: Depression is a common mental disorder. Some studies have demonstrated that people with diabetes are more likely to suffer from depression. Statins are an everyday use for diabetes. Trials of statin therapy have had conflicting findings on the potential risk of depression. METHODS: The National Health and Nutrition Examination Survey (NHANES) 2005-2018 was used to collect a representative sample. Weighted multivariate logistic regression models were used to evaluate odds ratios (ORs) and 95 % CIs for having depression symptoms. We performed stratified analyses to compare the effects of statins in subsamples with and without diabetes on depression symptoms. RESULTS: Statin use showed a significant and strong decreasing effect on having depression symptoms in participants with diabetes (aOR (adjusted OR) 0.59, p = 0.014) compared with that in non-diabetics (aOR 0.78, p = 0.128). Diabetic individuals with statin use for >5 years had a lower risk of having depression symptoms (aOR 0.42, p = 0.002) than those with shorter-term statin use (1-5 years, aOR 0.69, p = 0.111; <1 year: aOR 0.83, p = 0.646). Atorvastatin was more effective in decreasing depression symptoms either in diabetes (aOR 0.49, p = 0.018) or in non-diabetes (aOR 0.58, p = 0.033). LIMITATIONS: First, the dosage of statins cannot be obtained from NHANES datasets. Second, after being stratified, the number of participants for several statins was insufficient. Third, recall bias may exist in the survey. CONCLUSIONS: Diabetics with depression symptoms may benefit from long-term statin therapy. Atorvastatin and pravastatin should be recommended for diabetic patients with depression.

Hypomethylation-Mediated Upregulation of NFE2L3 Promotes Malignant Phenotypes of Clear Cell Renal Cell Carcinoma Cells.

This work aimed to study the effect of NFE2 like bZIP transcription factor 3 (NFE2L3) on clear cell renal cell carcinoma (ccRCC) cells and whether NFE2L3 expression was mediated by DNA methylation. Twenty-one ccRCC patients were collected. The gene methylation and expression data of TCGA-KIRC were accessed from TCGA. Candidate methylation driver genes were identified by "MethylMix" package, and finally, NFE2L3 was selected as the target gene. The methylation of NFE2L3 was assayed by Ms PCR and QMSP. mRNA level of NFE2L3 was analyzed by qRT-PCR. Protein level of NFE2L3 was measured by Western blot. Demethylation was performed with methylation inhibitor 5-Aza-2'-deoxycytidine (5-Aza-CdR). Proliferative, migratory, and invasive abilities of ccRCC cells were assayed via cell colony formation assay, scratch healing assay, and transwell assay, respectively. Analysis of TCGA database presented that DNA hypomethylation occurred in the NFE2L3 promoter region in ccRCC tissues. NFE2L3 was significantly upregulated in ccRCC tissues and cells. Its expression in cells treated with 5-Aza-CdR was proportional to the concentration of methylation inhibitor. In cell function experiments, overexpressing NFE2L3 or demethylation could stimulate proliferation, migration, and invasion abilities of ccRCC and normal cells. 5-Aza-CdR treatment rescued repressive impact of knockdown NFE2L3 on malignant phenotypes of ccRCC and normal cells. DNA hypomethylation could induce high expression of NFE2L3 and facilitate malignant phenotypes of ccRCC cells. These results may generate insights into ccRCC therapy.

Sfrp1 as a Pivotal Paracrine Factor in the Trained Pericardial Stem Cells that Foster Reparative Activity.

Tissue damage often induces local inflammation that in turn dictates a series of subsequential responses, such as stem cell activation and growth, to maintain tissue homeostasis. The aim of the study is to testify the possibility of using inflammation-trained stem cells as optimal donor cells to augment the efficacy of cell therapy. The pericardial stem/stromal cells derived from the animals after myocardial infarction (MI-pSC) showed an enhanced myogenic potential and augmented reparative activity after transplantation in the injured hearts, as compared to the Sham-pSC. Bulk RNA-Seq analysis revealed significant upregulation of a panel of myogenic and trophic genes in the MI-pSC and, notably, Sfrp1 as an important anti-apoptotic factor induced robustly in the MI-pSC. Injection of the MI-pSC yielded measurable numbers of surviving cardiomyocytes (Tunel and Casp-3 negative) within the infarct area, but the effects were significantly diminished by siRNA-based silence of Sfrp1 gene in the pSC. Primed Sham-pSC with pericardial fluid from MI rats mimicked the upregulation of Sfrp1 and enhanced myogenic potential and reparative activity of pSC. Taken together, our results illustrated the inflammation-trained pSC favor a reparative activity through upregulation of Sfrp1 gene that confers anti-apoptotic activity in the injured cardiomyocytes. Therefore, the active form of stem cells may be used as a cardiac protective agent to boost therapeutical potential of stem cells.

Comparison of various surrogate markers for venous congestion in predicting acute kidney injury following cardiac surgery: A cohort study.

BACKGROUND: Venous congestion has been demonstrated to increase the risk of acute kidney injury (AKI) after cardiac surgery. Although many surrogate markers for venous congestion are currently used in clinical settings, there is no consensus on which marker is most effective in predicting AKI. METHODS: We evaluated various markers of venous congestion, including central venous pressure (CVP), inferior vena cava (IVC) diameter, portal pulsatility fraction (PPF), hepatic vein flow pattern (HVF), intra-renal venous flow pattern (IRVF), and venous excess ultrasound grading score (VExUS) in adult patients undergoing cardiac surgery to compare their ability in predicting AKI. RESULTS: Among the 230 patients enrolled in our study, 53 (23.0%) developed AKI, and 11 (4.8%) required continuous renal replacement therapy (CRRT). Our multivariate logistic analysis revealed that IRVF, PPF, HVF, and CVP were significantly associated with AKI, with IRVF being the strongest predictor (odds ratio [OR] 2.27; 95% confidence interval [CI], 1.38-3.73). However, we did not observe any association between these markers and CRRT. CONCLUSION: Venous congestion is associated with AKI after cardiac surgery, but not necessarily with CRRT. Among the markers tested, IRVF exhibits the strongest correlation with AKI.

Male refractory hypospadias with sexual reversal: a case report.

BACKGROUND: Hypospadias is one of the most prevalent urogenital malformations in clinic. However, some hypospadias may have a more complex disorder of sex development. Usually, hypospadias in these patients is severe. Among them, the 46,XX male sex reversal syndrome is a rare disorder of sex development, and this may be the main reason for this type of hypospadias being difficult to repair. CASE PRESENTATION: We present a Han nationality 19-year-old male with failure of repeated repair of hypospadias. No sperm was found on semen analysis. Lingual mucosal graft was carried out for this patient. It still did not succeed after using lingual mucosal graft repair. Karyotype analysis of this patient confirmed 46,XX karyotype. CONCLUSION: Hypospadias with 46,XX male sex reversal syndrome is hard to repair. Chromosome karyotype examination in patients with hypospadias is suggested. Genetic testing is recommended. In the future, further research is needed on the pathogenesis of disease and how to treat and prevent it.

A Novel Equivalent Method for Computing Mechanical Properties of Random and Ordered Hyperelastic Cellular Materials.

Simulating the mechanical behavior of cellular materials stands as a pivotal step in their practical application. Nonetheless, the substantial multitude of unit cells within these materials necessitates a considerable finite element mesh, thereby leading to elevated computational expenses and requisites for formidable computer configurations. In order to surmount this predicament, a novel and straightforward equivalent calculation method is proposed for the computation of mechanical properties concerning both random and ordered hyper-elastic cellular materials. By amalgamating the classical finite element approach with the distribution attributes of cells, the proposed equivalent calculation method adeptly captures the deformation modes and force-displacement responses exhibited by cell materials under tensile and shear loads, as predicted through direct numerical simulation. This approach reflects the deformation characteristics induced by micro-unit cells, elucidates an equivalent principle bridging cellular materials and equivalent materials, and substantially curtails exhaustive computational burdens. Ultimately, this method furnishes an equivalent computational strategy tailored for the engineering applications of cellular materials.

Association between hepatitis B or hepatitis C virus infection and risk of pancreatic cancer: a systematic review and meta-analysis of cohort studies.

Background and aim: With conflicting data from previous observational studies on the relationship between hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and pancreatic cancer (PC), we decided to conduct a systematic review and meta-analysis in order to evaluate any potential association. Design: This is a systematic review and meta-analysis. Methods: We conducted a search of three databases (PubMed, Embase, and Web of Science) from the time of their creation up to June 2023. The summary results, including hazard ratio (HR) with 95% confidence interval (CI), were pooled using a generic inverse variance method and a random-effects model. Furthermore, subgroup and sensitivity analyses were conducted. Results: In this meta-analysis, 22 cohort studies with a total of 10,572,865 participants were analyzed. Meta-analysis from 15 cohort studies revealed that HBV infection was correlated with an increased risk of PC (HR = 1.53, 95% CI: 1.40-1.68, p < 0.00001) with no heterogeneity (I2 = 0%, p = 0.49). Meta-analysis from 14 cohort studies showed that HCV infection was associated with an increased risk of PC (HR = 1.82, 95% CI: 1.51-2.21, p < 0.00001). Most of our subgroup analyses yielded similar results. Meta-analysis from four cohort studies indicated that co-infection with HBV and HCV was linked to an increased risk of PC (HR = 2.32, 95% CI: 1.40-3.85, p = 0.001) with no heterogeneity observed (I2 = 0%, p = 0.60). The results of sensitivity analyses were robust. Conclusion: Our meta-analysis showed that HBV/HCV infection or co-infection with HBV and HCV was associated with an increased risk of PC. Future prospective cohort studies need to take into account various ethnicities and any confounding factors, as well as investigate the potential mechanisms of PC development in those with HBV/HCV. Trial registration: Open Science Framework registries (No: osf.io/n64ua).

CircRNA-CIRH1A Promotes the Development of Osteosarcoma by Regulating PI3K/AKT and JAK2/STAT3 Signaling Pathways.

Osteogenic sarcoma (OS), one of the mesenchymal tumors with a high degree of malignancy, mainly occurs in the metaphysis of the long bones and around the knee joints in children and adolescents. The poor diagnosis in patients with OS can be attributed to the lack of early clinical symptoms, although the growth of tumor mass gradually results in severe pain and systemic symptoms. The mechanisms underlying the pathogenesis of OS are not fully understood. Thus, identifying early diagnostic biomarkers and novel targets involved in the progression of OS is of critical significance in the management of OS. CircRNA is a class of non-coding RNAs characterized by the close-loop structure and increased stability, which are implicated in the regulation of cell proliferation, differentiation, migration, and apoptosis. Moreover, circRNAs also play significant roles in aging and chronic disorders, such as cancer and cardiovascular diseases. Accordingly, we reported the upregulation of circRNA-CIRH1A in OS tissues and cell lines. Silencing circRNA-CIRH1A in OS cell lines (U2OS, HOS, Saos-2, and MG-63) could inhibit the cell proliferation, invasion, migration, and apoptosis, which was also validated in xenograft tumorigenesis mouse model. We further demonstrated that circRNA-CIRH1A sponged miR-1276, which subsequently disrupted the effect of miR-1276 on PI3K/AKT and JAK2/STAT3 signaling pathways. Together, our study revealed the oncogenic role of circRNA-CIRH1A in OS, and identified miR-1276/ PI3K-AKT and JAK2-STAT3 signaling axis as the key downstream mediators of circRNA-CIRH1A.

DiffNILM: A Novel Framework for Non-Intrusive Load Monitoring Based on the Conditional Diffusion Model.

Non-intrusive Load Monitoring (NILM) is a critical technology that enables detailed analysis of household energy consumption without requiring individual metering of every appliance, and has the capability to provide valuable insights into energy usage behavior, facilitate energy conservation, and optimize load management. Currently, deep learning models have been widely adopted as state-of-the-art approaches for NILM. In this study, we introduce DiffNILM, a novel energy disaggregation framework that utilizes diffusion probabilistic models to distinguish power consumption patterns of individual appliances from aggregated power. Starting from a random Gaussian noise, the target waveform is iteratively reconstructed via a sampler conditioned on the total active power and encoded temporal features. The proposed method is evaluated on two public datasets, REDD and UKDALE. The results demonstrated that DiffNILM outperforms baseline models on several key metrics on both datasets and shows a remarkable ability to effectively recreate complex load signatures. The study highlights the potential of diffusion models to advance the field of NILM and presents a promising approach for future energy disaggregation research.

Direct Electrochemistry of Glucose Dehydrogenase-Functionalized Polymers on a Modified Glassy Carbon Electrode and Its Molecular Recognition of Glucose.

A glucose biosensor was layer-by-layer assembled on a modified glassy carbon electrode (GCE) from a nanocomposite of NAD(P)+-dependent glucose dehydrogenase, aminated polyethylene glycol (mPEG), carboxylic acid-functionalized multi-wall carbon nanotubes (fMWCNTs), and ionic liquid (IL) composite functional polymers. The electrochemical electrode was denoted as NF/IL/GDH/mPEG-fMWCNTs/GCE. The composite polymer membranes were characterized by cyclic voltammetry, ultraviolet-visible spectrophotometry, electrochemical impedance spectroscopy, scanning electron microscopy, and transmission electron microscopy. The cyclic voltammogram of the modified electrode had a pair of well-defined quasi-reversible redox peaks with a formal potential of -61 mV (vs. Ag/AgCl) at a scan rate of 0.05 V s-1. The heterogeneous electron transfer constant (ks) of GDH on the composite functional polymer-modified GCE was 6.5 s-1. The biosensor could sensitively recognize and detect glucose linearly from 0.8 to 100 µM with a detection limit down to 0.46 µM (S/N = 3) and a sensitivity of 29.1 nA µM-1. The apparent Michaelis-Menten constant (Kmapp) of the modified electrode was 0.21 mM. The constructed electrochemical sensor was compared with the high-performance liquid chromatography method for the determination of glucose in commercially available glucose injections. The results demonstrated that the sensor was highly accurate and could be used for the rapid and quantitative determination of glucose concentration.

Thrombospondin-1 mimic peptide PKHB1 induced endoplasmic reticulum stress-mediated but CD47-independent apoptosis in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is one of the most common malignancies with high morbidity and mortality. PKHB1, a serum-stable Thrombospondin-1 (TSP-1) mimic peptide, has shown some effective ability in triggering cell death against several cancers. Here, we aimed to study the potential biological function of PKHB1 and its molecular mechanism in NSCLC. Our results revealed that PKHB1 significantly suppressed NSCLC cell proliferation, cell migration, and induced apoptosis in a dose-dependent manner. Additionally, we found that PKHB1 treatment resulted in mitochondrial transmembrane potential depolarization, Ca2+ overloading as well as the upregulation of proapoptotic proteins. Mechanistically, PKHB1 induced NSCLC cells apoptosis in a CD47-independent manner. Further study revealed that PKHB1 provoked endoplasmic reticulum (ER) stress principally through the activation of CHOP and JNK signaling, which could be alleviated in the presence of 4-PBA, an ER stress inhibitor. Furthermore, xenograft tumor models showed that PKHB1 treatment could notably inhibit NSCLC tumor growth in vivo. In conclusion, these findings suggested that PKHB1 exerted antitumor efficacy in NSCLC via triggering ER stress-mediated but CD47-independent apoptosis, potentially functioned as a promising peptide-based therapeutic agent for NSCLC.

The association between serum copper and obesity and all-cause mortality: the NHANES 2011-2016.

Excessive serum copper has multiple effects on human health, while the association between copper and obesity remains unclear. The objective of this study is to examine the associations of serum copper concentrations with obesity and adiposity measures, including body fat composition and distribution among adults in the USA. This analysis utilized data from the National Health and Nutrition Examination Survey (NHANES) (2011-2016). A total of 7285 adults aged 18 years or older who had serum copper measures were included in this cross-sectional study. Multi-linear regression and logistic regression were used to estimate the independent risky effect of copper on fat deposition and all-cause mortality. Moreover, these associations were analyzed in stratification analysis by gender, age, and physical activity (PA). Generally, we found that participants who were females, non-Hispanic Black, or with inactive PA tended to have a higher serum level of copper. In addition, we observed positive associations between serum copper and adiposity measurements. Furthermore, a serum copper level higher than 133.9 µg/dL was a risk factor for all-cause mortality, which doubled the odds ratio of all-cause mortality compared to the normal serum copper level. Serum copper was positively associated with fat deposition of whole body and regional parts, and all-cause mortality. Furthermore, the effects of copper on fat distribution were also significant and could be modified by age, gender, and PA.