RuZn NPs with electroactivity and oxidase-like property for dual-mode anti-cancer drug monitoring.

6-mercaptopurine (6-MP) as the effective anti-cancer drug was used for the treatment of Crohn's disease and acute lymphoblastic leukaemia, but the response to maintenance therapy was variable with individual differences. In order to control the dosage and decrease the side effects of 6-MP, a sensitive and stable assay was urgently needed for 6-MP monitoring. Herein, RuZn NPs with electrochemical oxidation property and oxidase-like activity was proposed for dual-mode 6-MP monitoring. Burr-like RuZn NPs were prepared and explored to not only exhibit an electrochemical oxidation signal at 0.78 V, but also displayed excellent oxidase-like performances. RuZn NPs were utilized for the dual-mode monitoring of 6-MP, attributing to the formation of Ru-SH covalent bonding. The colorimetric method showed good linearity from 10 µM to 5 mM with the limit of detection (LOD) of 300 nM, while the electrochemical method provided a higher sensitivity with the LOD of 37 nM in range from 100 nM to 200 µM. This work provided a new way for the fabrication of dual-functional nanotags with electroactivity and oxidase-like property, and opened a dual-mode approach for the 6-MP detection applications with complementary and satisfactory results.

Hemorrhage profile associated with immune checkpoint inhibitors: a systematic review and a real-world study based on the FAERS database.

OBJECTIVES: To investigate the risk of hemorrhage associated with Immune Checkpoint Inhibitors (ICIs) and characterize its clinical features. METHODS: We systematically reviewed randomized clinical trials (RCTs) of hemorrhage related to ICIs and calculated odds ratios (ORs) with 95% confidence intervals (CIs). Pharmacovigilance studies were conducted by collecting ICIs-related hemorrhage cases from the FAERS database and assessing disproportionalities by reporting odds ratios (RORs) and information components (ICs). RESULTS: A total of 79 RCTs involving 45,100 patients were finally included in the systematic review, with four published RCTs (n = 1965) and 75 unpublished RCTs (n = 43135). The primary analysis showed no significant difference in ICIs compared to the control group (OR 1.18 [95% CI 1.00-1.38], p = 0.05). In subgroup analyses, anti-PD-L1 combined with anti-CTLA-4 increased the risk of hemorrhage (OR 1.95, p = 0.03), and anti-CTLA-4 increased the risk of hemorrhage in the gastrointestinal system (OR 2.23, p = 0.04). 3555 cases of hemorrhage from the FAERS database were included in the disproportionate analysis, and the result suggested that ICIs increased the risk of hemorrhage (IC025 = 0.23). CONCLUSION: Our study suggests that ICIs increase the risk of hemorrhage, and in particular, anti-CTLA-4 significantly increases the risk of hemorrhage in the gastrointestinal system.

Nucleus-targeting DNase I self-assembly delivery system guided by pirarubicin for programmed multi-drugs release and combined anticancer therapy.

The cell nucleus serves as the pivotal command center of living cells, and delivering therapeutic agents directly into the nucleus can result in highly efficient anti-tumor eradication of cancer cells. However, nucleus-targeting drug delivery is very difficult due to the presence of numerous biological barriers. Here, three antitumor drugs (DNase I, ICG: indocyanine green, and THP: pirarubicin) were sequentially triggered protein self-assembly to produce a nucleus-targeting and programmed responsive multi-drugs delivery system (DIT). DIT consisted of uniform spherical particles with a size of 282 ± 7.7 nm. The acidic microenvironment of tumors and near-infrared light could successively trigger DIT for the programmed release of three drugs, enabling targeted delivery to the tumor. THP served as a nucleus-guiding molecule and a chemotherapy drug. Through THP-guided DIT, DNase I was successfully delivered to the nucleus of tumor cells and killed them by degrading their DNA. Tumor acidic microenvironment had the ability to induce DIT, leading to the aggregation of sufficient ICG in the tumor tissues. This provided an opportunity for the photothermal therapy of ICG. Hence, three drugs were cleverly combined using a simple method to achieve multi-drugs targeted delivery and highly effective combined anticancer therapy.

Epidemiological Surveillance: Genetic Diversity of Rotavirus Group A in the Pearl River Delta, Guangdong, China in 2019.

Objective: This study aimed to understand the epidemic status and phylogenetic relationships of rotavirus group A (RVA) in the Pearl River Delta region of Guangdong Province, China. Methods: This study included individuals aged 28 days-85 years. A total of 706 stool samples from patients with acute gastroenteritis collected between January 2019 and January 2020 were analyzed for 17 causative pathogens, including RVA, using a Gastrointestinal Pathogen Panel, followed by genotyping, virus isolation, and complete sequencing to assess the genetic diversity of RVA. Results: The overall RVA infection rate was 14.59% (103/706), with an irregular epidemiological pattern. The proportion of co-infection with RVA and other pathogens was 39.81% (41/103). Acute gastroenteritis is highly prevalent in young children aged 0-1 year, and RVA is the key pathogen circulating in patients 6-10 months of age with diarrhea. G9P[8] (58.25%, 60/103) was found to be the predominant genotype in the RVA strains, and the 41 RVA-positive strains that were successfully sequenced belonged to three different RVA genotypes in the phylogenetic analysis. Recombination analysis showed that gene reassortment events, selection pressure, codon usage bias, gene polymorphism, and post-translational modifications (PTMs) occurred in the G9P[8] and G3P[8] strains. Conclusion: This study provides molecular evidence of RVA prevalence in the Pearl River Delta region of China, further enriching the existing information on its genetics and evolutionary characteristics and suggesting the emergence of genetic diversity. Strengthening the surveillance of genotypic changes and gene reassortment in RVA strains is essential for further research and a better understanding of strain variations for further vaccine development.

Intra-articular injection of miRNA-1 agomir, a novel chemically modified miRNA agonists alleviates osteoarthritis (OA) progression by downregulating Indian hedgehog in rats.

Our objective in this study is to determine whether intra-articular injection of miRNA-1 can attenuate the progression of OA in rats by down regulating Ihh. Knee chondrocytes were isolated from male Sprague-Dawley rats aged 2-3 days. Second-generation chondrocytes were transfected with miR-1 mimic and empty vector with lipo3000 for 6 h and then stimulated with 10 ng/mL IL-1ß for 24 h. OA-related and cartilage matrix genes were quantified using real-time quantitative polymerase chain reaction (RT-qPCR). Two-month-old male Sprague-Dawley rats were divided into three groups (n = 30?): sham operation group + 50 µL saline, anterior cruciate ligament transection (ACLT) group + 50 µL miR-1 agomir (concentration), and control group ACLT + 50 µL miR-1 agomir. Treatment was started one week after the operation. All animals were euthanized eight weeks after the operation. X-rays and micro-CT were used to detect imaging changes in the knee joints. FMT was used to monitor joint inflammation in vivo. Safranin O staining was used to detect morphological changes in articular cartilage. Immunohistochemistry was used to detect Col2, Col10, metalloproteinase-13 (MMP-13). RT-qPCR was used to detect gene changes includingmiR-1, Col2, Col10, MMP-13, Ihh, Smo, Gli1, Gli2, and Gli3. Overexpression of miR-1 in IL-1ß-stimulated chondrocytes reduced the levels of Ihh, MMP-13, and Col10 but increased the levels of Col2 and aggrecan. Intra-articular injection of miR-1 agomir reduced osteophyte formation, inflammation, and prevented cartilage damage. RT-qPCR results indicated that the miR-1 agomir increased articular cartilage anabolism and inhibited cartilage catabonism. miR-1 can attenuate the progression of OA by downregulating Ihh.

Induction of somatic cell haploidy by premature cell division.

Canonical mitotic and meiotic cell divisions commence with replicated chromosomes consisting of two sister chromatids. Here, we developed and explored a model of premature cell division, where nonreplicated, G0/G1-stage somatic cell nuclei are transplanted to the metaphase cytoplasm of mouse oocytes. Subsequent cell division generates daughter cells with reduced ploidy. Unexpectedly, genome sequencing analysis revealed proper segregation of homologous chromosomes, resulting in complete haploid genomes. We observed a high occurrence of somatic genome haploidization in nuclei from inbred genetic backgrounds but not in hybrids, emphasizing the importance of sequence homology between homologs. These findings suggest that premature cell division relies on mechanisms similar to meiosis I, where genome haploidization is facilitated by homologous chromosome interactions, recognition, and pairing. Unlike meiosis, no evidence of recombination between somatic cell homologs was detected. Our study offers an alternative in vitro gametogenesis approach by directly reprogramming diploid somatic cells into haploid oocytes.

The association between vitamin C intake and the risk of abdominal aortic calcification: A population-based study.

BACKGROUND: The beneficial effects of dietary vitamin C intake on human health have received widespread attention from the population. However, the correlation between vitamin C intake and abdominal aortic calcification remains unclear. The authors aimed to investigate the relationship between dietary vitamin C intake and AAC in US adults. METHODS: Our data for this study were obtained from the National Health and Nutrition Examination Survey (NHANES) 2013-2014, and participants had complete data on dietary vitamin C intake and AAC scores. We used weighted multivariate linear regression and multivariate logistic regression analyses to explore the independent relationship between vitamin C intake and AAC scores, along with subgroup analyses and restricted cubic splines. RESULTS: A total of 2876 participants were enrolled in this study, with a mean AAC score of 1.47 ± 0.14 and a prevalence of severe AAC of 8.12%. We observed a 0.5 unit decrease in AAC scores in participants in the highest quartile compared to those in the lowest quartile of VitC intake. In contrast, there was no significant correlation between VitC intake and risk of severe AAC. Besides, subgroup analysis and interaction tests showed that there was no dependence of the association between VitC intake and AAC. CONCLUSION: Dietary VitC intake was associated with reduced AAC scores, but there was no significant correlation between dietary VitC intake and risk of severe AAC.

Deep learning model to predict lupus nephritis renal flare based on dynamic multivariable time-series data.

OBJECTIVES: To develop an interpretable deep learning model of lupus nephritis (LN) relapse prediction based on dynamic multivariable time-series data. DESIGN: A single-centre, retrospective cohort study in China. SETTING: A Chinese central tertiary hospital. PARTICIPANTS: The cohort study consisted of 1694 LN patients who had been registered in the Nanjing Glomerulonephritis Registry at the National Clinical Research Center of Kidney Diseases, Jinling Hospital from January 1985 to December 2010. METHODS: We developed a deep learning algorithm to predict LN relapse that consists of 59 features, including demographic, clinical, immunological, pathological and therapeutic characteristics that were collected for baseline analysis. A total of 32 227 data points were collected by the sliding window method and randomly divided into training (80%), validation (10%) and testing sets (10%). We developed a deep learning algorithm-based interpretable multivariable long short-term memory model for LN relapse risk prediction considering censored time-series data based on a cohort of 1694 LN patients. A mixture attention mechanism was deployed to capture variable interactions at different time points for estimating the temporal importance of the variables. Model performance was assessed according to C-index (concordance index). RESULTS: The median follow-up time since remission was 4.1 (IQR, 1.7-6.7) years. The interpretable deep learning model based on dynamic multivariable time-series data achieved the best performance, with a C-index of 0.897, among models using only variables at the point of remission or time-variant variables. The importance of urinary protein, serum albumin and serum C3 showed time dependency in the model, that is, their contributions to the risk prediction increased over time. CONCLUSIONS: Deep learning algorithms can effectively learn through time-series data to develop a predictive model for LN relapse. The model provides accurate predictions of LN relapse for different renal disease stages, which could be used in clinical practice to guide physicians on the management of LN patients.

Dynamic Changes and Clinical Significance of Plasma Galectin-3 in Patients with Acute Ischemic Stroke Undergoing Endovascular Therapy.

Purpose: Galectin-3 is a key regulator of microglial proliferation and activation and may have dual and time-dependent effects on ischemic stroke. This study aimed to prospectively investigate the dynamic changes in Galectin-3 levels in patients with acute ischemic stroke receiving endovascular therapy and its clinical significance. Patients and Methods: A total of 105 patients with acute ischemic stroke who underwent endovascular therapy were prospectively enrolled. Plasma Galectin-3 was quantitatively detected by an enzyme-linked immunosorbent assay before the operation and at 1 day, 3 days and 7 days after the operation. A linear mixed-effect model, Pearson correlation analysis and receiver operating characteristic (ROC) curve analysis were used to evaluate the dynamic changes in the plasma Galectin-3 concentration and its relationship with clinical outcomes. Results: Increases in plasma Galectin-3 levels at 1 day and 3 days after surgery were associated with early neurological deterioration and death (both P <0.05). Increased Galectin-3 levels before surgery and at 1 day and 3 days after surgery were associated with poor prognosis (P <0.05). Pearson correlation analysis revealed that Galectin-3 levels before surgery (r =0.318, P =0.002), at 1 day (r =0.318, P =0.001), 3 days (r =0.429, P < 0.001) and 7 days after surgery (r =0.340, P =0.001) were positively correlated with NIHSS scores. The ROC curve results showed that Galectin-3 concentration had a certain predictive value for death at 1 day (AUC=0.707, P=0.013), 3 days (AUC=0.708, P=0.016) and 7 days after the operation (AUC=0.708, P=0.016), but this predictive value was lower than that of the NIHSS score. Conclusion: In acute ischemic stroke patients receiving endovascular therapy, an increase in the plasma Galectin-3 levels were associated with death, poor prognosis, and early neurological deterioration. Galectin-3 levels were significantly correlated with the NIHSS score and had a certain predictive value for death.

Vertical measurements of atmospheric CO2 and 14CO2 at the northern foot of the Qinling Mountains in China.

The CO2 and 14CO2 levels in air samples from the northern foot of the Qinling Mountains (Xi'an, China) were determined. In 2021, a hexacopter unmanned aerial vehicle sampled air at different heights, from near-ground to 2000 m. The objectives of this study were to determine vertical characteristics of CO2 and 14CO2, the sources of different-height CO2, and the influence of air mass transport. The CO2 concentrations mainly exhibited a slight decreasing trend with increasing height during summer observations, which was in contrast to the increasing trend that was followed by a subsequent gradual decreasing trend during early winter observations, with peak CO2 levels (443.4 ± 0.4-475.7 ± 0.5 ppm) at 100-500 m. The variation in vertical concentrations from 20 to 1000 m in early winter observations (21.6 ± 19.3 ppm) was greater than that in summer observations (14.6 ± 14.3 ppm), and the maximum vertical variation from 20 to ∼2000 m reached 61.1 ppm. Combining Δ14C and δ13C vertical measurements, the results showed that fossil fuel CO2 (CO2ff, 56.1 ± 15.2 %), which mainly come from coal combustion (81.2 ± 3.4 %), was the main contributor to CO2 levels in excess of the background level (CO2ex) during early winter observations. In contrast, biological CO2 (CO2bio) dominated CO2ex in summer observations. The vertical distributions of CO2ff in early winter observations and CO2bio in summer observations were consistent with those of CO2 during early winter and summer observations, respectively. The strong correlation between winter CO2bio and ΔCO (r = 0.81, p < 0.01) indicated that biomass burning was the main contributor to CO2bio during early winter observations. Approximately half of the air masses originated from the Guanzhong Basin during observations. The results provide insights into the vertical distribution of different-sources of atmospheric CO2 in scientific support of formulating carbon emission-reduction strategies.

Atmospheric CO2 and 14CO2 observations at the northern foot of the Qinling Mountains in China: Temporal characteristics and source quantification.

A two-year (March 2021 to February 2023) continuous atmospheric CO2 and a one-year regular atmospheric 14CO2 measurement records were measured at the northern foot of the Qinling Mountains in Xi'an, China, aiming to study the temporal characteristics of atmospheric CO2 and the contributions from the sources of fossil fuel CO2 (CO2ff) and biological CO2 (CO2bio) fluxes. The two-year mean CO2 mole fraction was 442.2 ± 16.3 ppm, with a yearly increase of 4.7 ppm (i.e., 1.1 %) during the two-year observations. Seasonal CO2 mole fractions were the highest in winter (452.1 ± 17.7 ppm) and the lowest in summer (433.5 ± 13.3 ppm), with the monthly CO2 levels peaking in January and troughing in June. Diurnal CO2 levels peaked at dawn (05:00-07:00) in spring, summer and autumn, and at 10:00 in winter. 14C analysis revealed that the excess CO2 (CO2ex, atmospheric CO2 minus background CO2) at this site was mainly from CO2ff emissions (67.0 ± 26.8 %), and CO2ff mole fractions were the highest in winter (20.6 ± 17.7 ppm). Local CO enhancement above the background mole fraction (ΔCO) was significantly (r = 0.74, p < 0.05) positively correlated with CO2ff in a one-year measurement, and ΔCO:CO2ff showed a ratio of 23 ± 6 ppb/ppm during summer and winter sampling days, much lower than previous measurements and suggesting an improvement in combustion efficiency over the last decade. CO2bio mole fractions also peaked in winter (14.2 ± 9.6 ppm), apparently due to biomass combustion and the lower and more stable wintertime atmospheric boundary layer. The negative CO2bio values in summer indicated that terrestrial vegetation of the Qinling Mountains had the potential to uptake atmospheric CO2 during the corresponding sampling days. This site is most sensitive to local emissions from Xi'an and to short distance transportation from the southern Qinling Mountains through the valleys.

Elevated levels of Zn, Cu and Co are associated with an increased risk of endometriosis: Results from a casecontrol study.

BACKGROUND: Endometriosis is a common gynecological disease that affects approximately 5 %∼10 % of reproductive-aged women. Zinc (Zn), selenium (Se), copper (Cu), cobalt (Co) and molybdenum (Mo) are essential trace elements and are very important for human health. However, studies on the relationship between mixtures of essential trace elements and the risk of endometriosis are limited and inconsistent. In particular, studies confirming the association via different sample types are limited. OBJECTIVE: This study aimed to investigate the associations between Zn, Se, Cu, Co and Mo concentrations in blood and follicular fluid (FF) and endometriosis risk in a Chinese population. METHODS: A total of 609 subjects undergoing in vitro fertilization (IVF) were recruited; 836 samples were analyzed, including 451 blood samples (234 controls and 217 cases) and 385 FF samples (203 controls and 182 cases). In addition, 227 subjects provided both blood and FF samples. Zn, Se, Cu, Co and Mo concentrations in blood and FF were quantified via inductively coupled plasma-mass spectrometry (ICP-MS). The associations between the levels of Zn, Se, Cu, Co and Mo and the risk of endometriosis were assessed using single-element models (logistic regression models), and the combined effect of the trace elements on endometriosis risk was assessed using multielement models (Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) regression). RESULTS: Based on the single-element models, significant associations of Zn concentrations in blood (high-level vs. low-level group: aOR = 14.17, 95 % CI: 7.31, 27.50) and FF (first tertile vs. second tertile group: aOR = 0.34, 95 % CI: 0.16, 0.71; third tertile vs. second tertile group: aOR = 2.32, 95 % CI: 1.38, 3.91, respectively) and Co concentrations in blood (first tertile vs. second tertile group, aOR = 0.24, 95 % CI: 0.12, 0.48) and FF (third tertile vs. second tertile group: aOR = 3.87, 95 % CI: 2.19, 6.84) with endometriosis risk were found after adjustment for all confounders. In FF, Cu and Mo levels were significantly greater among the cases than among the controls, with a positive association with endometriosis risk (Cu (first tertile vs. second tertile group: aOR = 0.39, 95 % CI: 0.19, 0.81; third tertile vs. second tertile group: aOR = 2.73, 95 % CI: 1.61, 4.66, respectively) and Mo (high-level vs. low-level group: aOR = 14.93, 95 % CI: 7.16, 31.12)). However, similar associations between blood Cu and Mo levels and endometriosis risk were not found. In addition, the levels of these five essential trace element mixtures in blood and in FF were significantly and positively associated with endometriosis risk according to the BKMR analyses; the levels of Zn and Cu in blood and the levels of Mo in FF were significantly related to the risk of endometriosis, and the posterior inclusion probabilities (PIPs) were 1.00, 0.99 and 1.00 for Zn and Cu levels in blood and Mo levels in FF, respectively. Furthermore, Zn and Mo were the highest weighted elements in blood and FF, respectively, according to WQS analyses. CONCLUSION: The risk of endometriosis was associated with elevated levels of several essential trace elements (Zn, Cu and Co). Elevated levels of these elements may be involved in the pathomechanism of endometriosis. However, further studies with larger sample sizes will be necessary to confirm these associations.

Using Bayesian and weighted regression to evaluate the association of idiopathic oligoastenoteratozoospermia with seminal plasma metal mixtures.

Idiopathic oligoastenoteratozoospermia (iOAT) affects 30% of infertile men of reproductive age. However, the associations between Cr, Fe, Cu, Se or Co levels and iOAT risk have not been determined. This research aimed to assess the associations between Cr, Fe, Cu, Se and Co levels as well as their mixtures in seminal plasma and the risk of iOAT and severe iOAT. Therefore, a case‒control study including 823 participants (416 iOAT patients and 407 controls) recruited from October 2021 to August 2022 at the reproductive medicine center of the First Affiliated Hospital of Anhui Medical University was conducted in Anhui, China. The concentrations of Cr, Fe, Cu, Se and Co in seminal plasma were detected via inductively coupled plasma‒mass spectrometry. Binary logistic regression models were used to assess the associations between the levels of Cr, Fe, Cu, Se and Co and the risk of iOAT and severe iOAT; additionally, Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) regressions were performed to evaluate the joint effect of seminal plasma levels of Cr, Fe, Cu, Se and Co on the risk of iOAT and explore which elements contributed most to the relationship. We found significant associations between the concentrations of Fe, Cu and Se in seminal plasma and iOAT risk after adjusting for covariates (Fe, lowest tertile vs. second tertile: aOR = 1.86, 95% CI = 1.31, 2.64; Cu, lowest tertile vs. second tertile: aOR = 1.95, 95% CI = 1.37, 2.76; Se, lowest tertile vs. second tertile: aOR = 1.65, 95% CI = 1.17, 2.35). A lower Se concentration in seminal plasma (lowest tertile vs. second tertile: aOR = 1.84, 95% CI = 1.10, 3.10) was positively associated with the risk of severe iOAT. Additionally, we also observed an association between the concentration of Cr in seminal plasma and the risk of iOAT before adjusting for covariates (Cr, third tertile vs. lowest tertile: OR=1.44, 95% CI: 1.03, 2.02). According to the BKMR analyses, the risk of iOAT increased when the overall concentrations were less than the 25th percentile. The results from the WQS regression indicated that a negative WQS index was significantly associated with the iOAT risk, while a positive WQS index was not. Se and Fe had significant weights in the negative direction. In conclusion, lower Cu, Fe and Se levels in seminal plasma were positively associated with iOAT risk, while higher Cr levels in seminal plasma were positively associated with iOAT risk according to the single element model, and lower levels of Se were related to a greater risk of severe iOAT; when comprehensively considering all the results from BKMR and WQS regression, Fe, Se and Cr levels contributed most to this relationship.

A dye sensitized photosynthesis cell for stable water oxidation mediated by photo-generated bromine.

The critical step of a dye-sensitized photoelectrochemical cell (DSPEC) is water oxidation. The photoanodes suffer rapid surface carrier recombination due to slow water oxidation kinetics and this results in low solar conversion efficiency and poor stability. Here, we design a novel sensitization-oxidation photo-anode, where the [Ru(4,4'-PO3H2-bpy)(bpy)2]2+ (RuP2+, bpy = 2,2'-bipyridine) chromophore and [Ru(bda)(pic)2] (pic = picoline, bda = 2,2'-bipyridine-6,6'-dicarboxylate) water oxidation catalyst (WOC) are immobilized separately on the surface of a mesoporous semiconductor thin film. The electrode creates a mobile and strong Br3- oxidant generated by the dye-sensitized electrode, which initiates water oxidation at a remote catalytic site. Under 100 mW cm-2 illumination in pH 4.65 in 0.1 M acetate buffer solution, the photoanode could perform a stable photoelectrochemical water oxidation for 6 hours with a photocurrent density of around 0.25 mA cm-2. This dual electrode could open a new door by utilizing an electron transfer mediator to design highly stable photoelectrochemical cells.

The association between C-reactive protein levels and the risk of kidney stones: a population-based study.

OBJECTIVES: The relationship between C-reactive protein (CRP) and the risk of developing kidney stones is unclear, and we aimed to assess the association between CRP and kidney stones in US adults. METHODS: We used data from NHANES 2007-2010, and we excluded participants who were under 18 years of age and lacked data on CRP and kidney stones. Finally, we included a total of 11,033 participants and performed weighted multivariate regression analysis and subgroup analysis to assess the independent relationship between CRP and kidney stones. RESULTS: The mean prevalence of kidney stones among the participants was 9.8%. Notably, as CRP levels increased, the prevalence of kidney stones exhibited a corresponding rise across quartiles (Kidney stones: Quartile 1: 7.59%; Quartile 2: 8.77%; Quartile 3: 9.64%; Quartile 4: 10.89%). CRP was positively associated with the risk of kidney stones (Model 1: OR = 1.09, 95% CI: 1.01-1.18, p = 0.03; Model 2: OR = 1.09, 95% CI: 1.00-1.18, p = 0.03, Model 3: OR = 1.14, 95%CI: 1.02-1.26, p = 0.04). Participants in the highest CRP quartile experienced a 69% increased risk of kidney stones compared to those in the lowest quartile (OR = 1.64, 95% CI: 1.04-2.59, p = 0.03). Notably, interaction tests revealed that gender, BMI, diabetes, hypertension, CKD and smoking or alcohol consumption status did not significantly influence the association between CRP and kidney stones. CONCLUSIONS: Our findings reveal a significant association between higher CRP levels and an increased risk of kidney stones. In clinical practice, heightened awareness of CRP as a potential biomarker could aid in risk assessment and management strategies for kidney stone patients.

Solid-state fermentation by S. cerevisiae with high resistance to ferulic acid improves the physicochemical properties of wheat bran and quality of bran-rich Chinese steamed bread.

Wheat bran has numerous health benefits, but its poor processing and sensory properties limit its application in the staple food industry. Fermentation by S. cerevisiae changes the performance of wheat bran. However, high levels of ferulic acid (FA) inhibit S. cerevisiae. The effects of solid-state fermentation of S. cerevisiae with high resistance to FA on the physicochemical properties of wheat bran and the quality of bran-rich Chinese steamed bread (CSB) were investigated. The results showed that the growth of S. cerevisiae was inhibited by FA in a dose-dependent manner. Short-term adaptation strategies efficiently improved the tolerance of S. cerevisiae to FA stress. Compared with the parental strain (PS), fermentation of the short-term adapted strains (adapted strains) significantly increased the FA, total phenol, and soluble dietary fiber content in wheat bran. Wheat bran fermented by the adapted strains had a higher antioxidant capacity than wheat bran fermented by PS. In addition, compared with the PS, the wheat bran fermented by the adapted strains can decrease the hardness, improve the specific volume, and the quality of CSB. Thus, solid-state fermentation of the adapted strain is a potentially effective method to improve the nutritional and physicochemical properties of wheat bran as a cereal food ingredient.

Jin-Gui-Shen-Qi Wan alleviates fibrosis in mouse diabetic nephropathy via MHC class II.

ETHNOPHARMACOLOGICAL RELEVANCE: Jin-Gui-Shen-Qi Wan (JGSQW) is a traditional Chinese medicine formula that has been traditionally used to alleviate urinary system ailments such as frequent urination and polyuria. Clinical studies have indicated that when combined with hypoglycaemic drugs, JGSQW exhibits a synergistic effect and can improve diabetic nephropathy (DN), yet its underlying mechanism and targets remain unclear. AIM OF THE STUDY: This study aims to investigate the therapeutic efficacy of JGSQW and its underlying mechanisms using a DN db/db mouse model. MATERIALS AND METHODS: Ultrahigh-performance liquid chromatography coupled with mass spectrometry was utilized to analyse the primary active compounds, blood levels, and pharmacokinetics of JGSQW. Additionally, the therapeutic effects of JGSQW and metformin on blood glucose levels, lipid levels, renal function, and renal pathology in diabetic nephropathy mice were investigated using a db/db mouse model. Proteomic analysis was carried out to identify the primary target of JGSQW in treating DN. The mechanism of action was verified by western blotting, immunohistochemistry, and immunofluorescence. Then, molecular docking and molecular dynamics, transfection, drug affinity responsive target stability (DARTS) assay and cell thermal migration assay (CETSA) further validated the targeted binding effect. RESULTS: JGSQW combined with metformin significantly improved the blood glucose levels, blood lipids, renal function, and renal pathology of DN mice. JGSQW mainly exerted its therapeutic effect on DN by targeting major histocompatibility complex class II (MHC class II) molecules. Immunohistochemistry results showed that JGSQW inhibited the expression of collagen I, fibronectin, and alpha smooth muscle actin (α-SMA) expression. Immunofluorescence and Western blot results showed that JGSQW inhibited the expression of H2-Ab1 and H2-Aa, which are MHC class II molecules, thereby suppressing CD4+ T-cell infiltration and improving diabetic kidney fibrosis. The binding ability of paeoniflorin to H2-Aa was predicted and verified by molecular, DARTS, and CETSA assays. Treatment with 80 µM paeoniflorin effectively alleviated high glucose-induced injury in the MPC-5 injury model. H2-Aa was overexpressed at this model concentration, and Western blotting further confirmed that paeoniflorin reduced glomerular podocyte fibrosis by regulating H2-Aa. CONCLUSIONS: JGSQW combined with metformin may have a synergistic effect to alleviates renal fibrosis in diabetic nephropathy by downregulating immune complex MHC class II molecules and attenuating the antigen presentation effect of MHC class II on CD4.

Preparation and Characterization of Ultrafine Nitroguanidine with Different Aspect Ratios.

In order to improve the mechanical properties and thermodynamic stability of the long needle-like raw material Nitroguanidine (NQ), it was pulverized by a mechanical pulverization method and dried by a spray drying method, and three ultrafine NQ samples with different aspect ratios (2.26, 1.87, and 1.25) were prepared. The samples were tested and characterized by scanning electron microscopy, digital imaging particle size analysis, X-ray diffraction, and differential scanning calorimetry (DSC), and the impact sensitivity and bulk density of the raw NQ and ultrafine NQ samples were also tested. The results show that ultrafine NQ has the smallest particle size D50 of 9.18 µm, with uniform particle size distribution, unchanged crystal structure, and no introduction of impurities, and the impact sensitivity was the same as that of the feedstock NQ, which was 0. In addition, with the decreasing aspect ratio of the NQ particles, their apparent activation energy increased, and the energy required to be absorbed in the thermal decomposition increased; their thermal stability was also better.

Physicochemical properties of different size fractions of potato starch cultivated in Highland China.

Location influences the properties of potato starch. Potato starch granules cultivated in highland of China were separated into three fractions according to the sedimentation time: large- (∼81 µm, large fraction potato starch, LFPS), medium- (∼28 µm, medium fraction potato starch, MFPS), and small-size (∼15 µm, small fraction potato starch, SFPS) fractions. SFPS showed a spherical shape, MFPS showed an ellipsoid shape and LFPS showed an elongated shape. The three fractions showed the similar XRD patterns, while the relative crystallinity decreased with the decrease of granule size (LFPS 23.61%, MFPS 20.74% and SFPS 20.48%). The water solubility was positively corelated with the granule size, while the swelling power showed a negative relationship with the granule size. For the rheological properties, all the three fractions showed a shear-shinning behavior; and SFPS had the highest peak temperature. However, the MFPS showed the lowest storage modulus during the temperature sweep. The granule size didn't influence the nutritional properties of potato starch and LFPS had the highest slowly digestible starch (SDS) (83.77%) and resistant starch (RS) (13.66%) contents. Some of the properties are different from the previous studies.

GPX2 acts as an oncogene and cudraflavone C has an anti-tumor effect by suppressing GPX2-dependent Wnt/ß-catenin pathway in colorectal cancer cells.

Colorectal carcinoma (CRC) is a common cancer associated with poor prognosis, and cudraflavone C (Cud C) is a natural flavonol with reported anti-CRC capacity. However, the precise mechanisms underlying the anti-CRC effect require further demonstration. The aim of present study was to evaluate the impact of Cud C on the cell viability and apoptosis of CRC cells and to determine the underlying mechanisms. The Human Protein Atlas (THPA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases were used to analyze the expression status of glutathione peroxidase 2 (GPX2) in CRC. Cell viability was examined using cell counting kit-8 (CCK-8) assay. Flow cytometry was utilized to evaluate apoptosis. The levels of gene transcription and protein expression of GPX2, caspase-3, cleaved caspase-3), ß-catenin, and c-Myc were determined by RT-qPCR and Western blotting. Our results showed that GPX2 was overexpressed in CRC as compared to normal tissue and the extent of GPX2 overexpression is greatest in CRC when compared with other cancers according to GEPIA and THPA databases. GPX2 knockdown significantly suppressed the cell viability, induced apoptosis of CRC cell lines, and restrained the activity of Wnt/ß-catenin pathway. Cud C treatment decreased cell viability, induced apoptosis in CRC cell lines, and diminished the expression level of GPX2-dependent activation of Wnt/ß-catenin pathway, while such effects can be abolished by GPX2 overexpression. In conclusion, Cud C suppressed GPX2-dependent Wnt/ß-catenin pathway to exert anti-CRC function.