The Chinese keratoconus (CKC) cohort study.

The Chinese keratoconus (CKC) cohort study is a population-based longitudinal prospective cohort study in the Chinese population involving a clinical database and biobanks. This ongoing study focuses on the prevention of KC progression and is the first to involve the effect of gene‒environment interactions on KC progression. The CKC cohort is hospital-based and dynamic and was established in Zhengzhou, China; KC patients (n = 1114) from a large geographical area were enrolled from January 2019 to June 2023, with a mean age of 22.23 years (6‒57 years). Demographic details, socioeconomic characteristics, lifestyle, disease history, surgical history, family history, and visual and social function data are being collected using questionnaires. General physical examination, eye examination, biological specimen collection, and first-degree relative data were collected and analyzed in the present study. The primary focus of the present study was placed on gene, environment and the effect of gene‒environment interactions on KC progression. The follow-up of the CKC cohort study is expected to include data collection at 3 months, 6 months, and 1 year after the initial examination and then at the annual follow-up examinations. The first follow-up of the CKC cohort study was recorded. A total of 918 patients completed the follow-up by June 1, 2023, with a response rate of 82.40%. Aside from the younger age of patients who were followed up, no significant differences were found between patients who were followed up and patients who were not.

Analysis of the Variation in Antioxidant Activity and Chemical Composition upon the Repeated Thermal Treatment of the By-Product of the Red Ginseng Manufacturing Process.

Steamed ginseng water (SGW) is a by-product of the repeated thermal processing of red ginseng, which is characterized by a high bioactive content, better skin care activity, and a large output. However, its value has been ignored, resulting in environmental pollution and resource waste. In this study, UHPLC-Q-Exactive-MS/MS liquid chromatography-mass spectrometry and multivariate statistical analysis were conducted to characterize the compositional features of the repeated thermal-treated SGW. The antioxidant activity (DPPH, ABTS, FRAP, and OH) and chemical composition (total sugars, total saponins, and reducing and non-reducing sugars) were comprehensively evaluated based on the entropy weighting method. Four comparison groups (groups 1 and 3, groups 1 and 5, groups 1 and 7, and groups 1 and 9) were screened for 37 important common difference markers using OPLS-DA analysis. The entropy weight method was used to analyze the weights of the indicators; the seventh SGW sample was reported to have a significant weight. The results of this study suggest that heat treatment time and frequency can be an important indicator value for the quality control of SGW cycling operations, which have great potential in antioxidant products.

Bioinformatics analysis of key candidate genes and pathways in Chinese patients with keratoconus.

Keratoconus (KC) is a multifactorial disease in which genetic factors played important roles in its pathogenesis. The purpose of the current study was to identify the key candidate genes and pathways in Chinese patients with KC through bioinformatics analysis. Totally, we identified 71 candidate genes by analyzing the results of whole exome sequencing on 51 Chinese patients with KC, combining with previous reports on differential expression at transcription and protein levels in KC. Gene enrichment analysis with GeneCodis demonstrated that two significantly enriched terms including 21 genes in biological process (BP) were detected, and six significantly enriched terms containing 14 genes in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were discovered. The STRING was utilized to construct the protein-protein interaction (PPI) network of identified genes. The result showed that a PPI network consisted of 14 nodes with 14 edges was constructed, and two gene modules were obtained. Eight hub genes (LAMB3, LAMA3, LAMA1, ITGA6, ITGA3, COL6A3, COL6A2, and COL6A1) were identified as key candidate genes for KC by cytoHubba in Cytoscape. Functional enrichment analysis with ClueGO and CluePedia indicated that the ECM-receptor interaction was the key pathway accounted for KC. The findings might provide novel insights on the genetic basis of KC.

Trio-based exome sequencing broaden the genetic spectrum in keratoconus.

Keratoconus (KC) is a complex corneal disorder with genetic factors involving in its pathogenesis. The genetic etiology of KC has not been fully elucidated. In this study, we aimed to expand the genetic spectrum in KC by trio-based exome sequencing. Trio-based exome sequencing was conducted in 20 patients with KC and their unaffected parents to broaden the genetic spectrum of the disease. With a series of filtering criteria, de novo, recessive homozygous, and compound heterozygous variants in candidate genes were identified, and the candidate genes were classified for further analysis. Finally, we identified 60 variants in 32 candidate genes through trio-based exome sequencing. Among the candidate genes, 10 genes (ARHGEF10, ARHGEF17, ASPM, FLNA, NDRG1, NEB, PLS3, STARD8, SYNE1, TTN) were classified as cytoskeleton-related genes, 4 genes (COL28A1, SDK1, STAB1, TENM2) were classified as cell adhesion-related genes, and 18 genes (APLP2, BCORL1, CCNB3, FOXN1, FUT8, GALNT10, HEPH, HHIP, HMGB3, HS6ST2, JADE3, KIAA0040, MCF2L, MYOF, QRICH2, RPS6KA6, SMARCA1, TNRC6A) were classified into other genes group. Additionally, the candidate rare deleterious variants in TTN were highly repeated in 25% trios. In conclusion, the study provided new insights into the genetic spectrum of KC which might underlie the genetic etiology for the disease. The findings would improve our understanding of pathogenesis in KC and provide critical clues to future functional validation.

Evaluating the accuracy and reliability of compound-specific carbon isotopic analysis using gas chromatography-combustion-isotope ratio mass spectrometry with the addition of a reduction furnace.

RATIONALE: Gas chromatography-combustion-isotope ratio mass spectrometry (GC/C/IRMS) is widely used for compound-specific carbon isotopic analysis. However, current isotopic analysis systems utilize the GC IsoLink combustion reactor, and independent reduction furnaces are not implemented. Therefore, whether this limitation in furnace use affects the precision of compound-specific carbon isotopic analysis needs to be evaluated. METHODS: We attempted to add a separate reduction furnace to the GC IsoLink interface and compared the δ13 C values of n-alkanes (including C and H elements), fatty acid methyl ester (including C, H, and O elements), caffeine (USGS61 and USGS62, including C, H, O, and N elements), and 9-ethylcarbazole (including C, H, and N elements) before and after the addition of the reduction furnace using the GC IsoLink combustion reactor. RESULTS: For n-alkanes and fatty acid methyl esters, the δ13 C differences between the measured values and their standard values were basically falling within 0.5‰ whether or not an independent reduction furnace was added. However, for the nitrogen-containing compounds (caffeine and 9-ethylcarbazole), the δ13 C differences between the measured values and their standard values were much larger without an independent reduction furnace (1.0-3.71‰ for USGS61, 1.78-2.19‰ for USGS62, and 0.39-1.13‰ for 9-ethylcarbazole) than with a reduction furnace (-0.31-0.68‰ for USGS61, -0.44-0.06‰ for USGS62, and -0.04-0.25‰ for 9-ethylcarbazole). CONCLUSIONS: The addition of an independent reduction furnace had no significant effect on the δ13 C of n-alkanes and fatty acid methyl esters, but it had a significant effect on the δ13 C of nitrogen-containing compounds. It is suggested that GC IsoLink needs an independent reduction furnace to effectively eliminate the interference of NOx on CO2 isotopic determination to improve the accuracy of δ13 C for nitrogen-containing compounds.

A high body mass index strengthens the association between the time of eye rubbing and keratoconus in a Chinese population: a case control study.

BACKGROUND: Although body mass index (BMI) and eye rubbing are linked to an increased risk of keratoconus (KC), the interactive effect of eye rubbing and BMI on KC is largely unknown. This study aimed to evaluate the independent and interactive effects of BMI and eye rubbing on KC and to further explore the role of environmental factors on the occurrence of KC. METHODS: A total of 621 individuals (291 KC patients and 330 control individuals) were enrolled in this hospital­based study on KC patients in Central China after individuals missing BMI data were excluded. BMI was calculated as weight in kilograms divided by the square of height in meters. Data on eye rubbing was recorded through face-to-face interviews. Generalized linear regression models were used to analyze associations among BMI, eye rubbing and KC. Interaction plots were used to describe the interactive effects of BMI and eye rubbing on KC. RESULTS: The ß and 95% confidence interval (CI) were 0.923 (0.112, 1.733) (p = 0.026) and 3.356 (1.953, 4.759) (p < 0.001), respectively, for the effect of each 10 kg/m2 increase in BMI and each 1 min increase in eye rubbing on KC. The interaction of BMI and eye rubbing were positively correlated with KC (p < 0.001). CONCLUSION: These findings suggested that a high BMI aggravated the negative effect of eye rubbing on KC, implying that individuals with a high BMI may be more susceptible to exposure to eye rubbing, which is related to an increased risk of KC.

[Effect of nanoparticles of different stiffness combined with menthol/curcumol on mechanical properties of bEnd.3 cells].

This study aimed to investigate the effects of nanoparticles PLGA-NPs and mesoporous silicon nanoparticles(MSNs) of different stiffness before and after combination with menthol or curcumol on the mechanical properties of bEnd.3 cells. The particle size distributions of PLGA-NPs and MSNs were measured by Malvern particle size analyzer, and the stiffness of the two nanoparticles was quantified by atomic force microscopy(AFM). The bEnd.3 cells were cultured in vitro, and the cell surface morphology, roughness, and Young's modulus were examined to characterize the roughness and stiffness of the cell surface. The changes in the mechanical properties of the cells were observed by AFM, and the structure and expression of cytoskeletal F-actin were observed by a laser-scanning confocal microscope. The results showed that both nanoparticles had good dispersion. The particle size of PLGA-NPs was(98.77±2.04) nm, the PDI was(0.140±0.030), and Young's modulus value was(104.717±8.475) MPa. The particle size of MSNs was(97.47±3.92) nm, the PDI was(0.380±0.016), and Young's modulus value was(306.019±8.822) MPa. The stiffness of PLGA-NPs was significantly lower than that of MSNs. After bEnd.3 cells were treated by PLGA-NPs and MSNs separately, the cells showed fine pores on the cell surface, increased roughness, decreased Young's modulus, blurred and broken F-actin bands, and reduced mean gray value. Compared with PLGA-NPs alone, PLGA-NPs combined with menthol or curcumol could allow deepened and densely distributed surface pores of bEnd.3 cells, increase roughness, reduce Young's modulus, aggravate F-actin band breakage, and diminish mean gray value. Compared with MSNs alone, MSNs combined with menthol could allow deepened and densely distributed surface pores of bEnd.3 cells, increase roughness, reduce Young's modulus, aggravate F-actin band breakage, and diminish mean gray value, while no significant difference was observed in combination with curcumol. Therefore, it is inferred that the aromatic components can increase the intracellular uptake and transport of nanoparticles by altering the biomechanical properties of bEnd.3 cells.

Real-world outcomes of regorafenib combined with immune checkpoint inhibitors in patients with advanced or metastatic microsatellite stable colorectal cancer: A multicenter study.

BACKGROUND: Treatment strategies are limited for patients with chemotherapy refractory microsatellite stable (MSS) colorectal cancer. We aim to evaluate the efficacy and safety of immune checkpoint inhibitors (ICIs) combined with regorafenib in this population in routine clinical practice. METHODS: We retrospectively analyzed patients with advanced or metastatic colorectal cancer who received at least one dose of ICIs combined with regorafenib in 14 Chinese medical centers. The primary outcome was objective response rate (ORR). This study was registered at ClinicalTrials.gov on February 2020 (NCT04771715). RESULTS: Eighty-four patients received ICIs combined with regorafenib from January 2019 to January 2021. Most patients (91%) received two or more systemic treatment lines before the study treatment. Seventy-six patients (90%) had confirmed MSS status. At a median follow-up of 5.5 months, four patients achieved partial response (5%) and 37 patients achieved stable disease (45%) as the best response. The median progression-free survival (PFS) was 3.1 months, and the median overall survival was 17.3 months. Eleven patients (13%) remained progression-free for more than 6 months. Baseline liver metastasis (HR 1.98, 95%CI 1.07-3.69, P = 0.03) and neutrophil-lymphocyte ratio (NLR) of ≥ 1.5 (HR 2.83, 95%CI 1.00-7.98, P = 0.05) were associated with shorter PFS in multivariate analysis. Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 16 patients (19%). CONCLUSION: The combination of ICIs with regorafenib can be a valuable treatment option for a proportion of patients with chemotherapy refractory MSS colorectal cancer. Patients with no liver metastasis and a low NLR at baseline may derive most benefit from this strategy.

Effects of dietary tributyrin and physterol ester supplementation on growth performance, intestinal morphology, microbiota and metabolites in weaned piglets.

AIM: This study was conducted to investigate the effects of dietary tributyrin (TB) and physterol ester (PSE) supplementation on the growth performance and intestinal health of weaned piglets. METHODS AND RESULTS: Ninety-six piglets were randomly allocated to one of four groups, including a control group (basal diet), TB group (basal diet + 1500 g t-1  TB), PSE group (basal diet + 300 g t-1 PSE) and TB + PSE group (basal diet + 1500 g t-1  TB + 300 g t-1 PSE). All groups had eight replicates with three piglets per replicate. The experiment lasted for 28 days. The results showed that dietary TB supplementation increased (p < 0.05) average daily feed intake and average daily gain, as well as the acetate and butyrate concentration in ileum, and dietary PSE supplementation decreased (p < 0.05) the ratio of feed to gain (F/G) on days 1-14 of the trial. Dietary TB or PSE alone supplementation improved the ratio of villus height to crypt depth (VH/CD) and the expression level of Occludin in ileum. The linear discriminant analysis effect size analysis identified eight biomarkers in the control group, 18 in the TB + PSE group, two in the PSE group in ileum respectively. Correlation analysis showed that the relative abundances of Enterococcus, and Streptococcus were positively correlated (p < 0.05) with propionate concentration, while the relative abundance of Clostridium_sensu_stricto_1 was negatively correlated (p < 0.05) with acetate concentration in ileum. CONCLUSION: These findings suggest that dietary TB or PSE alone supplementation could alter the growth performance, intestinal morphology, microbiota community and metabolites of weaned piglets. SIGNIFICANCE AND IMPACT OF THE STUDY: Weaning stress is a major cause of slow growth and increased diarrhoea in piglets. This study demonstrated that dietary TB and PSE presented a beneficial role in growth performance and gut health via regulating intestinal morphology, microbiota composition and metabolites.

Relationship between iron metabolism and gestational diabetes mellitus: A systemic review and meta analysis.

BACKGROUND AND OBJECTIVES: To investigate the relationship between serum iron metabolism indexes and gestational diabetes mellitus (GDM) using a meta-analysis. METHODS AND STUDY DESIGN: Databases including PubMed, Web of Science, Embase, and Cochrane Library were searched. Prospective cohort or case-control studies evaluating the relationships between serum iron metabolism indexes and GDM were retrieved from these data-bases. The outcome indicators, such as mean ± standard deviation, relative risk (RR), or odds ratio (OR) were extracted. The RR or OR, standard mean difference (SMD), and 95% confidence interval (CI) were used to calculate the combined effect sizes. RESULTS: A total of 32 studies on the relationships between serum iron metabolic indexes and GDM were included. The serum iron [SMD=0.40 mg/dL, 95% CI (0.16, 0.64), p=0.001], ferritin [SMD=0.58 ng/mL, 95% CI (0.35, 0.81), p˂0.001], hemoglobin [SMD=0.48 g/dL, 95% CI (0.28, 0.67), p˂0.001], transferrin saturation [SMD=0.83%, 95% CI (0.15, 1.52), p=0.000], and hepcidin [SMD=0.63 ng/mL, 95% CI (0.09, 1.18), p=0.023] levels were higher in the GDM group than in the non-GDM group, whereas total iron binding ability [SMD = -0.53 µg/dL, 95% CI (-1.05, -0.02), p=0.001] was lower in the GDM group than in the non-GDM group. High serum ferritin [OR=1.92, 95% CI (1.59, 2.32), p˂0.001] and hemoglobin levels [OR=1.30, 95% CI (1.04,1.63), p=0.023] were associated with GDM risk. CONCLUSIONS: Serum iron, ferritin, transferrin saturation, hepcidin, and hemoglobin levels were higher and total iron binding ability was lower in GDM patients than in those without GDM. High serum ferritin and hemoglobin levels were associated with GDM risk.

A bibliometric analysis of the top 100 most-cited articles on keratoconus.

PURPOSE: To explore the characteristics of the top 100 most-cited articles on keratoconus research. METHODS: The Web of Science database was searched to identify papers published from 1950 to 2020. A bibliometric analysis of the top 100 most-cited articles was conducted in the current study. The Kruskal-Wallis test was conducted to test the citation differences between basic research, clinical research, and reviews. The Spearman correlation analysis was used to investigate the association between citations and publication year. The VOSviewer software was used to create networks of co-authorship and keywords map. RESULTS: The median values of the number of citations, citations/year since publication, and citations since 2013 were 186.5, 13.90, and 11, respectively. A total of 79% of articles were clinical research. Reviews exhibited a higher value of citations/year since publication and citations since 2013 than basic research (all P < 0.05). The number of publications, total number of citations, citations/year since publication and citations since 2013 on the top 100 most-cited articles list increased with an increase in the publication year in three article types (all P < 0.05). The Journal of Cataract and Refractive Surgery had the highest number of articles. There were 37 articles from the USA. Rabinowitz, YS was the most-cited author with the greatest total link strength. Extensive collaboration existed among the main core nodes containing "cross-linking," "refractive surgery," and "penetrating keratoplasty." CONCLUSIONS: The present study focused on the comprehensive analysis of the top 100 most-cited articles on keratoconus research, providing insight into keratoconus research developments over the past decades.

Whole mitochondrial genome analysis in Chinese patients with keratoconus.

Purpose: Keratoconus (KC) is a corneal disorder characterized by corneal ectasia, progressive corneal thinning, and conical protrusion. This study aimed to elucidate the mitochondrial gene profile in Chinese patients with KC, analyze the mitochondrial haplogroup and heteroplasmy, and further explore the association between mitochondrial genes and KC. Methods: Mitochondrial sequencing was conducted on 100 patients with KC and 100 matched controls. Haplogroup analysis was conducted with logistic regression analysis. The heteroplasmy was analyzed with ANOVA (ANOVA) and Student t test. Sequence kernel association tests (SKATs) were performed to analyze the association between mitochondrial genes and KC. Mtoolbox, Mitoclass.1, and APOGEE were used to estimate the impact of the identified variants in protein-coding genes. PON-mt-tRNA was used to annotate the impact of the variants in tRNA. RNAstructure was used to predict the secondary structures of native and mutated tRNAs. Results: We identified 689 variants in patients with KC and 725 variants in controls (with 308 variants shared by both). The mitochondrial haplogroups exhibited no statistically significant differences between the two groups. Based on the heteroplasmy analysis, the number of heteroplasmic variants in the complete mitochondrial genome, RNA coding regions, and noncoding regions were statistically significantly different in the KC cases and controls (p<0.05). The heteroplasmic levels of the m.16180_16182delAA, m.16182insC, and m.14569 G>C variants in the KC cases were statistically significantly higher than those in the controls (p<0.05). The SKAT analysis showed that the COX3 and TRNH genes were statistically significantly associated with KC (p<0.05). Among the nine variants of COX3 included in the SKAT analysis (m.9300G>A, m.9316T>C, m.9327A>G, m.9355A>G, m.9468A>G, m.9612G>A, m.9804G>A, m.9957G>A, and m.9966 G>A), m.9612G>A was predicted to be deleterious by Mtoolbox. The m.9316T>C, m.9327A>G, m.9355A>G, m.9612G>A, m.9804G>A, and m.9957G>A variants were predicted to be damaging by Mitoclass.1. The m.9355A>G and m.9804G>A variants were predicted to be pathogenic by APOGEE. All identified variants located in TRNH (m.12153C>T, m.12178C>T, and m.12192G>A) were predicted to be neutral by the PON-mt-tRNA website. Conclusions: This study presents the mitochondrial gene profile of Chinese patients with KC and demonstrated that the COX3 and TRNH genes were associated with KC.

Associations of spicy food flavour and intake frequency with blood lipid levels and risk of abnormal serum lipid levels in Chinese rural population: a cross-sectional study.

OBJECTIVE: The purpose of the current study was to investigate associations between spicy food intake and serum lipids levels in Chinese rural population. DESIGN: Information on spicy food flavour and intake frequency was obtained using a two-item questionnaire survey. Dietary data were collected using a validated thirteen-item FFQ. Fasting blood samples were collected and measured for total cholesterol (TC), TAG, HDL-cholesterol and LDL-cholesterol. Multivariate linear and logistic regression models were employed to examine the relationship between spicy food and serum lipids levels according to the spicy food flavour and intake frequency, respectively. SETTING: A cross-sectional study in Henan Province. PARTICIPANTS: 38 238 participants aged 18-79 years old. RESULTS: Spicy flavour and intake frequency were consistently associated with decreased TC and non-HDL-cholesterol levels but mildly associated with elevated TAG levels. Each level increment in spicy flavour was inversely associated with high TC (OR: 0·91; 95 % CI 0·88, 0·93) and high non-HDL-cholesterol (OR: 0·88; 95 % CI 0·85, 0·91) but positively associated with high TAG (OR: 1·04; 95 % CI 1·01, 1·07). Similarly, 1-d increment in spicy food intake frequency was also inversely associated with high TC (OR: 0·92; 95 % CI 0·91, 0·94) and high non-HDL-cholesterol (OR: 0·91; 95 % CI 0·89, 0·93) but positively associated with high TAG (OR: 1·04; 95 % CI 1·02, 1·06). CONCLUSIONS: Spicy food intake was mildly associated with increased risk of abnormal TAG level, significantly associated with decreased risk of abnormal TC and non-HDL levels. Spicy food intake may be contribute to the management of lipid levels.

Quantitative Analysis of the RPC Vessel Density and the RNFL Thickness in Patients with Type 2 Diabetes Mellitus by Using OCT Angiography.

INTRODUCTION: This study aims to compare the structural differences in the optic disc blood perfusion and the peripapillary retinal nerve fibre layer (pRNFL) thickness in age-matched healthy subjects and patients with type 2 diabetes mellitus (DM) by using quantitative analysis with optical coherence tomography angiography (OCTA). METHODS: A cross-sectional cohort study on patients with type 2 DM with or without diabetic retinopathy (DR) and healthy subjects was conducted. The 4.5-mm scanning angio-disc pattern of the OCTA system was used to assess the optic disc. The analysed indices included radial peripapillary capillary (RPC) vessel density and pRNFL thickness. RESULTS: A total of 78 eyes from 78 patients with type 2 DM, including 27 without clinical DR (NDR), 26 with non-proliferative DR (NPDR), and 25 with proliferative DR (PDR), and 28 age-matched healthy subjects were enrolled. The average RPC vessel density of the whole (p < 0.001) and the peripapillary (p < 0.001) regions was significantly different in different groups, whereas the pRNFL was not statistically significant (p = 0.764). Compared with that in healthy subjects, the RPC vessel densities in 4, 5, and 8 peripapillary sectors in NDR (all p < 0.05), NPDR (all p < 0.05), and PDR (all p < 0.05) groups, respectively, were reduced. Compared with that in healthy subjects, the pRNFL thickness significantly decreased in the inferior nasal sector (p = 0.001) in NDR but significantly increased in the 2 sectors (all p < 0.01) in PDR. The DR severity was negatively correlated with the peripapillary RPC vessel density (r = -0.583, p < 0.001) but had no correlation with the pRNFL thickness (r = -0.045, p = 0.648). The positive correlation between the peripapillary RPC vessel density and the pRNFL thickness was statistically significant in the control (r = 0.531, p = 0.004), NDR (r = 0.528, p = 0.004), and NPDR (r = 0.405, p = 0.040) groups but not in the PDR group (r = 0.394, p = 0.05). CONCLUSIONS: The peripapillary RPC perfusion decreased with DR aggravation, which may be considered as a useful indicator of DR severity. However, the pRNFL thickness had little diagnostic power in differentiating healthy and DM eyes.

Cu2 MoS4 Nanozyme with NIR-II Light Enhanced Catalytic Activity for Efficient Eradication of Multidrug-Resistant Bacteria.

Nanozymes with unique enzyme-like catalytic properties and versatile functionalities are particularly attractive for the treatment of bacterial infections, especially for combating drug-resistant bacteria. However, inherently low catalytic activity significantly limits their antibacterial performance. Herein, a new near-infrared II (NIR-II) light responsive nanozyme (Cu2 MoS4 nanoplates, CMS NPs) is developed for efficient eradication of multidrug-resistant (MDR) bacteria. CMS NPs with intrinsic dual enzyme-like property can generate reactive oxygen species (ROS) by catalysis. Importantly, CMS NPs show NIR-II light enhanced oxidase- and peroxidase-like catalytic activities to improve ROS generation for highly efficient killing of bacteria. In vitro results demonstrate that CMS NPs (40 µg mL-1 ) achieve rapid killing of 8 log MDR Escherichia coli and 6 log MDR Staphylococcus aureus (S. aureus) under NIR-II light irradiation (1064 nm, 1 W cm-2 ) in 10 min. Moreover, CMS NPs exhibit excellent therapeutic efficacy of MDR S. aureus infection in vivo as well as negligible toxicity to cells and animals, indicating their potential use as antibacterial agents. This work provides a novel antibacterial strategy by combining the catalytic generation of ROS and NIR-II photothermal effect of nanozymes for efficient treatment of MDR bacteria-related infections.

Reproducibility and validity of an FFQ in the Henan Rural Cohort Study.

OBJECTIVE: The present study aimed to evaluate the validity and reproducibility of a thirteen-item FFQ regarding identification of dietary conditions in a rural population in China. DESIGN: A reproducibility study repeated the first FFQ (FFQ1) approximately 4 weeks later (FFQ2). A validity study evaluated the mean of three consecutive 24 h diet recalls as the reference measure. SETTING: Cross-sectional study. PARTICIPANTS: Residents of a rural area in Henan Province, which is located in the central region of China. RESULTS: A total of 295 individuals participated in the reproducibility study. In addition, 123 people agreed to participate in the validity study. Spearman's correlation coefficients between the two FFQ ranged from 0·06 (vegetables) to 0·58 (eggs). Spearman's correlation coefficients between the two methods of collection ranged from 0·01 for cereal to 0·49 for staple foods. The mean of the intraclass correlation coefficients of the two FFQ (FFQ1 v. FFQ2) was 0·19. Bland-Altman analysis indicated good agreement for most food groups across the range of intake for the two studies. CONCLUSIONS: The study demonstrated that our FFQ design could be used as a representative tool to conduct a dietary evaluation of a rural population.

Evaluation of the Associations of GC and CYP2R1 Genes and Gene-Obesity Interactions with Type 2 Diabetes Risk in a Chinese Rural Population.

INTRODUCTION: Group-specific component (GC) and cytochrome P450 family 2 subfamily R member 1 (CYP2R1) gene polymorphisms and obesity have been associated with an increased risk for development of type 2 diabetes mellitus (T2DM) in Asian populations. OBJECTIVE: This study assessed the associations of interactions between GC gene variants and CYP2R1 gene variants and between genes and obesity with T2DM risk. METHODS: A study that included 2,271 subjects was performed. Eight single nucleotide polymorphisms in the GC and CYP2R1 genes were genotyped. Interaction analysis was performed using rs7041 in the GC gene and rs1993116 in the CYP2R1 gene. The effects of multiplicative and additive gene-gene and gene-environment interactions on T2DM risk were assessed. RESULTS: The T2DM risk was significantly associated with being overweight/obese, abdominal obesity, rs7041, and rs1993116. A significant additive interaction between rs1993116 and rs7041 was associated with T2DM. In addition, there was a significant multiplicative interaction between rs7041 and body mass index (BMI) associated with elevated blood glucose levels, and at a higher BMI (>28.47), the G allele carrier showed a stronger effect than the TT genotype. CONCLUSIONS: The interactions between GC rs7041-CYP2R1 rs1993116 and GC rs7041-BMI may explain the mechanisms by which these factors increase the risk of T2DM development.

Mediation effect of body mass index on the association between spicy food intake and hyperuricemia in rural Chinese adults: the Henan rural cohort study.

BACKGROUND: The relationship of spicy food intake with hyperuricemia remains unknown. The objective of this study was to examine the association between spicy food intake and hyperuricemia, and whether this association was mediated by body mass index (BMI) in Chinese rural population. METHODS: 38, 027 adults aged 18-79 years were recruited from the Henan Rural Cohort Study. Information on spicy food intake was obtained using a validated questionnaire survey. Multivariable logistic regression model was used to estimate the association between spicy food intake and hyperuricemia, multiple linear regression model was performed to estimate the relationships between spicy food intake, BMI and serum urate level. BMI was used as a mediator to evaluate the mediation effect. RESULTS: After adjusting for potential confounders, compared with no spicy food flavor, the odds ratio (OR) and 95% confidence interval (CI) of mild, middle, and heavy flavor for hyperuricemia were 1.09 (1.00-1.19), 1.10 (0.97-1.24), and 1.21 (1.10-1.46), respectively (Ptrend = 0.017). Similarly, compared with those without intake in spicy food, the multivariable adjusted OR (95% CI) of 1-2 days/week, 3-5 days/week, and 6-7 days/week were 1.15 (1.01-1.31), 1.14 (1.01-1.30) and 1.15 (1.05-1.26), respectively (Ptrend = 0.007). However, when we further controlling for BMI, the associations were substantially attenuated. Furthermore, mediation analysis showed that BMI play a full mediating role in the relationship of spicy food intake with hyperuricemia. CONCLUSION: Spicy food flavor and intake frequency are positively related with hyperuricemia in Chinese rural population. BMI may play a full mediating role in the relationship. TRIAL REGISTRATION: The Henan Rural Cohort Study registered at Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699 ). Date of registration: 2015-07-06.

Epidemiology and prevalence of hyperuricemia among men and women in Chinese rural population: The Henan Rural Cohort Study.

Objective: The aim of this study was to explore the latest prevalence of hyperuricemia and influencing factors in Chinese rural population.Methods: A survey was conducted from July 2015 to September 2017. A total of 38,855 (15,371 men and 23,484 women) subjects were recruited from the Henan Rural Cohort Study. Hyperuricemia was defined as a serum urate level of >7.0 mg/dL for men and >6.0 mg/dL for women. A meta-analysis of 19 studies that focused on hyperuricemia prevalence was performed to validate the result of the cross-sectional survey.Results: The crude and age-standardized prevalence of hyperuricemia was 10.24% and 12.60%, respectively. The prevalence of hyperuricemia decreased in men with increasing age, but the opposite trend was observed in women. The results of meta-analysis demonstrated that hyperuricemia prevalence in Chinese rural areas was 11.7%, consistent with the result of current survey. Multivariate logistic regression revealed that overweight or obesity, hypercholesterolemia, hypertriglyceridemia, hypoalphalipoproteinemia and high serum creatinine level could increase the risk of hyperuricemia, while high physical activity and fasting plasma glucose were associated with a lower risk of hyperuricemia in all participants.Conclusion: The latest prevalence of hyperuricemia is high in rural China and is associated with multiple factors, indicating that prevention and control strategies for hyperuricemia are needed urgently.

Catalytically Selective Chemotherapy from Tumor-Metabolic Generated Lactic Acid.

Lactic acid (LA) is a powerful molecule as the metabolic driver in tumor microenvironments (TMEs). Inspired by its high intratumoral level (5-20 µmol g-1 ), a novel treatment paradigm via the cascade release of H2 O2 and ·OH from the LA generated by tumor metabolism is developed for catalytic and pH-dependent selective tumor chemotherapy. By utilizing the acidity and overexpression of LA within the TME, the constructed lactate oxidase (LOD)-immobilized Ce-benzenetricarboxylic acid (Ce-BTC) metal organic framework enables the intratumoral generation of ·OH via a cascade reaction: 1) the in situ catalytic release of H2 O2 from LA by LOD, and 2) the catalytic production of ·OH from H2 O2 by Ce-BTC with peroxidase-like activity. Highly toxic ·OH effectively induces tumor apoptosis/death. A new strategy for selective tumor chemotherapy is provided herein.