Association between per- and poly-fluoroalkyl substances and nonalcoholic fatty liver disease: A nested case-control study in northwest China.

Per- and poly-fluoroalkyl substances (PFAS) have been reported to have hepatotoxic effects. However, it is unclear whether they are linked to non-alcoholic fatty liver disease (NAFLD). This nested case-control study focused on the epidemiological links between PFAS and the prevalence of NAFLD. We selected 476 new cases of NAFLD and 952 age- and sex-matched controls from the Jinchang cohort population between 2014 and 2019. Serum concentrations of PFAS were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Only PFAS with a detection rate of ≥90 % were included for analysis, which included PFPeA, PFOA, PFNA, PFHxS, PFOS, and 9Cl-PF3ONS. The relationship between single and co-exposure to PFAS and the occurrence of NAFLD was evaluated using conditional logistic regression, Quantile g-computation (QgC), and Bayesian kernel machine regression (BKMR) model. Logistic regression indicated that PFPeA, PFOA, and 9Cl-PF3ONS were positive correlation with the incidence of NAFLD after adjusting for confounders, with odds ratios (OR) and 95 % confidence interval (CI) of 3.13 (95 % CI: 2.53, 3.86), 1.39 (95 % CI: 1.12, 1.73), and 1.41 (95 % CI: 1.20, 1.66), respectively. PFNA, PFHxS, and PFOS were nonlinearly and negatively associated with the incidence of NAFLD, with OR (95 % CI) of 0.53 (0.46, 0.62), 0.83 (0.73, 0.95), and 0.52 (0.44, 0.61), respectively. QgC showed a significant joint effect of PFAS mixture on NAFLD onset (OR: 1.52, 95 % CI: 1.24, 1.88). BKMR showed a weak positive trend between PFAS mixtures and NAFLD incidence. Positive correlations were primarily driven by PFPeA and 9Cl-PF3ONS, while negative correlations were mainly influenced by PFNA and PFOS. The BKMR model also suggested that there was an interaction between PFOS and PFNA and other four PFAS compounds. In conclusion, our findings suggest that individual and co-exposure to PFAS is associated with a risk of NAFLD onset.

Development of visual detection of African swine fever virus using CRISPR/LwCas13a lateral flow strip based on structural protein gene D117L.

African swine fever virus (ASFV) is a large double stranded DNA arbovirus that is highly contagious and seriously endangers domestic and wild pigs. In the past decade, African swine fever (ASF) has spread in many countries in the Caucasus, Russian Federation, Eastern Europe and Asia, causing significant losses to the pig industry. At present, there is a lack of effective vaccine and treatment for ASF. Therefore, the rapid and accurate detection is crucial for ASF prevention and control. In this study, we have developed a portable lateral flow strip (LFS) detection mediated by recombinase polymerase amplification (RPA) and CRISPR/LwCas13a, which is performed at 37 ℃ and visualized by eyes without the need for complex instruments. This RPA-LwCas13a-LFS is based on the ASFV structural protein p17 gene (D117L), with a detection sensitivity up to 2 gene copies. This method is highly specific and has no cross reactivity to 7 other pig viruses. In the detection of two batches of 100 clinical samples, the p17 (D117L) RPA-LwCas13a-LFS had 100% coincidence with conventional quantitative PCR (qPCR). These findings demonstrate the potential of this simple, rapid, sensitive, and specific ASFV detection method for on-site ASFV detection.

Case report: Resolution of Guillain-Barré syndrome in a patient with dual primary tumors after treatment with rituximab.

Guillain-Barré syndrome (GBS) is a rare immune-related adverse event (irAE) that can occur in solid tumors such as hepatocellular carcinoma, gastric cancer, breast cancer, and colorectal cancer. It is characterized by progressive myasthenia and mild sensory abnormalities. The emergence of immune checkpoint inhibitors (ICIs) has significantly improved cancer patients' life expectancy but can also trigger various irAEs, including GBS. We report a rare case of GBS in a 64-year-old male patient with dual primary tumors of the colon and stomach who received toripalimab and chemotherapy for liver metastases. After five treatments, the patient experienced weakness and numbness in his limbs. Lumbar puncture, electromyography, and other tests confirmed the diagnosis of GBS. Intravenous immunoglobulin (IVIG) and methylprednisolone did not improve the patient's symptoms, but rituximab, which is not a standard regimen for GBS, was effective in eliminating B cells and improving symptoms. Following this, we effectively shifted from a regimen combining immunotherapy and chemotherapy to a targeted therapy regimen, resulting in prolonged patient survival. Currently, limited studies have been undertaken to evaluate the efficacy of rituximab in managing refractory neurological adverse events associated with ICI therapy. Using this case, we reviewed similar cases and formed our views.

Value of GPR, APPRI and FIB-4 in the early diagnosis of hepatocellular carcinoma: a prospective cohort study.

OBJECTIVE: There is an urgent need for novel biomarkers that are inexpensive, effective and easily accessible to complement the early diagnosis of hepatocellular carcinoma. This study aimed to analyze the relationship between serum gamma-glutamate-transpeptidase to platelet ratio, alkaline phosphatase-to-platelet ratio index, fibrosis index based on four factors and the risk of hepatocellular carcinoma, and to determine the optimal cut-offs for predicting hepatocellular carcinoma. METHODS: Based on a prospective cohort study, 44 215 participants who were cancer-free at baseline (2011-13) were included in the study. Cox proportional hazard models and receiver operating characteristics curves were used to analyze the diagnostic value and optimal cut-off value of gamma-glutamyl-transpeptidase to platelet ratio, alkaline phosphatase-to-platelet ratio index and fibrosis index based on four factors in predicting hepatocellular carcinoma patients. RESULTS: Gamma-glutamyl-transpeptidase to platelet ratio, alkaline phosphatase-to-platelet ratio index and fibrosis index based on four factors can be used as early independent predictors of hepatocellular carcinoma risk. The risk of hepatocellular carcinoma in the fourth quantile of gamma-glutamyl-transpeptidase to platelet ratio and alkaline phosphatase-to-platelet ratio index was 4.04 times (hazard ratio = 4.04, 95% confidence interval: 2.09, 7.80) and 2.59 times (hazard ratio = 2.59, 95% confidence interval: 1.45, 4.61), respectively, compared with the first quantile. With fibrosis index based on four factors first quantile as a reference, fibrosis index based on four factors fourth quantile had the highest risk (hazard ratio = 18.58, 95% confidence interval: 7.55, 45.72). Receiver operating characteristic results showed that fibrosis index based on four factors had a stronger ability to predict the risk of hepatocellular carcinoma (area under curve = 0.81, 95% confidence interval: 0.80, 0.81), and similar results were shown for gender stratification. In the total population, the optimal cut-off values of gamma-glutamyl-transpeptidase to platelet ratio, alkaline phosphatase-to-platelet ratio index and fibrosis index based on four factors were 0.208, 0.629 and 1.942, respectively. CONCLUSIONS: Gamma-glutamyl-transpeptidase to platelet ratio, alkaline phosphatase-to-platelet ratio index and fibrosis index based on four factors were independent predictors of hepatocellular carcinoma risk. Amongst them, fibrosis index based on four factors shows a stronger predictive ability for hepatocellular carcinoma risk, and gamma-glutamyl-transpeptidase to platelet ratio and alkaline phosphatase-to-platelet ratio index can be used as complementary indicators.

Rapid Visual Detection of African Swine Fever Virus with a CRISPR/Cas12a Lateral Flow Strip Based on Structural Protein Gene D117L.

African swine fever virus (ASFV) is a large double-stranded DNA virus that is highly infectious and seriously affects domestic pigs and wild boars. African swine fever (ASF) has caused huge economic losses to endemic countries and regions. At present, there is still a lack of effective vaccines and therapeutics. Therefore, rapid and accurate detection is essential for the prevention and control of ASF. The portable DNA endonuclease (Cas12a)-mediated lateral flow strip detection method (Cas12a-LFS) combined with recombinant polymerase amplification (RPA) has been gradually recognized as effective for virus detection including ASFV. In this study, based on the ASFV structural protein p17 gene (D117L), an RPA-Cas12a-LFS detection method was established. The detection method exhibits a sensitivity of up to two gene copies and has no cross-reaction with nine other swine viruses. Thus, the method is highly sensitive and specific. In 68 clinical samples, the coincidence rate of the p17 strip was 100%, compared to the traditional quantitative PCR (qPCR). In conclusion, we have developed a simple, rapid, sensitive, and specific ASFV visual detection method and demonstrated the potential of on-site detection of ASFV.

Clearness qualitative comparative analysis of the spread of TikTok health science knowledge popularization accounts.

Objective: This study analyzed the popularity of TikTok health knowledge popularization accounts with the objective of creating a template for accounts suited to widely disseminating information, thereby enhancing the public's access to health knowledge on a broader scale. Methods: This study is based on 40 Chinese TikTok short video accounts that were active from February to April 2022 and were engaged in health science popularization. Data were validated by structured calibration using three qualitative anchors. It employs the "content-context" and the elaboration likelihood models as the theoretical framework. A qualitative comparative analysis is used to explore the factors affecting the popularity of this type of account mechanism. Results: Among the nine variables involved in the calculation, one reached 0.909091, demonstrating that the number of followers was both a necessary factor and a condition for the popularity of short health science video accounts. There were 16 paths in the complex solution with a consistency of 1, and their overall coverage reached 0.878788, indicating that approximately 87% of the cases could be explained. From the spread of the content and communication situation, professional medical knowledge, current hot topics, professionals, and serious issues were the most likely combinations for rapid spread. From the perspective of the central and edge paths, "likes" exceeding 100,000 and fans exceeding 1 million were essential combinations. Conclusions: The dissemination of medical knowledge has gained significant traction, especially with regard to trending and popular topics. When it comes to the tone of communication, a serious style proved effective in fostering what can be termed "hot communication." From the standpoint of central and peripheral paths, it is crucial that the number of likes in the past month and the total number of fans surpass 100,000 and one million, respectively.

Crocin exerts anti-tumor effect in colon cancer cells via repressing the JAK pathway.

Crocin has been reported to have therapeutic effects on multiple cancers including colon cancer, but its specific mechanism is still ambiguous and needs to be further explored. Human colorectal adenocarcinoma cells (HCT-116) and human normal colonic epithelial cells (CCD841) were first treated with increasing concentrations of crocin. Subsequently, with 150 and 200 µM of crocin, the cell vitality was examined by cell counting kit 8. Cell apoptosis and proliferation were tested by TUNEL staining and colony formation assay, respectively. The expression of Ki-67 was assessed by immunofluorescence. Enzyme-linked immunosorbent assay was used to evaluate the level of inflammation- and oxidative-related factors. The reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) were examined by flow cytometer. Janus kinase (JAK), signal transducer and activator of transcription 3 (STAT3), and extracellular regulated protein kinases (ERK) in HCT-116 cells were tested by Western blot. Different concentrations of crocin barely affected the CCD841 cell vitality, while crocin restrained the HCT-116 cells vitality, proliferation and the expression of Ki-67, while inducing apoptosis in a concentration-dependent manner. Moreover, the contents of inflammation- and oxidative-related factors in HCT-116 cells were largely blunted by crocin that enhanced ROS and restrained the MMP and suppressed p-JAK2/JAK2, p-STAT3/STAT3, and p-ERK/ERK expression in HCT-116 cells. Crocin induced apoptosis and restored mitochondrial function in HCT-116 cells via repressing the JAK pathway. If the threptic effect works in patients, it could herald a new, effective treatment for colon cancer, improving the patients' prognosis and quality of life.

The Chicken cGAS-STING Pathway Exerts Interferon-Independent Antiviral Function via Cell Apoptosis.

It has been recently recognized that the DNA sensing innate immune cGAS-STING pathway exerts an IFN-independent antiviral function; however, whether and how chicken STING (chSTING) exerts such an IFN-independent antiviral activity is still unknown. Here, we showed that chSTING exerts an antiviral activity in HEK293 cells and chicken cells, independent of IFN production. chSTING was able to trigger cell apoptosis and autophagy independently of IFN, and the apoptosis inhibitors, rather than autophagy inhibitors, could antagonize the antiviral function of chSTING, suggesting the involvement of apoptosis in IFN-independent antiviral function. In addition, chSTING lost its antiviral function in IRF7-knockout chicken macrophages, indicating that IRF7 is not only essential for the production of IFN, but also participates in the other activities of chSTING, such as the apoptosis. Collectively, our results showed that chSTING exerts an antiviral function independent of IFN, likely via apoptosis.

The relationship between media use and sports participation behavior: A meta-analysis.

Objective: The use of media profoundly affects people's sports participation behavior. Past research has presented mixed results on the relationship between media use and sports participation behaviors. Therefore, the relationship between media use and sports participation behavior should be revisited. Methods: A meta-analysis of 17 independent studies from 12 literature was conducted to determine whether (a) media use positively influences sports participation behaviors, and (b) form of media, media measurement methods, study subjects, and culture moderated these relationships. Pearson's correlation was used to conduct a random-effects meta-analysis and examine the moderating effects. Results: The results showed a positive correlation between media use and sports participation behaviors (r = 0.193, 95% CI = [0.047,0.329]). Traditional media showed stronger correlations and moderating effects than new media; however, the time variable (in media measurement methods) and primary and secondary school students (in study subjects) showed negative correlations between media use and sports participation behavior. The positive and moderating effects on this relationship were higher in Eastern cultures than in Western cultures. These results suggest that media use and sports participation behavior were positively correlated, moderated by the form of media, media measurement methods, study subjects, and culture within studies. Conclusions: From the effect test results, a significant positive relationship was found between media use and sports participation behavior (both physical participation behavior and consumption behavior). The two were influenced by several moderating variables including the form of media, media measurement methods, study subjects, and culture, and the influence of media measurement methods was the greatest.

Progression from different blood glucose states to cardiovascular diseases: a prospective study based on multi-state model.

AIMS: To quantify the trajectories from normoglycaemia to pre-diabetes, subsequently to type 2 diabetes mellitus (T2DM), cardiovascular diseases (CVD), and cardiovascular death, and the effects of risk factors on the rates of transition. METHODS AND RESULTS: We used data from the Jinchang Cohort of 42 585 adults aged 20-88 free of coronary heart disease (CHD) and stroke at baseline. A multistate model was applied for analysing the progression of CVD and its relation to various risk factors. During a median follow-up of 7 years, 7498 participants developed pre-diabetes, 2307 developed T2DM, 2499 developed CVD, and 324 died from CVD. Among 15 postulated transitions, transition from comorbid CHD and stroke to cardiovascular death had the highest rate (157.21/1000 person-years), followed by transition from stroke alone to cardiovascular death (69.31/1000 person-years) and transition from pre-diabetes to normoglycaemia (46.51/1000 person-years). Pre-diabetes had a sojourn time of 6.77 years, and controlling weight, blood lipids, blood pressure, and uric acid within normal limits may promote reversion to normoglycaemia. Among transitions to CHD alone and stroke alone, transition from T2DM had the highest rate (12.21/1000 and 12.16/1000 person-years), followed by transition from pre-diabetes (6.81/1000 and 4.93/1000 person-years) and normoglycaemia (3.28/1000 and 2.39/1000 person-years). Age and hypertension were associated with an accelerated rate for most transitions. Overweight/obesity, smoking, dyslipidaemia, and hyperuricaemia played crucial but different roles in transitions. CONCLUSION: Pre-diabetes was the optimal intervention stage in the disease trajectory. The derived transition rates, sojourn time, and influence factors could provide scientific support for the primary prevention of both T2DM and CVD.

Former single-outcome studies on the relationship between glycaemia and cardiovascular disease (CVD) may ignore the complexity and multi-transformations across the multiple stages from normoglycaemia to CVD in real-world setting. We aimed to quantify the trajectories from normoglycaemia to pre-diabetes, subsequently to type 2 diabetes, CVD, and cardiovascular death. Pre-diabetes was the optimal intervention stage in the disease trajectory. Transitions from CVD to death had much higher rates than other transitions. Age and hypertension were associated with an accelerated rate for most transitions. Overweight/obesity, smoking, dyslipidaemia, and hyperuricaemia played crucial but different roles in transitions.

Genomic characterization of two new viruses infecting Ageratum conyzoides in China.

Two new RNA viruses were identified in Ageratum conyzoides in China using high-throughput sequencing, and their genome sequences were determined using PCR and rapid amplification of cDNA ends. The new viruses, which have positive-sense, single-stranded RNA genomes, were provisionally named "ageratum virus 1" (AgV1) and "ageratum virus 2" (AgV2). AgV1 has a genome of 3,526 nucleotides with three open reading frames (ORFs) and shares 49.9% nucleotide sequence identity with the complete genome of Ethiopian tobacco bushy top virus (genus Umbravirus, family Tombusviridae). The genome of AgV2 consists of 5,523 nucleotides and contains five ORFs that are commonly observed in members of the genus Enamovirus of the family Solemoviridae. Proteins encoded by AgV2 exhibited the highest amino acid sequence similarity (31.7-75.0% identity) to the corresponding proteins of pepper enamovirus R1 (an unclassified enamovirus) and citrus vein enation virus (genus Enamovirus). Based on their genome organization, sequence, and phylogenetic relationships, AgV1 is proposed to be a new umbra-like virus of the family Tombusviridae, and AgV2 is proposed to be a new member of the genus Enamovirus of the family Solemoviridae.

Ambient temperature variability and blood pressure in a prospective cohort of 50,000 Chinese adults.

Blood pressure has been shown to change by outdoor temperature, but whether intra- and inter-day temperature variability (TV) will bring higher effect on BP is not clear. Based on a prospective cohort study, the mixed effect model was selected to estimate the relationship between TV (daily temperature variability (DTV) and hourly temperature variability (HTV)) and BP (systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and mean arterial pressure (MAP)) after adjusting for confounding variables. We found that there was a positive linear correlation between TV and BP. The results of DTV and HTV were basically consistent, but the effect estimates of HTV seemed to be larger. Gender, age, BMI, education level and BP status may modify the relationship between TV and BP. The effect of TV on BP was greater in non-heating season than in heating season. Our work contributes to a further macro mechanism evidence for the TV-CVDs association.

Effects of short-term exposure to gaseous pollutants on metabolic health indicators of patients with metabolic syndrome in Northwest China.

Currently few studies have explored the relationship between exposure to gaseous pollutants and metabolic health indicators in patients, especially in patients with metabolic syndrome (Mets). This study collected 15,520 patients with Mets in a prospective cohort of nearly 50,000 people with 7 years of follow-up from 2011 to 2017, and matched air pollutants and meteorological data during the same period. The mixed effects model was used to analyze the relationship between different short exposure windows (1-week, 1-month, 2-month, and 3-month) of gaseous pollutants (SO2, NO2, and O3) and the metabolic health indicators of patients after controlled the confounding factors. Stratified analysis was performed by demographic characteristics and behavioral factors. The effects of gaseous pollutants on patients with different Met components were also analyzed. The results showed that the short-term exposure to SO2, NO2, and O3 had a certain effect on the metabolic health indicators of patients with Mets in different exposure windows, and with the extension of the exposure window period, the effects increased. The stratified analysis showed that gender, age, and life behaviors might modify these detrimental effects. In addition, the effects of gaseous pollutants on metabolic health indicators in G4 and G7 were more obvious than other Met components, and the effects of gaseous pollutants on the level of LDL-C were found to be statistically significant in most components. Therefore, patients with Mets should pay more attention to the influence of gaseous pollutants to take appropriate protection to reduce potential health risk.

Synthesis, insecticidal activity, and mode of action of novel imidazopyridine mesoionic derivatives containing an amido group.

BACKGROUND: In our previous work, we applied a new synthetic strategy to design and synthesize a series of imidazopyridine mesoionic derivatives with an ester group. The newly synthesized compounds had excellent insecticidal activity against aphids; however, insecticidal activity against planthoppers was less than satisfactory. In the present study, we designed and synthesized a series of novel imidazopyridine mesoionic compounds, containing an amido group, and these compounds were found to have improved insecticidal activity against planthoppers. RESULTS: The bioassay results demonstrated that most of the target compounds had moderate-to-good insecticidal activity against Sogatella furcifera, and some exhibited good-to-excellent insecticidal activity against Aphis craccivora. Among them, compound C6 had the highest insecticidal activity against S. furcifera and A. craccivora, with LC50 values of 10.5 and 2.09 µg mL-1 , respectively. Proteomic results suggested that the differentially expressed proteins mainly were enriched in the nervous system-related pathways after compound C6 treatment. Enzymatic assay results showed that compound C6 and triflumezopyrim had a certain inhibitory effect on acetylcholinesterase. Molecular docking and real-time quantitative PCR results indicated that compound C6 not only may act on the nicotinic acetylcholine receptor, but also may interact with the α4 and ß1 subunits of this receptor. CONCLUSION: The results reported here contribute to the development of new mesoionic insecticides and further our understanding of the mode-of-action of imidazopyridine mesoionic derivatives. © 2022 Society of Chemical Industry.

A long-term travel delay measurement study based on multi-modal human mobility data.

Understanding human mobility is of great significance for sustainable transportation planning. Long-term travel delay change is a key metric to measure human mobility evolution in cities. However, it is challenging to quantify the long-term travel delay because it happens in different modalities, e.g., subway, taxi, bus, and personal cars, with implicated coupling. More importantly, the data for long-term multi-modal delay modeling is challenging to obtain in practice. As a result, the existing travel delay measurements mainly focus on either single-modal system or short-term mobility patterns, which cannot reveal the long-term travel dynamics and the impact among multi-modal systems. In this paper, we perform a travel delay measurement study to quantify and understand long-term multi-modal travel delay. Our measurement study utilizes a 5-year dataset of 8 million residents from 2013 to 2017 including a subway system with 3 million daily passengers, a 15 thousand taxi system, a 10 thousand personal car system, and a 13 thousand bus system in the Chinese city Shenzhen. We share new observations as follows: (1) the aboveground system has a higher delay increase overall than that of the underground system but the increase of it is slow down; (2) the underground system infrastructure upgrades decreases the aboveground system travel delay increase in contrast to the increase the underground system travel delay caused by the aboveground system infrastructure upgrades; (3) the travel delays of the underground system decreases in the higher population region and during the peak hours.

Effect of Magnetic Stirring on Microstructures and Properties of Ag-1.5Cu-1.0Y Alloy.

The microstructure of alloys is an important factor that affects their application. In this work, the Ag-1.5Cu-1.0Y alloys were prepared by the permanent magnet stirring method at different rates. The secondary dendrite arm spacing, dendritic segregation, density, microhardness, electrical resistivity, and sulfuration corrosion resistance were analyzed to investigate the effects of different rotation speeds on the microstructures and properties of the Ag-1.5Cu-1.0Y alloy. The results showed that the primary dendrite was refined and the secondary dendrite arm spacing decreased with the increase in the stirring rate of the permanent magnets. The Ag-1.5Cu-1.0Y alloys prepared with a 900 r/min stirring rate had the largest microhardness, relatively high density, and the best sulfuration corrosion resistance. However, the stirring rate had little effect on the electrical resistivity of the Ag-1.5Cu-1.0Y alloys. To sum up, the Ag-1.5Cu-1.0Y alloy had the best comprehensive properties when the permanent magnet stirring rate was 900 r/min, including the most refined dendrites, relatively high density, the largest microhardness, and the best sulfuration corrosion resistance. The study of the effects of permanent magnet stirring speed on the microstructures and properties of the Ag-1.5Cu-1.0Y alloy provides an experimental basis for future alloy casting optimization and property improvement of silver-based alloys.

Sodium Benzoate Delays the Development of Drosophila melanogaster Larvae and Alters Commensal Microbiota in Adult Flies.

Sodium benzoate (SB), the sodium salt of benzoic acid, is widely used as a preservative in foods and drinks. The toxicity of SB to the human body attracted people's attention due to the excessive use of preservatives and the increased consumption of processed and fast foods in modern society. The SB can inhibit the growth of bacteria, fungi, and yeast. However, less is known of the effect of SB on host commensal microbial community compositions and their functions. In this study, we investigated the effect of SB on the growth and development of Drosophila melanogaster larvae and whether SB affects the commensal microbial compositions and functions. We also attempted to clarify the interaction between SB, commensal microbiota and host development by detecting the response of commensal microbiota after the intervention. The results show that SB significantly retarded the development of D. melanogaster larvae, shortened the life span, and changed the commensal microbial community. In addition, SB changed the transcription level of endocrine coding genes such as ERR and DmJHAMT. These results indicate that the slow down in D. melanogaster larvae developmental timing and shortened life span of adult flies caused by SB intake may result from the changes in endocrine hormone levels and commensal microbiota. This study provided experimental data that indicate SB could affect host growth and development of D. melanogaster through altering endocrine hormone levels and commensal microbial composition.

Advantages of a Novel Model for Predicting Hepatic Fibrosis in Chronic Hepatitis B Virus Carriers Compared with APRI and FIB-4 Scores.

Background and Aims: Aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) are widely used to assess liver fibrosis in chronic hepatitis B virus (HBV) infection. Currently, the definition of normal alanine aminotransferase (ALT) is controversial. We aimed to examine the diagnostic value of APRI and FIB-4 in chronic HBV carriers with different upper limits of normal (ULNs) for ALT. Methods: 581 chronic HBV carriers were divided into the following four groups based on different ULNs for ALT: chronic HBV carriers I, II, III, and IV. Furthermore, 106 chronic HBV carriers formed an external validation group. Predictive values of APRI and FIB-4 were elucidated using the area under the curve (AUC). A liver fibrosis-predictive model-GPSA (named for its measure of gamma glutamyl transpeptidase, platelet count, HBsAg and albumin) was developed using multivariate logistic regression analysis. Results: In chronic HBV carriers I, the AUCs of APRI and FIB-4 were 0.680 and 0.609 for significant fibrosis and 0.678 and 0.661 for cirrhosis, respectively. The AUCs of GPSA for significant fibrosis in the training group, internal group, and external validation group were 0.877, 0.837, and 0.871, respectively. The diagnostic value of GPSA differed among chronic HBV carriers I, II, III, and IV, with AUCs for significant fibrosis being 0.857, 0.853, 0.868, and 0.905 and AUCs for cirrhosis being 0.901, 0.905, 0.886, and 0.913, respectively. GPSA showed a higher diagnostic value than APRI and FIB-4 for predicting significant fibrosis in the four groups. Conclusions: The GPSA model allows for accurate diagnosis of liver fibrosis in chronic HBV carriers with different ULN for ALT.

Interaction effect of blood glucose and pressure on the risk of chronic kidney disease: a population-based prospective cohort study.

OBJECTIVE: To evaluate the interaction effect of blood glucose and blood pressure on the risk of chronic kidney disease (CKD). METHODS: 31,165 subjects were selected without CKD at baseline and had completed the first follow-up from "Jinchang cohort". Cox regression model and restricted cubic splines functions were used to evaluate the effects of blood glucose or pressure on the incidence of CKD and dose-response relationship after adjusting for confounding covariates. Synergic effect was assessed by the multiplicative or additive interaction scale. RESULTS: Among 31,165 subjects, 1307 new-onset CKD were observed during 68905.78 person-years follow-up, and the incidence density was 18.97 per 1000 person-years. The risk of CKD gradually increased with the increase of blood pressure in diabetes, pre-diabetes and normal groups (Ptrend < 0.05). And, the risk was greatest when SBP/DBP reached ≥150/≥110 mmHg in three groups, and HRs (95% CI) were 1.610 (1.070-2.422), 2.142 (1.396-3.288) and 2.455 (1.941-3.106), respectively. Additionally, among hypertension, pre-hypertension and normal groups, the risk of CKD increased by 16.0%, 14.3% and 25.2% for each 1 mmol/L of FPG. When FPG level was more than 9.0 mmol/L, the risk was greatest and adjusted HRs (95% CI) were 2.856 (2.176-3.748), 2.979 (1.828-4.854) and 7.520 (4.517-12.519). Furthermore, the risk was highest when hypertension was accompanied by diabetes (HR = 4.915, 95% CI: 3.923-6.157). This analysis supported a less than multiplicative effect (HR = 0.634, 95% CI: 0.417-0.964) for the interaction term of diabetes and hypertension, while there was no additive interaction towards CKD in all interaction term. CONCLUSIONS: Blood glucose and pressure were independent risk factors in incidence of CKD, but there was only a negative multiplicative interaction between hypertension and diabetes, but no additive interaction effect between them.

Discovery of Pyrido[1,2-a]pyrimidine Mesoionic Compounds Containing Benzo[b]thiophene Moiety as Potential Pesticide Candidates.

The increasing evolution of insect resistance has made it challenging for traditional insecticides to control the bean aphid (Aphis craccivora Koch). To address this pending issue, a range of pyrido[1,2-a]pyrimidine mesoionic compounds containing benzo[b]thiophene were designed and synthesized. The biological activity test results of the target compounds indicated that they had moderate to outstanding insecticidal activity against the bean aphid (Aphis craccivora) and moderate insecticidal activity against the white-backed planthopper (Sogatella furcifera). Compound L14 exhibited significant insecticidal activity against A. craccivora, with an LC50 value of 1.82 µg/mL, which was superior to triflumezopyrim (LC50 = 4.76 µg/mL). The results of enzyme activity assay showed that compound L14 had a definite inhibitory effect on ATPase. Moreover, the proteomics and docking findings of compound L14 suggested that it may act on the central nervous system of aphids and interact with nicotinic acetylcholine receptors. Therefore, compound L14 is a potentially novel insecticide candidate for further utilization.