Prediction on the spatial distribution of the seropositive rate of schistosomiasis in Hunan Province, China: a machine learning model integrated with the Kriging method.

Schistosomiasis remains a formidable challenge to global public health. This study aims to predict the spatial distribution of schistosomiasis seropositive rates in Hunan Province, pinpointing high-risk transmission areas and advocating for tailored control measures in low-endemic regions. Six machine learning models and their corresponding hybrid machine learning-Kriging models were employed to predict the seropositive rate. The optimal model was selected through internal and external validations to simulate the spatial distribution of seropositive rates. Our results showed that the hybrid machine learning-Kriging model demonstrated superior predictive performance compared to basic machine learning model and the Cubist-Kriging model emerged as the most optimal model for this study. The predictive map revealed elevated seropositive rates around Dongting Lake and its waterways with significant clustering, notably in the central and northern regions of Yiyang City and the northeastern areas of Changde City. The model identified gross domestic product, annual average wind speed and the nearest distance from the river as the top three predictors of seropositive rates, with annual average daytime surface temperature contributing the least. In conclusion, our research has revealed that integrating the Kriging method significantly enhances the predictive performance of machine learning models. We developed a Cubist-Kriging model with high predictive performance to forecast the spatial distribution of schistosomiasis seropositive rates. These findings provide valuable guidance for the precise prevention and control of schistosomiasis.

Changing seroprevalence of schistosomiasis japonica in China from 1982 to 2020: A systematic review and spatial analysis.

BACKGROUND: Schistosomiasis is a global public health issue. In China, while the seroprevalence of Schistosomiasis japonica has currently reduced to a relatively low level, risk of infection still exists in certain areas. However, there has been a lack of comprehensive research on the long-term trends of national seroprevalence, changes across age groups, and characteristics in spatial distribution, which is crucial for effectively targeting interventions and achieving the goal of eliminating schistosomiasis by 2030. Our study aimed to address this gap by analyzing the long-term trends of Schistosomiasis japonica seroprevalence in China from 1982 to 2020 based on the data from diverse sources spanning a period of 39 years. METHODOLOGY: Seroprevalence data were collected from literature databases and national schistosomiasis surveillance system. Meta-analysis was conducted to estimate the seroprevalence. Joinpoint model was used to identify changing trend and inflection point. Inverse distance weighted interpolation was used to determine the spatial distribution of seroprevalence. PRINCIPAL FINDINGS: The seroprevalence decreased from 34.8% in 1982 to 2.4% in 2020 in China. Before 2006, the seroprevalence was higher in the middle age group, and a pattern of increasing with age was observed afterwards. The areas with high seroprevalence existed in Dongting Lake, Poyang Lake, Jianghan Plain, the Anhui branch of the Yangtze River and some localized mountainous regions in Sichuan and Yunnan provinces. CONCLUSIONS/SIGNIFICANCE: There was a significant decline in the seroprevalence of Schistosomiasis japonica from 1982 to 2020 in China. Nevertheless, schistosomiasis has not been eradicated; thus, implementing precise and personalized monitoring measures is crucial for the elimination of schistosomiasis, especially in endemic areas and with a particular focus on the elderly.

Impact of historical disease conditions on mortality and life expectancy in patients with advanced schistosomiasis in Hunan Province, China.

BACKGROUND: Although the prognosis of advanced schistosomiasis patients has significantly improved, the impact of historical disease conditions on life expectancy remains unclear. METHODS: Utilizing data from an advanced schistosomiasis cohort (n=10 362) from 2008 to 2019 in Hunan, China, we examined five historical disease conditions: times of praziquantel treatment, the history of ascites, splenectomy, upper gastrointestinal bleeding (UGIB) and hepatic coma. Using latent class analysis, participants were categorized into three groups: Group 1 (characterized by no risk conditions), Group 2 (had ≤3 times of praziquantel treatment without UGIB history) and Group 3 (had UGIB history). Life expectancies were calculated using the life table method. RESULTS: At the age of 45 y, patients with ≤3 times of praziquantel treatment, a history of ascites, UGIB, hepatic coma and those without splenectomy exhibited lower life expectancies. Groups 1, 2 and 3 had estimated life expectancies of 32.32, 26.76 and 25.38 y, respectively. Compared with Group 1, women in Group 3 experienced greater life expectancy loss than those in Group 2, with the difference narrowing with age. CONCLUSIONS: Based on the consideration of overall physical conditions, tailored treatment and healthcare, along with public health interventions targeting diverse populations, could mitigate the prevalence of poor disease conditions and premature deaths.

Pre-treatment plasma retinol binding protein 4 level and its change after treatments predict systemic treatment response in psoriasis patients.

BACKGROUND: Retinol binding protein 4 (RBP4) is a mediator of inflammation and related to skin lesion formation, which suggests its engagement in psoriasis pathology and progression. This study intended to explore the change in RBP4 after systemic treatments, and its ability to predict treatment response in psoriasis patients. METHODS: This prospective study enrolled 85 psoriasis patients and 20 healthy subjects. Plasma RBP4 was detected by enzyme-linked immunosorbent assay at baseline and 12th week (W12) after systemic treatments in psoriasis patients, as well as after enrollment in healthy subjects. Psoriasis Area and Severity Index (PASI) 75 and PASI 90 were evaluated at W12 in psoriasis patients. RESULTS: RBP4 at baseline was higher in psoriasis patients than in healthy subjects [median (interquartile range): 13.39 (9.71-22.92) versus 9.59 (6.57-13.72) µg/mL] (P = 0.003). In psoriasis patients, 50 (58.8%) patients achieved PASI 75 at W12, and 25 (29.4%) patients achieved PASI 90 at W12. RBP4 was decreased at W12 compared to its level at baseline (P < 0.001). Lower RBP4 at baseline predicted achieving PASI 75 at W12 (P = 0.038). Greater RBP4 change (baseline-W12) precited achieving PASI 75 (P = 0.036) and PASI 90 (P = 0.045) at W12. Receiver operating characteristic curves suggested that after adjustment for all clinical features, RBP4 at baseline and RBP4 change (baseline-W12) had an acceptable ability to predict PASI 75 and PASI 90 at W12 with all area under curve values > 0.7. CONCLUSION: Plasma RBP4 is decreased after systemic treatments, and its low baseline level and greater decline after treatments predict good treatment response in psoriasis patients.

Interactive and lag effects of environmental factors on the density of schistosome-transmitting Oncomelania hupensis: A twelve-year monthly repeated survey.

Schistosomiasis is a significant public health threat, and Oncomelania hupensis is the only intermediate host for schistosoma japonicum. We conducted 12-year monthly repeated surveys to explore the interactive and lag effects of environmental factors on snail density and to monitor their long-term and seasonal trends in a bottomland around the Dongting Lake region in China. Relevant environmental data were obtained from multiple sources. A Bayesian kernel machine regression model and a Bayesian temporal model combined with a distributed lag model were constructed to analyze interactive and lag effects of environmental factors on snail density. The results indicated the average annual snail density in the study site exhibited an increasing and then decreasing trend, peaking in 2013. Snail densities were the highest in October and the lowest in January in a year. Normalized Difference Vegetation Index (NDVI) and water level were the most effective predictors of snail density, with potential interactions among temperature, precipitation, and NDVI. The mean minimum temperature in January, water level, precipitation and NDVI were positively correlated with snail density at lags ranging from 1 to 4 months. These findings could serve as references for relevant authorities to monitor the changing trend of snail density and implement control measures, thereby reducing the occurrence of schistosomiasis.

Identification and functional study of a novel variant of PAX9 causing tooth agenesis.

OBJECTIVES: To search for pathogenic gene of a family with non-syndromic tooth agenesis, and explore the possible pathogenesis. MATERIALS AND METHODS: A Chinese family with non-syndromic tooth agenesis was recruited and screened for the pathogenic variants by whole exome sequencing technology and co-segregation analysis. The subcellular localization of wild-type and mutant protein was detected by immunofluorescence assay. Cycloheximide chase assay was performed to examine the difference in degradation rate between mutant protein and wild-type one. Dual-luciferase reporter assays were conducted to explore the alterations of mutant protein in the regulation of downstream target genes. RESULTS: A novel missense variant of PAX9 (c.296C>A:p.A99D) was found in this family. Bioinformatics software showed ß-return and the random coil were shortened in the p.A99D. The variant did not affect the subcellular localization of PAX9, but the degradation rate of p.A99D was accelerated (p < 0.05). p.A99D inhibited the activation of downstream target gene BMP4 (p < 0.05). CONCLUSIONS: This novel variant expands the pathogenic gene spectrum. The variant impaired the protein structure, accelerated the degradation of protein, and inhibited the activation of the downstream target gene BMP4, an upstream molecule in the TGF-ß/BMP pathway, which may contribute to tooth agenesis in this family.

miR-30a-5p targets ITGA6 to inhibit oral squamous cell carcinoma progression.

OBJECTIVE: Nowadays, many studies focus on the relationship between microRNAs (miRs) and the development of oral squamous cell carcinoma (OSCC). Here, we broaden the understanding of miR-30a-5p in OSCC. METHODS: In silico analysis was implemented to screen differentially expressed genes in OSCC and the related upstream regulatory miR. OSCC SCC9 cells were manipulated with lentivirus-mediated miR-30a-5p mimic, oe-ITGA6 or sh-ITGA6 and LY294002 (the PI3K/AKT pathway inhibitor) for studying their roles in cell biological processes. Tumors were xenografted in nude mouse for in vivo mechanism verification. RESULTS: In silico analysis results depicted that ITGA6 was highly expressed in OSCC, and that miR-30a-5p was the upstream regulatory miR of ITGA6. miR-30a-5p was downregulated and ITGA6 was highly expressed in OSCC tissues and cells. miR-30a-5p targeted and downregulated ITGA6. ITGA6 promoted epithelial-mesenchymal transition, migration and invasion in OSCC cells by activating PI3K/AKT pathway. miR-30a-5p could suppress the in vivo growth and metastasis of OSCC by inhibiting the ITGA6/PI3K/AKT axis. CONCLUSION: Taken together, miR-30a-5p prevents OSCC progression by inhibiting PI3K/AKT pathway through inhibition of ITGA6 expression.

Evaluation of phase-adjusted interventions for COVID-19 using an improved SEIR model.

A local COVID-19 outbreak with two community clusters occurred in a large industrial city, Shaoxing, China, in December 2021 after serial interventions were imposed. We aimed to understand the reason by analysing the characteristics of the outbreak and evaluating the effects of phase-adjusted interventions. Publicly available data from 7 December 2021 to 25 January 2022 were collected to analyse the epidemiological characteristics of this outbreak. The incubation period was estimated using Hamiltonian Monte Carlo method. A well-fitted extended susceptible-exposed-infectious-recovered model was used to simulate the impact of different interventions under various combination of scenarios. There were 387 SARS-CoV-2-infected cases identified, and 8.3% of them were initially diagnosed as asymptomatic cases. The estimated incubation period was 5.4 (95% CI 5.2-5.7) days for all patients. Strengthened measures of comprehensive quarantine based on tracing led to less infections and a shorter duration of epidemic. With a same period of incubation, comprehensive quarantine was more effective in containing the transmission than other interventions. Our findings reveal an important role of tracing and comprehensive quarantine in blocking community spread when a cluster occurred. Regions with tense resources can adopt home quarantine as a relatively affordable and low-impact intervention measure compared with centralized quarantine.

Prediction of Oncomelania hupensis distribution in association with climate change using machine learning models.

BACKGROUND: Oncomelania hupensis is the sole intermediate host of Schistosoma japonicum. Its emergence and recurrence pose a constant challenge to the elimination of schistosomiasis in China. It is important to accurately predict the snail distribution for schistosomiasis prevention and control. METHODS: Data describing the distribution of O. hupensis in 2016 was obtained from the Yunnan Institute of Endemic Disease Control and Prevention. Eight machine learning algorithms, including eXtreme Gradient Boosting (XGB), support vector machine (SVM), random forest (RF), generalized boosting model (GBM), neural network (NN), classification and regression trees (CART), k-nearest neighbors (KNN), and generalized additive model (GAM), were employed to explore the impacts of climatic, geographical, and socioeconomic variables on the distribution of suitable areas for O. hupensis. Predictions of the distribution of suitable areas for O. hupensis were made for various periods (2030s, 2050s, and 2070s) under different climate scenarios (SSP126, SSP245, SSP370, and SSP585). RESULTS: The RF model exhibited the best performance (AUC: 0.991, sensitivity: 0.982, specificity: 0.995, kappa: 0.942) and the CART model performed the worst (AUC: 0.884, sensitivity: 0.922, specificity: 0.943, kappa: 0.829). Based on the RF model, the top six important variables were as follows: Bio15 (precipitation seasonality) (33.6%), average annual precipitation (25.2%), Bio2 (mean diurnal temperature range) (21.7%), Bio19 (precipitation of the coldest quarter) (14.5%), population density (13.5%), and night light index (11.1%). The results demonstrated that the overall suitable habitats for O. hupensis were predominantly distributed in the schistosomiasis-endemic areas located in northwestern Yunnan Province under the current climate situation and were predicted to expand north- and westward due to climate change. CONCLUSIONS: This study showed that the prediction of the current distribution of O. hupensis corresponded well with the actual records. Furthermore, our study provided compelling evidence that the geographical distribution of snails was projected to expand toward the north and west of Yunnan Province in the coming decades, indicating that the distribution of snails is driven by climate factors. Our findings will be of great significance for formulating effective strategies for snail control.

The mechanism of IL-13 targeting IL-13Rα2 in regulating oral mucosal FBs through PI3K/AKT/mTOR.

OBJECTIVE: The objective of this investigation was to examine the presence of interleukin (IL)-13 and its receptor IL-13Rα2 in the tissues of oral submucous fibrosis (OSF), investigate their biological functions, and explore the underlying mechanisms involved in the development of OSF. MATERIALS AND METHODS: The expression of IL-13 and IL-13Rα2 in the oral mucosa of patients with OSF and normal individuals was determined through immunohistochemistry and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Primary fibroblasts (FBs) were extracted through enzymatic digestion and then cultured. Immunofluorescence was employed to identify the FB cultures and the location of IL-13Rα2. The effects of IL-13/IL-13Rα2/PI3K/AKT/mTOR on the migration, proliferation, and secretion of fiber-related proteins of FBs were explored via the wound healing assay, CCK-8 assay, EDU assay, and RT-qPCR. The impact of IL-13Rα2 silencing and PI3K/AKT inhibition on the effect of IL-13 on FBs was analyzed by RT-qPCR and Western blotting. RESULTS: IL-13 and IL-13Rα2 were highly expressed in OSF. Primary FBs were successfully extracted and cultured. IL-13Rα2 was found to be localized in myofibroblasts. IL-13 promoted the proliferation, migration, and secretion of fibril-associated proteins in FBs. The proliferation, migration, and secretion of fibril-associated proteins of FBs were decreased following IL-13Rα2 silencing and inhibition of the PI3K/AKT/mTOR pathway. CONCLUSION: IL-13 may promote the proliferation, migration, and secretion of fiber-related proteins of FBs through the PI3K/AKT/mTOR pathway by targeting IL-13Rα2.

Identifying determinants for the seropositive rate of schistosomiasis in Hunan province, China: A multi-scale geographically weighted regression model.

BACKGROUND: Schistosomiasis is of great public health concern with a wide distribution and multiple determinants. Due to the advances in schistosomiasis elimination and the need for precision prevention and control, identifying determinants at a fine scale is urgent and necessary, especially for resource deployment in practice. Our study aimed to identify the determinants for the seropositive rate of schistosomiasis at the village level and to explore their spatial variations in local space. METHODOLOGY: The seropositive rates of schistosomiasis were collected from 1714 villages or communities in Human Province, and six spatial regression models including ordinary least squares (OLS), spatial lag model (SLM), spatial error model (SEM), geographically weighted regression (GWR), robust GWR (RGWR) and multiscale GWR (MGWR) were used to fit the data. PRINCIPAL/FINDINGS: MGWR was the best-fitting model (R2: 0.821, AICc:2727.092). Overall, the nearest distance from the river had the highest mean negative correlation, followed by proportion of households using well water and the annual average daytime surface temperature. The proportions of unmodified toilets showed the highest mean positive correlation, followed by the snail infested area, and the number of cattle. In spatial variability, the regression coefficients for the nearest distance from the river, annual average daytime surface temperature and the proportion of unmodified toilets were significant in all villages or communities and varied little in local space. The other significant determinants differed substantially in local space and had significance ratios ranging from 41% to 70%, including the number of cattle, the snail infested area and the proportion of households using well water. CONCLUSIONS/SIGNIFICANCE: Our study shows that MGWR was well performed for the spatial variability of schistosomiasis in Hunan province. The spatial variability was different for different determinants. The findings for the determinants for the seropositive rate and mapped variability for some key determinants at the village level can be used for developing precision intervention measure for schistosomiasis control.

Three Gorges Dam: Potential differential drivers and trend in the spatio-temporal evolution of the change in snail density based on a Bayesian spatial-temporal model and 5-year longitudinal study.

BACKGROUND: Snail abundance varies spatially and temporally. Few studies have elucidated the different effects of the determinants affecting snail density between upstream and downstream areas of the Three Gorges Dam (TGD). We therefore investigated the differential drivers of changes in snail density in these areas, as well as the spatial-temporal effects of these changes. METHODS: A snail survey was conducted at 200 sites over a 5-year period to monitor dynamic changes in snail abundance within the Yangtze River basin. Data on corresponding variables that might affect snail abundance, such as meteorology, vegetation, terrain and economy, were collected from multiple data sources. A Bayesian spatial-temporal modeling framework was constructed to explore the differential determinants driving the change in snail density and the spatial-temporal effects of the change. RESULTS: Volatility in snail density was unambiguously detected in the downstream area of the TGD, while a small increment in volatility was detected in the upstream area. Regarding the downstream area of the TGD, snail density was positively associated with the average minimum temperature in January of the same year, the annual Normalized Difference Vegetation Index (NDVI) of the previous year and the second, third and fourth quartile, respectively, of average annual relative humidity of the previous year. Snail density was negatively associated with the average maximum temperature in July of the previous year and annual nighttime light of the previous year. An approximately inverted "U" curve of relative risk was detected among sites with a greater average annual ground surface temperature in the previous year. Regarding the upstream area, snail density was positively associated with NDVI and with the second, third and fourth quartile, respectively, of total precipitation of the previous year. Snail density was negatively associated with slope. CONCLUSIONS: This study demonstrated a rebound in snail density between 2015 and 2019. In particular, temperature, humidity, vegetation and human activity were the main drivers affecting snail abundance in the downstream area of the TGD, while precipitation, slope and vegetation were the main drivers affecting snail abundance in the upstream area. These findings can assist authorities to develop and perform more precise strategies for surveys and control of snail populations.

Interleukin-13 contributes to the occurrence of oral submucosal fibrosis.

Oral submucous fibrosis (OSF) is a chronic progressive fibrosis disease that affects in oral mucosal tissues. Interleukin (IL)-13 has been implicated in the development of fibrosis in multiple organs. Indeed, it contributes to diseases such as pulmonary fibrosis, liver cirrhosis among others. Currently, its expression in OSF and the specific mechanisms are not well understood. The aim of this study was to investigate the role of IL-13 in OSF and further explore whether IL-13 regulates-polarization of M2-macrophages in OSF. Initially, in the tissues of patients with OSF, we observed a high expression of M2-macrophages and IL-13 protein. Additionally, we found a correlation between the expression of IL-13 and the stage of OSF. Arecoline inhibited the proliferation of fibroblasts (FBs) and promoted IL-13 production in vitro. Furthermore, our observations revealed that M2-macrophages increased upon co-culturing M0-macrophages with supernatants containing the IL-13 cytokine. In conclusion, our study demonstrated that arecoline stimulates FBs leading to increased secretion of IL-13, which in turn IL-13 leads to polarization of M2-macrophages and promotes the occurrence of OSF. This suggests that IL-13 may be a potential therapeutic target of OSF.

A classifier-combined method for grading breast cancer based on Dempster-Shafer evidence theory.

Background: Preoperative non-invasive histologic grading of breast cancer is essential. This study aimed to explore the effectiveness of a machine learning classification method based on Dempster-Shafer (D-S) evidence theory for the histologic grading of breast cancer. Methods: A total of 489 contrast-enhanced magnetic resonance imaging (MRI) slices with breast cancer lesions (including 171 grade Ⅰ, 140 grade Ⅱ, and 178 grade Ⅲ lesions) were used for analysis. All the lesions were segmented by two radiologists in consensus. For each slice, the quantitative pharmacokinetic parameters based on a modified Tofts model and the textural features of the segmented lesion on the image were extracted. Principal component analysis was then used to reduce feature dimensionality and obtain new features from the pharmacokinetic parameters and texture features. The basic confidence assignments of different classifiers were combined using D-S evidence theory based on the accuracy of three classifiers: support vector machine (SVM), Random Forest, and k-nearest neighbor (KNN). The performance of the machine learning techniques was evaluated in terms of accuracy, sensitivity, specificity, and the area under the curve. Results: The three classifiers showed varying accuracy across different categories. The accuracy of using D-S evidence theory in combination with multiple classifiers reached 92.86%, which was higher than that of using SVM (82.76%), Random Forest (78.85%), or KNN (87.82%) individually. The average area under the curve of using the D-S evidence theory combined with multiple classifiers reached 0.896, which was larger than that of using SVM (0.829), Random Forest (0.727), or KNN (0.835) individually. Conclusions: Multiple classifiers can be effectively combined based on D-S evidence theory to improve the prediction of histologic grade in breast cancer.

Three Gorges Dam: the changing trend of snail density in the Yangtze River basin between 1990 and 2019.

BACKGROUND: The area of Oncomelania hupensis snail remains around 3.6 billion m2, with newly emerging and reemergent habitats continuing to appear in recent years. This study aimed to explore the long-term dynamics of snail density before and after the operation of Three Gorges Dam (TGD). METHODS: Data of snail survey between 1990 and 2019 were collected from electronic databases and national schistosomiasis surveillance. Meta-analysis was conducted to estimate the snail density. Joinpoint model was used to identify the changing trend and inflection point. Inverse distance weighted interpolation (IDW) was used to determine the spatial distribution of recent snail density. RESULTS: A total of 3777 snail survey sites with a precise location of village or beach were identified. For the downstream area, snail density peaked in 1998 (1.635/0.11 m2, 95% CI: 1.220, 2.189) and fluctuated at a relatively high level before 2003, then declined steadily from 2003 to 2012. Snail density maintained lower than 0.150/0.11 m2 between 2012 and 2019. Joinpoint model identified the inflection of 2003, and a significant decreasing trend from 2003 to 2012 with an annual percentage change (APC) being - 20.56% (95% CI: - 24.15, - 16.80). For the upstream area, snail density peaked in 2005 (0.760/0.11 m2, 95% CI: 0.479, 1.207) and was generally greater than 0.300/0.11 m2 before 2005. Snail density was generally lower than 0.150/0.11 m2 after 2011. Snail density showed a significant decreasing trend from 1990 to 2019 with an APC being - 6.05% (95% CI: - 7.97, - 7.09), and no inflection was identified. IDW showed the areas with a high snail density existed in Poyang Lake, Dongting Lake, Jianghan Plain, and the Anhui branch of the Yangtze River between 2015 and 2019. CONCLUSIONS: Snail density exhibited a fluctuating downward trend in the Yangtze River basin. In the downstream area, the operation of TGD accelerated the decline of snail density during the first decade period, then snail density fluctuated at a relatively low level. There still exists local areas with a high snail density. Long-term control and monitoring of snails need to be insisted on and strengthened.

Cyr61 Mediates Angiotensin II-Induced Podocyte Apoptosis via the Upregulation of TXNIP.

Purpose: It is well documented that angiotensin II (Ang II) elevation promotes apoptosis of podocytes in vivo and vitro, but the potential mechanism is still oscular. The current study is aimed at probing into the assignment of cysteine-rich protein 61 (Cyr61) in Ang II-induced podocyte apoptosis. Methods: Podocytes were treated with Ang II (10-6 mol/L) for 48 hours to establish an injury model in vitro. Western blot assays were detected the expression of Cyr61, Cyt-c, Bax, and Bcl-2. Gene microarray was used to analyze the expression of mRNAs after treatment with Ang II. CRISPR/Cas9 technology was used to knock down Cyr61 and overexpress TXNIP gene, respectively. Results: The expression of Cyr61, TXNIP, Cyt-c, and Bax in podocytes treated with Ang II were upregulated, but the expression and apoptotic rates of Bcl-2 in podocytes were inhibited. The level of the above factors was not significantly different after the knockdown of Cyr61 with Ang II in podocytes. In Ang II group, when knocked down Cyr61, the expressed level of TXNIP, Cyt-c, and Bax was diminished after Ang II treatment; interestingly Bcl-2 expression and podocyte apoptotic rate were reduced. Under the stimulation of Ang II, the expression of Cyt-c and Bax were growing, whereas Bcl-2 was reduced, and the apoptotic rates were higher in the TXNIP overexpression group. Cyt-c and Bax were put on, whereas that of Bcl-2 was to be cut down when the Cyr61 was knockdown, and the apoptotic rates were gained in the TXNIP overexpression+Cyr61 knockdown group. Conclusions: The results of the study extrapolate that Cyr61 plays a dominant role in Ang II-induced podocyte apoptosis. Additionally, Cyr61 may mediate the Ang II-induced podocyte apoptosis by promoting the expression of TNXIP.

The preliminary exploration of immune microenvironment in oral leukoplakia concomitant with oral submucosal fibrosis: A comparative immunohistochemical study.

BACKGROUND: Oral leukoplakia concomitant with oral submucous fibrosis is a high-risk oral potentially malignant disorder, but little is known about its immune microenvironment. METHODS: Thirty samples of oral leukoplakia concomitant with oral submucous fibrosis, 30 oral leukoplakia samples, and 30 oral submucous fibrosis samples were collected from two hospitals. Immunohistochemistry was performed to analyze expression of T cell biomarkers [CD3, CD4, CD8, and Forkhead box P3 (Foxp3)], a B cell biomarker (CD20), macrophage biomarkers (CD68 and CD163), an immune inhibitory receptor ligand (PD-L1), and Ki-67. RESULTS: The numbers of CD3+ (p < 0.001), CD4+ (p = 0.018), and CD8+ (p = 0.031) cells in oral leukoplakia concomitant with oral submucous fibrosis were less than those in oral leukoplakia. The number of CD4+ cells (p = 0.035) in oral leukoplakia concomitant with oral leukoplakia was higher than that in oral submucous fibrosis. More CD3+ (p < 0.001), CD4+ (p < 0.001), Foxp3+ (p = 0.019), and CD163+ (p = 0.029) cells were found in oral leukoplakia than in oral submucous fibrosis. CONCLUSION: Various levels of immune infiltration were observed among oral leukoplakia concomitant with oral submucous fibrosis, oral leukoplakia, and oral submucous fibrosis. Characterization of the immune microenvironment may contribute to personalized immunotherapy.

Global Distribution of Culex tritaeniorhynchus and Impact Factors.

Culex tritaeniorhynchus is the primary vector of Japanese encephalitis (JE) and has a wide global distribution. However, the current and future geographic distribution maps of Cx. tritaeniorhynchus in global are still incomplete. Our study aims to predict the potential distribution of Cx. tritaeniorhynchus in current and future conditions to provide a guideline for the formation and implementation of vector control strategies all over the world. We collected and screened the information on the occurrence of Cx. tritaeniorhynchus by searching the literature and online databases and used ten algorithms to investigate its global distribution and impact factors. Cx. tritaeniorhynchus had been detected in 41 countries from 5 continents. The final ensemble model (TSS = 0.864 and AUC = 0.982) indicated that human footprint was the most important factor for the occurrence of Cx. tritaeniorhynchus. The tropics and subtropics, including southeastern Asia, Central Africa, southeastern North America and eastern South America, showed high habitat suitability for Cx. tritaeniorhynchus. Cx. tritaeniorhynchus is predicted to have a wider distribution in all the continents, especially in Western Europe and South America in the future under two extreme emission scenarios (SSP5-8.5 and SSP1-2.6). Targeted strategies for the control and prevention of Cx. tritaeniorhynchus should be further strengthened.

Corrigendum: Involvement of the GABAergic system in PTSD and its therapeutic significance.

[This corrects the article DOI: 10.3389/fnmol.2023.1052288.].

Involvement of the GABAergic system in PTSD and its therapeutic significance.

The neurobiological mechanism of post-traumatic stress disorder (PTSD) is poorly understood. The inhibition of GABA neurons, especially in the amygdala, is crucial for the precise regulation of the consolidation, expression, and extinction of fear conditioning. The GABAergic system is involved in the pathophysiological process of PTSD, with several studies demonstrating that the function of the GABAergic system decreases in PTSD patients. This paper reviews the preclinical and clinical studies, neuroimaging techniques, and pharmacological studies of the GABAergic system in PTSD and summarizes the role of the GABAergic system in PTSD. Understanding the role of the GABAergic system in PTSD and searching for new drug targets will be helpful in the treatment of PTSD.