An inulin-based glycovesicle for pathogen-targeted drug delivery to ameliorate salmonellosis.

The gut microbiota plays a significant role in the pathogenesis and remission of inflammatory bowel disease. However, conventional antibiotic therapies may alter microbial ecology and lead to dysbiosis of the gut microbiome, which greatly limits therapeutic efficacy. To address this challenge, novel nanomicelles that couple inulin with levofloxacin via disulfide bonds for the treatment of salmonellosis were developed in this study. Owing to their H2S-responsiveness, the nanomicelles can target the inflamed colon and rapidly release levofloxacin to selectively fight against enteric pathogens. Moreover, the embedded inulin can serve as prebiotic fiber to increase the amount of Bifidobacteria and Lactobacilli in mice with salmonellosis, thus maintaining the intestinal mechanical barrier and regulating the balance of the intestinal flora. Therefore, multifunctional nanomicelles had a better curative effect than pure levofloxacin on ameliorating inflammation in vivo. The pathogen-targeted glycovesicle represents a promising drug delivery platform to maximize the efficacy of antibacterial drugs for the treatment of inflammatory bowel disease.

Conjugated linoleic acid (CLA) reduces intestinal fatty acid uptake and chylomicron formation in HFD-fed mice associated with the inhibition of DHHC7-mediated CD36 palmitoylation and the downstream ERK pathway.

The anti-obesity effect of conjugated linoleic acid (CLA) has been well elucidated, but whether CLA affects fat deposition by regulating intestinal dietary fat absorption remains largely unknown. Thus, this study aimed to investigate the effects of CLA on intestinal fatty acid uptake and chylomicron formation and explore the possible underlying mechanisms. We found that CLA supplementation reduced the intestinal fat absorption in HFD (high fat diet)-fed mice accompanied by the decreased serum TG level, increased fecal lipids and decreased intestinal expression of ApoB48 and MTTP. Correspondingly, c9, t11-CLA, but not t10, c12-CLA induced the reduction of fatty acid uptake and TG content in PA (palmitic acid)-treated MODE-K cells. In the mechanism of fatty acid uptake, c9, t11-CLA inhibited the binding of CD36 with palmitoyltransferase DHHC7, thus leading to the decreases of CD36 palmitoylation level and localization on the cell membrane of the PA-treated MODE-K cells. In the mechanism of chylomicron formation, c9, t11-CLA inhibited the formation of the CD36/FYN/LYN complex and the activation of the ERK pathway in the PA-treated MODE-K cells. In in vivo verification, CLA supplementation reduced the DHHC7-mediated total and cell membrane CD36 palmitoylation and suppressed the formation of the CD36/FYN/LYN complex and the activation of the ERK pathway in the jejunum of HFD-fed mice. Altogether, these data showed that CLA reduced intestinal fatty acid uptake and chylomicron formation in HFD-fed mice associated with the inhibition of DHHC7-mediated CD36 palmitoylation and the downstream ERK pathway.

Burnout and depression in college students.

Research on burnout has garnered considerable attention since its inception. However, the ongoing debate persists regarding the conceptual model of burnout and its relationship with depression. Thus, we conducted a network analysis to determine the dimensional structure of burnout and the burnout-depression overlap. The Maslach Burnout Inventory-Student Survey and Patient Health Questionnaire-9 were used to measure burnout and depression among 1096 college students. We constructed networks for burnout, depression, and a burnout-depression co-occurrence network. The results showed that cynicism symptom was the most central to the burnout network. In the co-occurrence network, depressive symptoms ("anhedonia", "fatigue") and burnout symptom ("doubting the significance of studies") were the most significant in causing burnout-depression comorbidity. Community detection revealed three communities within burnout symptoms, aligning closely with their three dimensions identified through factor analysis. Additionally, there was no overlap between burnout and depression. In conclusion, our findings support a multidimensional structure of burnout, affirming it as a distinct concept separate from depression. Cynicism, rather than exhaustion, plays the most important role in burnout and the burnout-depression comorbidity.

Knockdown of the VEGFB/VEGFR1 signaling suppresses pubertal mammary gland development of mice via the inhibition of PI3K/Akt pathway.

Vascular endothelial growth factor B (VEGFB) has been well demonstrated to play a crucial role in regulating vascular function by binding to the VEGF receptors (VEGFRs). However, the specific role of VEGFB and VEGFRs in pubertal mammary gland development remains unclear. In this study, we observed that blocking the VEGF receptors with Axitinib suppressed the pubertal mammary gland development. Meanwhile, the proliferation of mammary epithelial cells (HC11) was repressed by blocking the VEGF receptors with Axitinib. Additionally, knockdown of VEGFR1 rather than VEGFR2 and NRP1 elicited the inhibition of HC11 proliferation, suggesting the essential role of VEGFR1 during this process. Furthermore, Axitinib or VEGFR1 knockdown led to the inhibition of the PI3K/Akt pathway. However, the inhibition of HC11 proliferation induced by Axitinib and or VEGFR1 knockdown was eliminated by the Akt activator SC79, indicating the involvement of the PI3K/Akt pathway. Finally, the knockdown of VEGFB and VEGFR1 suppressed the pubertal development of mice mammary gland with the inhibition of the PI3K/Akt pathway. In summary, the results showed that knockdown of the VEGFB/VEGFR1 signaling suppresses pubertal mammary gland development of mice via the inhibition of the PI3K/Akt pathway, which provides a new target for the regulation of pubertal mammary gland development.

Epidemiological characteristics and temporal-spatial clustering analysis on human brucellosis in Jiangsu Province, 2006-2021.

The marked increase in the incidence rate of brucellosis is a serious public health concern in Jiangsu Province. However, its temporal and spatial distribution has not been studied in depth. The main purpose of this study is to depict the demographic, temporal and spatial distribution patterns and clustering characteristics of brucellosis cases in Jiangsu Province, China, from 2006 to 2021 to develop and implement effective scientific prevention and control strategies. Data for human brucellosis cases in Jiangsu Province from 2006 to 2021 were obtained from the Nationwide Notifiable Infectious Diseases Reporting Information System (NIDRIS). Spatial autocorrelation analysis and temporal-spatial scan statistics were used to identify potential changes in the spatial and temporal distributions of human brucellosis in Jiangsu Province. During the years 2006-2021, 1347 brucellosis cases were reported in Jiangsu Province, with an average annual incidence rate of 0.1036 per 100,000 individuals. Middle-aged and elderly individuals (aged 40-69 years) were the main infected populations, accounting for 69.72% (939/1347) of all reported cases. The incidence of brucellosis in Jiangsu showed a long-term increasing trend and displayed pronounced seasonal variations, with the peak occurring between April and June annually. The incidence gradually expanded from the northern and southern areas to the central areas between 2006 and 2021. Global spatial autocorrelation analysis demonstrated a positive correlation in the incidence of brucellosis between 2008 and 2012-2021. Temporal-spatial clustering analysis showed that the primary cluster was detected in the northern, highly endemic regions of Jiangsu, and the three secondary clusters were in areas where there had been outbreaks of brucellosis. Human brucellosis remains a serious public health issue in Jiangsu Province. Northern and southern Jiangsu regions, with high rates of brucellosis, may require special plans and measures to monitor and control the disease. Additionally, the capacity to respond to outbreaks in high-incidence areas should be improved to prevent further brucellosis outbreaks.

Browning of Mammary Fat Suppresses Pubertal Mammary Gland Development of Mice via Elevation of Serum Phosphatidylcholine and Inhibition of PI3K/Akt Pathway.

Mammary fat plays a profound role in the postnatal development of mammary glands. However, the specific types (white, brown, or beige) of adipocytes in mammary fat and their potential regulatory effects on modulating mammary gland development remain poorly understood. This study aimed to investigate the role of the browning of mammary fat on pubertal mammary gland development and explore the underlying mechanisms. Thus, the mammary gland development and the serum lipid profile were evaluated in mice treated with CL316243, a ß3-adrenoceptor agonist, to induce mammary fat browning. In addition, the proliferation of HC11 cells co-cultured with brown adipocytes or treated with the altered serum lipid metabolite was determined. Our results showed that the browning of mammary fat by injection of CL316243 suppressed the pubertal development of mice mammary glands, accompanied by the significant elevation of serum dioleoylphosphocholine (DOPC). In addition, the proliferation of HC11 was repressed when co-cultured with brown adipocytes or treated with DOPC. Furthermore, DOPC suppressed the activation of the PI3K/Akt pathway, while the DOPC-inhibited HC11 proliferation was reversed by SC79, an Akt activator, suggesting the involvement of the PI3K/Akt pathway in the DOPC-inhibited proliferation of HC11. Together, the browning of mammary fat suppressed the development of the pubertal mammary gland, which was associated with the elevated serum DOPC and the inhibition of the PI3K/Akt pathway.

Proline hydroxylase 2 (PHD2) promotes brown adipose thermogenesis by enhancing the hydroxylation of UCP1.

OBJECTIVE: Brown adipose tissue (BAT) plays a crucial role in regulating non-shivering thermogenesis under cold exposure. Proline hydroxylases (PHDs) were found to be involved in adipocyte differentiation and lipid deposition. However, the effects of PHDs on regulatory mechanisms of BAT thermogenesis are not fully understood. METHODS: We detected the expression of PHDs in different adipose tissues by using immunoblotting and real-time PCR. Further, immunoblotting, real-time PCR, and immunostaining were performed to determine the correlation between proline hydroxylase 2 (PHD2) and UCP1 expression. Inhibitor of PHDs and PHD2-sgRNA viruses were used to construct the PHD2-deficiency model in vivo and in vitro to investigate the impacts of PHD2 on BAT thermogenesis. Afterward, the interaction between UCP1 and PHD2 and the hydroxylation modification level of UCP1 were verified by Co-IP assays and immunoblotting. Finally, the effect of specific proline hydroxylation on the expression/activity of UCP1 was further confirmed by site-directed mutation of UCP1 and mass spectrometry analysis. RESULTS: PHD2, but not PHD1 and PHD3, was highly enriched in BAT, colocalized, and positively correlated with UCP1. Inhibition or knockdown of PHD2 significantly suppressed BAT thermogenesis under cold exposure and aggravated obesity of mice fed HFD. Mechanistically, mitochondrial PHD2 bound to UCP1 and regulated the hydroxylation level of UCP1, which was enhanced by thermogenic activation and attenuated by PHD2 knockdown. Furthermore, PHD2-dependent hydroxylation of UCP1 promoted the expression and stability of UCP1 protein. Mutation of the specific prolines (Pro-33, 133, and 232) in UCP1 significantly mitigated the PHD2-elevated UCP1 hydroxylation level and reversed the PHD2-increased UCP1 stability. CONCLUSIONS: This study suggested an important role for PHD2 in BAT thermogenesis regulation by enhancing the hydroxylation of UCP1.

Early markers of neurodevelopmental disorders based on general movements for very preterm infants: study protocol for a multicentre prospective cohort study in a clinical setting in China.

INTRODUCTION: Very preterm (VPT) infants may experience varying degrees of neurodevelopmental challenges. Lack of early markers for neurodevelopmental disorders may delay referral to early interventions. The detailed General Movements Assessment (GMA) could help us to identify early markers for VPT infants at risk of atypical neurodevelopmental clinical phenotype in the very early stage of life as soon as possible. Preterm infants with high risk of atypical neurodevelopmental outcomes will have the best possible start to life if early precise intervention in critical developmental windows is allowed. METHODS AND ANALYSIS: This is a nationwide, multicentric prospective cohort study that will recruit 577 infants born <32 weeks of age. This study will determine the diagnostic value of the developmental trajectory of general movements (GMs) at writhing and fidgety age with qualitative assessment for different atypical developmental outcomes at 2 years evaluated by the Griffiths Development Scales-Chinese. The difference in the General Movement Optimality Score (GMOS) will be used to distinguish normal (N), poor repertoire (PR) and cramped sychronised (CS) GMs. We plan to build the percentile rank of GMOS (median, 10th, 25th, 75th and 90th percentile rank) in N, PR and CS of each global GM category and analyse the relationship between GMOS in writhing movements and Motor Optimality Score (MOS) in fidgety movements based on the detailed GMA. We explore the subcategories of the GMOS list, and MOS list that may identify specific early markers that help us to identify and predict different clinical phenotypes and functional outcomes in VPT infants. ETHICS AND DISSEMINATION: The central ethical approval has been confirmed from the Research Ethical Board of Children's Hospital of Fudan University (ref approval no. 2022(029)) and the local ethical approval has been also obtained by the corresponding ethics committees of the recruitment sites. Critical analysis of the study results will contribute to providing a basis for hierarchical management and precise intervention for preterm infants in very early life. TRIAL REGISTRATION NUMBER: ChiCTR2200064521.

Analysis of fatal cases of severe fever with thrombocytopenia syndrome in Jiangsu province, China, between 2011 and 2022: A retrospective study.

Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS virus (SFTSV), which has a high fatality rate. This disease has become increasingly prevalent in recent years in Jiangsu province, with a noticeable rise in its incidence. Notably, fatal cases have also been increasing. Our study aimed to analyze the epidemiological characteristics and risk factors associated with the fatal cases of SFTS in Jiangsu province from 2011 to September 2022. Methods: A retrospective study was performed among 698 SFTS cases during 2011-2022 in Jiangsu Province, China. Cox regression analyses were used to determine the dependent and independent risk factors that affected patient survival time. ArcGIS 10.7 was used for the visualization of the geographical distribution of the deaths from SFTS. Results: There were 698 SFTS cases reported, with an increasing incidence, over the 12-year period. Among these cases, 43 deaths were reported. Fatal cases of SFTS were reported in 12 district counties from 2011 to 2022. Notably, most of the deaths occurred in Lishui county of Nanjing City. The median age of those who died was 69 years, with age ranges from 50 to 83 years. Multivariable Cox regression analysis showed that older age (>70) and living in Lishui county were risk factors for death from SFTS in Jiangsu province. Therefore, older adults aged over 70 years and residing in Lishui county were the high-risk group for SFTS mortality. Discussion: Over the past 12 years, we have observed a consistent rise in the incidence of SFTS, accompanied by a relatively high case fatality rate, making it a critical public health issue. Therefore, it is urgently necessary to study the impact of meteorological factors on SFTS epidemics and devise prevention and control strategies.

Epidemiological and spatiotemporal analysis of severe fever with thrombocytopenia syndrome in Eastern China, 2011-2021.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease, which is caused by severe fever with thrombocytopenia syndrome virus (SFTSV) with high fatality. Recently, the incidence of SFTS increased obviously in Jiangsu Province. However, the systematic and complete analysis of spatiotemporal patterns and clusters coupled with epidemiological characteristics of SFTS have not been reported so far. METHODS: Data on SFTS cases were collected during 2011-2021. The changing epidemiological characteristics of SFTS were analyzed by adopting descriptive statistical methods. GeoDa 1.18 was applied for spatial autocorrelation analysis, and SaTScan 10.0 was used to identify spatio-temporal clustering of cases. The results were visualized in ArcMap. RESULTS: The annual incidence of SFTS increased in Jiangsu Province from 2011 to 2021. Most cases (72.4%) occurred during May and August with the obvious peak months. Elderly farmers accounted for most cases, among which both males and females were susceptible. The spatial autocorrelation and spatio-temporal clustering analysis indicated that the distribution of SFTS was not random but clustered in space and time. The most likely cluster was observed in the western region of Jiangsu Province and covered one county (Xuyi county) (Relative risk = 8.18, Log likelihood ratio = 122.645, P < 0.001) located in southwestern Jiangsu Province from January 1, 2017 to December 31, 2021. The Secondary cluster also covered one county (Lishui county) (Relative risk = 7.70, Log likelihood ratio = 94.938, P < 0.001) from January 1, 2017 to December 31, 2021. CONCLUSIONS: The annual number of SFTS cases showed an increasing tendency in Jiangsu Province from 2011 to 2021. Our study elucidated regions with SFTS clusters by means of ArcGIS in combination with spatial analysis. The results demonstrated solid evidences for the orientation of limited sanitary resources, surveillance in high-risk regions and early warning of epidemic seasons in future prevention and control of SFTS in Jiangsu Province.

Experimental Studies of the Attention Processing Model in Multiple Object Tracking Task.

(1) Background: Attention is an important cognitive process in daily life. However, limited cognitive resources have been allocated to attention, especially for multiple objects and its mechanism is still unclear. Most of the previous studies have been based on the static attention paradigms with relatively lower ecological validity. Thus, we aimed to explore the attention processing mechanism in a multiple object tracking (MOT) task by using a dynamic attention paradigm. Two experiments were conducted to assess whether there was a multi-focus attention processing model, and whether the processing model changes with the number of target balls. (2) Methods: During the experiments, 33 university students completed MOT combined with the simultaneous-sequential paradigm, with tracking accuracy and reaction time of correct reaction as indicators. (3) Results: (i) When there were two target balls, an obvious bilateral field advantage was apparent. (ii) When there were four target balls, participants' performance was significantly better when stimuli were presented simultaneously than when they were presented sequentially, showing a multi-focus attention processing model. (4) Conclusion: Attention processing is characterized by flexibility, providing strong evidence to support the multi-focus theory.

Applying network analysis to understand the relationships between impulsivity and social media addiction and between impulsivity and problematic smartphone use.

Background: Prior studies have revealed the relationships between impulsivity and social media addiction (SMA) and between impulsivity and problematic smartphone use (PSU) based on total scores on standardized self-report scales. However, there has been a lack of studies exploring how the dimensions of impulsivity and components of SMA or PSU are interrelated. The present study aimed to investigate the structural relationships between the dimensions of impulsivity and components of SMA and PSU and determine the critical bridge node using network analysis. Methods: A total of 325 healthy adults aged 18-36 years participated in the study. SMA and PSU were assessed using the Bergen Social Media Addiction Scale (BSMAS) and Smartphone Application-Based Addiction Scale (SABAS), respectively. Impulsivity was measured by the Barratt Impulsiveness Scale Version 11 (BIS-11). Network analysis was used to construct an SMA-Impulsivity network and a PSU-Impulsivity network. Bridge centrality (bridge expected influence, BEI) was estimated to identify influential bridge nodes. Results: In addition to relationships within each community, network analysis revealed that the dimensions of impulsivity were closely associated with the components of SMA and PSU. Particularly, I2 "motor impulsivity" had a relatively strong connection with SMA3 "mood modification" and SMA4 "relapse" in the SMA-Impulsivity network, and with PSU2 "conflict" and PSU5 "withdrawal" in the PSU-Impulsivity network. Moreover, I2 "motor impulsivity" was identified as the most critical bridge node in both networks. Conclusion: These findings demonstrate potential pathways between different dimensions of impulsivity and the components of SMA and PSU, providing new evidence relevant to understanding the underlying mechanisms that account for how highly impulsive individuals develop SMA and PSU, and highlight the critical bridge node-motor impulsivity-that may be a promising and effective target for the prevention and treatment of SMA and PSU.

The relations between emotion regulation, depression and anxiety among medical staff during the late stage of COVID-19 pandemic: a network analysis.

Existing research proposed that moving from a disorder-level analysis to a symptom-level analysis may provide a more fine-grained understanding of psychopathology. This study aimed to explore the relations between two dimensions (i.e., cognitive reappraisal, CR; expressive suppression, ES) of emotion regulation and individual symptoms of depression and anxiety among medical staff during the late stage of COVID-19 pandemic. We examined depression symptoms, anxiety symptoms and emotion regulation among 420 medical staff during the late stage of COVID-19 pandemic via network analysis. Two networks (i.e. emotion regulation-depression network and emotion regulation-anxiety network) were constructed in the present study. Bridge centrality index was calculated for each variable within the two networks. Among the present sample, the prevalences of depression and anxiety are 39.5% and 26.0%. CR and ES showed distinct connections to symptoms of depression and anxiety. Results of bridge centrality showed that in both networks, CR had a negative bridge expected influence value while ES had a positive bridge expected influence value. The results revealed the specific role of CR and ES in relation to depression and anxiety at a symptom level. Implications for clinical preventions and interventions are discussed.

Reservoir Physical Properties and Micropore Nanocharacteristics of Cores in the Shihezi Formation, Sudong District, Sulige Gas Field, Ordos Basin.

Sulige gas field is a very complex large-scale gas field with low porosity, low permeability, low abundance, and strong heterogeneity. In this study, the nanopore structure of the reservoir in the study area was analyzed. The analysis of reservoir physical properties and core microscopic pore characteristics of Shihezi formation in Sudong District, Sulige gas field, Ordos Basin, was put forward. According to core observation, thin section identification, and grain size analysis, the lithology of gas reservoirs in Shan-1 member and He-8 member in the study area is mainly lithic sandstone, lithic quartz sandstone, and quartz sandstone. According to the analysis of physical data in the study area, the reservoirs in Shan-1 member and He-8 member have typical characteristics of low porosity and low permeability. According to that microscopic observation of sandstone thin section and cast thin section combined with the analysis of scan electron microscope, the results show that both Shan-1 member and He-8 member of Sudong area 2 in Sulige gas field are dominated by class I reservoirs and class II reservoirs. Especially, class I reservoirs are widely distributed, with the cumulative area of this type of reservoirs accounting for 70.12% of the total area in Shan section and 64.12% in He-8 section. Class I reservoirs are scattered in the study area, accounting for 0.27% of the total area in the mountain section and 0.36% in the He-8 section. Class IV reservoirs are distributed dispersedly and have a small distribution area. The cumulative area of reservoirs in mountain section accounts for 5.38% of the total area and that in He-8 section accounts for 5.46%. Therefore, Sudong area 2 in Sulige gas field is a typical low porosity and low permeability reservoir. On the basis of geological background, sedimentary microfacies, diagenesis, and pore structure characteristics of the study area, it is considered that the pore structure of sandstone in the study area is mainly controlled by sedimentary characteristics and diagenesis of sandstone.

Meteorological factors and tick density affect the dynamics of SFTS in jiangsu province, China.

BACKGROUND: This study aimed to explore whether the transmission routes of severe fever with thrombocytopenia syndrome (SFTS) will be affected by tick density and meteorological factors, and to explore the factors that affect the transmission of SFTS. We used the transmission dynamics model to calculate the transmission rate coefficients of different transmission routes of SFTS, and used the generalized additive model to uncover how meteorological factors and tick density affect the spread of SFTS. METHODS: In this study, the time-varying infection rate coefficients of different transmission routes of SFTS in Jiangsu Province from 2017 to 2020 were calculated based on the previous multi-population multi-route dynamic model (MMDM) of SFTS. The changes in transmission routes were summarized by collecting questionnaires from 537 SFTS cases in 2018-2020 in Jiangsu Province. The incidence rate of SFTS and the infection rate coefficients of different transmission routes were dependent variables, and month, meteorological factors and tick density were independent variables to establish a generalized additive model (GAM). The optimal GAM was selected using the generalized cross-validation score (GCV), and the model was validated by the 2016 data of Zhejiang Province and 2020 data of Jiangsu Province. The validated GAMs were used to predict the incidence and infection rate coefficients of SFTS in Jiangsu province in 2021, and also to predict the effect of extreme weather on SFTS. RESULTS: The number and proportion of infections by different transmission routes for each year and found that tick-to-human and human-to-human infections decreased yearly, but infections through animal and environmental transmission were gradually increasing. MMDM fitted well with the three-year SFTS incidence data (P<0.05). The best intervention to reduce the incidence of SFTS is to reduce the effective exposure of the population to the surroundings. Based on correlation tests, tick density was positively correlated with air temperature, wind speed, and sunshine duration. The best GAM was a model with tick transmissibility to humans as the dependent variable, without considering lagged effects (GCV = 5.9247E-22, R2 = 96%). Reported incidence increased when sunshine duration was higher than 11 h per day and decreased when temperatures were too high (>28°C). Sunshine duration and temperature had the greatest effect on transmission from host animals to humans. The effect of extreme weather conditions on SFTS was short-term, but there was no effect on SFTS after high temperature and sunshine hours. CONCLUSIONS: Different factors affect the infection rate coefficients of different transmission routes. Sunshine duration, relative humidity, temperature and tick density are important factors affecting the occurrence of SFTS. Hurricanes reduce the incidence of SFTS in the short term, but have little effect in the long term. The most effective intervention to reduce the incidence of SFTS is to reduce population exposure to high-risk environments.

Hydrogen sulfide-sensitive Chitosan-SS-Levofloxacin micelles with a high drug content: Facile synthesis and targeted Salmonella infection therapy.

The delivery system of antibiotics plays an important role in increasing the drug efficacy and reducing the risks of off-target toxicities and antibiotic resistance. The pathophysiology of bacterial infections is similar to that of tumor tissues, but only a few delivery systems have been able to target and release antibiotics on demand. Herein, we designed and developed a robust Chitosan-SS-Levofloxacin (CS-SS-LF) micelles for targeted antibiotic delivery, in which disulfide bond can be reduced by hydrogen sulfide (H2S), a typical product of Salmonella, and subsequently released antibiotic to eradicate Salmonella infection. CS-SS-LF micelles showed uniform size and sharp response to H2S. Compared with levofloxacin alone, these micelles possessed a better capacity in disrupting Salmonella biofilms and reducing bacterial burden in organs. The H2S-sensitive CS-SS-LF micelles might enable a new way to address bacterial infections.

Modelling the transmission dynamics of severe fever with thrombocytopenia syndrome in Jiangsu Province, China.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that is regionally distributed in Asia, with high fatality. Constructing the transmission model of SFTS could help provide clues for disease control and fill the gap in research on SFTS models. METHODS: We built an SFTS transmission dynamics model based on the susceptible-exposed-infectious-asymptomatic-recovered (SEIAR) model and the epidemiological characteristics of SFTS in Jiangsu Province. This model was used to evaluate the effect by cutting off different transmission routes and taking different interventions into account, to offer clues for disease prevention and control. RESULTS: The transmission model fits the reported data well with a minimum R2 value of 0.29 and a maximum value of 0.80, P < 0.05. Meanwhile, cutting off the environmental transmission route had the greatest effect on the prevention and control of SFTS, while isolation and shortening the course of the disease did not have much effect. CONCLUSIONS: The model we have built can be used to simulate the transmission of SFTS to help inform disease control. It is noteworthy that cutting off the environment-to-humans transmission route in the model had the greatest effect on SFTS prevention and control.

Epidemiological and clinical characteristics of severe fever with thrombocytopenia syndrome bunyavirus human-to-human transmission.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) was listed as one of the most severe infectious disease by world health organization in 2017. It can mostly be transmitted by tick bite, while human-to-human transmission has occurred on multiple occasions. This study aimed to explore the epidemiological and clinical characteristics and make risk analysis of SFTS human-to-human transmission. METHODS: Descriptive and spatial methods were employed to illustrate the epidemiological and clinical characteristics of SFTS human-to-human transmission. The risk of SFTS human-to-human transmission was accessed through secondary attack rate (SAR) and basic reproductive number (R0). Logistic regression analysis was used to identify the associated risk factors. RESULTS: A total of 27 clusters of SFTS human-to-human transmission were reported in China and South Korea during 1996-2019. It mainly occurred among elder people in May, June and October in central and eastern China. The secondary cases developed milder clinical manifestation and better outcome than the index cases. The incubation period was 10.0 days (IQR:8.0-12.0), SAR was 1.72%-55.00%, and the average R0 to be 0.13 (95%CI:0.11-0.16). Being blood relatives of the index case, direct blood/bloody secretion contact and bloody droplet contact had more risk of infection (OR = 6.35(95%CI:3.26-12.37), 38.01 (95%CI,19.73-73.23), 2.27 (95%CI,1.01-5.19)). CONCLUSIONS: SFTS human-to-human transmission in China and South Korea during 1996-2019 had obvious spatio-temporal distinction. Ongoing assessment of this transmission risk is crucial for public health authorities though it continues to be low now.

The antitumor properties of metformin and phenformin reflect their ability to inhibit the actions of differentiated embryo chondrocyte 1.

BACKGROUND: Differentiated embryo chondrocyte 1 (DEC1) is a helix-loop-helix transcription factor that directly binds to the class B E-box in target genes. DEC1 exerts both pro-survival and pro-apoptotic effects in a cell- and tissue-dependent manner. Its actions play role the progression of cancer remains unclear. METHODS: We first examined the functional roles of DEC1 using the transient promoter reporter assay. Then, the knockdown of DEC1 expression was performed with the short hairpin RNA strategy in HeLa and A2058 cancer cell lines to check the cell cycle and mitochondrial function profile using the flow cytometry and Seahorse assays. We later clarified the role of DEC1 in the tumorigenesis using the colony formation, anchorage-independent growth assay, and cellular proliferation analysis. RESULTS: In the present study, we tested two guanide-containing drugs, metformin and phenformin, and found that both exhibit cytotoxicity against HeLa cervical carcinoma and A2058 melanoma cells. This effect was mediated, at least in part, through activation of the AMPK pathway; degradation of important cellular proteins, such as DEC1 and p53; and suppression of mitochondrial function, colony formation, and anchorage-independent cell proliferation. Our results further suggest that the cytotoxicity of metformin and phenformin reflect the impact of the repressive actions of DEC1 on gene expression, including DEC1 itself. This in turn suppresses both anchorage-independent growth and cell proliferation. CONCLUSION: These findings provide several lines of evidence suggesting that DEC1 activity contributes to tumorigenicity and that the antitumor properties of biguanides reflect their ability to inhibit DEC1 functions.

Spatiotemporal epidemiology of scarlet fever in Jiangsu Province, China, 2005-2015.

BACKGROUND: A marked increase in the incidence rate of scarlet fever imposed a considerable burden on the health of children aged 5 to 15 years. The main purpose of this study was to depict the spatiotemporal epidemiological characteristics of scarlet fever in Jiangsu Province, China in order to develop and implement effective scientific prevention and control strategies. METHODS: Smoothed map was used to demonstrate the spatial distribution of scarlet fever in Jiangsu Province. In addition, a retrospective space-time analysis based on a discrete Poisson model was utilized to detect clusters of scarlet fever from 2005 to 2015. RESULTS: During the years 2005-2015, a total of 15,873 scarlet fever cases occurred in Jiangsu Province, with an average annual incidence rate of 1.87 per 100,000. A majority of the cases (83.67%) occurred in children aged 3 to 9 years. Each year, two seasonal incidence peaks were observed, the higher occurring between March and July, the lower between November and the following January. The incidence in the southern regions of the province was generally higher than that in the northern regions. Seven clusters, all of which occurred during incidence peaks, were detected via space-time scan statistical analysis. The most likely cluster and one of the secondary clusters were detected in the southern and northern high endemic regions, respectively. CONCLUSION: The prevalence of scarlet fever in Jiangsu Province had a marked seasonality variation and was relatively endemic in some regions. Children aged 3 to 9 years were the major victims of this disease, and kindergartens and primary schools were the focus of surveillance and control. Targeted strategies and measures should be taken to reduce the incidence.