The innate immune system can be boosted in response to subsequent triggers by pre-exposure to microbes or microbial products, known as “trained immunity”. Compared to classical immune memory, innate trained immunity has several different features. Firstly, the molecules involved in trained immunity differ from those involved in classical immune memory. Innate trained immunity mainly involves innate immune cells (e.g., myeloid immune cells, natural killer cells, innate lymphoid cells) and their effector molecules (e.g., pattern recognition receptor (PRR), various cytokines), as well as some kinds of non-immune cells (e.g., microglial cells). Secondly, the increased responsiveness to secondary stimuli during innate trained immunity is not specific to a particular pathogen, but influences epigenetic reprogramming in the cell through signaling pathways, leading to the sustained changes in genes transcriptional process, which ultimately affects cellular physiology without permanent genetic changes (e.g., mutations or recombination). Finally, innate trained immunity relies on an altered functional state of innate immune cells that could persist for weeks to months after initial stimulus removal. An appropriate inducer could induce trained immunity in innate lymphocytes, such as exogenous stimulants (including vaccines) and endogenous stimulants, which was firstly discovered in bone marrow derived immune cells. However, mature bone marrow derived immune cells are short-lived cells, that may not be able to transmit memory phenotypes to their offspring and provide long-term protection. Therefore, trained immunity is more likely to be relied on long-lived cells, such as epithelial stem cells, mesenchymal stromal cells and non-immune cells such as fibroblasts. Epigenetic reprogramming is one of the key molecular mechanisms that induces trained immunity, including DNA modifications, non-coding RNAs, histone modifications and chromatin remodeling. In addition to epigenetic reprogramming, different cellular metabolic pathways are involved in the regulation of innate trained immunity, including aerobic glycolysis, glutamine catabolism, cholesterol metabolism and fatty acid synthesis, through a series of intracellular cascade responses triggered by the recognition of PRR specific ligands. In the view of evolutionary, trained immunity is beneficial in enhancing protection against secondary infections with an induction in the evolutionary protective process against infections. Therefore, innate trained immunity plays an important role in therapy against diseases such as tumors and infections, which has signature therapeutic effects in these diseases. In organ transplantation, trained immunity has been associated with acute rejection, which prolongs the survival of allografts. However, trained immunity is not always protective but pathological in some cases, and dysregulated trained immunity contributes to the development of inflammatory and autoimmune diseases. Trained immunity provides a novel form of immune memory, but when inappropriately activated, may lead to an attack on tissues, causing autoinflammation. In autoimmune diseases such as rheumatoid arthritis and atherosclerosis, trained immunity may lead to enhance inflammation and tissue lesion in diseased regions. In Alzheimer’s disease and Parkinson’s disease, trained immunity may lead to over-activation of microglial cells, triggering neuroinflammation even nerve injury. This paper summarizes the basis and mechanisms of innate trained immunity, including the different cell types involved, the impacts on diseases and the effects as a therapeutic strategy to provide novel ideas for different diseases.

Objective To investigate the population density and seasonal fluctuations of Aedes albopictus in Guangzhou City, Guangdong Province, from 2021 to 2023, so as to provide insights into A. albopictus control and management of dengue fever. Methods The surveillance of A. albopictus density was performed in all surveillance sites assigned across all streets (townships) in Guangzhou City during the period from January to December from 2021 to 2023. The surveillance frequency was twice every half month from May to September, and once every month for the rest of a year. In each surveillance period, A. albopictus mosquito larvae were captured from indoor and outdoor small water containers in residential areas, parks, medical facilities, schools, other government sectors and social organizations, construction sites, special industries and others for mosquito species identification. Adult mosquitoes were captured using electric mosquito suction apparatus for species identification and gender classification. Adult mosquitoes and mosquito eggs were collected with mosquito and egg traps at the breeding and dwelling places of Aedes mosquitoes for identification. The mosquito oviposition index (MOI), Breteau index (BI), adult mosquito density index (ADI) and standard space index (SSI) were calculated. The A. albopictus density was classified into grades 0, 1, 2 and 3 in each surveillance site, with Grade 0 density defined eligible, and the eligible rate of A. albopictus density was calculated at all surveillance sites each year from 2021 to 2023. In addition, the changing trends in MOI, SSI, BI and ADI of A. albopictus were analyzed in Guangzhou City from 2021 to 2023. Results The eligible rates of A. albopictus density were 61.69%, 68.75% and 55.15% in surveillance sites of Guangzhou City from 2021 to 2023 (χ² = 297.712, P < 0.001), and appeared a tendency towards a reduction followed by a rise each year, which gradually reduced since January, maintained at a low level during the period between May and October, and gradually increased from November to December. The MOI, SSI, BI and ADI of A. albopictus all appeared a tendency towards a rise followed by a reduction in Guangzhou City during the period between January and December from 2021 to 2023. The BI of A. albopictus peaked in the first half of June in 2021 (4.03), the first half of July in 2022 (3.89) and the last half of August in 2023 (5.02), and the SSI of A. albopictus peaked in the last half of June in 2021 (0.93), the last half of May in 2022 (0.59), and the last half of June (0.94) and the first half of September in 2023 (1.12). In addition, the MOI of A. albopictus peaked in the first half of May in 2021 (8.64), the first half of June in 2022 (8.96), and the last half of May (10.21) and the last half of June in 2023 (10.89), and the ADI of A. albopictus peaked in the first half of June in 2021 (3.41), the last half of June in 2022 (4.06), and the first half of July in 2023 (3.61). Conclusions The density of A. albopictus is high in Guangzhou City during the period from May to October, and the risk of local outbreak caused by imported dengue fever is high. Persistent intensified surveillance of the density and seasonal fluctuation of A. albopictus is recommended and timely mosquito prevention and control is required according to the fluctuation in the A. albopictus density.

To clarify the occurrence and distribution of broad bean wilt virus 2(BBWV2) on Rehmannia glutinosa, this study collected 87 R. glutinosa samples with typical symptoms of viral disease such as chlorosis and crumple from Wenxian county and Wuzhi county in Jiaozuo city, Henan province and Qiaocheng district in Bozhou city, Anhui province. The BBWV2 CP target band was amplified from 37 R. glutinosa samples by RT-PCR technology. The total detection rate reached 42.5%, among which 43.0% was detected in samples from Henan province. The detection rate in samples from Anhui province was 37.5%. 37 BBWV2 CP sequences were obtained by cloning and sequencing of BBWV2 positive samples(data has been submitted to GenBank, accession numbers: PP407959-PP407995), and the sequence analysis of these CP sequences with 91 other BBWV2 isolates in GenBank showed a high genetic diversity with a consistency rate of 70.8%-100%. Meanwhile, phylogenetic analysis showed that BBWV2 could be divided into three groups according to CP sequences, among which the BBWV2 in R. glutinosa isolates obtained in this study were all located in group 3. This study identified the differences in the occurrence, distribution, and genetic diversity of BBWV2 in R. glutinosa from Henan province and Anhui province and provided a theoretical basis for the prevention and control of BBWV2.
Rehmannia/virology* ; Phylogeny ; Plant Diseases/virology* ; China ; Molecular Sequence Data ; Fabavirus/classification*

This study investigated the therapeutic effects and mechanisms of Modified Yiyi Fuzi Baijiang Powder on ulcerative colitis(UC) in rats from the perspective of dampness. SD rats were randomly allocated into six groups(n=10): control, model, mesalazine, and Modified Yiyi Fuzi Baijiang Powder at low(3.96 g·kg~(-1)·d~(-1)), medium(7.92 g·kg~(-1)·d~(-1)), and high(15.84 g·kg~(-1)·d~(-1)) doses. UC was induced in all groups except the control by administration with 3% dextran sulfate sodium(DSS) solution for 7 days. The disease activity index(DAI) was recorded, and the colon tissue was collected for analysis. Histopathological changes were assessed by hematoxylin-eosin staining. Serum levels of D-lactic acid(D-LA) and diamine oxidase(DAO) were measured by ELISA. Immunohistochemistry and PCR were employed to evaluate the expression of aquaporins(AQP3, AQP4) and tight junction proteins [zonula occludens-1(ZO-1) and occludin] at both protein and mRNA levels. Compared with the control group, the model group showed an increased DAI scores(P<0.05), intestinal mucosal damage, elevated serum levels of DAO and D-LA(P<0.05), and decreased expression of AQP3, AQP4, ZO-1, and occludin(P<0.05). Treatment with Modified Yiyi Fuzi Baijiang Powder reduced the DAI scores(P<0.05), lowered the serum levels of D-LA and DAO(P<0.05), and upregulated the expression of AQP3, AQP4, ZO-1, and occludin at both protein and mRNA levels compared with the model group. These findings suggest that Modified Yiyi Fuzi Baijiang Powder exerts therapeutic effects on UC by reducing the intestinal mucosal permeability, promoting colonic mucosal repair, and regulating abnormal intestinal water metabolism, which may involve the upregulation of AQP3 and AQP4 expression.
Animals ; Colitis, Ulcerative/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Rats ; Intestinal Mucosa/metabolism* ; Male ; Aquaporin 3/metabolism* ; Aquaporin 4/metabolism* ; Permeability/drug effects* ; Humans ; Powders ; Intestinal Barrier Function

OBJECTIVE: To investigate possible associations between physical function assessment scales, such as Short Physical Performance Battery (SPPB) and Berg Balance Scale (BBS), with all-cause mortality in acute decompensated heart failure (ADHF) patients. METHODS: A total of 108 ADHF patients were analyzed from October 2020 to October 2022, and followed up to May 2023. The association between baseline clinical characteristics and all-cause mortality was analyzed by univariate Cox regression analysis, while for SPPB and BBS, univariate Cox regression analysis was followed by receiver operating characteristic curves, in which the area under the curve represented their predictive accuracy for all-cause mortality. Incremental predictive values for both physical function assessments were measured by calculating net reclassification index and integrated discrimination improvement scores. Optimal cut-off value for BBS was then identified using restricted cubic spline plots, and survival differences below and above that cut-off were compared using Kaplan-Meier survival curves and the log-rank test. The clinical utility of BBS was measured using decision curve analysis. RESULTS: For baseline characteristics, age, female, blood urea nitrogen, as well as statins, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or angiotensin receptor-neprilysin inhibitors, were predictive for all-cause mortality for ADHF patients. With respect to SPPB and BBS, higher scores were associated with lower all-cause mortality rates for both assessments; similar area under the curves were measured for both (0.774 for SPPB and 0.776 for BBS). Furthermore, BBS ≤ 36.5 was associated with significantly higher mortality, which was still applicable even adjusting for confounding factors; BBS was also found to have great clinical utility under decision curve analysis. CONCLUSIONS BBS or SPPB could be used as tools to assess physical function in ageing ADHF patients, as well as prognosticate on all-cause mortality. Moreover, prioritizing the improvement of balance capabilities of ADHF patients in cardiac rehabilitation regimens could aid in lowering mortality risk.

In the mammalian central nervous system (CNS), astrocytes are the ubiquitous glial cells that have complex morphological and molecular characteristics. These fascinating cells play essential neurosupportive and homeostatic roles in the healthy CNS and undergo morphological, molecular, and functional changes to adopt so-called 'reactive' states in response to CNS injury or disease. In recent years, interest in astrocyte research has increased dramatically and some new biological features and roles of astrocytes in physiological and pathological conditions have been discovered thanks to technological advances. Here, we will review and discuss the well-established and emerging astroglial biology and functions, with emphasis on their potential as therapeutic targets for CNS injury, including traumatic and ischemic injury. This review article will highlight the importance of astrocytes in the neuropathological process and repair of CNS injury.
Astrocytes/drug effects* ; Humans ; Animals ; Central Nervous System/pathology* ; Central Nervous System Diseases/physiopathology*

Objective:To analyze and predict the future trend of the premature mortality of major chronic and non-communicable diseases in Anhui Province, evaluate the implementation of the "Healthy China 2030" Plan, and explore its influencing factors.Methods:Using data from death-cause surveillance and statistical yearbooks in Anhui, the trend prediction and analysis on influencing factors were conducted by using methods such as time series accumulation and logarithmic linear Joinpoint regression, principal component regression.Results:In Anhui, 28.10% of the deaths were premature ones, of which 84.40% were attributed to chronic and non-communicable diseases. In premature deaths attributed to chronic and non-communicable diseases, the deaths caused by malignant tumor and cardiovascular disease accounted for 45.88% and 41.65% respectively. The prediction results showed that the premature mortality of major chronic and non-communicable diseases would decrease in Anhui in the future, and by 2030, the goal in the "Healthy China 2030" Plan would be reached only in rural area. To reduce premature death, it is necessary to pay attention to the prevention and control of malignant tumor and cardiovascular disease. Men in urban area are the key population. Factors that reflect urban infrastructure had a significant impact on premature mortality of major chronic non-communicable diseases, such as garden and green space area per capita. Factors such as concentration of PM 2.5 had a negative impact on premature mortality of chronic non-communicable diseases, while factors such as garden and green space area per capita had a positive impact. Conclusions:Disease burden caused by chronic and non-communicable diseases, such as malignant tumor, exits in Anhui. Men in urban area are key population in the prevention and control of chronic and non-communicable diseases in the future.

Objective: To investigate the prospective effects of intake of each food group on the development of lung function of pupils,so as to provide theoretical basis for promoting the healthy development of lung function and preventing chronic respiratory diseases in Chinese children. Methods: A cluster stratified sampling method was used to select a total of 893 pupils in grades 2-5 from Chengdu in November 2021. Dietary data of respondents were collected using a food frequency questionnaire within the past year,then the food group intake was categorized into T1, T2 and T3 from low to high by the trichotomous method, and anthropometric measurements including lung capacity were obtained in 2022. Logistic regression models and test for trend were used to analyze the prospective effects of intake of each food group on lung function development of pupils. Results: Among male students, consumption of vegetables [118.6(50.5, 188.2)g/d] and milk and dairy products [200.0(73.3, 250.0)g/d] were higher in the excellent lung capacity group than in the non excellent lung capacity group [90.0(37.1, 192.9), and 178.6(35.7, 250.0)g/d],with statistically significant differences ( Z =-1.98, -2.24); among girls, the group with excellent lung capacity consumed less staple food [391.1(273.6, 511.4)g/d] than the group with non excellent lung capacity [407.4(309.5, 594.3)g/d], and the group with excellent lung capacity consumed more aquatic products [31.2(14.6, 69.8)g/d] and milk and dairy products [215.0(107.1, 250.1) g/d ] than that of the non excellent lung capacity [19.4(10.7, 58.3), 114.3(35.7, 250.0)g/d] ( Z =-2.01, -3.33, -5.10)( P < 0.05 ). After adjusting for energy, body mass index Z score(BMI Z ), mother s education level, averge family income monthly, whether presence of smokers in the living environment, and whether participation in physical activities during the past week, among male students, T3 group of vegetable intake ( OR =0.48, 95% CI = 0.27-0.86), T2 group of bean and soy product intake ( OR = 0.52 , 95% CI =0.27-0.96)，T2 and T3 groups of milk and dairy products intake (T2： OR =0.54, 95% CI =0.31-0.93; T3： OR = 0.52 , 95% CI =0.30-0.90) were negatively associated with non excellent lung capacity ( P <0.05). Among girls, T3 group of aquatic product intake( OR =0.52, 95% CI =0.28-0.97), T2 and T3 groups of milk and dairy product (T2: OR =0.44, 95% CI =0.25- 0.76 ;T3: OR =0.33, 95% CI =0.19-0.59) were negatively associated with nonexcellent lung capacity, whereas the T2 group of red meat intake ( OR =2.51, 95% CI =1.37-4.67) was positively associated with non excellent lung capacity. Non excellent lung capacity was found to be negatively associated with vegetable and milk and dairy product intake in boys by test for trend; in girls, milk and dairy products intake was negatively associated with non excellent lung capacity, whereas red meat intake was positively associated with non excellent lung capacity ( t =-1.13，-0.44；-3.03，1.95, P trend <0.05). Conclusions Milk and dariy products intakes reduce the risk of non excellent lung capacity in pupils, vegetables intakes reduce the risk of non excellent lung capacity in boys, and the intake of red meat increases the risk of non excellent lung capacity in girls. Promoting rational food choices is necessary for children to improve healthy lung development.

The heat shock protein 90 (Hsp90) protein family is a cluster of highly conserved molecules that play an important role in maintaining cellular homeostasis. Hsp90 and its co-chaperones regulate a variety of pathways and cellular functions, such as cell growth, cell cycle control and apoptosis. Hsp90 is closely associated with the occurrence and development of tumors and other diseases, making it an attractive target for cancer therapeutics. Inhibition of Hsp90 expression can affect multiple oncogenic pathways simultaneously. Most Hsp90 small molecule inhibitors are in clinical trials due to their low efficacy, toxicity or drug resistance, but they have obvious synergistic anti-tumor effect when used with histone deacetylase (HDAC) inhibitors, tubulin inhibitors or topoisomerase II (Topo II) inhibitors. To address this issue, the design of Hsp90 dual-target inhibitors can improve efficacy and reduce drug resistance, making it an effective tumor treatment strategy. In this paper, the domain and biological function of Hsp90 are briefly introduced, and the design, discovery and structure-activity relationship of Hsp90 dual inhibitors are discussed, in order to provide reference for the discovery of novel Hsp90 dual inhibitors and clinical drug research from the perspective of medicinal chemistry.

Objective: To explore the differences in the gut microbiota of primary school students with different levels of sugar sweetened beverage intake, so as to provide scientific evidence for better identification of health risks in children and the development of targeted health policies. Methods: In June 2022, a total of 192 healthy primary school students from Chengdu were selected using a stratified cluster random sampling method. The sugar sweetened beverage intake was assessed through a dietary frequency questionnaire. Based on the median daily sugar sweetened beverage intake, primary school students were categorized into a low intake group ( n =96) and a high intake group ( n =96). The gut microbiota in fresh fecal samples from the two groups of primary school students was analyzed using 16S rRNA high throughput sequencing, and the diversity and community structure differences in the gut microbiota were compared. Results: Children in the low intake group had a sugar sweetened beverage intake of (21.3±1.6) mL/d, while the high intake group had an intake of (269.6±37.3) mL/d. Diversity analysis results showed that there were no statistically significant differences between the low intake and the high intake group in terms of α diversity metrics: Observed_otus index [298.50 (259.75, 342.25), 305.50 (244.25, 367.75)], Goods_coverage index [1.00 (1.00, 1.00), 1.00 (1.00, 1.00)], Chao index [304.18 (260.75, 348.78), 305.88 (245.68, 370.88)], Shannon index [5.88 (5.29, 6.45), 5.71 (4.89, 6.28)] and Simpson index [0.95 (0.91, 0.97), 0.94 (0.88, 0.97)] ( Z =-0.64, -0.76, -0.54, -1.76, -1.67, P >0.05). Furthermore, no statistically significant difference was observed in β diversity between the two groups ( R 2=0.006, P >0.05). At the genus level, the abundance of Blautia [0.033 (0.018, 0.055)] and Fusicatenibacter [0.009 (0.005, 0.015)] were higher in the low intake group compared to the high intake group [0.024 (0.013, 0.041),0.006 (0.003, 0.011)]and differences were statistically significant ( Z =-2.52, -2.81, P <0.05). LEfSe analysis highlighted intergroup differences primarily in Blautia, Fusicatenibacter and Sarcina( LDA= 3.56,3.12,3.53, P <0.05). Conclusions There is no significant difference in the diversity and overall structure of the gut microbiota in primary school students with different levels of sugar sweetened beverage intake. However, there are species variations at the genus level. The information can serve as a scientific basis for identifying health risks in primary school students and formulating targeted health strategies.