Tris(2-ethylhexyl) phosphate induces cytotoxicity in TM3 Leydig cells by modulating autophagy and endoplasmic reticulum stress.

Tris (2-ethylhexyl) phosphate (TEHP) is a frequently used organophosphorus flame retardant with significant ecotoxicity and widespread human exposure. Recent research indicates that TEHP has reproductive toxicity. However, the precise cell mechanism is not enough understood. Here, by using testicular mesenchymal stromal TM3 cells as a model, we reveal that TEHP induces apoptosis. Then RNA sequencing analysis, immunofluorescence, and western blotting results show that THEP inhibits autophagy flux and enhances endoplasmic reticulum (ER) stress. Moreover, the activation of the ER stress is critical for TEHP-induced cell injury. Interestingly, TEHP-induced ER stress is contributed to autophagic flux inhibition. Furthermore, pharmacological inhibition of autophagy aggravates, and activation of autophagy attenuates TEHP-induced apoptosis. In summary, these findings indicate that TEHP triggers apoptosis in mouse TM3 cells through ER stress activation and autophagy flux inhibition, offering a new perspective on the mechanisms underlying TEHP-induced interstitial cytotoxicity in the mouse testis.

An ultrasound-activated nanoplatform remodels tumor microenvironment through diverse cell death induction for improved immunotherapy.

Although nanomaterial-based nanomedicine provides many powerful tools to treat cancer, most focus on the "immunosilent" apoptosis process. In contrast, ferroptosis and immunogenic cell death, two non-apoptotic forms of programmed cell death (PCD), have been shown to enhance or alter the activity of the immune system. Therefore, there is a need to design and develop nanoplatforms that can induce multiple modes of cell death other than apoptosis to stimulate antitumor immunity and remodel the immunosuppressive tumor microenvironment for cancer therapy. In this study, a new type of multifunctional nanocomposite mainly consisting of HMME, Fe3+ and Tannic acid, denoted HFT NPs, was designed and synthesized to induce multiple modes of cell death and prime the tumor microenvironment (TME). The HFT NPs consolidate two functions into one nano-system: HMME as a sonosensitizer for the generation of reactive oxygen species (ROS) 1O2 upon ultrasound irradiation, and Fe3+ as a GSH scavenger for the induction of ferroptosis and the production of ROS ·OH through inorganic catalytic reactions. The administration of HFT NPs and subsequent ultrasound treatment caused cell death through the consumption of GSH, the generation of ROS, ultimately inducing apoptosis, ferroptosis, and immunogenic cell death (ICD). More importantly, the combination of HFT NPs and ultrasound irradiation could reshape the TME and recruit more T cell infiltration, and its combination with immune checkpoint blockade anti-PD-1 antibody could eradicate tumors with low immunogenicity and a cold TME. This new nano-system integrates sonodynamic and chemodynamic properties to achieve outstanding therapeutic outcomes when combined with immunotherapy. Collectively, this study demonstrates that it is possible to potentiate cancer immunotherapy through the rational and innovative design of relatively simple materials.

Indispensable biomolecules for plant defense against pathogens: NBS-LRR and "nitrogen pool" alkaloids.

In a complex natural environment, plants have evolved intricate and subtle defense response regulatory mechanisms for survival. Plant specific defenses, including the disease resistance protein nucleotide-binding site leucine-rich repeat (NBS-LRR) protein and metabolite derived alkaloids, are key components of these complex mechanisms. The NBS-LRR protein can specifically recognize the invasion of pathogenic microorganisms to trigger the immune response mechanism. Alkaloids, synthesized from amino acids or their derivatives, can also inhibit pathogens. This study reviews NBS-LRR protein activation, recognition, and downstream signal transduction in plant protection, as well as the synthetic signaling pathways and regulatory defense mechanisms associated with alkaloids. In addition, we clarify the basic regulation mechanism and summarize their current applications and the development of future applications in biotechnology for these plant defense molecules. Studies on the NBS-LRR protein and alkaloid plant disease resistance molecules may provide a theoretical foundation for the cultivation of disease resistant crops and the development of botanical pesticides.

An evaluation of the qualitative superiority of the Mongolian medicinal herb hurdan-tsagaan (Platycodi Radix) from five different geographic origins based on anti-inflammatory effects.

ETHNOPHARMACOLOGICAL RELEVANCE: The contents and types of the active compounds in medicinal herbs depend greatly on their extraction methods, sources of origin and the modes of cultivation. Platycodon grandiflorus (Jacq.) A.DC. is an ethnic medicinal herb widely cultivated in China, and its dried root, Platycodi Radix (PR), is an important ingredient in herbal formulae for attenuating lung issues in Mongolian medical practice. However, research evaluating the superiority of PR based on harvesting regions is relatively limited. AIM: This study aimed to evaluate the qualitative superiority of PR from different regions based on anti-inflammatory effect. MATERIALS AND METHODS: A total of three commercial PR samples were obtained from Anguo, Bozhou and Shangluo, and two wild samples were obtained from Chifeng and Hinggan. PR extract (PRE) was prepared by water distillation, and platycodin D content in the extract was examined by HPLC-UVD. An optimal dose of PRE was administered to BALB/c mice with S. pneumoniae pneumonia, and IL-10 and TNF-α levels in lung tissue were examined by ELISA. HepG2 cells were treated with PRE, and an analysis of differentially expressed gene and functional enrichment was performed using an HTS2 assay. RESULTS: The contents of moisture, total ash, crude extract and platycodin D in the raw roots met the quality control requirements outlined in the Chinese Pharmacopoeia (2020 edition). The platycodin D content in the aqueous extract of the roots in descending order was 24.16% in PRE_Shangluo, 22.91% in PRE_Hinggan, 21.41% in PRE_Bozhou, 17.8% in PRE_Chifeng and 15.92% in PRE_Anguo. Furthermore, administration of PREs at an optimal dose of 2.0 g/kg resulted in some anti-inflammatory effect in mice with Streptococcus pneumoniae pneumonia, among which PRE_Shangluo administration exhibited a more obvious anti-inflammatory impact as shown by a significant decrease in the plasma white cell count (p < 0.05) and IL-10 level elevation and TNF-α reduction in lung tissue (p < 0.05) after treatment. In HepG2 cells treated with 100 µg/ml of each PRE, PRE_Hinggan and PRE_Shangluo resulted in significant differential expression of genes such as nuclear factor kappa B subunit 1 (NFKB1) and significant enrichment of pathways involved in the immune system, such as PI3K-Akt, MAPK and NF-kappa B signaling pathways. CONCLUSIONS: In this study, based on the anti-inflammatory effect, the quality of PR of Shangluo origin was superior to that of PR from the other four regions.

The effect of air temperature on hospital admission of adults with community acquired pneumonia in Baotou, China.

The relationship between air temperature and the hospital admission of adult patients with community-acquired pneumonia (CAP) was analyzed. The hospitalization data pertaining to adult CAP patients (age ≥ 18 years) in two tertiary comprehensive hospitals in Baotou, Inner Mongolia Autonomous Region, China from 2014 to 2018 and meteorological data there in the corresponding period were collected. The exposure-response relationship between the daily average temperature and the hospital admission of adult CAP patients was quantified by using a distributed lag non-linear model. A total of 4466 cases of adult patients with CAP were admitted. After eliminating some confounding factors such as relative humidity, wind speed, air pressure, long-term trend, and seasonal trend, a lower temperature was found to be associated with a higher risk of adult CAP. Compared to 21 °C, lower temperature range of 4 to -12 °C was associated with a greater number of CAP hospitalizations among those aged ≥ 65 years, and the highest relative risk (RR) was 2.80 (95% CI 1.15-6.80) at a temperature of - 10 °C. For those < 65 years, lower temperature was not related to CAP hospitalizations. Cumulative lag RRs of low temperature with CAP hospitalizations indicate that the risk associated with colder temperatures appeared at a lag of 0-7 days. For those ≥ 65 years, the cumulative RR of CAP hospitalizations over lagging days 0-5 was 1.89 (95% CI 1.01-3. 56). In brief, the lower temperature had age-specific effects on CAP hospitalizations in Baotou, China, especially among those aged ≥ 65 years.

Chitosan modifies glycemic levels in people with metabolic syndrome and related disorders: meta-analysis with trial sequential analysis.

BACKGROUND: Chitosan supplementation has been shown to modulate glycemic levels; however, studies have reported conflicting results. The present meta-analysis with trial sequential analysis was conducted to verify the overall influence of chitosan on glycemic levels in patients with metabolic syndrome. METHODS: The PubMed, Cochrane library, and EMBASE databases were systematically searched for randomized controlled studies of chitosan intake and glycemic levels. RESULTS: A total of ten clinical trials including 1473 subjects were included in this meta-analysis. Pooled effect sizes were determined by random-effects meta-analysis. Subgroup analysis was performed to analyze the sources of heterogeneity and their influence on the overall results. The results revealed a significant reduction in fasting glucose levels (SMD: - 0.39 mmol/L, 95% CI: - 0.62 to - 0.16) and hemoglobin A1c (HbA1c) levels (SMD: -1.10; 95% CI: - 2.15 to - 0.06) following chitosan supplementation but no effect on insulin levels (SMD: - 0.20 pmol/L, 95% CI: - 0.64 to 0.24). Subgroup analyses further demonstrated significant reductions in fasting glucose levels in subjects administered 1.6-3 g of chitosan per day and in studies longer than 13 weeks. Trial sequential analysis of the pooled results of the hypoglycemic effect demonstrated that the cumulative Z-curve crossed both the conventional boundary and trial sequential monitoring boundary for glucose and HbA1c. CONCLUSIONS: The glucose level of patients who are diabetic and obese/overweight can be improved by supplementation with chitosan for at least 13 weeks at 1.6-3 g per day. Additional clinical research data are needed to confirm the role of chitosan, particularly in regulating glycosylated hemoglobin and insulin.

Assessing the effects of meteorological factors on daily children's respiratory disease hospitalizations: A retrospective study.

Respiratory disease symptoms in children are aggravated by frequent changes in meteorological conditions. The net effective temperature (NET) integrates temperature, relative humidity, and wind speed as a cooling indicator. This study aims to assess the effect of daily changes in meteorological factors and corresponding NET data on children's hospitalizations for different ages, genders and subtypes of respiratory infections in Baotou, China. Distributed lag non-linear models were constructed to simultaneously assess the exposure-response associations between daily admission counts of children with respiratory diseases and daily NET and other meteorological factors, as well as their lag dependencies. As air pollution significantly affects the respiratory tract, it was considered as confounding factor. In general, the cumulative meteorological factors had greater effects on lower respiratory tract infections than upper respiratory tract infections (RR: temperature [5.21 vs. 2.33], wind speed [4.89 vs. 3.12], and humidity [1.77 vs. 0.97]). The effects of cumulative meteorological factors on female children were greater than those on male children (RR: temperature [2.14 vs. 1.82], wind speed [5.46 vs. 1.90], and humidity [1.60 vs. 1.55]). Temperature and wind speed showed an influence on 4-7-year-old children, but these factors had no influence on other age groups; humidity only showed an influence on the 0-3-year-old group. The NET value had a large effect on lower respiratory infections, in the 4-7-year-old group and female children. In conclusion, a complex non-linear relationship exists between climate variability and children's respiratory diseases. The results of the study can be used to support the development of important meteorological information tools for early warnings of respiratory disease events in children. Concurrently, the NET values can be used for comprehensive assessments of climate change in the future, which will help the government and health authorities better minimize the impacts of children's respiratory diseases.

[Application and analysis of ethnic medicines in "Three Minorities" in Inner Mongolia].

This paper investigates and counts the ethnic medicines of the Ewenki,Daur and Oroqen ethnic groups,which are known as the " Three Minorities" in Inner Mongolia. Through the methods of literature collection,interview investigation,and resource investigation,different ethnic medicines were collected on the main diseases,drug varieties,drug-injection sites,and drug administration methods. Through data statistics and SPSS analysis,the similarities and individual differences between the three ethnic groups were clarified. The results indicated the predicament of the current national medicine,which is helpful for the protection and inheritance of ethnic medicine.

Effects of Four Compounds from Gentianella acuta (Michx.) Hulten on Hydrogen Peroxide-Induced Injury in H9c2 Cells.

In previous studies, Gentianella acuta (Michx.) Hulten was reported to contain xanthones, iridoids, terpenoids, and sterols and is mainly used to cure hepatitis, jaundice, fever, headache, and angina pectoris. In this study, we used bioassay guided fractionation to identify compounds from G. acuta and investigated their activity against hydrogen peroxide (H2O2)-induced apoptosis of H9c2 cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and glutamate-cysteine ligase catalytic (GCLC) expression were assessed using quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was evaluated using western blot. The results showed that all four compounds had protective effects on H9c2 cells. The transcription levels of HO-1 and GCLC significantly increased in H9c2 cells pretreated with norswertianolin (1), swetrianolin (2), demethylbellidifolin (3), and bellidifolin (4). However, compared to the model group, the transcription levels of Nrf2 were not enhanced by pretreatment with compounds 1, 2, and 4. The protein expression levels of HO-1 and GCLC in H9c2 cells were greater than that in the H2O2-treated group, and the expression of Nrf2 was not significantly changed except by swetrianolin treatment; inhibitors can reverse the protective effect by ZnPP (15 µM), BSO (10 µM), and brusatol (10 µM). The results indicated that the four compounds isolated from G. acuta inhibited the oxidative injury induced by H2O2 by activating the Nrf2/ARE pathway in H9c2 cells and provide evidence that G. acuta may be a potential therapeutic agent for the treatment of cardiovascular diseases.

[Status analysis and strategic thinking on Mongolian medicine standardization].

Standardization is the progress of human civilization. It is also an important technical system for normalizing economy and social development and a basic element in the core competitive power of a country. This paper emphasized on the importance of accelerating the standardization of Mongolian medicine for international development of national medicine and improving the international competitiveness. Summed up the Mongolian medicine standardization work achieved the stage results. Achievements on Mongolian medicine standardization were summarized and the existed problems were also analyzed. Such as, imperfect Mongolian medicine standard system and operation mechanism, the lack of application and personnel of Mongolian medicine. Corresponding measures, such as improving the Mongolian medicine standardization system and its support system construction; establishing personnel long-term training mechanism; the establishment of Mongolian medicine standard implementation-promotion-evaluation-feedback mechanism and other corresponding measures, were also provide.

[Ecology suitability study of Cistanche deserticola in Alxa].

The distribution information of Cistanche deserticola was collected by interview investigation and field survey, and 55 related environmental factors were collected, the habitat suitability study was conducted based on geographic information system (GIS) and Maximum entropy model. The AUCs of ROC curve were both above 0.9, indicating that the predictive results with the maxent model were highly precise. The results showed that 14 major environmental factors have obvious influence on ecology suitability distributions of C. deserticola, including vegetation type et al, the suitable distribution areas are mainly concentrated in the central of Alxa Youqi, the north of Alxa Zouqi and the south-east of Ejin Banner, including Tamusu towns, Alateng towns et al, The zoning results basically coincide with the genuine producing areas, and further afford new suitable distribution areas, which can provide reference for the siting of introduction and cultivation of C. deserticola.