Paeoniflorin Alleviates Anxiety and Visceral Hypersensitivity via HPA Axis and BDNF/TrkB/PLCγ1 Pathway in Maternal Separation-induced IBS-like Rats.

BACKGROUND: Irritable Bowel Syndrome (IBS) is a prevalent gastrointestinal disorder that significantly diminishes the quality of life for affected individuals. The pathophysiology of IBS remains poorly understood, and available therapeutic options for IBS are limited. The crucial roles of brain-gut interaction, which is mediated by the Hypothalamic-Pituitary-Adrenocortical (HPA) axis and the autonomic nervous system in IBS, have attracted increasing attention. OBJECTIVE: The objective of this study was to examine the impact of paeoniflorin (PF) on anxiety and visceral hypersensitivity in maternal separation-induced IBS-like rats. METHODS: The IBS-like rat model was established through the implementation of Maternal Separation (MS) and subsequently subjected to various doses of PF administered via oral gavage for 14 days. Anxiety-like behavior was evaluated using the Open Field Test (OFT) and Elevated Plus Maze (EPM) test. The assessment of visceral sensitivity involved the utilization of the Abdominal Withdrawal Reflex (AWR) score and electromyographic (EMG) responses of the external oblique muscle in response to colorectal distention. The levels of adrenocorticotropic hormone (ACTH), corticosterone (CORT), and corticotrophin-releasing hormone (CRH) were examined by ELISA. Quantitative real-time PCR (qRT-PCR) and immunofluorescence were employed to detect the expressions of CRH receptors 1 (CRHR1) and 2 (CRHR2). Glucocorticoid receptors (GR), mineralocorticoid receptor (MR), brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TrkB), and phospholipase C γ1 (PLCγ1) were examined by Western blot. RESULTS AND DISCUSSION: The results showed that MS induced anxiety-like behavior and visceral hypersensitivity, while PF treatment attenuated these changes. Furthermore, the HPA axis hyperactivity in MS rats was attenuated by PF treatment, indicated by reduced serum ACTH, CORT, and CRH levels and recovered hippocampal CRHR1 and GR expressions. In addition, PF inhibited BDNF/TrkB signaling by downregulating the protein levels of BDNF, TrkB, and phospho-PLCγ1 in the colon. CONCLUSION: These findings suggest that PF alleviated anxiety and visceral hypersensitivity in MS-induced IBS-like rats, which may be the modulation of HPA axis activity and BDNF/TrkB/PLCγ1 signaling pathway.

Microneedle-assisted dual delivery of PUMA gene and celastrol for synergistic therapy of rheumatoid arthritis through restoring synovial homeostasis.

Abnormal proliferation of aggressive fibroblast-like synoviocytes (FLS) and perpetuate synovial inflammation can inevitably accelerate the progression of rheumatoid arthritis (RA). Herein, a strategy of simultaneously promoting FLS apoptosis and inhibiting inflammation as mediated by macrophages is proposed to restore synovial homeostasis for effective RA therapy. A hyaluronic acid-based dissolvable microneedle (MN) is fabricated for transdermal delivery of dual human serum albumin (HSA)-contained biomimetic nanocomplexes to regulate RA FLS and macrophages. Upon skin insertion, dual nanocomplexes are released rapidly from the MN and accumulate in RA joint microenvironment through both passive and active targeting as mediated by HSA. Thioketal-crosslinked fluorinated polyethyleneimine 1.8 K (TKPF) was constructed to bind the plasmid encoding pro-apoptotic gene PUMA with HSA coating layer (TKPF/pPUMA@HSA, TPH). TPH nanocomplexes can upregulate PUMA through RA FLS transfection to trigger efficient apoptosis. Also, HSA nanocomplexes encapsulating the classic anti-inflammatory natural product celastrol (Cel@HSA, CH) can inhibit inflammation of macrophages through blocking NF-κB pathway activation. TPH/CH MN can deplete RA FLS and inhibit M1 macrophage activation, suppress synovial hyperplasia as well as reduce bone and cartilage erosion in a collagen-induced arthritis (CIA) mouse model, demonstrating a promising strategy for efficient RA treatment.

Estimating the water quality index based on interpretable machine learning models.

The water quality index (WQI) is an important tool for evaluating the water quality status of lakes. In this study, we used the WQI to evaluate the spatial water quality characteristics of Dianchi Lake. However, the WQI calculation is time-consuming, and machine learning models exhibit significant advantages in terms of timeliness and nonlinear data fitting. We used a machine learning model with optimized parameters to predict the WQI, and the light gradient boosting machine achieved good predictive performance. The machine learning model trained based on the entire Dianchi Lake water quality data achieved coefficient of determination (R2), mean square error, and mean absolute error values of 0.989, 0.228, and 0.298, respectively. In addition, we used the Shapley additive explanations (SHAP) method to interpret and analyse the machine learning model and identified the main water quality parameter that affects the WQI of Dianchi Lake as NH4+-N. Within the entire range of Dianchi Lake, the SHAP values of NH4+-N varied from -9 to 3. Thus, in future water environmental governance, it is necessary to focus on NH4+-N changes. These results can provide a reference for the treatment of lake water environments.

A design of a nature-like fishway to solve the fractured river connectivity caused by small hydropower based on hydrodynamics and fish behaviors.

Achieving a harmonious alignment between the biological characteristics of fish and hydrodynamics patterns is crucial for ensuring the efficacy of fish passage facilities. In this study, based on the hydrodynamic characteristics of the river and the biological characteristics of fish, we evaluated the internal flow field in the nature-like fishway of Congen II hydropower station located along the Chabao river and explored methods to improve the operation efficiency. Based on comprehensive considerations of the flow field, turbulent kinetic energy, and the migration pathways of fish, it is found that the implementation of a continuous oblique bottom slope represents a more cost-effective and operationally convenient solution. The influence of different permutation of bulkheads in the nature-like fishway on operational efficiency was further examined. Our investigation revealed that the nature-like fishway with the continuous slope of 2% and the arrangement of three bulkheads in each row (model 3) exhibited a relatively simple velocity distribution and linear flow line, which poses challenges for fish in locating resting areas. In addition, the distribution of low turbulence kinetic energy area in the mainstream made it less favorable for fish to transition from the mainstream to the rest area within the fishway. The nature-like fishway with the continuous slope of 2% and the arrangement of two or three bulkheads in staggered rows (model 4) demonstrated better performance. Several potential fish migration routes for both model 3 and model 4 were proposed based on the numerical simulation results. In model 3, fish exhibited a continuous sprint through the concentrated high-speed area, which was less favorable for fish to rest and forage. In contrast, model 4 exhibited a diversified flow velocity distribution, enabling fish to make timely changes in their direction during migration. This feather proved to be advantageous in enhancing fish migration within the passage. The design of nature-like fishway in this study provides an important reference and technical support for the construction and optimization of the nature-like fishway for low dams, and is of great significance for restoring river connectivity destroyed by small hydropower construction and improving fish migration.

Conflict between urbanization and water environmental protection: Lessons from the Xiangjiang River Basin in China.

China, the largest developing country, has experienced rapid urbanization since its reform and opening-up. However, the increasing pollution load from urban areas has deteriorated urban river water quality, contradicting the concept of sustainable and green development promoted by the Chinese government. This situation elucidates governmental shortcomings in systematic environmental protection. Our study revealed that the current wastewater treatment plant (WWTP) discharge standards in urban areas are insufficient for attaining the desired urban river water quality and thus intensify the conflict between urbanization and water environmental protection. As urbanization continues, the urban population will grow, further exacerbating pollution and conflict. Our focus was the Xiangjiang River basin in Zunyi, a typical urbanized city in China. Using a validated one-dimensional mathematical model, we compared the water quality in the Xiangjiang River between current and upgraded WWTP discharge standards. The results showed that the water quality in the Xiangjiang River falls short of the standards, with more than 60 % of the river exceeding limits. However, upgrading WWTP discharge standards significantly reduces the proportion of river sections exceeding limits, with only 0.4 % exceeding standards during specific periods. This enhancement greatly improved the Xiangjiang River's water quality, aided in restoring the entire water environment in the basin, and supported water environmental protection goals. Our research findings offer crucial support for local governments in shaping comprehensive water environmental protection policies and insights for addressing similar environmental challenges caused by rapid urbanization in other developing regions.

Nomogram and Web Calculator Based on Lasso-Logistic Regression for Predicting Persistent Organ Failure in Acute Pancreatitis Patients.

Purpose: Acute pancreatitis is a common gastrointestinal emergency. Approximately 20% of patients with acute pancreatitis develop organ failure, which is significantly associated with adverse outcomes. This study aimed to establish an early prediction model for persistent organ failure in acute pancreatitis patients using 24-hour admission indicators. Patients and Methods: Clinical data and 24-h laboratory indicators of patients diagnosed with acute pancreatitis from January 1, 2017 to January 1, 2022 in Shanxi Bethune Hospital were collected. Patients from 2017 to 2021 were used as the training cohort to establish the prediction model, and patients from 2021 to 2022 were used as the validation cohort. Univariate logistic regression and LASSO regression were used to establish prediction models. The performance of the model was evaluated using area under the curve (AUC), calibration curves, and decision curve analysis (DCA), and subsequently validated in the validation group. Results: A total of 1166 patients with acute pancreatitis were included, a total of 145 patients suffered from persistent organ failure from 2017 to 2021. Data were initially selected for 100 variables, and after inclusion and exclusion, 46 variables were used for further analysis. Two prediction models were established and nomogram was drawn respectively. After comparison, the prediction values of the two models were similar (The univariate model AUC was 0.867, 95% CI (0.834-0.9). The LASSO model AUC was 0.864, 95% CI (0.828-0.895)), and the model established by LASSO regression was more parsimonious. A web calculator was developed using the model established by LASSO. Conclusion: Predictive model including 6 risk indicators can be used to predict the risk of persistent organ failure in patients with acute pancreatitis.

Effect of total dissolved gas supersaturation and flow velocity on survival and swimming ability of juvenile Schizothorax prenanti.

Although developing large-scale hydropower cascades in the upper Yangtze River effectively improves the hydropower resource utilization, it produces total dissolved gas (TDG) supersaturation. In the flood season, the high level of TDG supersaturation (TDGS) frequently occurs in the downstream of dams, causing migratory fish to suffer from gas bubble trauma (GBT) and reducing their survival and swimming ability. Currently, there is a deficiency in particular approaches to evaluate the ecological hazard posed by TDGS on migratory fish as they traverse different flow velocities within their migratory routes. This study assessed the vulnerability of juvenile Schizothorax prenanti (S. prenanti) to GBT from the static setting to 9.0 BL/s during exposure to nominal levels of 100%, 110%, 120% and 130% TDG. The mortality occurs when the flow velocity surpasses 6.0 and 7.5 BL/s in 100% and 110% TDG levels, respectively. For fish exposed to 120% and 130% TDG levels, the relationship between survival time and flow velocity is an approximately inverse bell-shaped curve with increasing velocity. The optimal velocity of maximal survival time of juvenile S. prenanti is 3.0 and 4.5 BL/s in 120% and 130% TDG-supersaturated water. Both TDG level and flow velocity significantly affect burst swimming speed (Uburst) and critical swimming speed (Ucrit). The cases involving GBT showed substantial declines in Uburst and Ucrit, exceeding 6.0 BL/s and TDG levels greater than 120%. The results may contribute to formulating a specific management strategy for hydropower operation during the migratory period and conserving vulnerable species in the Yangtze River.

Reactive oxygen species and nitric oxide scavenging nanoparticles alleviating rheumatoid arthritis through adjusting the seeds and growing soils.

Normalizing inflamed soils including reactive oxygen species (ROS), nitric oxide (NO), cell-free DNA, and regulating inflammation-related seeds such as macrophages, neutrophils, fibroblasts, represent a promising strategy to maintain synovial tissue homeostasis for rheumatoid arthritis (RA) treatment. Herein, ROS scavenging amphiphilic block copolymer PEGylated bilirubin and NO-scavenging PEGylated o-phenylenediamine were fabricated to self-assemble into a dually responsive nanoparticle loaded with JAK inhibitor notopterol (Not@BR/oPDA-PEG, NBOP NPs). The simultaneous ROS and NO depletion combined with JAK-STAT pathway inhibition could not only promote M2 polarization to reduce further ROS and NO generation, but also decrease cytokines and chemokines to prevent immune cell recruitment. Specifically, NBOP NPs responded to high level ROS and NO, and disintegrated to release notopterol in inflamed joints as the hydrophobic heads BR and oPDA were transformed into hydrophilic ones. The released notopterol could inhibit the JAK-STAT pathway of inflammatory cells to reduce the secretion of pro-inflammatory cytokines and chemokines. This strategy represented an effective way to regulate RA soils and seeds through breaking the positive feedback loop of inflammation aggravation, achieving an excellent anti-RA efficacy in a collagen-induced arthritis rat model. Taken together, our work offered a reference to adjust RA soils and seeds for enhanced RA treatment.

Cognitive status and its risk factors in patients with hypertension and diabetes in a low-income rural area of China: A cross-sectional study.

OBJECTIVES: The proportion of older people with dementia in China is gradually increasing with the increase in the aging population over recent years. Hypertension and diabetes are common non-communicable diseases among rural populations in China. However, it remains unclear whether these conditions affect the occurrence and development of cognitive impairment as there is limited research on cognitive status and its risk factors among residents of rural areas. METHODS: A multi-stage stratified cluster random sampling method was used to select 5400 participants from rural permanent residents. A self-designed structured questionnaire was used to investigate demographic data of the participants. Cognitive function was assessed using the Montreal Cognitive Function Assessment Scale (MoCA). The results were analyzed using chi-square test, ANOVA and multiple linear regression analysis. RESULTS: A total of 5028 participants returned the survey, giving a response rate of 93.1%. Higher education (odds ratio (OR) = 3.2, 95% confidence interval (CI) 2.87-3.54, p < 0.001), higher income (OR = 1.61, 95% CI 1.16-2.07, p < 0.001), and dietary control (OR = 0.66, 95%CI 0.34-0.98, p < 0.001) were protective factors. A visual representation of the relationship between annual income and MoCA score showed an inverted U-curve, the group with an annual income of 6000-7999 RMB had a maximum OR of 1.93 (95%CI 0.12-2.74, p < 0.001). While difficulty in maintaining sleep were risk factors for cognitive impairment (OR = -2.28, 95% CI-4.18-0.39, p = 0.018). CONCLUSIONS: Participants with middle incomes had better cognitive status than those with the highest incomes. Higher education, proper diet control and good sleep are beneficial to the cognitive status of residents in rural areas.

BPDE-DNA adduct formation and alterations of mRNA, protein, and DNA methylation of CYP1A1, GSTP1, and GSTM1 induced by benzo[a]pyrene and the intervention of aspirin in mice.

Benzo[a]pyrene (B[a]P), one typical environmental pollutant, the toxicity mechanisms, and potential prevention remain perplexing. Available evidence suggests cytochrome P450 1A1 (CYP1A1) and glutathione S-transferases (GSTs) metabolize B[a]P, resulting in metabolic activation and detoxification of B[a]P. This study aimed to reveal the impact of B[a]P exposure on trans-7,8-diol-anti-9,10-epoxide DNA (BPDE-DNA) adduct formation, level of CYP1A1, glutathione S-transferase pi (GSTP1) and glutathione S-transferase mu1 (GSTM1) mRNA, protein and DNA methylation in mice, and the potential prevention of aspirin (ASP). This study firstly determined the BPDE-DNA adduct formation in an acute toxicity test of a large dose in mice induced by B[a]P, which subsequently detected CYP1A1, GSTP1, and GSTM1 at levels of mRNA, protein, and DNA methylation in the organs of mice in a subacute toxicity test at appropriate doses and the potential prevention of ASP, using the methods of real-time quantitative PCR (QPCR), western blotting, and real-time methylation-specific PCR (MSP), respectively. The results verified that B[a]P induced the formation of BPDE-DNA adduct in all the organs of mice in an acute toxicity test, and the order of concentration of which was lung > kidney > liver > brain. In a subacute toxicity test, following B[a]P treatment, mice showed a dose-dependent slowdown in body weight gain and abnormalities in behavioral and cognitive function and which were alleviated by ASP co-treatment. Compared to the controls, following B[a]P treatment, CYP1A1 was significantly induced in all organs in mice at mRNA level (P < 0.05), was suppressed in the lung and cerebrum of mice at protein level, and inhibited at DNA methylation level in the liver, lung, and cerebrum, whereas GSTP1 and GSTM1 at mRNA, protein, and DNA methylation levels showed organ-specific changes in mice following B[a]P treatment, which was generally alleviated by ASP intervention. In conclusion, B[a]P induced BPDE-DNA adduct formation in all organs in mice and altered the mRNA, protein, and DNA methylation levels in CYP1A1, GSTP1, and GSTM1 in an organ-dependent pattern, which could be related to the organ toxicity and mechanism of B[a]P. ASP intervention may be an effective measure to prevent B[a]P toxicity. The findings provide scientific evidence for further study on the organ toxicity and mechanisms of B[a]P.

Restoration of a fish-attracting flow field downstream of a dam based on the swimming ability of endemic fishes: A case study in the upper Yangtze River basin.

The construction of fish passage facilities can mitigate the negative effects of dams and other water engineering construction on river connectivity and have a significant positive effect on the conservation of local fish diversity. To attract target fishes into fish passage facilities effectively, the optimal flow velocity range to attract fish must be determined. Three local endemic species of the Mishi Reservoir were considered as the protection targets. However, their swimming abilities remain unclear. Therefore, the induced swimming speed (Uind), critical swimming speed (Ucrit) and burst swimming speed (Uburst) of three fish species were tested. Based on these results, we identified the optimal flow velocity to attract fish, which falls within the range of 0.15-0.51 m/s. A validated three-dimensional hydrodynamic model was used to simulate different schemes. By comparing the flow field simulation results of different schemes, we obtained the optimal measure to restore the flow field, namely, a multiple engineering measure combining increased the fish attraction flow in the fish collection pond and the construction of a spur dike. This study offers a solution for the specific case and enhances the database of swimming characteristics of endemic fish in the upstream reaches of the Yangtze River. It also provides a valuable reference for designing fish-attracting flows and potential measures for restoring flow fields in similar future projects.

[Pharmacokinetics and tissue distribution of four alkaloids in Ermiao Pills and Sanmiao Pills in normal and arthritic model rats].

This work aimed to investigate the differences of pharmacokinetics and tissue distribution of four alkaloids in Ermiao Pills and Sanmiao Pills in normal and arthritic model rats. The rat model of arthritis was established by injecting Freund's complete adjuvant, and ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) in the positive ion multiple reaction monitoring(MRM) mode was used for the determination of four alkaloids in plasma and tissues of normal and arthritic rats after administration of Ermiao Pills and Sanmiao Pills, respectively. The differences in pharmacokinetics and tissue distribution of the four active components were compared, and the effect of Achyranthis Bidentatae Radix on the major components of Sanmiao Pills was explored. This study established an UPLC-MS/MS for simultaneous determination of four alkaloids, and the specificity, linearity, accuracy, precision, and stability of this method all met the requirements. Pharmacokinetics study found that as compared with normal rats, the AUC and C_(max) of phellodendrine, magnoflorine, berberine and palmatine in model rats were significantly decreased after administration of Ermiao Pills, the clearance rate CL/F was significantly increased, and the distribution and tissue/plasma concentration ratio of the four alkaloids in the liver, kidney, and joint were significantly reduced. Achyranthis Bidentatae Radix increased the AUC of phellodendrine, berberine, and palmatine, reduced the clearance rate, and significantly increased the distribution of the four alkaloids in the liver, kidney, and joints in arthritic rats. However, it had no significant effect on the pharmacokinetics and tissue distribution of the four alkaloids in normal rats. These results suggest that Achyranthis Bidentatae Radix may play a guiding role in meridian through increasing the tissue distribution of effective components in Sanmiao Pills under arthritis states.

Quantitative assessment methodology framework of the impact of global climate change on the aquatic habitat of warm-water fish species in rivers.

Global climate change (GCC), with global warming as the main characteristic, has become a global issue widely concerned by people. GCC impacts the hydrological regime at the watershed scale and affects the hydrodynamic force and the habitat conditions of freshwater ecosystems at the river scale. The impact of GCC on water resources and the water cycle is a research hotspot. However, there are few studies on water environment ecology related to hydrology and the influence of changes in discharge and water temperature on warm-water fish habitats. This study proposes a quantitative assessment methodology framework for predicting and analyzing the impact of GCC on the warm-water fish habitat. This system integrates GCC, downscaling, hydrological, hydrodynamic, water temperature and habitat models and was applied to the middle and lower reaches of the Hanjiang River (MLHR), where there are four major Chinese carps resource reduction problems. The results showed that the calibration and validation of the statistical downscaling model (SDSM) and the hydrological, hydrodynamic, and water temperature models were carried out using the observed meteorological factors, discharge, water level, flow velocity and water temperature data. The change rule of the simulated value was in good agreement with the observed value, and the models and methods used in the quantitative assessment methodology framework were applicable and accurate. The rise of water temperature caused by GCC will ease the problem of low-temperature water in the MLHR, and the weighted usable area (WUA) for spawning of the four major Chinese carps will appear in advance. Meanwhile, the increase in future annual discharge will play a positive role in WUA. In general, the rise in confluence discharge and water temperature caused by GCC will increase WUA, which is beneficial to the spawning ground of four major Chinese carps.

Effect of the Reelin-Dab1 signaling pathway on the abnormal metabolism of Aß protein induced by aluminum.

Aluminum (Al) is a common neurotoxic element that can exacerbate intracellular ß-amyloid (Aß) deposition. Reelin is a highly conserved extracellular glycoprotein that is involved in intracellular Aß deposition. However, the action of Reelin on aluminum-induced Aß deposition is not fully understood. Here, we investigated the effects of the Reelin-Dab1 signaling pathway on Aß deposition in aluminum maltol (Al(mal)3) exposure in rat pheochromocytoma-derived cells (PC12). Our results showed that Al(mal)3 exposure decreased activity of PC12, increased expression of Aß42, and decreased expression of Aß40. Moreover, Al(mal)3 exposure in PC12 induced Reelin-Dab1 signaling pathway-associated proteins changed, decreased expression of Reelin and Dab1, and increased expression of pdab1. Moreover, the expression of Reelin, Dab1, and Aß40 was found to be elevated in PC12 exposed to Al(mal)3 and corticosterone compared to those exposed to Al(mal)3. Also, the expression of Reelin, Dab1, and Aß40 was found to be depressed in PC12 exposed to Al(mal)3 and streptozotocin compared with cells exposed to Al(mal)3 alone. These results suggested that Al(mal)3 inhibits the expression of the Reelin-Dab1 signaling pathway, promoting Aß deposition. Thus, our findings provided important evidence to better understand how the Reelin-Dab1 signaling pathway may be a potential mechanism of Aß deposition induced by aluminum.

Determining the position of a fish passage facility entrance based on endemic fish swimming abilities and flow field.

Hydropower development can significantly mitigate climate change and reduce carbon emissions, but it can also have substantial negative impacts on river environments and fish biodiversity. Fish passage facilities are built to ensure sustainable hydropower development and the biodiversity of fish populations. The locations of the entrances to these facilities play a key role in their efficiency. This study presents a reliable approach that combines the swimming ability of fish and a numerical flow field simulation to determine the optimal location for a fish passage facility entrance. In this study, we used the Gujun Reservoir upstream of the Yangtze River as a case study. A field experiment was conducted, and the swimming abilities of eight endemic fish species in the upstream region of the Yangtze River were measured. Among the tested species, the fastest induced swimming speed (0.14 m/s) was achieved by Glyptothorax sinense, while the slowest critical swimming speed (0.30 m/s) was observed for Paracobitis potanini. We propose that the velocity near the fish passage facility entrance should be higher than the maximum induced swimming speed and lower than the minimum critical swimming speed, making the suitable range between 0.14 and 0.30 m/s. On this basis, velocity fields 500 m downstream of the dam of the Gujun Reservoir under 4 operating conditions with discharge flows of 5.7 m3/s, 23.3 m3/s, 32.5 m3/s, and 41.1 m3/s were calculated. The results showed that the flow field variation downstream of the dam was between 0.1 and 0.9 m/s. After comparing the suitable areas for the target species, the left bank at location 2 was recommended as the optimal location for the fish passage facility entrance in the Gujun Reservoir.

Knowledge, attitude, and practice of hypertension prevention and control among rural residents in Shanxi Province / 预防医学

Objective@#To investigate the current status and influencing factors of knowledge, attitude, and practice of hypertension prevention and control among rural residents in Shanxi Province, so as to provide insights into implementation of health education pertaining to hypertension control in rural areas. @*Methods@#A total of 7 403 residents were sampled using a multi-stage cluster random sampling method from rural areas of Yangqu, Daning, and Yonghe counties of Shanxi Province from November 2020 to July 2021 for face-to-face questionnaire surveys and physical examinations. Residents' basic characteristics, knowledge, attitude, and practice of hypertension prevention and control, and height, weight, blood pressure were collected, and factors affecting knowledge, attitude, and practice of hypertension prevention and control were identified using a generalized linear model. @*Results@#A total of 7 403 questionnaires were allocated, and 7 031 effective questionnaires were recovered, with an effective response rate of 94.98%. The respondents included 3 035 men (43.17%) and 3 996 women (56.83%), and had a mean age of (58.45±13.75) years. The median scores of hypertension prevention and control knowledge, attitude and practice were 5 (interquartile range, 4), 16 (interquartile range, 5) and 14 (interquartile range, 7) points, with scoring percentages of 48.40%, 80.55% and 54.41%, respectively. Generalized linear model analysis showed that an educational level of junior high school and above, annual family income per capita of ≥4 000 RMB, family history of hypertension, development of hypertension among family members or friends, overweight/obesity and presence of depression resulted in high scores for hypertension prevention and control knowledge; annual family income per capita of ≥10 000 RMB, family history of hypertension, presence of hypertension among family members or friends, mild/severe insomnia and presence of depression resulted in high scores for hypertension prevention and control attitude, while age of ≥65 years and blood pressure of ≥140/≥90 mmHg resulted in low scores for attitude; females, age of ≥45 years, an educational level of junior high school and above, blood pressure of ≥140/≥90 mmHg, family history of hypertension, presence of hypertension among family members or friends and overweight/obesity resulted in high scores for hypertension prevention and control practice, and residents had a low body weight had a low score for practice (all P<0.05).@*Conclusions@#The hypertension prevention and control attitude is satisfactory among rural residents in Shanxi Province; however, the hypertension prevention and control knowledge and practice are poor. Health education pertaining to hypertension prevention and control should be strengthened, and personalized health education is needed targeting individuals with a low educational level and low income.

Development and validation of a nomogram for predicting Mycoplasma pneumoniae pneumonia in adults.

The study aimed to explore predictors of Mycoplasma pneumoniae pneumonia (MPP) in adults and develop a nomogram predictive model in order to identify high-risk patients early. We retrospectively analysed the clinical data of a total of 337 adult patients with community-acquired pneumonia (CAP) and divided them into MPP and non-MPP groups according to whether they were infected with MP. Univariate and multivariate logistic regression analyses were used to screen independent predictors of MPP in adults and to developed a nomogram model. Receiver operating characteristic (ROC) curve, calibration curve, concordance index (C-index), and decision curve analysis (DCA) were used for the validation of the evaluation model. Finally, the nomogram was further evaluated by internal verification. Age, body temperature, dry cough, dizziness, CRP and tree-in-bud sign were independent predictors of MPP in adults (P < 0.05). The nomogram showed high accuracy with C-index of 0.836 and well-fitted calibration curves in both the training and validation sets. The area under the receiver operating curve (AUROC) was 0.829 (95% CI 0.774-0.883) for the training set and 0.847 (95% CI 0.768-0.925) for the validation set. This nomogram prediction model can accurately predict the risk of MPP occurrence in adults, which helps clinicians identify high-risk patients at an early stage and make drug selection and clinical decisions.

Reactive oxygen species activated by mitochondria-specific camptothecin prodrug for enhanced chemotherapy.

Camptothecin (CPT) has attracted much attention due to its potent antitumor activities. However, the undesirable physicochemical properties, including poor water-solubility, unstable lactone ring and severe adverse effects limit its further application. In this study, two water-soluble prodrugs, CPT-lysine (CPTK) and CPT-arginine (CPTR), were designed and synthesized by conjugating lysine or arginine with CPT, improving its solubility, pharmacokinetic properties and tumor penetration. Importantly, the introduction of arginine into CPTR contributed to the mitochondria-specific delivery, which increased mitochondrial reactive oxygen species (ROS) generation, induced mitochondria dysfunction and enhanced cell apoptosis and in vivo anti-cancer effect. This strategy is believed to hold great potential for organelle-specific synergistic anti-tumor therapy.

River habitat assessment and restoration in high dam flood discharge systems with total dissolved gas supersaturation.

The success of river habitat restoration relies on accurate assessment proxies. However, determining how to quantitatively assess the impact of multiple stressors during flood discharge from high dams in riverine ecosystems and where and how to implement more reliable recovery interventions remain challenges. Here, we developed a bottom-up mechanistic framework for assessing the effects of total dissolved gas supersaturation (TDGS) and hydrodynamics on fish habitat quality and applied it to the downstream river reach of the Xiangjiaba Dam in Southwest China. The results showed that the available habitat area of river sturgeon was the smallest, while Chinese sucker had the largest available habitat area among the three target species under all discharge scenarios. Although the TDGS levels were evenly mixed laterally, the habitat suitability index indicated that the suitable habitats were primarily within both sides of the river reach under all scenarios, which is contrary to findings based on the traditional TDGS risk assessment model. The traditional TDGS risk assessment model overestimates the impact of dams on habitats. This divergence reflected the sensitivity of the habitat assessment to fish habitat preferences, fish tolerance to TDGS and the biological response of fish under TDGS. Additionally, the priority areas for restoration can be identified by habitat suitability index with lower values. We simulated twenty-four schemes and found that interventions such as stone groups, ecological spur dike, water-retaining weir and river dredging can enhance habitat suitability for fish species under multiple stressors, providing novel insights into where and how to mitigate the impact of TDGS. Our findings offer a transferable framework for the quantitative evaluation of fish habitat and implementation of restoration management during dam flood discharge periods, thus providing a new perspective for biodiversity conservation and habitat restoration in dam-regulated rivers with TDGS around the world.

Swimming performance of a pelagic species in the Yangtze River under different exposure modes of the total dissolved gas supersaturation.

During flood discharges of upstream dams in the Yangtze River, the pelagic fish have a stress risk from total dissolved gas (TDG) supersaturation in the river water. This study took the silver carp as the object and systematically evaluated the effects of TDG supersaturation levels and exposure time on their critical swimming speed (Ucrit) at different temperatures. The external symptoms of gas bubble disease were found when TDG levels exceeded 130%. Both exposure time and TDG level did not significantly impact the Ucrit of fish under 6 days of non-lethal exposure (110%, 120%, 130% TDG) with lower or higher water temperature. Significant differences in Ucrit were found among different exposure times at 11.0 ± 1.0°C under 10 hours of lethal exposure (135%, 140%, 150% TDG) and the Ucrit reduced by 59.88%, 83.32%, and 92.40%, respectively. TDG level had a significant impact on the Ucrit at 21.0 ± 1.0°C when exposure time exceeded 8 hours. Ucrit at 21.0 ± 1.0°C water were significantly greater than those at 11.0 ± 1.0°C water where conditions had the same TDG supersaturation and exposure time. Differences in Ucrit between temperatures ranged from 3.24 to 6.12 BL/s under non-lethal exposure and from 6.38 to 13.88 BL/s under lethal exposure. The results of this study can provide a reference for fish conservation during flood discharge.