Baicalin nanodelivery system based on functionalized metal-organic framework for targeted therapy of osteoarthritis by modulating macrophage polarization.

Intra-articular drugs used to treat osteoarthritis (OA) often suffer from poor pharmacokinetics and stability. Nano-platforms as drug delivery systems for drug delivery are promising for OA therapy. In this study, we reported an M1 macrophage-targeted delivery system Bai@FA-UIO-66-NH2 based on folic acid (FA) -modified metal-organic framework (MOF) loaded with baicalin (Bai) as antioxidant agent for OA therapy. With outstanding biocompatibility and high drug loading efficiency, Bai@FA-UIO-66-NH2 could be specifically uptaken by LPS-induced macrophages to serve as a potent ROS scavenger, gradually releasing Bai at the subcellular level to reduce ROS production, modulate macrophage polarization to M2, leading to alleviation of synovial inflammation in OA joints. The synergistic effect of Bai@FA-UIO-66-NH2 on macrophage polarization and ROS scavenging significantly improved the therapeutic efficacy of OA, which may provide a new insight into the design of OA precision therapy.

Mitochondrial-targeting Mn3O4/UIO-TPP nanozyme scavenge ROS to restore mitochondrial function for osteoarthritis therapy.

Excessive reactive oxygen species (ROS)-induced mitochondrial damage has impact on osteoarthritis (OA). Nanozyme mimics as natural enzyme alternatives to scavenge excessive ROS has offered a promising strategy for OA therapy. Herein, we reported a novel mitochondrial-targeting Mn3O4/UIO-TPP nanozyme using metal-organic frameworks with loaded Mn3O4 as the enzyme-like active core combining mitochondria-targeting triphenylphosphine (TPP) groups to serve as ROS scavengers for therapy of OA. With sequential catalysis of superoxide dismutase-like, catalase (CAT)-like, and hydroxyl radical (·OH) scavenging potentials, the nanozyme can target mitochondria by crossing subcellular barriers to effectively eliminate ROS to restore mitochondrial function and inhibit inflammation and chondrocyte apoptosis. It also has favorable biocompatibility and biosafety. Based on anterior cruciate ligament transection-induced OA joint models, this mitochondrial-targeting nanozyme effectively mitigated the inflammatory response with the Pelletier score reduction of 49.9% after 8-week therapy. This study offers a prospective approach to the design of nanomedicines for ROS-related diseases.

Remote sensing inversion and prediction of land use land cover in the middle reaches of the Yangtze River basin, China.

Land use and land cover (LULC) changes are dynamic and have been extensively studied; the change in LULC has become a crucial factor in decision making for planners and conservationists owing to its impact on natural ecosystems. Deriving accurate LULC data and analyzing their changes are important for assessing the energy balance, carbon balance, and hydrological cycle in a region. Therefore, we investigated the best classification method from the four methods and analyzed the change in LULC in the middle Yangtze River basin (MYRB) from 2001 to 2020 using the Google Earth Engine (GEE). The results suggest that (1) GEE platform enables to rapidly acquire and process remote sensing images for deriving LULC, and the random forest (RF) algorithm was able to calculate the highest overall accuracy and kappa coefficient (KC) of 87.7% and 0.84, respectively; (2) forestland occupied the largest area from 2001 to 2020, followed by water bodies and buildings. During the study period, there was a significant change in area occupied by both water bodies (overall increase of 46.2%) and buildings (decrease of 14.3% from 2001 to 2005); and (3) the simulation of LULC in the MYRB area was based on the primary drivers in the area, of which elevation changes had the largest effect on LULC changes. The patch generated land use simulation model (PLUS) was used to produce the simulation, with an overall accuracy and KC of 89.6% and 0.82, respectively. This study not only was useful for understanding the spatial and temporal characteristics of LULC in the MYRB, but also offered the basis for the simulation of ecological quality in this region.

Evaluation of water resource carrying capacity in the middle reaches of the Yangtze River Basin using the variable fuzzy-based method.

The middle reaches of Yangtze River Basin (MYRB) are rich in water resources, with a large number of rivers and lakes. However, in recent years, water resources from this basin are no longer sufficient to support the region's rapid economic development. This study established a model to evaluate the water resource carrying capacity incorporating water resources, population, and socio-economic data. The characteristic values of water resource carrying capacity were calculated using the variable fuzzy evaluation method in MYRB from 2005 to 2020. Although both population and GDP in the MYRB showed an increasing trend between 2005 and 2020, the water supply capacity increased and then decreased. The weights of each index for evaluating the water resource carrying capacity of perennial botanical gardens were as follows: degree of water resource development (0.311) > total water resources (0.24) > population density (0.156) > GDP per capita (0.097) > water resources per capita (0.077) > water supply per capita (0.064) > water resources per unit area (0.055). Furthermore, the water resource carrying capacity in the MYRB showed an increasing trend from 2005 to 2020. In 2020, the carrying capacity of water resources in Changsha, Jingmen, Xiangtan, Hengyang, Wuhan, Xiaogan, Nanyang, and Xiangyang was attributed an evaluation grade of level 3, which indicates that the development and utilization of water resources in these areas were at their saturation point.

Changes in the water environment and its major driving factors in Poyang Lake from 2016 to 2019, China.

The hydrological exchange process between Poyang Lake (PYL), the largest freshwater lake in China, and the Yangtze River leads to drastic changes in water area (WA) and water level (WL), as well as apparent fluctuations in lake nutrients, algal organisms, and trophic level index. This study investigated the current status of the PYL water environment and the influence of hydrological changes on the nutrient status of the floodplain of the lake. Based on monthly measured data from six hydrological stations from 2016 to 2019, it was hypothesized that WA and WL were the key regulators of the spatial and temporal distribution patterns of lake water quality and algal growth, including water temperature, water clarity (Secchi depth [SD]), and nutrient levels. The results revealed that (1) the spatial and temporal distribution characteristics of major nutrients in PYL were influenced by dynamic changes in hydrological characteristics (SD, total nitrogen [TN], and total phosphorus [TP]); (2) the eutrophication level in PYL has been in a steady state in recent years, while the central area has been more prone to the risk of eutrophication (e.g., the peak eutrophication index during Period 1 [January to April] in the water near the Duchang station reached 70); and (3) there were significant correlations among environmental variables, nutrients, and algal organisms, with different spatial and temporal distribution characteristics (p < 0.05), while the changes in WA and WL considerably influenced the water environment in the PYL.

Land use/land cover prediction and analysis of the middle reaches of the Yangtze River under different scenarios.

Land use and land cover (LULC) projections are critical for climate models to predict the impacts of LULC change on the Earth system. Different assumptions and policies influence LULC changes, which are a key factor in the decisions of planners and conservationists. Therefore, we predicted and analyzed LULC changes in future scenarios (SSP1-26, SSP2-45, SSP5-85) in the middle reaches of the Yangtze River basin (MYRB). We obtain historical (i.e., 2005-2020) LULC data from the Google Earth Engine (GEE) platform using the random forest (RF) classification method. LULC data for different future scenarios are also obtained by the driving factors of LULC changes in future shared socioeconomic pathways (SSPs), representative concentration pathways (RCPs) (SSP-RCP) scenarios (i.e., 2035-2095) and the patch-generated land use simulation (PLUS) model. The major findings are as follows: (1) simulation using the PLUS model based on the acquired classification data and the selected drivers can obtain accurate land use data in MYRB and a Kappa coefficient of 89.6% and 0.82, respectively; (2) as for the LULC changes in the MYRB, forests increased by 3.9% and decreased by 1.2% in the SSP1-26 and SSP5-85 scenarios, respectively, while farmland decreased by 9.2% and increased by 13.4% in SSP 1-26 and SSP 2-45, respectively, during 2080-2095; and (3) the main conversions in LULC in the MYRB were farmland to forest, forests/water bodies to farmland, and forests/grasslands to farmland/buildings in SSP1-2.6, SSP2-4.5, and SSP 5-8.5, respectively. This can be mainly attributed to gross domestic product (GDP), population (POP), temperature, and precipitation. Overall, this study not only contributes to the understanding of the mechanisms of LULC changes in the MYRB but also provides a basis for ecological and climatic studies.

Risk assessment of water resource shortages in the Aksu River basin of northwest China under climate change.

As most of the runoff resulting from snow-ice melt is related to climate change factors in the arid region of northwest China, the risk to water resource systems threatens the socio-economic and ecological environment and is becoming increasingly prevalent. Therefore, we explored the risks of water resource shortages for different periods (2010, 2020, and 2030) in the Aksu River basin (ARB) in the northwest arid region of China by reconstructing a risk model based on the framework proposed by the Intergovernmental Panel on Climate Change (IPCC) with an improved vulnerability (V) module and a more suitable hazard probability in the cost module. The major conclusions are as follows: (1) the simulation of the Community Land Model-Distributed Time Variant Gain Model (CLM-DTVGM) and the Vegetation Interface Processes model (VIP) was suitable for the eco-hydrological processes in the ARB under climate change (i.e., R2 ≥ 0.583; Nash coefficient ≥0.371; and relative mean standard ≤155.727 for CLM-DTVGM; R2 = 0.798 for VIP); (2) the vulnerability of the water resource system in the ARB was medium in 2010, and dropped to a medium-low to non-vulnerable level in 2020 before increasing in 2030 under different Representative Concentration Pathways (RCP) (RCP2.6, RCP4.5, and RCP8.5); and (3) there was a medium-low risk of water resource shortages in the ARB in 2010 (i.e., 0.246), and although the risk of water resource shortages decreased in 2020 due to the increasing water supply from mountainous areas, the risk predicted to increase significantly in 2030, to a medium-high risk level. This study is critical for accurately predicting and understanding the impact of climate change on water resource systems as well as on the drought risk in arid regions.

Reduced inspiratory muscle strength increases pneumonia in patients with acute myocardial infarction.

BACKGROUND: Inspiratory muscle strength is associated with pneumonia in patients after surgery or those with subacute stroke. However, inspiratory muscle strength in patients with acute myocardial infarction (AMI) has not been studied. OBJECTIVE: To evaluate the predictive value of inspiratory muscle strength for pneumonia in patients with AMI. METHODS: Patients with AMI were consecutively enrolled from March 2019 to September 2019. Measurements of maximal inspiratory pressure (MIP) were used to estimate inspiratory muscle strength and mostly were taken within 24 hr after culprit-vessel revascularization. Patients were divided into 3 groups by MIP tertile (T1: <56.1cm H2O, n=88; T2: 56.1-84.9cm H2O, n=88; T3: >84.9cm H2O, n=89). The primary endpoint was in-hospital pneumonia. RESULTS: Among 265 enrolled patients, pneumonia developed in 26 (10%). The rates of pneumonia were decreased from MIP T1 to T3 (T1: 17%, T2: 10%, T3: 2%, P=0.004). In-hospital all-cause mortality and major adverse cardiovascular events (MACEs) did not differ between groups. Multivariate logistic regression confirmed increased MIP associated with reduced risk of pneumonia (odds ratio 0.78, 95% confidence interval 0.65-0.94, P=0.008). Receiver operating characteristic curve analysis indicated that MIP had good performance for predicting in-hospital pneumonia, with an area under the curve of 0.72 (95% confidence interval 0.64-0.81, P<0.001). CONCLUSIONS: The risk of pneumonia but not in-hospital mortality and MACEs was increased in AMI patients with inspiratory muscle weakness. Future study focused on training inspiratory muscle may be helpful.

Effect of Surgical Masks on Cardiopulmonary Function in Healthy Young Subjects: A Crossover Study.

Objective: Mask plays an important role in preventing infectious respiratory diseases. The influence of wearing masks in physical exercise on the human body needs to be studied. The purpose of this study is to explore the influence of wearing surgical masks on the cardiopulmonary function of healthy people during exercise. Methods: The physiological responses of 71 healthy subjects (35 men and 36 women, age 27.77 ± 7.76 years) to exercises with and without surgical masks (mask-on and mask-off) were analyzed. Cardiopulmonary function and metabolic reaction were measured by the cardiopulmonary exercise test (CPET). All tests were carried out in random sequence and should be completed in 1 week. Results: The CPETs with the mask-on condition were performed undesirably (p < 0.05), and the Borg scale was higher than the mask-off (p < 0.001). Rest oxygen uptake ( V . O 2 ) and carbon dioxide production ( V . CO2) with the mask-on condition were lower than mask-off (p < 0.01), which were more obvious at peak exercise ( V . O2 peak : 1454.8 ± 418.9 vs. 1628.6 ± 447.2 ml/min, p < 0.001; V . CO2 peak : 1873.0 ± 578.7 vs. 2169.9 ± 627.8 ml/min, p = 0.005), and the anaerobic threshold (AT) brought forward (p < 0.001). At different stages of CPET with the mask-on condition, inspiratory and expiratory time (Te) was longer (p < 0.05), and respiratory frequency (Rf) and minute ventilation ( V . E ) were shorter than mask-off, especially at peak exercise (Rf peak : 33.8 ± 7.98 vs. 37.91 ± 6.72 b/min, p < 0.001; V . Epeak : 55.07 ± 17.28 vs. 66.46 ± 17.93 l/min, p < 0.001). V T was significantly lower than mask-off just at peak exercise (1.66 ± 0.45 vs. 1.79 ± 0.5 l, p < 0.001). End-tidal oxygen partial pressure (PetO2), end-tidal carbon dioxide partial pressure (PetCO2), oxygen ventilation equivalent ( V . E / V . O2), and carbon dioxide ventilation equivalent ( V . E / V . CO2) with mask-on, which reflected pulmonary ventilation efficiency, were significantly different from mask-off at different stages of CPET (p < 0.05), but no significant difference in percutaneous oxygen saturation (SpO2) was found. Differences in oxygen pulse ( V . O2/HR), oxygen uptake efficiency slope (OUES), work efficiency (△ V . O2/△W), peak heart rate (HR), and peak systolic blood pressure (BP) existed between two conditions (p < 0.05). Conclusion: Wearing surgical masks during aerobic exercise showed certain negative impacts on cardiopulmonary function, especially during high-intensity exercise in healthy young subjects. These results provide an important recommendation for wearing a mask at a pandemic during exercises of varying intensity. Future research should focus on the response of wearing masks in patients with related cardiopulmonary diseases.

The Safety and Efficacy of Inspiratory Muscle Training for Patients With Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention: Study Protocol for a Randomized Controlled Trial.

Background: Uncommonly high rates of pneumonia in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) have been observed during recent years. Inspiratory muscle training (IMT) could reduce pneumonia in patients undergoing coronary artery bypass grafting and other cardiac surgeries. The relationship between IMT and AMI is unknown. Here, we describe the feasibility and potential benefit of IMT in patients at high risk for pneumonia with AMI who have undergone primary PCI. Methods: Our study is a prospective, randomized, controlled, single-center clinical trial. A total of 60 participants will be randomized into an IMT group and control group with 30 participants in each group. Participants in the IMT group will undergo training for 15 min per session, twice a day, from 12 to 24 h after primary PCI, until 30 days post-randomization; usual care will be provided for the control group. The primary endpoint is the change in inspiratory muscle strength, the secondary endpoint included feasibility, pneumonia, major adverse cardiovascular events, length of stay, pulmonary function tests measure, and quality of life. Discussion: Our study is designed to evaluate the feasibility of IMT and its effectiveness in improving inspiratory muscle strength in participants with AMI who have undergone primary PCI. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04491760.