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Diabetic nephropathy (DN), a severe complication of diabetes, is widely recognized as a primary contributor to end-stage renal disease. Recent studies indicate that the inflammation triggered by Toll-like receptor 4 (TLR4) is of paramount importance in the onset and progression of DN. TLR4 can bind to various ligands, including exogenous ligands such as proteins and polysaccharides from bacteria or viruses, as well as endogenous ligands such as biglycan, fibrinogen, and hyaluronan. In DN, the expression or release of TLR4-related ligands is significantly elevated, resulting in excessive TLR4 activation and increased production of proinflammatory cytokines through downstream signaling pathways. This process is closely associated with the progression of DN. Natural compounds are biologically active products derived from natural sources that have advantages in the treatment of certain diseases. Various types of natural compounds, including alkaloids, flavonoids, polyphenols, terpenoids, glycosides, and polysaccharides, have demonstrated their ability to improve DN by affecting the TLR4 signaling pathway. In this review, we summarize the mechanism of action of TLR4 in DN and the natural compounds that can ameliorate DN by modulating the TLR4 signaling pathway. We specifically highlight the potential of compounds such as curcumin, paclitaxel, berberine, and ursolic acid to inhibit the TLR4 signaling pathway, which provides an important direction of research for the treatment of DN.

Liver diseases are a significant global health burden and are among the most common diseases. Ginssennoside Rg3 (Rg3), which is one of the most abundant ginsenosides, has been found to have significant preventive and therapeutic effects against various types of diseases with minimal side effects. Numerous studies have demonstrated the significant preventive and therapeutic effects of Rg3 on various liver diseases such as viral hepatitis, acute liver injury, nonalcoholic liver diseases (NAFLD), liver fibrosis and hepatocellular carcinoma (HCC). The underlying molecular mechanism behind these effects is attributed to apoptosis, autophagy, antioxidant, anti-inflammatory activities, and the regulation of multiple signaling pathways. This review provides a comprehensive description of the potential molecular mechanisms of Rg3 in the development of liver diseases. The article focuses on the regulation of apoptosis, oxidative stress, autophagy, inflammation, and other related factors. Additionally, the review discusses combination therapy and liver targeting strategy, which can accelerate the translation of Rg3 from bench to bedside. Overall, this article serves as a valuable reference for researchers and clinicians alike.

Chlorophyll content is an important physiological indicator reflecting the growth status of crops. Traditional methods for obtaining crop chlorophyll content are time-consuming and labor-intensive. The rapid development of UAV remote sensing platforms offers new possibilities for monitoring chlorophyll content in field crops. To improve the efficiency and accuracy of monitoring chlorophyll content in maize canopies, this study collected RGB, multispectral (MS), and SPAD data from maize canopies at the jointing, tasseling, and grouting stages, constructing a dataset with fused features. We developed maize canopy chlorophyll content monitoring models based on four machine learning algorithms: BP neural network (BP), multilayer perceptron (MLP), support vector regression (SVR), and gradient boosting decision tree (GBDT). The results showed that, compared to single-feature methods, the MS and RGB fused feature method achieved higher monitoring accuracy, with R² values ranging from 0.808 to 0.896, RMSE values between 2.699 and 3.092, and NRMSE values between 10.36% and 12.26%. The SVR model combined with MS–RGB fused feature data outperformed the BP, MLP, and GBDT models in monitoring maize canopy chlorophyll content, achieving an R² of 0.896, an RMSE of 2.746, and an NRMSE of 10.36%. In summary, this study demonstrates that by using the MS–RGB fused feature method and the SVR model, the accuracy of chlorophyll content monitoring can be effectively improved. This approach reduces the need for traditional methods of measuring chlorophyll content in maize canopies and facilitates real-time management of maize crop nutrition.

Diabetes mellitus is a widespread metabolic disorder with increasing incidence worldwide, posing a considerable threat to human health because of its complications. Therefore, cost-effective antidiabetic drugs with minimal side effects are urgently needed. Dioscin, a naturally occurring compound, helps to reduce the complications of diabetes mellitus by regulating glucose and lipid metabolism, protecting islet β cells, improving insulin resistance, and inhibiting oxidative stress and inflammatory response. Plant-derived dioscin reduces the risk of toxicity and side effects associated with chemically synthesized drugs. It is a promising option for treating diabetes mellitus because of its preventive and therapeutic effects, which may be attributed to a variety of underlying mechanisms. However, data compiled by current studies are preliminary. Information about the molecular mechanism of dioscin remains limited, and no high-quality human experiments and clinical trials for testing its safety and efficacy have been conducted. As a resource for research in this area, this review is expected to provide a systematic framework for the application of dioscin in the treatment of diabetes mellitus and its complications.

Abstract Background Natural killer (NK) cell-based immunotherapies have demonstrated substantial potential for the treatment of hematologic malignancies. However, its application is limited due to the difficulty in the production of a large number of NK cells in vitro and the insufficient therapeutic efficacy against solid tumors in vivo. Engineered antibodies or fusion proteins targeting activating receptors and costimulatory molecules of NK cells have been developed to encounter these problems. They are mostly produced in mammalian cells with high cost and long processing times. Yeast systems, such as Komagataella phaffii, present a convenient manipulation of microbial systems with the key advantages of improved folding machinery and low cost. Results In this study, we designed an antibody fusion protein scFvCD16A-sc4-1BBL, composed of the single chain variant fragment (scFv) of anti-CD16A antibody and the three extracellular domains (ECDs) of human 4-1BBL in a single-chain format (sc) with the GS linker, aiming to boost NK cell proliferation and activation. This protein complex was produced in the K. phaffii X33 system and purified by affinity chromatography and size exclusion chromatography. The scFvCD16A-sc4-1BBL complex showed comparable binding abilities to its two targets human CD16A and 4-1BB as its two parental moieties (scFvCD16A and monomer ECD (mn)4-1BBL). scFvCD16A-sc4-1BBL specifically stimulated the expansion of peripheral blood mononuclear cell (PBMC)-derived NK cells in vitro. Furthermore, in the ovarian cancer xenograft mouse model, adoptive NK cell infusion combined with intraperitoneal (i.p) injection of scFvCD16A-sc4-1BBL further reduced the tumor burden and prolonged the survival time of mice. Conclusion Our studies demonstrate the feasibility of the expression of the antibody fusion protein scFvCD16A-sc4-1BBL in K. phaffii with favourable properties. scFvCD16A-sc4-1BBL stimulates PBMC-derived NK cell expansion in vitro and improves the antitumor activity of adoptively transferred NK cells in a murine model of ovarian cancer and may serve as a synergistic drug for NK immunotherapy in future research and applications.

Abstract Background Innate immune responses play essential roles in skeletal muscle recovery after injury. Programmed cell death protein 1 (PD-1) contributes to skeletal muscle regeneration by promoting macrophage proinflammatory to anti-inflammatory phenotype transition. Interferon (IFN)-γ induces proinflammatory macrophages that appear to hinder myogenesis in vitro. Therefore, we tested the hypothesis that blocking IFN-γ in PD-1 knockout mice may dampen inflammation and promote skeletal muscle regeneration via regulating the macrophage phenotype and neutrophils. Methods Anti-IFN-γ antibody was administered in PD-1 knockout mice, and cardiotoxin (CTX) injection was performed to induce acute skeletal muscle injury. Hematoxylin and eosin (HE) staining was used to view morphological changes of injured and regenerated skeletal muscle. Masson’s trichrome staining was used to assess the degree of fibrosis. Gene expressions of proinflammatory and anti-inflammatory factors, fibrosis-related factors, and myogenic regulator factors were determined by real-time polymerase chain reaction (PCR). Changes in macrophage phenotype were examined by western blot and real-time PCR. Immunofluorescence was used to detect the accumulation of proinflammatory macrophages, anti-inflammatory macrophages, and neutrophils. Results IFN-γ blockade in PD-1 knockout mice did not alleviate skeletal muscle damage or improve regeneration following acute cardiotoxin-induced injury. Instead, it exacerbated skeletal muscle inflammation and fibrosis, and impaired regeneration via inhibiting macrophage accumulation, blocking macrophage proinflammatory to anti-inflammatory transition, and enhancing infiltration of neutrophils. Conclusion IFN-γ is crucial for efficient skeletal muscle regeneration in the absence of PD-1.

Browning of white adipose tissue (WAT) is a focus of research in type 2 diabetes mellitus (T2DM) and metabolism, which may be a potential molecular mechanism for high-intensity interval training (HIIT) to improve T2DM. In this study, male C57BL/6J wild-type mice were subjected to an 8-week HIIT regimen following T2DM induction through a high-fat diet (HFD) combined with streptozotocin (STZ) injection. We found that HIIT improved glucose metabolism, body weight, and fat mass in T2DM mice. HIIT also decreased adipocyte size and induced browning of WAT. Our data revealed a decrease in TNFα and an increase in IL-10 with HIIT, although the expression of chemokines MCP-1 and CXCL14 was increased. We observed increased pan-macrophage infiltration induced by HIIT, along with a simultaneous decrease in the expression of M1 macrophage markers (iNOS and CD11c) and an increase in M2 macrophage markers (Arg1 and CD206), suggesting that HIIT promotes M2 macrophage polarization. Additionally, HIIT upregulated the expression of Slit3 and neurotrophic factors (BDNF and NGF). The expression of the sympathetic marker tyrosine hydroxylase (TH) and the nerve growth marker GAP43 was also increased, demonstrating the promotion of sympathetic nerve growth and density by HIIT. Notably, we observed macrophages co-localizing with TH, and HIIT induced the accumulation of M2 macrophages around sympathetic nerves, suggesting a potential association between M2 macrophages and increased density of sympathetic nerves. In conclusion, HIIT induces adipose tissue browning and improves glucose metabolism in T2DM mice by enhancing M2 macrophage polarization and promoting sympathetic nerve growth and density.

Background: Adipose tissue pathology plays a crucial role in the pathogenesis of type 2 diabetes mellitus. Understanding the impact of exercise training on adipose tissue adaptation is of paramount importance in enhancing metabolic health. In this study, we aimed to investigate the effects of various exercise modalities on three distinct adipose tissue depots, namely, interscapular brown adipose tissue (iBAT), subcutaneous white adipose tissue (sWAT), and epididymal white adipose tissue (eWAT), in a murine model of diabetes.Methods: Male C57BL/6J mice received a 12-week high-fat diet and a single injection of streptozotocin, followed by an 8-week exercise intervention. The exercise intervention included swimming, resistance training, aerobic exercise, and high-intensity interval training (HIIT).Results: We found that exercise training reduced body weight and body fat percentage, diminished adipocyte size and increased the expression of mitochondria-related genes (PGC1, COX4, and COX8B) in three adipose tissue depots. The effects of exercise on inflammatory status include a reduction in crown-like structures and the expression of inflammatory factors, mainly in eWAT. Besides, exercise only induces the browning of sWAT, which may be related to the expression of the sympathetic marker tyrosine hydroxylase. Among the four forms of exercise, HIIT was the most effective in reducing body fat percentage, increasing muscle mass and reducing eWAT adipocyte size. The expression of oxidative phosphorylation and thermogenesis-related genes in sWAT and eWAT was highest in the HIIT group.Conclusion: When targeting adipose tissue to improve diabetes, HIIT may offer superior benefits and thus represents a more advantageous choice.

Melanin produced by melanocytes protects our skin against ultraviolet (UV) radiation-induced cell damage and oxidative stress. Melanin overproduction by hyperactivated melanocytes is the direct cause of skin hyperpigmentary disorders, such as freckles and melasma. Exploring natural whitening agents without the concern of toxicity has been highly desired. In this study, we focused on a Bifidobacterium longum strain, ZJ1, isolated from a Chinese centenarian, and we evaluated the anti-melanogenic activity of the distinctive extracts of ZJ1. Our results demonstrated that whole lysate (WL) and bacterial lysate (BL) of ZJ1 ferments efficiently reduce α-melanocyte-stimulating hormone (α-MSH)-induced melanin production in B16-F10 cells as well as the melanin content in zebrafish embryos. BL and WL downregulate melanogenesis-related gene expression and indirectly inhibit intracellular tyrosinase activity. Furthermore, they both showed antioxidant activity in a menadione-induced zebrafish embryo model. Our results suggest that ZJ1 fermentation lysates have application potential as therapeutic reagents for hyperpigmentary disorders and whitening agents for cosmetics.

This paper focuses on determining the spatial and temporal characteristics of the sensitivity coefficients (SCs) between potential evapotranspiration (ET0) and key climatic factors across the Shiyang River Basin (SYRB) from 1981 to 2015. Penman–Monteith equation and a sensitivity analysis were used to calculate ET0 and the SCs for key climatic factors. Sen's slope was used to analyze the observed series. According to the results, the sensitivity significances were in the order of relative humidity (RH) > net solar radiation (NSR) > wind speed (WS) > maximum air temperature (Tmax) > minimum air temperature (Tmin). The SCs for the RH and NSR were larger in the upper mountainous region, while the other three coefficients were larger in the middle and lower reaches. All five climatic factors for the ET0 SCs showed increasing trends in the mountainous region, and the Tmax, WS and RH SCs increased in the middle and lower reaches. Over the past 35 years, the change in ET0 was dominated by the air temperature (T), RH and NSR, and the increase in ET0 during the studied period was mainly due to the increases in T and NSR. HIGHLIGHTS Determined the spatial and temporal characteristics of the sensitivity coefficients between ET0 and key climatic factors across the SYRB.; Explored the causes of ET0 changes and their responses to climate change in the SYRB.; Quantified the contribution rate of each climatic element to ET0 in the SYRB from 1981 to 2015.;

Understanding changes in the intensity and frequency of extreme precipitation is vital for flood control, disaster mitigation, and water resource management. In this study, 12 extreme precipitation indices and the best-fitting extreme value distribution were used to analyze the spatiotemporal characteristics of extreme precipitation in the upper reaches of the Hongshui River Basin (UHRB). The possible links between extreme precipitation and large-scale circulation were also investigated. Most extreme precipitation indices increased from west to east in the UHRB, indicating that the eastern region is a humid area with abundant precipitation. The indices for consecutive wet days (CWD) and precipitation events (R0.1) decreased significantly, indicating that the UHRB tends to be dry, with few precipitation events. The probability distribution functions of most extreme precipitation indices, especially that of R0.1, shifted significantly to the left in 1988–2016 compared with 1959–1987, further indicating that the UHRB has experienced a significant drying trend in recent decades. The East Asian summer monsoon and the El Niño–Southern Oscillation/Pacific Decadal Oscillation were confirmed to influence extreme precipitation in the UHRB. These findings are helpful for understanding extreme precipitation variation trends in the UHRB and provide references for further research. HIGHLIGHTS We do not focus on the Pearl River Basin (453,690 km2) but pay attention to a sub-basin (98,500 km2) within it.; Most extreme precipitation indices decreased slightly and nonsignificantly in the UHRB.; The number of consecutive wet days and precipitation events decreased significantly.; The UHRB has tended to be dry, with few precipitation events.; The El Niño–Southern Oscillation /Pacific Decadal Oscillation and East Asian summer monsoon have strong effects on extreme precipitation.;

Study region: Three Gorges Reservoir area, the largest reservoir area in China Study focus: The frequency and intensity of extreme weather events increase with climate warming, and the local climate effects in the large reservoir area may also change the local precipitation structure. Therefore, based on the precipitation sequence data in the Three Gorges Reservoir (TGR) area from 1959 to 2019, the proposed multi-time-scale mutual information entropy (MTSMIE) method was used to reveal the cyclic synchronous changes of drought-flood abrupt alternation and precipitation concentration. New hydrological insights: The results demonstrate that (1) the spatial distribution of the precipitation concentration index in the TGR area has obvious regional variability. On the temporal scale, the precipitation concentration increased by 5.5% and decreased by 8.2% after impoundment at the head and tail of the TGR, respectively. (2) The frequency of drought-to-flood (DTF) events from the head of the reservoir area to the tail of the reservoir area presents a ''more-less'' feature. The frequency of DTF events after impoundment was less than that before the impoundment of the reservoir. However, the flood-to-drought (FTD) events are the opposite. (3) The period of reliable research and monitoring of DFAA and precipitation concentration in the Three Gorges region is about 15–17 years through the MTSMIE method.

Abstract Background Interleukin-15 (IL-15) is a critical cytokine for the development, proliferation, and function of natural killer (NK) cells, NKT cells, and CD8+ memory T cells and has become one of the most promising protein molecules for the treatment of cancer and viral diseases. However, there are several limitations in applying IL-15 in therapy, such as its low yield in vitro, limited potency, and short half-life in vivo. To date, there are several recombinant IL-15 agonists based on configurational modifications that are being pursued in the treatment of cancer, such as ALT-803, which are mainly produced from mammalian cells. Results In this study, we designed two different forms of the IL-15 complex, which were formed by the noncovalent assembly of IL-15 with dimeric or monomeric sushi domain of IL-15 receptor α (SuIL-15Rα)-IgG4 Fc fusion protein and designated IL-15/SuIL-15Rα-dFc and IL-15/SuIL-15Rα-mFc, respectively. The two IL-15 complexes were expressed in Pichia pastoris (P. pastoris), and their activities and half-lives were evaluated and compared. Pharmacokinetic analysis showed that IL-15/SuIL-15Rα-dFc had a half-life of 14.26 h while IL-15/SuIL-15Rα-mFc had a half-life of 9.16 h in mice, which were much longer than the 0.7-h half-life of commercial recombinant human IL-15 (rhIL-15). Treatment of mice with intravenous injection of the two IL-15 complexes resulted in significant increases in NK cells, NKT cells, and memory CD8+ T cells, which were not observed after rhIL-15 treatment. Treatment of human peripheral blood mononuclear cells (PBMCs) from healthy donors with the two IL-15 complexes yielded enhanced NK and CD8+ T cell activation and proliferation, which was comparable to the effect of rhIL-15. Conclusions These findings indicate that the IL-15/SuIL-15Rα-dFc and IL-15/SuIL-15Rα-mFc produced in P. pastoris exhibit potent activities and prolonged half-lives and may serve as superagonists for immunotherapy in further research and applications.

Abstract Background Although checkpoint-based immunotherapy has shown exciting results in the treatment of tumors, around 70% of patients have experienced unresponsiveness. PVRIG is a recently identified immune checkpoint receptor and blockade of which could reverse T cell exhaustion to treat murine tumor; however, its therapeutic potential via NK cells in mice and human remains seldom reported. Methods In this study, we used patient paraffin-embedded colon adenocarcinoma sections, various murine tumor models (MC38 colon cancer, MCA205 fibrosarcoma and LLC lung cancer), and human NK cell- or PBMC-reconstituted xenograft models (SW620 colon cancer) to investigate the effect of PVRIG on tumor progression. Results We found that PVRIG was highly expressed on tumor-infiltrating NK cells with exhausted phenotype. Furthermore, either PVRIG deficiency, early blockade or late blockade of PVRIG slowed tumor growth and prolonged survival of tumor-bearing mice by inhibiting exhaustion of NK cells as well as CD8+ T cells. Combined blockade of PVRIG and PD-L1 showed better effect in controlling tumor growth than using either one alone. Depletion of NK or/and CD8+ T cells in vivo showed that both cell types contributed to the anti-tumor efficacy of PVRIG blockade. By using Rag1 −/− mice, we demonstrated that PVRIG blockade could provide therapeutic effect in the absence of adaptive immunity. Further, blockade of human PVRIG with monoclonal antibody enhanced human NK cell function and inhibited human tumor growth in NK cell- or PBMC-reconstituted xenograft mice. Conclusions Our results reveal the importance of NK cells and provide novel knowledge for clinical application of PVRIG-targeted drugs in future.

Abstract Understanding the impact of climate change on runoff is essential for effective water resource management and planning. In this study, the regional climate model (RCM) RegCM4.5 was used to dynamically downscale near-future climate projections from two global climate models to a 50-km horizontal resolution over the upper reaches of the Yangtze River (UYRB). Based on the bias-corrected climate projection results, the impacts of climate change on mid-twenty-first century precipitation and temperature in the UYRB were assessed. Then, through the coupling of a large-scale hydrological model with RegCM4.5, the impacts of climate change on river flows at the outlets of the UYRB were assessed. According to the projections, the eastern UYRB will tend to be warm-dry in the near-future relative to the reference period, whereas the western UYRB will tend to be warm-humid. Precipitation will decreases at a rate of 19.05–19.25 mm/10 a, and the multiyear average annual precipitation will vary between − 0.5 and 0.5 mm/day. Temperature is projected to increases significantly at a rate of 0.38–0.52 °C/10 a, and the projected multiyear average air temperature increase is approximately 1.3–1.5 ℃. The contribution of snowmelt runoff to the annual runoff in the UYBR is only approximately 4%, whereas that to the spring runoff is approximately 9.2%. Affected by climate warming, the annual average snowmelt runoff in the basin will be reduced by 36–39%, whereas the total annual runoff will be reduced by 4.1–5%, and the extreme runoff will be slightly reduced. Areas of projected decreased runoff depth are mainly concentrated in the southeast region of the basin. The decrease in precipitation is driving this decrease in the southeast, whereas the decreased runoff depth in the northwest is mainly driven by the increase in evaporation.

Abstract Background Ovarian clear cell carcinoma (OCCC) is a special pathological type of epithelial ovarian carcinoma (EOC). We conducted this research to investigate the clinical characteristics and outcomes of OCCC and to provide additional supporting evidence to aid in the clinical diagnosis and management. Methods This was a retrospective study investigating the clinical characteristics and survival outcomes of 86 patients with OCCC treated at our center between January 2010 and March 2020. Survival analysis was also performed on 179 patients with OCCC obtained from the Surveillance, Epidemiology and End Results (SEER) cancer registry database. Results The median age of participants was 49.21 ± 9.91 years old, and 74.42% of them were diagnosed at early stage. The median CA125 level was 601.48 IU/mL, while 19.77% of the patients had normal CA125 levels. Sixteen patients (18.60%) had co-existing endometriosis and 8 patients (9.3%) developed venous thromboembolism (VTE). There were 5 patients received suboptimal cytoreduction. Sixty-six patients (76.74%) underwent lymphadenectomy, and only 3 (4.55%) patients had positive lymph nodes. Patients diagnosed at an early stage had higher 3-year overall survival (OS) and progression-free survival (PFS) rates than those with advanced stage OCCC. CA19–9 (P = 0.025) and ascites (P = 0.001) were significantly associated with OS, while HE4 (P = 0.027) and ascites (P = 0.001) were significantly associated with PFS. Analysis of data from the SEER database showed that positive lymph nodes is also an independent prognostic factor for OS (P = 0.001). Conclusions OCCC often presents at an early stage and young age with a mildly elevated CA125. CA19–9, HE4, massive ascites, and positive lymph node are independent prognostic factors.

Water conservancy projects are one of the main sources of carbon emissions. Nearly 60% of river revetments in developed countries are treated with ecological slope protection technologies to reduce carbon emissions. Ecological river revetment has been widely adopted as a measure for slope protection. Presently, the study on carbon emission reduction mainly focuses on agricultural production, petroleum exploitation, residential life, and transportation. No significant research has been made on the effects of river revetment protection projects on carbon emissions. This study evaluates the carbon emissions from structural and ecological revetments, and its impact on China's climate. Results show that the ecological revetment can reduce carbon emissions significantly, by 93% as compared to the structural revetment. Moreover, the construction cost of an ecological slope is 37% cheaper than that of a structural slope. This research proves that ecological river slope protection technologies are vital for reducing China's carbon emission. HIGHLIGHTS At present, the research on carbon emission reduction does not contribute much to the research on carbon emission of river slope protection projects.; This study evaluates the carbon emissions from the structural slope and the ecological slope.; Quantify the carbon emissions from the structural slope and the ecological slope construction.; Consider the carbon storage capacity of green plants to compare the carbon emissions of the structural and ecological slope.; We study the contribution of ecological slope in reducing the carbon emissions and improving the climate and environment.;

It is important to understand how actual evapotranspiration (ETa) changes occur and what the dominant contributing factors are. This study investigated the impacts of climatic factor and vegetation coverage on the variations of ETa using a Budyko-based framework. Climatic seasonal index and vegetation coverage index were selected as indicating factors. Two reservoir watersheds, i.e. the Wangkuai Reservoir Watershed and the Xidayang Reservoir Watershed, of the Daqing River Basin were selected as case studies. Also, relationships between the ETa and climatic and vegetation factors were analyzed. Results showed that the improved vegetation conditions positively contributed to the ETa changes, leading to an increase of 42.15 and 58.56 mm of ETa in the two watersheds, while the increasing climate seasonality had a negative effect, resulting in a drop of 11.48 and 13.47 mm of ETa. Vegetation coverage was recognized as the dominant factor to the changes of ETa, compared to the climatic factor. Our research could offer supporting information for water resources management, agricultural production improvement and eco-environment construction in arid regions. HIGHLIGHTS This study investigated the impacts of climatic factor and vegetation coverage on the variations of actual evapotranspiration using a Budyko-based framework.; The water-heat coupling controlling parameter of the Budyko-based framework was quantified by fitting the simulated actual evapotranspiration to observed actual evapotranspiration in a semi-empirical formula.;

Abstract Background High-solids enzymatic hydrolysis has attracted increasing attentions for the production of bioethanol from lignocellulosic biomass with its advantages of high product concentration, water saving, and low energy and capital costs. However, the increase of solids content would worsen the rheological properties, resulting in heat/mass transfer limitation and higher mixing energy. To address these issues, ball milling was applied to corn stover prior to enzymatic hydrolysis, and the rheological behaviors and digestibility of ball-milled corn stover under high-solids loading were investigated. Results Ball milling significantly modified the physicochemical properties of corn stover. The apparent viscosity of slurries at 30% solid loading decreased by a factor of 500 after milling for 60 min, and the yield stress was less than 10 Pa. The dramatic decrease of viscosity and yield stress enabled the hydrolysis process to be conducted in shake flask, and remained good mixing. Meanwhile, the estimated energy consumption for mixing during saccharification decreased by 400-fold compared to the untreated one. The resultant hydrolysate using 10 FPU g−1 solids was determined to contain 130.5 g L−1 fermentable sugar, and no fermentation inhibitors were detected. Conclusions The proposed ball milling pretreatment improved rheological behavior and sugar yield of high-solids corn stover slurry. Ball milling enables high-solids slurry to maintain low viscosity and yield stress while obtaining a non-toxic high-concentration fermentable syrup, which is undoubtedly of great significance for inter-unit processing, mixing and downstream process. In addition, the energy input for ball milling could be balanced by the reduced mixing energy. Our study indicates ball milling a promising pretreatment process for industrial bioethanol production.

Improving flood forecasting performance is critical for flood management. Real-time flood forecasting correction techniques (e.g., proportional correction (PC) and Kalman filter (KF)) coupled with the Muskingum method improve the forecasting performance but have limitations (e.g., short lead times and inadequate performance, respectively). Here, particle filter (PF) and combination forecasting (CF) are coupled with the Muskingum method and then applied to 10 flood events along the Shaxi River, China. Two indexes (overall consistency and permissible range) are selected to compare the performances of PC, KF, PF and CF for 3 h lead time. The changes in overall consistency for different lead times (1–6 h) are used to evaluate the applicability of PC, KF, PF and CF. The main conclusions are as follows: (1) for 3 h lead time, the two indexes indicate that the PF performance is optimal, followed in order by KF and PC; CF performance is close to PF and better than KF. (2) The performance of PC decreases faster than that of KF and PF with increases in the lead time. PC and PF are applicable for short (1–2 h) and long lead times (3–6 h), respectively. CF is applicable for 1–6 h lead times; however, it has no advantage over PC and PF for short and long lead times, respectively, which may be due to insufficient training and increase in cumulative errors.

Natural killer (NK) cells represent a promising future for tumor immunotherapy because of their unique biological functions and characteristics. This review focuses on technical advances in NK cell-based cellular immunotherapy and summarizes the developments of recent years in cell sources, genetic modification, manufacturing systems, clinical programs, and outcomes. Future prospects and challenges in NK cell immunotherapy are also discussed, including off-the-shelf NK cell exploitation, automatic and closed manufacturing systems, cryopreservation, and therapies involving regulatory checkpoints.

Variations of precipitation type can exert substantial impacts on hydrological processes, yet few studies have quantified the impacts of precipitation type variations on runoff changes in high−altitude regions. In this study, we attempted to examine the potential impacts of precipitation type variations induced by the warming climate on the runoff changes of the source regions of the Yangtze River and Yellow River basins from 1979 to 2018, where the mean elevation is over 4000 m. A modified precipitation type identification method using the wet-bulb temperature, and a runoff change attribution method based on a modified Budyko framework has been applied. Results showed that fluctuations of precipitation contributed to the majority of the runoff variations in the source regions of the Yangtze River basin, which accounted for 51.64%. However, the changes of characteristic parameter n, which indicates the impacts of the underlying surface, explained 56.22% of the runoff changes in the source regions of the Yellow River. It was shown that the trend of shifting from snowfall to rainfall due to a warming climate could result in runoff decreasing, which contributed to 24.06% and 11.29% of the runoff changes in the two source regions, comparatively.

High-intensity interval training (HIIT), a new type of exercise, can effectively prevent the progression of metabolic diseases. The aim of this study was to investigate the effects of HIIT on liver inflammation and metabolic disorders in type 2 diabetes mellitus (T2DM) mice induced by a high-fat diet (HFD) combined with streptozotocin (STZ) and to explore the possible mechanisms of macrophage polarization and mitochondrial dynamics. Our results showed that HIIT can increase fatty acid oxidation-related gene (PPARα, CPT1α, and ACOX1) mRNA levels and decrease adipogenesis-related gene (PPARγ) mRNA levels to improve liver metabolism in T2DM mice. The improvement of lipid metabolism disorder may occur through increasing liver mitochondrial biosynthesis-related genes (PGC-1α and TFAM) and restoring mitochondrial dynamics-related gene (MFN2 and DRP1) mRNA levels. HIIT can also reduce the mRNA levels of liver inflammatory factors (TNF-α, IL-6, and MCP-1) in T2DM mice. The reduction in liver inflammation may occur through reducing the expression of total macrophage marker (F4/80) and M1 macrophage marker (CD86) mRNA and protein and increasing the expression of M2 macrophage marker (CD163, CD206, and Arg1) mRNA and protein in the liver. HIIT can also increase the expression of insulin signaling pathway (IRS1, PI3K, and AKT) mRNA and protein in the liver of T2DM mice, which may be related to the improvements in liver inflammation and lipid metabolism. In conclusion, these results suggested that 8 weeks of HIIT can improve inflammation and lipid metabolism disorders in the liver of type 2 diabetes mellitus mice, macrophage M1/M2 polarization, and mitochondrial dynamics may be involved in this process.

Clarifying the response of the terrestrial water cycle to the influence of climate change and human activities and accurately grasping the variations in the water cycle and water resources under the changing environment are the scientific basis for achieving the sustainable development of the Yangtze River Economic Belt. In this paper, a dataset of rasterized water consumption in the Yangtze River Basin was constructed, and an artificial water withdrawal module considering the process of water intake, water consumption and drainage was designed, which was coupled with the land surface model CLM4.5. Based on the multi-scale validation in the Yangtze River Basin, two numerical simulation experiments were carried out to reveal the impact of artificial water withdrawal on the water cycle process in the Yangtze River Basin. The results indicate that artificial water withdrawal leads to an 0.1–0.3 m increase in groundwater table depth in most areas of the basin, and agricultural irrigation leads to a 0–0.03 mm3/mm3 increase in soil moisture in most areas. Climate change dominates the variation of discharge in the Yangtze River basin and leads to an increase in discharge at most stations.

Black tea leaves were pulverized at an organ-scale (~mm), tissue-scale (500–100 μm) and cell-scale (E) of 39.63 and an L value of 55.78. There was no obvious difference in the oil-holding capacity (OHC) of the organ- and tissue-scale powders (3.71–3.74 g/g), while the OHC increased significantly to 4.08 g/g in cell-scale powders. The soluble dietary fiber (SDF) content of cell-scale powders increased remarkably to 10.41%, indicating a potential application as a high-SDF food. Further, cell-scale pulverization of black tea enhanced its DPPH scavenging activity and ferric-ion-reducing antioxidant power (FRAP). However, the polyphenol content (13.18–13.88%) and the protein content (27.63–28.09%), as well as the Pb2+ adsorption capacity (1.97–1.99 mg/g) were not affected by multiscale pulverizations. The mean particle size (D50) correlated linearly with tap density (TD), color parameters of L and b, SDF content, DPPH scavenging activity and FRAP. The results indicate that black tea powders pulverized at a cell-scale can be used as a soluble fiber-rich functional food additive with a bright color, enhanced OHC and antioxidant capacity.

Ovarian cancer is one of the most common gynecologic cancers that has the highest mortality rate. Endometrioid ovarian cancer, a distinct subtype of epithelial ovarian cancer, is associated with endometriosis and Lynch syndrome, and is often accompanied by synchronous endometrial carcinoma. In recent years, dysbiosis of the microbiota within the female reproductive tract has been suggested to be involved in the pathogenesis of endometrial cancer and ovarian cancer, with some specific pathogens exhibiting oncogenic having been found to contribute to cancer development. It has been shown that dysregulation of the microenvironment and accumulation of mutations are stimulatory factors in the progression of endometrioid ovarian carcinoma. This would be a potential therapeutic target in the future. Simultaneously, multiple studies have demonstrated the role of four molecular subtypes of endometrioid ovarian cancer, which are of particular importance in the prediction of prognosis. This literature review aims to compile the potential mechanisms of endometrioid ovarian cancer, molecular characteristics, and molecular pathological types that could potentially play a role in the prediction of prognosis, and the novel therapeutic strategies, providing some guidance for the stratified management of ovarian cancer.

Cellulose triacetate (CTA) was successfully synthesized from corn stover cellulose (CSC) in the presence of [PyPS]3PW12O40 (IL-POM). The effects of IL-POM contents, reaction temperature, and reaction time on the yield and degree of substitution of CTA were investigated. The synthesized CTA was characterized by SEM, FTIR, and TGA, and the degree of polymerization and solubility in various organic solvents were evaluated. Results showed that the optimum reaction conditions were as follows: 0.04 g of IL-POM, reaction temperature of 140 °C, and reaction time of 45 min, for 0.4 g of CSC and 9 mL of glacial acetic acid. The yield of CTA under optimum reaction conditions was as high as 79.27%, and the degree of substitution was 2.95. SEM and FTIR results showed that the cellulose acetylation occurred, and CTA was synthesized. The TGA results revealed that the decomposition temperature of CTA increased by about 30 °C when compared with that of CSC. A simple, environment-friendly, and efficient process for the preparation of CTA from CSC was constructed, which provides a new pathway for the high-value utilization of corn stover.

The heart is the core organ of the circulatory system. Through the blood circulation system, it has close contact with all tissues and cells in the body. An exosome is an extracellular vesicle enclosed by a phospholipid bilayer. A variety of heart tissue cells can secrete and release exosomes, which transfer RNAs, lipids, proteins, and other biomolecules to adjacent or remote cells, mediate intercellular communication, and regulate the physiological and pathological activities of target cells. Cardiogenic exosomes play an important role in regulating almost all pathological and physiological processes of the heart. In addition, they can also reach distant tissues and organs through the peripheral circulation, exerting profound influence on their functional status. In this paper, the composition and function of cardiogenic exosomes, the factors affecting cardiogenic exosomes and their roles in cardiovascular physiology and pathophysiology are discussed, and the close relationship between cardiovascular system and motor system is innovatively explored from the perspective of exosomes. This study provides a reference for the development and application of exosomes in regenerative medicine and sports health, and also provides a new idea for revealing the close relationship between the heart and other organ systems.

Angiogenesis is an important process under both physiological and pathophysiological conditions. Here we investigated the role and the underlying mechanism of PD-1 in hindlimb ischemia-induced inflammation and angiogenesis in mice. We found that inhibition of PD-1 by genetic PD-1 knockout or pharmacological PD-1 blocking antibodies dramatically attenuated hindlimb blood perfusion, angiogenesis, and exercise capacity in mice after femoral artery ligation. Mechanistically, we found that PD-1 knockout significantly exacerbated ischemia-induced muscle oxidative stress, leukocyte infiltration and IFN-γ production before abnormal angiogenesis in these mice. In addition, we found that the percentages of IFN-γ positive macrophages and CD8 T cells were significantly increased in P-1 knockout mice after hindlimb ischemia. Macrophages were the major leukocyte subset infiltrated in skeletal muscle, which were responsible for the enhanced muscle leukocyte-derived IFN-γ production in PD-1 knockout mice after hindlimb ischemia. Moreover, we demonstrated that IFN-γ significantly attenuated vascular endothelial cell proliferation, tube formation and migration in vitro. IFN-γ also significantly enhanced vascular endothelial cell apoptosis. In addition, the total number of TNF-α positive leukocytes/muscle weight were significantly increased in PD-1-/- mice after hindlimb ischemia. These data indicate that PD-1 exerts an important role in ischemia-induced muscle inflammation and angiogenesis.

The purpose of this study was to investigate the effect of exogenous hydrogen sulfide (H2S) treatment on skeletal muscle contusion. We established a skeletal muscle contusion model (S group) and an H2S treated of skeletal muscle contusion model (H2S group). Gastrocnemius muscles (GMs) were collected at day 1, day 5, day 10, and day 15 after injury, and comprehensive morphological and genetic analyses was conducted. H2S treatment reduced M1 macrophage (CD68), profibrotic cytokines (TGF-β), pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, and IL-6), chemokines (CCL2, CCR2, CCL3, CCL5, CXCL12, and CXCR4), matrix metalloproteinases (MMP-1, MMP-2, MMP-9, and MMP-14) and oxidative stress factor (gp91phox) expression levels, improved M2 macrophage (CD206) level. Thus, exogenous H2S treatment reduced inflammation and oxidative stress, attenuated skeletal muscle fibrosis, and partly improved skeletal muscle injury.

High-intensity interval training has been reported to lower fasting blood glucose and improve insulin resistance of type 2 diabetes without clear underlying mechanisms. The purpose of this study was to investigate the effect of high-intensity interval training on the glycolipid metabolism and mitochondrial dynamics in skeletal muscle of high-fat diet (HFD) and one-time 100 mg/kg streptozocin intraperitoneal injection-induced type 2 diabetes mellitus (T2DM) mice. Our results confirmed that high-intensity interval training reduced the body weight, fat mass, fasting blood glucose, and serum insulin of the T2DM mice. High-intensity interval training also improved glucose tolerance and insulin tolerance of the T2DM mice. Moreover, we found that high-intensity interval training also decreased lipid accumulation and increased glycogen synthesis in skeletal muscle of the T2DM mice. Ultrastructural analysis of the mitochondria showed that mitochondrial morphology and quantity were improved after 8 weeks of high-intensity interval training. Western blot analysis showed that the expression of mitochondrial biosynthesis related proteins and mitochondrial dynamics related proteins in high-intensity interval trained mice in skeletal muscle were enhanced. Taken together, these data suggest high-intensity interval training improved fasting blood glucose and glucose homeostasis possibly by ameliorating glycolipid metabolism and mitochondrial dynamics in skeletal muscle of the T2DM mice.

The maturation of dendritic cells (DCs) is essential in adaptive immunity. B cell adapter for phosphoinositide 3-kinase (BCAP) has been shown a divergent activities in cell type dependent manner including B cells, NK cells, macrophages, and plasmacytoid DCs (pDCs), however, its role in conventional DCs (cDCs) remains unknown. Here, we report that BCAP negatively regulates Toll-like receptor-induced cDC maturation and inhibits cDCs from inducing antigen-specific T cell responses, thereby weakening the antibacterial adaptive immune responses of mice in a Listeria monocytogenes-infection model. Furthermore, we demonstrate that BCAP simultaneously modulates the activation of the NF-κB and PI3K/AKT signaling by dynamically interacting with, respectively, MyD88 and the p85α subunit of PI3K. Our study thus reveals non-redundant roles for BCAP in regulating cDC maturation and reveals a bilateral signal transduction mechanism.

Abstract Background The invention of efficient systems for lignocellulose conversion is essential for economically feasible production of bio-based chemicals and biofuels. One limiting step is highly selective processes to quickly decrystallize the compact cellulose structure for efficient hydrolysis. We evaluated the impact of trifluoroacetic acid (TFA) and phosphorous acid (PA)-induced swelling of crystalline cellulose on enhancement of enzymatic digestion. Results In this study, two swelling agents, TFA and PA, are compared and found to be highly efficient for cellulose decrystallization at low temperatures within 1 h. After treatment, the microfibril structure of swollen celluloses was observed to develop distinct microscopic morphology and subsequent enzymatic hydrolysis resulted over 90% cellulose conversion within 24 h. The crystalline cellulose change was determined by reduction of loss of X-ray diffractability, and loss of resistance to enzymatic hydrolysis. NMR results suggest that both TFA and PA efficiently converted most of the crystalline cellulose regions to amorphous regions through cellulose chain relocation that inhibits recrystallization. It was found that the swelling mechanism is different between TFA and PA. To the best of our knowledge, it is the first time to compare and quantify the cellulose regions transformation by swelling agents. Conclusion This study shows the low-temperature swelling of different celluloses in TFA and PA reduces recalcitrance of crystalline cellulose to enzymatic hydrolysis. TFA and PA are both ideal candidate swelling agents for a closed system for ease of solvent recovery by either simple distillation or filtration. This study provides potentially useful agents in large-scale deconstruction of biomass.

Natural killer (NK) cells have shown great therapeutic potential against a wide range of cancers due to their pan-specific target recognition. Numerous reports indicate that NK cell immunotherapy is an effective therapeutic approach for treating hematological malignancies, but shows limited effects against solid tumors. In this study, several models of ovarian cancer (OC) were used to test the anti-cancer effects of NK cells derived from human peripheral blood mononuclear cells and expanded using a feeder cell-free expansion system (eNKs). The results show that eNKs exhibit potent inhibitory activity on tumor growth in different ovarian cancer xenograft mice (i.e., solid tumors, abdominal metastatic tumors, and ascites), importantly, in a dose-dependent manner. Moreover, adoptive transfer of eNKs resulted in significant reduction in ascites formation in OC peritoneal tumor models, and especially in reducing intraperitoneal ascites. We found that eNKs could migrate to the tumor site, retain their activity, and proliferate to maintain high cell counts in cutaneous xenograft mice. In addition, when increased the infusion with a high dose of 12 × 107 cells/mouse, Graft-versus-host disease could be induced by eNK. These data show that eNK cell immunotherapy could be a promising treatment strategy for ovarian cancers, including solid tumors and ascites.

Coal mining and soil-water conservation are the two major human interventions on the Loess Plateau in China. Analyzing their impacts on hydrological processes is of great significance for sustainable water resource management. Using hydrological simulation (Soil and Water Assessment Tool, SWAT) and a data-driven method (double mass curve, DMC), the contributions of these two human activities and climate change to the runoff decrease were analyzed in the upper Fenhe River. The runoff in the three affected periods (1967–1987, 1988–1994, and 1995–2017) decreased by 7.5%, 28.2%, and 24.1%, respectively, compared with the base period (1957–1966). In the first affected period (1967–1987), the amount of coal mining activities was small, human activities had little impact on runoff. In the second (1988–1994) and third (1995–2017) periods, as the coal mining and soil-water conservation intensified, their contributions to the runoff decrease rapidly increased. Due to the uncertainties in the model structure and parameters, in addition to the impact of the data accuracy, the results obtained from the two methods were different, but the proportions and the trends of the contribution rates in the different periods were consistent.

Abstract Background The crystallinity of cellulose is a principal factor limiting the efficient hydrolysis of biomass to fermentable sugars or direct catalytic conversion to biofuel components. We evaluated the impact of TFA-induced gelatinization of crystalline cellulose on enhancement of enzymatic digestion and catalytic conversion to biofuel substrates. Results Low-temperature swelling of cotton linter cellulose in TFA at subzero temperatures followed by gentle heating to 55 °C dissolves the microfibril structure and forms composites of crystalline and amorphous gels upon addition of ethanol. The extent of gelatinization of crystalline cellulose was determined by reduction of birefringence in darkfield microscopy, loss of X-ray diffractability, and loss of resistance to acid hydrolysis. Upon freeze-drying, an additional degree of crystallinity returned as mostly cellulose II. Both enzymatic digestion with a commercial cellulase cocktail and maleic acid/AlCl3-catalyzed conversion to 5-hydroxymethylfurfural and levulinic acid were markedly enhanced with the low-temperature swollen cellulose. Only small improvements in rates and extent of hydrolysis and catalytic conversion were achieved upon heating to fully dissolve cellulose. Conclusions Low-temperature swelling of cellulose in TFA substantially reduces recalcitrance of crystalline cellulose to both enzymatic digestion and catalytic conversion. In a closed system to prevent loss of fluorohydrocarbons, the relative ease of recovery and regeneration of TFA by distillation makes it a potentially useful agent in large-scale deconstruction of biomass, not only for enzymatic depolymerization but also for enhancing rates of catalytic conversion to biofuel components and useful bio-products.

The ketone bodies, especially β-hydroxybutyrate (β-HB), derive from fatty acid oxidation and alternatively serve as a fuel source for peripheral tissues including the brain, heart, and skeletal muscle. β-HB is currently considered not solely an energy substrate for maintaining metabolic homeostasis but also acts as a signaling molecule of modulating lipolysis, oxidative stress, and neuroprotection. Besides, it serves as an epigenetic regulator in terms of histone methylation, acetylation, β-hydroxybutyrylation to delay various age-related diseases. In addition, studies support endogenous β-HB administration or exogenous supplementation as effective strategies to induce a metabolic state of nutritional ketosis. The purpose of this review article is to provide an overview of β-HB metabolism and its relationship and application in age-related diseases. Future studies are needed to reveal whether β-HB has the potential to serve as adjunctive nutritional therapy for aging.

Skeletal muscle injury is one of the most common injuries in sports medicine. Our previous study found that macrophage depletion impairs muscle regeneration and that mechano growth factor (MGF) may play an important role in this process. However, whether injection of MGF protects against impaired muscle regeneration after macrophage depletion has not been explored. Therefore, we generated a muscle contusion and macrophage depletion mouse model and injected MGF into the damaged muscle. Comprehensive morphological and genetic analyses were performed on the injured skeletal muscle after macrophage depletion and MGF injection. The results showed that injection of MGF did not exert a protective effect on muscle fiber regeneration; however, it did decrease fibrosis in the contused skeletal muscle after macrophage depletion. Moreover, MGF injection decreased the expression of muscle inflammatory cytokines (TNF-α, IFN-γ, IL-1β, and TGF-β), chemokines (CCL2, CCL5, and CXCR4), oxidative stress factors (gp91phox) and matrix metalloproteinases (MMP-1, MMP-2, MMP-9, MMP-10, and MMP-14). These results suggest that the impairment of skeletal muscle regeneration induced by macrophage depletion could be partly ameliorated by MGF injection and that inflammatory cytokines, oxidative stress factors, chemokines, and MMP may be involved in this process.

Skeletal muscle contusion is one of the most common muscle injuries in sports medicine and traumatology. Bone marrow mesenchymal stem cell (BMSC) transplantation has been proposed as a promising strategy to promote skeletal muscle regeneration. However, the roles and underlying mechanisms of BMSCs in the regulation of skeletal muscle regeneration are still not completely clear. Here, we investigated the role of BMSC transplantation after muscle contusion. BMSCs were immediately transplanted into gastrocnemius muscles (GMs) following direct contusion. Comprehensive morphological and genetic analyses were performed after BMSC transplantation. BMSC transplantation exacerbated muscle fibrosis and inflammation, as evidenced by increased leukocyte and macrophage infiltration, increased inflammatory cytokines and chemokines, and increased matrix metalloproteinases. BMSC transplantation also increased muscle oxidative stress. Overall, BMSC transplantation aggravated inflammation, oxidative stress and fibrosis and impaired skeletal muscle regeneration. These results, shed new light on the role of BMSCs in regenerative medicine and indicate that caution is needed in the application of BMSCs for muscle injury.

Background: Though the mechanisms of skeletal muscle regeneration are deeply understood, those involved in muscle contusion, one of the most common muscle injuries in sports medicine clinics, are not. The objective of this study is to explore the mechanisms involved in muscle regeneration after contusion injury. Methods: In this study, a total of 72 mice were used. Eight of them were randomly chosen for the control group, while the rest were subjected to muscle contusion. Subsequently, their gastrocnemius muscles were harvested at different time points. The changes in muscle morphology were assessed by hematoxylin and eosin (HE) stain. In addition, the gene expression was analyzed by real-time polymerase chain reaction. Results: The data showed that the expression of many genes, i.e., specific markers of immune cells and satellite cells, regulatory factors for muscle regeneration, cytokines, and chemokines, increased in the early stages of recovery, especially in the first 3 days. Furthermore, there were strict rules in the expression of these genes. However, almost all the genes returned to normal at 14 days post-injury. Conclusion: The sequence of immune cells invaded after muscle contusion was neutrophils, M1 macrophages and M2 macrophages. Some CC (CCL2, CCL3, and CCL4) and CXC (CXCL10) chemokines may be involved in the chemotaxis of these immune cells. HGF may be the primary factor to activate the satellite cells after muscle contusion. Moreover, 2 weeks are needed to recover when acute contusion happens as used in this study.

The aim of this study was to evaluate the effect of strenuous exercise on the functions of peritoneal macrophages in rats and to test the hypothesis that branched-chain amino acid (BCAA) supplementation will be beneficial to the macrophages of rats from strenuous exercise. Forty male Wistar rats were randomly divided into five groups: (C) Control, E) Exercise, (E1) Exercise with one week to recover, (ES) Exercise + Supplementation and (ES1) Exercise + Supplementation with 1 week to recover. All rats except those of the sedentary control were subjected to four weeks of strenuous exercise. Blood hemoglobin, serum testosterone and BCAA levels were tested. Peritoneal macrophages functions were also determined at the same time. The data showed that hemoglobin, testosterone, BCAA levels, and body weight in group E decreased significantly as compared with that of group C. Meanwhile, phagocytosis capacity (decreased by 17.07%, p = 0.031), reactive oxygen species (ROS) production (decreased by 26%, p = 0.003) and MHC II mRNA (decreased by 22%, p = 0.041) of macrophages decreased in the strenuous exercise group as compared with group C. However, the chemotaxis of macrophages did not change significantly. In addition, BCAA supplementation could slightly increase the serum BCAA levels of rats from strenuous exercise (increased by 6.70%, p > 0.05). Moreover, the body weight, the blood hemoglobin, the serum testosterone and the function of peritoneal macrophages in group ES did not change significantly as compared with group E. These results suggest that long-term intensive exercise impairs the function of macrophages, which is essential for microbicidal capability. This may represent a novel mechanism of immunosuppression induced by strenuous exercise. Moreover, the impaired function of macrophage induced by strenuous exercise could not be ameliorated by BCAA supplementation in the dosing and timing used for this study.

The statistical characteristics of precipitation play important roles not only in flood and drought risk assessments but also in water resource management. This paper implements a statistical analysis to study the spatial and temporal variability in precipitation in the upper reaches of the Hongshui River basin (UHRB), southwestern China, by analysing time series of daily precipitation from 18 weather stations during the period of 1959 to 2015. To detect precipitation concentrations and the associated patterns, three indices, the precipitation concentration index (PCI), precipitation concentration degree (PCD), and precipitation concentration period (PCP), were used. The relationships between the precipitation concentration indices (PCI, PCD, and PCP) and geographic variables (latitude, longitude, and elevation), large-scale atmospheric circulation indices, and summer monsoon indices were investigated to identify specific dependencies and spatial patterns in the precipitation distribution and concentration. The results show that high PCI values were mainly observed in the northeastern portion of the basin, whereas low PCI values were mainly detected in the southwest. The Mann-Kendall test results demonstrate that the majority of the UHRB is characterized by nonsignificant trends in the PCI, PCD, and PCP from 1959 to 2015. The PCP results reveal that rainfall in the UHRB mainly occurs in summer months, and the rainy season arrives earlier in the eastern UHRB than in the western UHRB. Additionally, the PCD results indicate that the rainfall in the western UHRB is more dispersed throughout the year than that in the eastern UHRB. Compared with other geographical factors, longitude is the most important variable that governs the spatial distribution and variations in annual precipitation and the precipitation concentration indices. Due to a combination of topography, the Indian subtropical high, and monsoon weakening, precipitation may be more concentrated in one period, especially in the eastern part of the basin, which increases the risk of drought.

Microwave heating was applied in the liquefaction of corn stover with polyhydric alcohol to establish a rapid process for converting corn stover into polyols. With ethylene glycol (EG) as liquefacient and 3.5% sulfuric acid as a catalyst, the residue content was reduced to 4.7% after 20 min of microwave liquefaction at 160 °C. Effects of liquefaction parameters on the residue content were investigated. It was found that the reaction temperature had a greater influence on the residue content than the sulfuric acid concentration and reaction time. The liquefied mixture was characterized as complexes of ester and ether type polyols by means of Fourier transform infrared spectroscopy. 3-(2-Methyl-1,3-dioxolan-2-yl) propanoic acid was characterized as the main degradation product of corn stover, besides the large amount of condensation product of EG.

Corn stover was successfully liquefied by microwave heating at 160 °C with ethylene glycol (EG) used as the solvent and sulfuric acid as a catalyst. Gas chromatography and mass spectrometry (GC-MS) data indicated that methyl esters, including 3-(2-methyl-1,3-doxolane-2-yl) propionic acid methyl ester (PAME), levulinic acid isopropyl ester (LAE), methyl laurate, and methyl palmitate were the major degradation compounds, in addition to EG derivatives in the liquefied product of corn stover (LPCS). For high value-added utilization of LPCS, solvent extraction was applied to characterize the components and to separate it into useful fractions. After being dispersed in water, the water-soluble fraction of the LPCS was then extracted with organic solvents, including hexane, chloroform, diethyl ether, and ethyl acetate. Levulinic acid isopropyl ester showed the highest distribution in chloroform and ethyl acetate, while the lowest in hexane and ether. Levulinic acid isopropyl ester was selectively enriched to 28.76% and 43.65% by sequential extraction with chloroform and ethyl acetate, respectively, in accordance with the quantitative analysis.

Evapotranspiration (ET) has undergone profound changes as a result of global climate change and anthropogenic activities. The construction of the Three Gorges Reservoir (TGR) has led to changes in its land use/land cover (LUCC) and local climate, which in turn has changed ET processes in the TGR region. In this paper, the CLM4.5 land surface model is used to simulate and analyze the spatiotemporal variability of ET between 1993 and 2013. Four experiments were conducted to quantify the contribution rate of climate change and LUCC to changes in ET processes. The results show that the climate showed a warming and drying trend from 1993 to 2013, and the LUCC indicates decreasing cropland with increasing forest, grassland, water bodies and urban areas. These changes increased the mean annual ET by 13.76 mm after impoundment. Spatially, the vegetation transpiration accounts for the largest proportion in ET. The decreasing relative humidity and increasing wind speeds led to an increase in vegetation transpiration and ground evaporation, respectively, in the center of the TGR region, while the LUCC drove changes in ET in water bodies, urban areas and high-altitude regions in the TGR region.

In this study, a coupled water−energy balance equation at an arbitrary time scale was proposed as an extension of the Budyko hypothesis. The second mixed partial derivative was selected to represent the magnitude of the interaction. The extended hydrological sensitivity method was used to quantitatively evaluate the impacts of climate change, anthropogenic activities, and their interaction on dry season runoff in the Lhasa River. In addition, an ABCD model, which is a monthly hydrological model included a snowmelt module, was used to calculate the change in soil water and groundwater storage. The Mann−Kendall test, Spearman’s test, dynamic linear model (DLM), and Yamamoto’s method were used to identify trends and change points in hydro-climatic variables from 1956−2016. The results found that dry season runoff increased non-significantly over the last 61 years. Climate change, which caused an increase in dry season runoff, was the dominant factor, followed by anthropogenic activities and their interaction, which led to varying degrees of decrease. This study concluded that the methods tested here performed well in quantifying the relative impacts of climate change, anthropogenic activities, and their interaction on dry season runoff change.

As the penetration of intermittent renewable energy increases and unexpected market behaviors continue to occur, new challenges arise for system operators to ensure cost effectiveness while maintaining system reliability under uncertainties. To systematically address these uncertainties and challenges, innovative advanced methods and approaches are needed. Motivated by these, in this paper, we consider an energy integrated system with renewable energy and pumped-storage units involved. In addition, we propose a data-driven risk-averse two-stage stochastic model that considers the features of forbidden zones and dynamic ramping rate limits. This model minimizes the total cost against the worst-case distribution in the confidence set built for an unknown distribution and constructed based on data. Our numerical experiments show how pumped-storage units contribute to the system, how inclusions of the aforementioned two features improve the reliability of the system, and how our proposed data-driven model converges to a risk-neutral model with historical data.

The frequent occurrence of geophysical disasters under climate change has drawn Chinese scholars to pay their attention to disaster relations. If the occurrence sequence of disasters could be identified, long-term disaster forecast could be realized. Based on the Earth Degassing Effect (EDE) which is valid, this paper took the magnitude, epicenter, and occurrence time of the earthquake, as well as the epicenter and occurrence time of the rainstorm floods as basic factors to establish an integrated model to study the correlation between rainstorm floods and earthquakes. 2461 severe earthquakes occurred in China or within 3000 km from China and the 169 heavy rainstorm floods occurred in China over the past 200+ years as the input data of the model. The computational results showed that although most of the rainstorm floods have nothing to do with the severe earthquakes from a statistical perspective, some floods might relate to earthquakes. This is especially true when the earthquakes happen in the vapor transmission zone where rainstorms lead to abundant water vapors. In this regard, earthquakes are more likely to cause big rainstorm floods. However, many cases of rainstorm floods could be found after severe earthquakes with a large extent of uncertainty.