Plant litter loss exacerbates drought influences on grasslands.

Plant litter is known to affect soil, community, and ecosystem properties. However, we know little about the capacity of litter to modulate grassland responses to climate change. Using a 7-yr litter removal experiment in a semiarid grassland, here we examined how litter removal interacts with a 2-yr drought to affect soil environments, plant community composition, and ecosystem function. Litter loss exacerbates the negative impacts of drought on grasslands. Litter removal increased soil temperature but reduced soil moisture and nitrogen mineralization, which substantially increased the negative impacts of drought on primary productivity and the abundance of perennial rhizomatous graminoids. Moreover, complete litter removal shifted plant community composition from grass-dominated to forb-dominated and reduced species and functional group asynchrony, resulting in lower ecosystem temporal stability. Our results suggest that ecological processes that lead to reduction in litter, such as burning, grazing, and haying, may render ecosystems more vulnerable and impair the capacity of grasslands to withstand drought events.

OX40L enhances the immunogenicity of dendritic cells and inhibits tumor metastasis in mice.

A well preserved immune system is a powerful tool to prevent foreign invasion or to suppress internal mutation, which must be tightly controlled by co-stimulatory molecules in different pathophysiological conditions. One such critical molecule is OX40L expressed on activated antigen-presenting cells (APCs). Consistently, its abnormality is associated with various immunological disorders such as autoinflammatory diseases and allergy. However, a comprehensive analysis of the immune-moderating role of OX40L in dendritic cells (DCs), the most powerful APCs to initiate immune responses in vivo, and investigation of its anti-tumor efficacy in the disease setting have not been performed properly. In this study, genetic approaches for both gain-of-function and reduction-of-function were employed to reveal that OX40L was required for the efficient presentation, but not uptake, of antigens by DCs to stimulate CD4+ , as well as CD8+ T cells in vivo. As a result, CD4+ T cells were promoted towards Th1, but inhibited on Treg differentiation, by the LPS-induced OX40L on DCs, which was supported by their altered expression of co-inhibitory receptor, PD-L1. CD8+ T cells, on the other hand, also enhanced their cytotoxicity towards target cells in response to OX40L expression on the DCs transferred in vivo. Finally, in a DC-mediated tumor immunity model, the strong immunogenic roles of OX40L on DCs led to better metastasis inhibition in vivo. Collectively, our results demonstrate that OX40L could serve as a potential target in the DC-based vaccine for enhanced anti-tumor efficacy in vivo.

Space-for-time substitution leads to carbon emission overestimation in eutrophic lakes.

Lacustrine eutrophication is generally considered as an important contributor of carbon emissions to the atmosphere; however, there is still a huge challenge in accuracy estimating carbon emissions from lakes. To test the effect of widely used space-for-time substitution on lake carbon emissions, this study monitored different processes of carbon emissions, including the carbon production potential, dissolved carbon concentrations, and carbon release fluxes in eight lakes along the trophic gradients on a spatial scale and the typical eutrophic Lake Taihu for one year on a temporal scale. Eutrophication promoted carbon production potential, dissolved carbon concentrations, and carbon release fluxes, especially for CH4. Trophic lake index (TLI) showed positive correlations with the CH4 production potential, dissolved CH4 concentrations, and CH4 release fluxes, and also positive correlations with the CO2 production potential, dissolved CO2 concentrations, and CO2 release fluxes. The space-for-time substitution led to an overestimation for the influence of eutrophication on carbon emissions, especially the further intensification of lake eutrophication. On the spatial scale, the average CH4 production potential, dissolved CH4 concentrations and CH4 release fluxes in eutrophic lakes were 268.6, 0.96 µmol/L, and 587.6 µmol m-2·h-1, respectively, while they were 215.8, 0.79 µmol/L, and 548.6 µmol m-2·h-1 on the temporal scale. Obviously, CH4 and CO2 emissions on the spatial scale were significantly higher than those on the temporal scale in eutrophic lakes. The primary influencing factors were the seasonal changes in the physicochemical environments of lake water, including dissolved oxygen (DO) and temperature. The CH4 and CO2 release fluxes showed negative correlations with DO, while temperature displayed positive correlations, respectively. These results suggest that the effects of DO and temperature on lake carbon emissions should be considered, which may be ignored during the accurate assessment of lake carbon budget via space-for-time substitution in eutrophic lakes.

Clinical efficacy of beraprost sodium in treating chronic kidney disease: A six-month prospective study.

Objective: To investigate the clinical efficacy of beraprost sodium (BPS) in the treatment of chronic kidney disease (CKD). Methods: In this single-centre, prospective, controlled, single-blind study, 252 patients diagnosed with CKD and treated at the Affiliated Hospital of Xuzhou Medical University were enrolled from September 2018 to June 2021. All participants were randomised into three groups: the control, BPS 40 µg, and BPS 20 µg groups. Both treatment groups were administered conventional therapy for 6 months. Renal function in the three groups was measured and compared 3 and 6 months post-treatment. Results: 1. Renal function in the BPS 20 µg and BPS 40 µg groups was better than that in the control group after 3 and 6 months of treatment. 2. After 3 months of treatment, the levels of serum creatinine (P = 0.043), cystatin C (P = 0.039), and 24 h urinary total protein (P = 0.041) in the BPS 40 µg group were significantly lower than those in the BPS 20 µg group, the eGFR (P = 0.046) level was higher than that in the BPS 20 µg group, and the index improvement rate was better than that in the BPS 20 µg group (P < 0.05). 3. After 6 months of treatment, the improvement in renal function in the BPS 20 µg group was close to that in the BPS 40 µg group (P > 0.05). Conclusion: BPS improved renal function, reduced urinary protein levels, and delayed CKD progression. The clinical efficacy of BPS in the 40 µg group was faster than that in the BPS 20 µg group. The long-term use of BPS is effective in patients with CKD.

A clinical study on roxadustat for anemia in diabetic nephropathy: a 8-week study.

PURPOSE: The development of roxadustat is a standard treatment for renal anemia, and multiple clinical trials have proved its safety and efficacy. However, less information is available from trials of the population with diabetic nephropathy (DN). This study aimed to determine whether roxadustat is effective for treating DN. METHODS: This was a single-center, retrospective, institutional review board-approved cohort study. The patients with DN were chosen and given roxadustat or erythropoietin (EPO) for 8 weeks. The mean hemoglobin (Hb) level after 8 weeks of treatment served as the primary outcome. Alterations in the iron index and lipid levels were considered secondary objectives. Sub-group analysis was performed to observe the impact of inflammation and glycemic status on Hb. RESULTS: A total of 80 patients were enrolled, 40 in each group. After 8 weeks of treatment, the Hb levels in the roxadustat group were higher than those in the control group. The number of patients who achieved Hb response was higher in the roxadustat group than in the control group (77.5% versus 27.5%; P < 0.001). In addition to lowering total cholesterol and low-density lipoprotein cholesterol, roxadustat decreased ferritin and elevated total iron-binding capacity. Compared to the control group, roxadustat was more beneficial for patients with an inflammatory condition and poor glycemic control. CONCLUSIONS: Roxadustat treatment remarkably corrected anemia in patients with DN, and its effectiveness was unaffected by inflammation or glycemic control levels. In addition, roxadustat can also reduce a patient's blood lipid level and enhance the body's use of iron. CLINICAL TRIAL REGISTRATION: ChiCTR2200057232.

Construction of Host Plant Insect-Resistance Mutant Library by High-Throughput CRISPR/Cas9 System and Identification of A Broad-Spectrum Insect Resistance Gene.

Insects pose significant challenges in cotton-producing regions. Here, they describe a high-throughput CRISPR/Cas9-mediated large-scale mutagenesis library targeting endogenous insect-resistance-related genes in cotton. This library targeted 502 previously identified genes using 968 sgRNAs, generated ≈2000 T0 plants and achieved 97.29% genome editing with efficient heredity, reaching upto 84.78%. Several potential resistance-related mutants (10% of 200 lines) their identified that may contribute to cotton-insect molecular interaction. Among these, they selected 139 and 144 lines showing decreased resistance to pest infestation and targeting major latex-like protein 423 (GhMLP423) for in-depth study. Overexpression of GhMLP423 enhanced insect resistance by activating the plant systemic acquired resistance (SAR) of salicylic acid (SA) and pathogenesis-related (PR) genes. This activation is induced by an elevation of cytosolic calcium [Ca2+ ]cyt flux eliciting reactive oxygen species (ROS), which their demoted in GhMLP423 knockout (CR) plants. Protein-protein interaction assays revealed that GhMLP423 interacted with a human epidermal growth factor receptor substrate15 (EPS15) protein at the cell membrane. Together, they regulated the systemically propagating waves of Ca2+ and ROS, which in turn induced SAR. Collectively, this large-scale mutagenesis library provides an efficient strategy for functional genomics research of polyploid plant species and serves as a solid platform for genetic engineering of insect resistance.

Insight into the specific virulence related genes and toxin-antitoxin virulent pathogenicity islands in swine streptococcosis pathogen Streptococcus equi ssp. zooepidemicus strain ATCC35246.

BACKGROUND: Streptococcus equi ssp. zooepidemicus (S. zooepidemicus) is an important pathogen causing swine streptococcosis in China. Pathogenicity islands (PAIs) of S. zooepidemicus have been transferred among bacteria through horizontal gene transfer (HGT) and play important roles in the adaptation and increased virulence of S. zooepidemicus. The present study used comparative genomics to examine the different pathogenicities of S. zooepidemicus. RESULTS: Genome of S. zooepidemicus ATCC35246 (Sz35246) comprises 2,167,264-bp of a single circular chromosome, with a GC content of 41.65%. Comparative genome analysis of Sz35246, S. zooepidemicus MGCS10565 (Sz10565), Streptococcus equi. ssp. equi. 4047 (Se4047) and S. zooepidemicus H70 (Sz70) identified 320 Sz35246-specific genes, clustered into three toxin-antitoxin (TA) systems PAIs and one restriction modification system (RM system) PAI. These four acquired PAIs encode proteins that may contribute to the overall pathogenic capacity and fitness of this bacterium to adapt to different hosts. Analysis of the in vivo and in vitro transcriptomes of this bacterium revealed differentially expressed PAI genes and non-PAI genes, suggesting that Sz35246 possess mechanisms for infecting animals and adapting to a wide range of host environments. Analysis of the genome identified potential Sz35246 virulence genes. Genes of the Fim III operon were presumed to be involved in breaking the host-restriction of Sz35246. CONCLUSION: Genome wide comparisons of Sz35246 with three other strains and transcriptome analysis revealed novel genes related to bacterial virulence and breaking the host-restriction. Four specific PAIs, which were judged to have been transferred into Sz35246 genome through HGT, were identified for the first time. Further analysis of the TA and RM systems in the PAIs will improve our understanding of the pathogenicity of this bacterium and could lead to the development of diagnostics and vaccines.

Effect of roxadustat on iron metabolism in patients with peritoneal dialysis: a real-world 24-week study.

BACKGROUND: Roxadustat is an oral hypoxia inducing factor-prolyl hydroxylase inhibitor (HIF-PHI) that regulates iron metabolism in patients with chronic kidney disease (CKD) primarily by reducing hepcidin levels and mobilizing internal iron stores. More data are needed to demonstrate the efficacy of roxadustat in regulating iron metabolism in patients with peritoneal dialysis (PD) compared with erythropoiesis stimulating agents (ESAs). METHODS: This prospective cohort study enrolled PD patients with a mean hemoglobin level of 60-100 g/L. All subjects were randomized into two groups at a ratio of 2:1 the roxadustat group (106 cases), and the ESA group (53 cases). The primary endpoint was the change in the iron biomarker levels and the proportion of patients with absolute iron deficiency and functional iron deficiency. RESULTS: Compared with ESAs, roxadustat significantly decreased hepcidin level (difference, - 20.09 ng/mL; 95% CI, - 30.26 to - 9.92), attenuated the increase in serum soluble transferrin receptor (sTFR) level (difference, - 7.87 nmol/L; 95% CI, - 12.11 to - 3.64), and reduced the proportion of patients with functional iron deficiency (roxadustat, 11.43%; ESA, 33.33%). There was no significant difference in safety of the two groups over the duration of the study. CONCLUSIONS: Compared with ESA group, roxadustat group showed significant differences in all iron biomarker levels except serum ferritin (sFt) and transferrin saturation (TSAT). These results suggest that roxadustat was superior to ESAs as a therapy for iron metabolism in PD patients. TRIAL REGISTRATION: This study completed Chinese Clinical Trial Registration on March 4, 2022 (registration number: ChiCTR2200057231).

A review of starch swelling behavior: Its mechanism, determination methods, influencing factors, and influence on food quality.

Swelling behavior involves the process of starch granules absorbing enough water to swell and increase the viscosity of starch suspension under hydrothermal conditions, making it one of the important aspects in starch research. The changes that starch granules undergo during the swelling process are important factors in predicting their functional properties in food processing. However, the factors that affect starch swelling and how swelling, in turn, affects the texture and digestion characteristics of starch-based foods have not been systematically summarized. Compared to its long chains, the short chains of amylose easily interact with amylopectin chains to inhibit starch swelling. Generally, reducing the swelling of starch could increase the strength of the gel while limiting the accessibility of digestive enzymes to starch chains, resulting in a reduction in starch digestibility. This article aims to conduct a comprehensive review of the mechanism of starch swelling, its influencing factors, and the relationship between swelling and the pasting, gelling, and digestion characteristics of starch. The role of starch swelling in the edible quality and nutritional characteristics of starch-based foods is also discussed, and future research directions for starch swelling are proposed.

Particulate organic carbon potentially increases methane emissions from oxic water of eutrophic lakes.

Lakes are hot spots for methane (CH4) emissions and particulate organic carbon (POC) production, which describes the methane paradox phenomenon. However, the current understanding of the source of POC and its effect on CH4 emissions during eutrophication remains unclear. In this study, 18 shallow lakes in different trophic states were selected to investigate the POC source and its contribution to CH4 production, particularly to reveal the underlying mechanisms of the methane paradox. The carbon isotopic analysis showed that the δ13Cpoc ranged from -30.28 ‰ to -21.14 ‰, indicating that cyanobacteria-derived carbon is an important source of POC. The overlying water was aerobic but contained high concentrations of dissolved CH4. Particularly, in hyper-eutrophic lakes, such as Lakes Taihu, Chaohu, and Dianshan, the dissolved CH4 concentrations were 2.11, 1.01, and 2.44 µmol/L, while the dissolved oxygen concentrations were 3.11, 2.92, and 3.17 mg/L, respectively. The intensified eutrophication increased the POC concentration, concomitantly promoting the dissolved CH4 concentration and the CH4 flux. These correlations revealed the role of POC in CH4 production and emission fluxes, particularly as a possible cause of the methane paradox, which is crucial for accurately evaluating the carbon budget and balance in shallow freshwater lakes.

Single-cell resolution analysis reveals the preparation for reprogramming the fate of stem cell niche in cotton lateral meristem.

BACKGROUND: Somatic embryogenesis is a major process for plant regeneration. However, cell communication and the gene regulatory network responsible for cell reprogramming during somatic embryogenesis are still largely unclear. Recent advances in single-cell technologies enable us to explore the mechanism of plant regeneration at single-cell resolution. RESULTS: We generate a high-resolution single-cell transcriptomic landscape of hypocotyl tissue from the highly regenerable cotton genotype Jin668 and the recalcitrant TM-1. We identify nine putative cell clusters and 23 cluster-specific marker genes for both cultivars. We find that the primary vascular cell is the major cell type that undergoes cell fate transition in response to external stimulation. Further developmental trajectory and gene regulatory network analysis of these cell clusters reveals that a total of 41 hormone response-related genes, including LAX2, LAX1, and LOX3, exhibit different expression patterns in the primary xylem and cambium region of Jin668 and TM-1. We also identify novel genes, including CSEF, PIS1, AFB2, ATHB2, PLC2, and PLT3, that are involved in regeneration. We demonstrate that LAX2, LAX1 and LOX3 play important roles in callus proliferation and plant regeneration by CRISPR/Cas9 editing and overexpression assay. CONCLUSIONS: This study provides novel insights on the role of the regulatory network in cell fate transition and reprogramming during plant regeneration driven by somatic embryogenesis.

Dashboard Layout Effects on Drivers' Searching Performance and Heart Rate: Experimental Investigation and Prediction.

Carsharing scale has been increasing rapidly with sharing economy. However, many users are reluctant to rent cars any longer due to the low-quality of interactive experience and usability, especially in terms of the dashboard design. This challenge should be urgently addressed in order to maintain the sustainable development of car-sharing industry and its environmental benefits. This study aims to investigate the relationship between users' driving activities (e.g., searching time, reading time, eye movement, heart rate) and dashboard layout. This study was conducted based on the experimental investigation among 58 respondents who were required to complete driving tasks in four types of cars with different dashboard layouts. Afterwards, a prediction model was developed to predict users heart rate (HR) based on the long short-term memory model, and logistic models were used to examine the relationship between the occurrence probability of minimum HR and dashboard reading. The results showed that the system usability of a dashboard was related to the drivers' eye movement characteristics including fixation duration, fixation times and pupil diameter. Most indicators had significant effects (p < 0.05) on the system usability score of corresponding dashboard. The long short-term memory model network (RMSE = 1.105, MAE = 0.009) was capable of predicting heart rate (HR) that happened in the process of instrument reading, which presented a periodic pattern rather than a continuous increase or decrease. It reflected that the network could better fit the non-linear and time-sequential laws of HR data. Furthermore, the probability of the lowest heart rate occurrence during the interaction with four dashboards was influenced by the average searching time, reading time and reading accuracy that were related to a specific layout. Overall, this study provided a theoretical reference for uncovering users' adaptive behaviors with the central control screen and for the optimal choice of a suitable dashboard layout in interface design.

Progress and prospects of Sacubitril/Valsartan: Based on heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is present in nearly half of patients with heart failure. The prevalence of heart failure with normal or near-normal ejection fractions increases more rapidly than in patients with reduced ejection fractions. Angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), aldosterone antagonist, ß-blocker, and calcium channel blocker have not shown significant efficacy in HFpEF clinical trials. Sacubitril/Valsartan, combined angiotensin receptor blocker (Valsartan) with neprilysin inhibitor (Sacubitril), was the first-of-its-kind angiotensin receptor-neprilysin inhibitor (ARNI) to be developed. It has shown significant efficacy on HFpEF in recent studies. It is considered that most of the current Sacubitril/Valsartan studies are still concentrated in the field of heart failure, especially heart failure with reduced ejection fraction (HFrEF). This review discusses the latest advances in cardiovascular, renal, and metabolic aspects of Sacubitril/Valsartan, mainly in HFpEF, providing more evidence for further future research on Sacubitril/Valsartan and raising issues that should be paid attention. At the same time, this review will introduce the academic consensus on Sacubitril/Valsartan in treating HFpEF in China.

Development of chitosan/tannic acid/corn starch multifunctional bilayer smart films as pH-responsive actuators and for fruit preservation.

The design of intelligent films for pH-responsive actuators fully constructed from natural biopolymers remains challenging. This study used natural biopolymers to develop a new type of smart and multifunctional chitosan/tannic acid/corn starch (CHT/TA/CS) bilayer films, which can be used for pH-responsive actuators and fruit preservation. We studied the microstructural morphology, physicochemical, antioxidant, antimicrobial properties of the films. Compared with the CHT film, the water vapor permeability (WVP) values of the CHT/TA/CS bilayer films were reduced by 3.1 times, and the tensile strength was increased by 4.6 times. The CHT/TA/CS bilayer films also exhibited high 1,1-diphenyl-2-picrylhydrazyl (DPPH) (94.6%) and hydroxyl (OH) (97.5%) radical scavenging activity. The bilayer films had good antimicrobial activity. The CHT/TA/CS bilayer films exhibited different directional deformation behaviors in acid-base solutions and could be used as pH-responsive actuators. By changing the solution's pH, the bilayer films could grab and release heavy objects 21 times heavier than themselves. Furthermore, the CHT/TA/CS bilayer coating prolonged the bananas' storage time from three to six days, and its weight loss was reduced by 14%. The developed CHT/TA/CS bilayer films have potential application in degradable materials, soft robotics fields, and food packaging materials.

Effect of Sacubitril/Valsartan on renal function in patients with chronic kidney disease and heart failure with preserved ejection fraction: A real-world 12-week study.

Patients with chronic kidney disease (CKD) are often complicated with heart failure with preserved ejection fraction (HFpEF). However, several drugs, including angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB), have not shown apparent benefits in terms of morbidity and mortality of HFpEF. PARAMOUNT and other studies have shown the potential benefits of Sacubitril/Valsartan on patients with HFpEF, but its effects on renal function and the effect of low-dose Sacubitril/Valsartan in actual clinical conditions have not been thoroughly evaluated. In our longitudinal and observational research, 353 patients were followed up for 12 weeks. We evaluated renal function [urinary protein, serum creatinine and estimated glomerular filtration rate (eGFR)] and cardiac function [NT-proBNP (brain natriuretic peptide), New York Heart Association (NYHA) classification, left ventricular ejection fraction (LVEF), left atrial width and left ventricular end-diastolic width] at baseline and during follow-up. Worsening renal function (WRF) was defined as an increased serum creatinine≥26.5umol/L or decreased eGFR≥20%. The decline of eGFR in the Sacubitril/Valsartan group was slower than that in the control group (p = 0.021). The outcome of proteinuria in the ACEI/ARB group was significantly better than that in the Sacubitril/Valsartan group (p = 0.001). In terms of echocardiogram, the average left atrial width in Sacubitril/Valsartan group decreased by 1.38 ± 3.02 mm, which was significantly lower than that in the ACEI/ARB group (p = 0.02). The increase of urine protein class in the ACEI/ARB group increased the risk of WRF with statistical significance (OR = 2.36, 95%CI 1.01-5.49, p = 0.047), but no statistical significance was found in all the patients or Sacubitril/Valsartan group. In conclusion, Sacubitril/Valsartan could more effectively slow down renal function decline and reverse myocardial remodeling in patients with CKD and HFpEF than ACEI/ARB, even at low doses, though its protective effect on urinary protein is not as good as that of ACEI/ARB.

Improvement of pasting and gelling properties of potato starch using a direct vapor-heat moisture treatment.

Conventional hydrothermal methods are lengthy and require high energy consumption. In this study, a quick and energy-saving direct vapor-heat moisture treatment (DV-HMT) method was used to improve the pasting and gelling properties of potato starch under the condition of high temperature (130 °C) and short periods (1, 3, 5, and 7 min). X-ray diffraction analysis exhibited that the relative crystallinity of DV-HMT starches decreased with the extension of treatment time. Small angle X-ray scattering measurements showed that the average thickness of the crystalline lamellae decreased from 6.193 to 5.937 nm, while the average thickness of the amorphous lamellae increased from 3.160 to 3.395 nm. Rapid visco-analyzer measurements exhibited that the breakdown values decreased to 0 mPa s for DV-HMT starches, indicating that this hydrothermal treatment led to starches with high resistance to heating and shearing. The gel hardness of starch treated by DV-HMT for 3 min (266 g) was around 5.4-fold higher than for non-treated starch (41 g). Considering the simple operation of DV-HMT and the short treatment periods (≤ 7 min) used in this study, DV-HMT could be a superior option to enhance the physicochemical and functional properties of starch.