Intestinal CXCR6+ ILC3s migrate to the kidney and exacerbate renal fibrosis via IL-23 receptor signaling enhanced by PD-1 expression.

Group 3 innate lymphoid cells (ILC3s) regulate inflammation and tissue repair at mucosal sites, but whether these functions pertain to other tissues-like the kidneys-remains unclear. Here, we observed that renal fibrosis in humans was associated with increased ILC3s in the kidneys and blood. In mice, we showed that CXCR6+ ILC3s rapidly migrated from the intestinal mucosa and accumulated in the kidney via CXCL16 released from the injured tubules. Within the fibrotic kidney, ILC3s increased the expression of programmed cell death-1 (PD-1) and subsequent IL-17A production to directly activate myofibroblasts and fibrotic niche formation. ILC3 expression of PD-1 inhibited IL-23R endocytosis and consequently amplified the JAK2/STAT3/RORγt/IL-17A pathway that was essential for the pro-fibrogenic effect of ILC3s. Thus, we reveal a hitherto unrecognized migration pathway of ILC3s from the intestine to the kidney and the PD-1-dependent function of ILC3s in promoting renal fibrosis.

A global meta-analysis of yield-scaled N2 O emissions and its mitigation efforts for maize, wheat, and rice.

Maintaining or even increasing crop yields while reducing nitrous oxide (N2 O) emissions is necessary to reconcile food security and climate change, while the metric of yield-scaled N2 O emission (i.e., N2 O emissions per unit of crop yield) is at present poorly understood. Here we conducted a global meta-analysis with more than 6000 observations to explore the variation patterns and controlling factors of yield-scaled N2 O emissions for maize, wheat and rice and associated potential mitigation options. Our results showed that the average yield-scaled N2 O emissions across all available data followed the order wheat (322 g N Mg-1 , with the 95% confidence interval [CI]: 301-346) > maize (211 g N Mg-1 , CI: 198-225) > rice (153 g N Mg-1 , CI: 144-163). Yield-scaled N2 O emissions for individual crops were generally higher in tropical or subtropical zones than in temperate zones, and also showed a trend towards lower intensities from low to high latitudes. This global variation was better explained by climatic and edaphic factors than by N fertilizer management, while their combined effect predicted more than 70% of the variance. Furthermore, our analysis showed a significant decrease in yield-scaled N2 O emissions with increasing N use efficiency or in N2 O emissions for production systems with cereal yields >10 Mg ha-1 (maize), 6.6 Mg ha-1 (wheat) or 6.8 Mg ha-1 (rice), respectively. This highlights that N use efficiency indicators can be used as valuable proxies for reconciling trade-offs between crop production and N2 O mitigation. For all three major staple crops, reducing N fertilization by up to 30%, optimizing the timing and placement of fertilizer application or using enhanced-efficiency N fertilizers significantly reduced yield-scaled N2 O emissions at similar or even higher cereal yields. Our data-driven assessment provides some key guidance for developing effective and targeted mitigation and adaptation strategies for the sustainable intensification of cereal production.

Shifts in soil ammonia-oxidizing community maintain the nitrogen stimulation of nitrification across climatic conditions.

Anthropogenic nitrogen (N) loading alters soil ammonia-oxidizing archaea (AOA) and bacteria (AOB) abundances, likely leading to substantial changes in soil nitrification. However, the factors and mechanisms determining the responses of soil AOA:AOB and nitrification to N loading are still unclear, making it difficult to predict future changes in soil nitrification. Herein, we synthesize 68 field studies around the world to evaluate the impacts of N loading on soil ammonia oxidizers and nitrification. Across a wide range of biotic and abiotic factors, climate is the most important driver of the responses of AOA:AOB to N loading. Climate does not directly affect the N-stimulation of nitrification, but does so via climate-related shifts in AOA:AOB. Specifically, climate modulates the responses of AOA:AOB to N loading by affecting soil pH, N-availability and moisture. AOB play a dominant role in affecting nitrification in dry climates, while the impacts from AOA can exceed AOB in humid climates. Together, these results suggest that climate-related shifts in soil ammonia-oxidizing community maintain the N-stimulation of nitrification, highlighting the importance of microbial community composition in mediating the responses of the soil N cycle to N loading.

Urbanization can accelerate climate change by increasing soil N2 O emission while reducing CH4 uptake.

Urban land-use change has the potential to affect local to global biogeochemical carbon (C) and nitrogen (N) cycles and associated greenhouse gas (GHG) fluxes. We conducted a meta-analysis to (1) assess the effects of urbanization-induced land-use conversion on soil nitrous oxide (N2 O) and methane (CH4 ) fluxes, (2) quantify direct N2 O emission factors (EFd ) of fertilized urban soils used, for example, as lawns or forests, and (3) identify the key drivers leading to flux changes associated with urbanization. On average, urbanization increases soil N2 O emissions by 153%, to 3.0 kg N ha-1  year-1 , while rates of soil CH4 uptake are reduced by 50%, to 2.0 kg C ha-1  year-1 . The global mean annual N2 O EFd of fertilized lawns and urban forests is 1.4%, suggesting that urban soils can be regional hotspots of N2 O emissions. On a global basis, conversion of land to urban greenspaces has increased soil N2 O emission by 0.46 Tg N2 O-N year-1 and decreased soil CH4 uptake by 0.58 Tg CH4 -C year-1 . Urbanization driven changes in soil N2 O emission and CH4 uptake are associated with changes in soil properties (bulk density, pH, total N content, and C/N ratio), increased temperature, and management practices, especially fertilizer use. Overall, our meta-analysis shows that urbanization increases soil N2 O emissions and reduces the role of soils as a sink for atmospheric CH4 . These effects can be mitigated by avoiding soil compaction, reducing fertilization of lawns, and by restoring native ecosystems in urban landscapes.

In situ 15 N-N2 O site preference and O2 concentration dynamics disclose the complexity of N2 O production processes in agricultural soil.

Arable soil continues to be the dominant anthropogenic source of nitrous oxide (N2 O) emissions owing to application of nitrogen (N) fertilizers and manures across the world. Using laboratory and in situ studies to elucidate the key factors controlling soil N2 O emissions remains challenging due to the potential importance of multiple complex processes. We examined soil surface N2 O fluxes in an arable soil, combined with in situ high-frequency measurements of soil matrix oxygen (O2 ) and N2 O concentrations, in situ 15 N labeling, and N2 O 15 N site preference (SP). The in situ O2 concentration and further microcosm visualized spatiotemporal distribution of O2 both suggested that O2 dynamics were the proximal determining factor to matrix N2 O concentration and fluxes due to quick O2 depletion after N fertilization. Further SP analysis and in situ 15 N labeling experiment revealed that the main source for N2 O emissions was bacterial denitrification during the hot-wet summer with lower soil O2 concentration, while nitrification or fungal denitrification contributed about 50.0% to total emissions during the cold-dry winter with higher soil O2 concentration. The robust positive correlation between O2 concentration and SP values underpinned that the O2 dynamics were the key factor to differentiate the composite processes of N2 O production in in situ structured soil. Our findings deciphered the complexity of N2 O production processes in real field conditions, and suggest that O2 dynamics rather than stimulation of functional gene abundances play a key role in controlling soil N2 O production processes in undisturbed structure soils. Our results help to develop targeted N2 O mitigation measures and to improve process models for constraining global N2 O budget.

Coupled anaerobic methane oxidation and metal reduction in soil under elevated CO2.

Continued current emissions of carbon dioxide (CO2 ) and methane (CH4 ) by human activities will increase global atmospheric CO2 and CH4 concentrations and surface temperature significantly. Fields of paddy rice, the most important form of anthropogenic wetlands, account for about 9% of anthropogenic sources of CH4 . Elevated atmospheric CO2 may enhance CH4 production in rice paddies, potentially reinforcing the increase in atmospheric CH4 . However, what is not known is whether and how elevated CO2 influences CH4 consumption under anoxic soil conditions in rice paddies, as the net emission of CH4 is a balance of methanogenesis and methanotrophy. In this study, we used a long-term free-air CO2 enrichment experiment to examine the impact of elevated CO2 on the transformation of CH4 in a paddy rice agroecosystem. We demonstrate that elevated CO2 substantially increased anaerobic oxidation of methane (AOM) coupled to manganese and/or iron oxides reduction in the calcareous paddy soil. We further show that elevated CO2 may stimulate the growth and metabolism of Candidatus Methanoperedens nitroreducens, which is actively involved in catalyzing AOM when coupled to metal reduction, mainly through enhancing the availability of soil CH4 . These findings suggest that a thorough evaluation of climate-carbon cycle feedbacks may need to consider the coupling of methane and metal cycles in natural and agricultural wetlands under future climate change scenarios.

Characteristics of annual NH3 emissions from a conventional vegetable field under various nitrogen management strategies.

High N-fertilizer applications to conventional vegetable production systems are associated with substantial emissions of NH3, a key substance that triggers haze pollution and ecosystem eutrophication and thus, causing considerable damage to human and ecosystem health. While N fertilization effects on NH3 volatilization from cereal crops have been relatively well studied, little is known about the magnitude and yield-scaled emissions of NH3 from vegetable systems. Here we report on a 2-year field study investigating the effect of various types and rates of fertilizer application on NH3 emissions and crop yields for a pepper-lettuce-cabbage rotation system in southwest China. Our results show that both NH3 emissions and direct emission factors of applied N varied largely across seasons over the 2-year period, highlighting the importance of measurements spanning entire cropping years. Across all treatments varying from solely applying urea fertilizers to only using organic manures, annual NH3 emissions ranged from 0.64 to 92.4 kg N ha-1 yr-1 (or 0.07-6.84 g N kg-1 dry matter), equivalent to 0.05-5.99% of the applied N. At annual scale, NH3 emissions correlated positively with soil δ15N values, indicating that soil δ15N may be used as an indicator for NH3 losses. NH3 emissions from treatments fertilized partially or fully with manure were significantly lower compared with the urea fertilized treatment, while vegetable yields remained unaffected. Moreover, full substitution of urea by manure as compared to the partial substitution further reduced the yield-scaled annual NH3 emissions by 79.0-92.4%. Across all vegetable seasons, there is a significant negative relationship between yield-scaled NH3 emissions and crop N use efficiency. Overall, our results suggest that substituting urea by manure and reducing total N inputs by 30-50% allows to reduce NH3 emissions without jeopardizing yields. Such a change in management provides a feasible option to achieve environmental sustainability and food security in conventional vegetable systems.

A synthesis of nitric oxide emissions across global fertilized croplands from crop-specific emission factors.

Nitrogen (N) fertilizer application to agricultural soils results in substantial emissions of nitric oxide (NO), a key substance in tropospheric chemistry involved in climate forcing and air pollution. However, the estimates of global cropland NO emissions remain uncertain due to a lack of information on direct NO emission factors (EFd s) of applied N for various cropping systems at seasonal or annual scales. Here we quantified the crop-specific seasonal and annual-scale NO EFd s through synthesizing 1094 measurements from 125 field-based studies worldwide. The global mean crop-specific seasonal EFd was 0.53%, with the highest for vegetables (0.75%). Among cereal crops, the EFd of maize (0.45%) or wheat (0.47%) was about three times higher than for rice (0.12%). At annual scale, the mean EFd across all cropping systems was 0.58%, with tea plantations having the highest (1.54%). For other cropping systems, the annual-scale EFd s ranged from 0.02% to 1.07%. Besides crop type, also soil organic carbon, total N, and pH as well as N fertilizer type were the main factors explaining the variations of NO EFd s. Based on obtained specific EFd s for each crop type, we estimated that NO emissions due to the use of synthetic fertilizers from global croplands are about 0.42-0.62 Tg N year-1 . Our budgets are relatively lower if compared to estimates derived by the use of IPCC defaults for NO emissions (0.72-1.66 Tg N year-1 ) or reported elsewhere (0.67-1.04 Tg N year-1 ). In our estimates, cash crops (vegetable, tea and orchard), which cover only 9% of the world cropland area, contributed about 31% to total NO emissions from global fertilized croplands. Overall, our meta-analysis provides improved crop-specific NO EFd s reflecting current stage of knowledge. The work also highlights the relative importance of cash crop production as sources for atmospheric NO, that is, agricultural systems on which mitigation efforts may focus.

Potential benefits of liming to acid soils on climate change mitigation and food security.

Globally, about 50% of all arable soils are classified as acidic. As crop and plant growth are significantly hampered under acidic soil conditions, many farmers, but increasingly as well forest managers, apply lime to raise the soil pH. Besides its direct effect on soil pH, liming also affects soil C and nutrient cycles and associated greenhouse gas (GHG) fluxes. In this meta-analysis, we reviewed 1570 observations reported in 121 field-based studies worldwide, to assess liming effects on soil GHG fluxes and plant productivity. We found that liming significantly increases crop yield by 36.3%. Also, soil organic C (SOC) stocks were found to increase by 4.51% annually, though soil respiration is stimulated too (7.57%). Moreover, liming was found to reduce soil N2 O emission by 21.3%, yield-scaled N2 O emission by 21.5%, and CH4 emission and yield-scaled CH4 emission from rice paddies by 19.0% and 12.4%, respectively. Assuming that all acid agricultural soils are limed periodically, liming results in a total GHG balance benefit of 633-749 Tg CO2 -eq year-1 due to reductions in soil N2 O emissions (0.60-0.67 Tg N2 O-N year-1 ) and paddy soil CH4 emissions (1.75-2.21 Tg CH4  year-1 ) and increases in SOC stocks (65.7-110 Tg C year-1 ). However, this comes at the cost of an additional CO2 release (c. 624-656 Tg CO2  year-1 ) deriving from lime mining, transport and application, and lime dissolution, so that the overall GHG balance is likely neutral. Nevertheless, liming of acid agricultural soils will increase yields by at least 6.64 × 108  Mg year-1 , covering the food supply of 876 million people. Overall, our study shows for the first time that a general strategy of liming of acid agricultural soils is likely to result in an increasing sustainability of global agricultural production, indicating the potential benefit of liming acid soils for climate change mitigation and food security.

Elevated atmospheric CO2 reduces yield-scaled N2 O fluxes from subtropical rice systems: Six site-years field experiments.

Increasing levels of atmospheric CO2 are expected to enhance crop yields and alter soil greenhouse gas fluxes from rice paddies. While elevated CO2 ( E CO 2 ) effects on CH4 emissions from rice paddies have been studied in some detail, little is known how E CO 2 might affect N2 O fluxes or yield-scaled emissions. Here, we report on a multi-site, multi-year in-situ FACE (free-air CO2 enrichment) study, aiming to determine N2 O fluxes and crop yields from Chinese subtropical rice systems as affected by E CO 2 . In this study, we tested various N fertilization and residue addition treatments, with rice being grown under either E CO 2 (+200 µmol/mol) or ambient control. Across the six site-years, rice straw and grain yields under E CO 2 were increased by 9%-40% for treatments fertilized with ≥150 kg N/ha, while seasonal N2 O emissions were decreased by 23%-73%. Consequently, yield-scaled N2 O emissions were significantly lower under E CO 2 . For treatments receiving insufficient fertilization (≤125 kg N/ha), however, no significant E CO 2 effects on N2 O emissions were observed. The mitigating effect of E CO 2 upon N2 O emissions is closely associated with plant N uptake and a reduction of soil N availability. Nevertheless, increases in yield-scaled N2 O emissions with increasing N surplus suggests that N surplus is a useful indicator for assessing N2 O emissions from rice paddies. Our findings indicate that with rising atmospheric CO2 soil N2 O emissions from rice paddies will decrease, given that the farmers' N fertilization is usually sufficient for crop growth. The expected decrease in N2 O emissions was calculated to compensate 24% of the simultaneously observed increase in CH4 emissions under E CO 2 . This shows that for an agronomic and environmental assessment of E CO 2 effects on rice systems, not only CH4 emissions, but also N2 O fluxes and yield-scaled emissions need to be considered for identifying most climate-friendly and economically viable options for future rice production.

Serum Sodium Modifies the Association of Systolic Blood Pressure with Mortality in Peritoneal Dialysis Patients.

INTRODUCTION: High serum sodium is associated with increased blood pressure (BP) in dialysis patients, which is a risk factor for cardiovascular (CV) disease. However, the interaction between serum sodium and BP and their association with clinical outcomes in peritoneal dialysis (PD) patients is uncertain. METHODS: We analyzed a retrospective cohort of 1,656 incident PD patients from January 2006 to December 2013, who were followed up until December 2018. Cox proportional hazards regression models were used to evaluate the association of serum sodium and BP with all-cause and CV mortality. A priori interaction between serum sodium and systolic BP (SBP) was explored, and a subgroup analysis was performed by stratifying SBP into the following 3 groups: <110, 110-130, and >130 mm Hg. RESULTS: Mean baseline serum sodium was 140.2 ± 3.6 mmol/L, mean SBP was 137 ± 20 mm Hg, and diastolic BP was 85 ± 14 mm Hg. During a median (range) follow-up time of 46.5 (2.6-154.3) months, 507 patients died, 252 of whom died due to CV disease. SBP did not predict all-cause and CV mortality when BP was assessed as a continuous variable. However, SBP >130 or <110 mm Hg was associated with higher risk of all-cause and CV mortality compared with SBP of 110-130 mm Hg. There was a significant interaction between baseline serum sodium and SBP for all-cause mortality (p for interaction = 0.016). In subgroup analysis, among those with SBP >130 mm Hg, the risk of all-cause mortality was elevated in those with serum sodium ≥140 mmol/L (adjusted hazard ratio [aHR] 1.45 [95% confidence interval (CI): 1.07-1.98]), but not for those with serum sodium <140 mmol/L (aHR 1.27 [95% CI: 0.89-1.82]). Conversely, among those with SBP <110 mm Hg, those with serum sodium <140 mmol/L had an elevated risk of mortality (aHR 1.99 [95% CI: 1.31-3.02]), but not those with serum sodium ≥140 mmol/L (aHR 1.15 [95% CI: 0.74-1.79]) (p for interaction = 0.028). CONCLUSION: The association of BP with mortality was modified by serum sodium levels in PD patients. Further studies are needed to evaluate whether individualized BP control based on serum sodium levels contributes to improve patient outcomes.

Urgent-start peritoneal dialysis for patients with end stage renal disease: a 10-year retrospective study.

BACKGROUND: Urgent-start peritoneal dialysis (PD) can help patients with end-stage renal diseases (ESRD) that are referred late to dialysis. However, catheter patency and related complications of urgent-start PD have not been thoroughly clarified. We investigated the clinical outcomes of urgent-start PD in a Chinese cohort. METHODS: We enrolled ESRD patients who received urgent-start PD (starting PD within 14 days after catheter insertion) in our center from January 1, 2006 to December 31, 2014, and followed them up for 10 years. The primary outcome was catheter failure. Secondary outcomes included short-term and long-term complications related to urgent-start PD. RESULTS: Totally 2059 patients (58.9% male, mean age 47.6 ± 15.9 years) were enrolled. Few perioperative complications were observed, including significant hemorrhage (n = 3, 0.1%) and bowel perforation (n = 0). Early peritonitis occurred in 24 (1.2%) patients (0.28 episodes per patient-year). Within the first month after catheter insertion, functional catheter malfunction occurred in 85 (4.1%) patients, and abdominal wall complications (including hernia, hydrothorax, hydrocele, and leakage) in 36 (1.7%) patients. During a median 36.5 (17.7-61.4) months of follow-up, 75 (3.6%) patients experienced catheter failure, and 291 (14.1%) had death-censoring technique failure. At the end of 1-month, 1 -year, 3-year, and 5-year, catheter patency rate was 97.6, 96.4, 96.2, 96.2%; and technique survival rate was 99.5, 97.0, 90.3, 82.7%, respectively. After adjusting for confounders, every 5-year increase in age was associated with 19% decrease of risk for catheter failure (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.73-0.89). Male sex (HR: 1.43, 95% CI: 1.00-2.04), diabetic nephropathy (HR: 1.56, 95% CI: 1.08-2.25) and low hemoglobin levels (HR: 0.89, 95% CI: 0.81-0.98) were independent risk factors for abdominal wall complications. CONCLUSIONS: Urgent-start PD is a safe and efficacious option for unplanned ESRD patients. A well-trained PD team, a standardized catheter insertion procedure by experienced nephrologists, and a carefully designed initial PD prescription as well as comprehensive follow-up care, might be essential for the successful urgent-start PD program.

Characterizing nitric oxide emissions from two typical alpine ecosystems.

A portion of alpine meadows has been and will continue to be cultivated due to the concurrent increasing demands for animal- and crop-oriented foods and global warming. However, it remains unclear how these long-term changes in land use will affect nitric oxide (NO) emission. At a field site with a calcareous soil on the Qinghai-Tibetan Plateau, the authors measured the year-round NO fluxes and related variables in a typically winter-grazed natural alpine meadow (NAM) and its adjacent forage oat field (FOF). The results showed that long-term plow tillage, fertilization and growing forage oats significantly yielded ca. 2.7 times more (p < 0.01) NO emissions from the FOF than the NAM (conservatively 208 vs. 56 g N/(ha·year) on average). The spring freeze-thaw period and non-growing season accounted for 17%-35% of the annual emissions, respectively. The Q10 of surface soil temperature (Ts) was 8.9 in the NAM (vs. 3.8 in the FOF), indicating increases of 24%-93% in NO emissions per 1-3 °C increase. However, the warming-induced increases could be smaller than those due to land use change and management practices. The Ts and concentrations of ammonium, nitrate and water-extractable organic carbon jointly explained 69% of the variance in daily NO fluxes from both fields during the annual period (p < 0.001). This result indicates that temporally and/or spatially distributed NO fluxes from landscapes with calcareous soils across native alpine meadows and/or fields cultivated with forage oats can be predicted by simultaneous observations of these four soil variables.

Grazing-induced reduction of natural nitrous oxide release from continental steppe.

Atmospheric concentrations of the greenhouse gas nitrous oxide (N(2)O) have increased significantly since pre-industrial times owing to anthropogenic perturbation of the global nitrogen cycle, with animal production being one of the main contributors. Grasslands cover about 20 per cent of the temperate land surface of the Earth and are widely used as pasture. It has been suggested that high animal stocking rates and the resulting elevated nitrogen input increase N(2)O emissions. Internationally agreed methods to upscale the effect of increased livestock numbers on N(2)O emissions are based directly on per capita nitrogen inputs. However, measurements of grassland N(2)O fluxes are often performed over short time periods, with low time resolution and mostly during the growing season. In consequence, our understanding of the daily and seasonal dynamics of grassland N(2)O fluxes remains limited. Here we report year-round N(2)O flux measurements with high and low temporal resolution at ten steppe grassland sites in Inner Mongolia, China. We show that short-lived pulses of N(2)O emission during spring thaw dominate the annual N(2)O budget at our study sites. The N(2)O emission pulses are highest in ungrazed steppe and decrease with increasing stocking rate, suggesting that grazing decreases rather than increases N(2)O emissions. Our results show that the stimulatory effect of higher stocking rates on nitrogen cycling and, hence, on N(2)O emission is more than offset by the effects of a parallel reduction in microbial biomass, inorganic nitrogen production and wintertime water retention. By neglecting these freeze-thaw interactions, existing approaches may have systematically overestimated N(2)O emissions over the last century for semi-arid, cool temperate grasslands by up to 72 per cent.

N2O emissions from an apple orchard in the coastal area of Bohai Bay, China.

Using static chambers and gas chromatography, nitrous oxide (N2O) fluxes from an apple orchard soil in the Bohai Bay region of China were measured from February 2010 to February 2011. In this study, two nitrogen (N) fertilizer treatments were designed--without (CK) or with (SN) synthetic N fertilizers (800 kg N ha(-1)). The annual cumulative N2O emissions from CK and SN were 34.6 ± 3.0 (mean ± standard error) and 44.3 ± 6.0 kg N2O-N ha(-1), respectively. Such high emissions resulted from the intensive N fertilization in the experimental and previous years. The direct emission factor (EFd) of N2O induced by the applied synthetic N fertilizers was 1.2%. The EFd is within the range of previous studies carried out in other croplands, which suggests that it is reasonable to estimate regional N2O emissions from apple orchards using the EFd obtained in other croplands. In addition, significant positive correlations existed between N2O fluxes and soil temperatures or soil dissolved organic carbon contents.

Targeted therapies for lupus nephritis: Current perspectives and future directions.

ABSTRACT: Lupus nephritis (LN), a severe manifestation of systemic lupus erythematosus, poses a substantial risk of progression to end-stage renal disease, with increased mortality. Conventional therapy for LN relies on broad-spectrum immunosuppressants such as glucocorticoids, mycophenolate mofetil, and calcineurin inhibitors. Although therapeutic regimens have evolved over the years, they have inherent limitations, including non-specific targeting, substantial adverse effects, high relapse rates, and prolonged maintenance and remission courses. These drawbacks underscore the need for targeted therapeutic strategies for LN. Recent advancements in our understanding of LN pathogenesis have led to the identification of novel therapeutic targets and the emergence of biological agents and small-molecule inhibitors with improved specificity and reduced toxicity. This review provides an overview of the current evidence on targeted therapies for LN, elucidates the biological mechanisms of responses and failure, highlights the challenges ahead, and outlines strategies for subsequent clinical trials and integrated immunomodulatory approaches.

Three years of CO2, CH4 and N2O fluxes from different sheepfolds in a semiarid steppe region, China.

To better assess greenhouse gas (GHG) emissions from livestock folds in semi-arid steppe zones and reduce uncertainties in regional and national GHG emission inventories, we measured the fluxes of carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O) from sheepfolds under contrasting management regimes (i.e., summer sheepfolds under continuous and rotational grazing strategies and the winter sheepfold) for 3 consecutive years. Our results showed that these GHG fluxes had high intra-annual and interannual variations, emphasizing the importance of multi-year measurement for achieving temporally representative annual budgets. Sheep presence and temperature appeared to be the key factors driving CH4, CO2 and N2O fluxes from sheepfolds, e.g., higher GHG emissions usually occurred in seasons with sheep presence. However, the sheepfold type exerted a distinct influence on the temperature sensitivity of GHG fluxes, i.e., the Q10 values for GHG fluxes were generally higher in summer sheepfolds than in winter sheepfold. The annual CH4, CO2 and N2O emissions for the 3 sheepfolds were estimated to be 1.5-16.5 kg C ha-1 yr-1 (or 1.9-2.6 g C yr-1sheep-1), 8.6-16.0 t C ha-1 yr-1 (or 5.1-6.6 kg C yr-1sheep-1) and 28.3-41.9 kg N ha-1 yr-1 (or 19.0-26.8 g N yr-1sheep-1), respectively. Averaging across the 3 years, the annual net GHG emissions (CH4 + CO2 + N2O) for all sheepfolds ranged from 47 to 71 t CO2-eq ha-1 yr-1 (or 27-36 kg CO2-eq yr-1 sheep-1), of which CO2 and N2O emissions contributed the most; moreover, the annual net GHG emissions had no significant differences between sheepfold types or grazing strategies. Given that local steppe soils have a lower magnitude of soil respiration (CO2) and N2O emissions and are also net sink for atmospheric CH4, the sheepfold sites in this region are undoubtedly one of the significant hotspots for GHG emissions and could be key areas to focus mitigation action.

A Natural Small Molecule Mitigates Kidney Fibrosis by Targeting Cdc42-mediated GSK-3ß/ß-catenin Signaling.

Kidney fibrosis is a common fate of chronic kidney diseases (CKDs), eventually leading to renal dysfunction. Yet, no effective treatment for this pathological process has been achieved. During the bioassay-guided chemical investigation of the medicinal plant Wikstroemia chamaedaphne, a daphne diterpenoid, daphnepedunin A (DA), is characterized as a promising anti-renal fibrotic lead. DA shows significant anti-kidney fibrosis effects in cultured renal fibroblasts and unilateral ureteral obstructed mice, being more potent than the clinical trial drug pirfenidone. Leveraging the thermal proteome profiling strategy, cell division cycle 42 (Cdc42) is identified as the direct target of DA. Mechanistically, DA targets to reduce Cdc42 activity and down-regulates its downstream phospho-protein kinase Cζ(p-PKCζ)/phospho-glycogen synthase kinase-3ß (p-GSK-3ß), thereby promoting ß-catenin Ser33/37/Thr41 phosphorylation and ubiquitin-dependent proteolysis to block classical pro-fibrotic ß-catenin signaling. These findings suggest that Cdc42 is a promising therapeutic target for kidney fibrosis, and highlight DA as a potent Cdc42 inhibitor for combating CKDs.

Quantification of N and C cycling during aerobic composting, including automated direct measurement of N2, N2O, NO, NH3, CO2 and CH4 emissions.

Closing the carbon (C) and nitrogen (N) balance has yet to be achieved in aerobic bioprocess due to current methodological drawbacks in the frequency of sampling and detection and the challenge in direct measurement of instantaneous N2 emission. To address this issue, a novel system was developed enabling simultaneous and online determination of gaseous C and N species (N2, N2O, NO, NH3, CO2 and CH4) from aerobic composting at a high frequency of 120 times·d-1. A helium­oxygen gas mixture was used to replace the air in the system to enable direct measurement of N2 emission, and three different gas exchange methods were assessed in their ability to minimize atmospheric background N2: 1) the N2-free gas purging method; 2) one cycle of the evacuation-refilling procedure; 3) one cycle of evacuating and refilling followed by N2-free gas purging. Method 3 was demonstrated as an optimum N2-removal method, and background N2 concentrations decreased to ~66 µmol·mol-1 within 11.6 h. During the N2-free gas purging period, low temperature incubation at 15 °C reduced CO2, CH4, NO, N2O and NH3 losses by 80.5 %, 41-fold, 10-fold, 11,403-fold and 61.4 %, respectively, compared with incubation at 30 °C. Therefore, a fast and low-perturbation N2 removal method was developed, namely the evacuating/refilling-low temperature purging method. Notably, all C and N gases exhibited large within-day variations during the peak emission period, which can be addressed by high-frequency measurement. Based on the developed method, up to 97.8 % of gaseous C and 95.6 % of gaseous N losses were quantified over a 43-day compost incubation, with N2 emission accounting (on average) for 5.8 % of the initial total N. This system for high frequency measurement of multiple gases (including N2) provides a novel tool for obtaining a deeper understanding of C and N turnover and more accurate estimation of reactive N and greenhouse gas emissions during composting.

The feasibility and efficiency for constructing arteriovenous fistula with <2 mm vein-a systematic review and meta-analysis.

Background: Autogenous arteriovenous fistula (AVF) is an efficient hemodialysis access for patients with end-stage kidney disease (ESKD). The specific threshold of vein diameter still not reached a consensus. Method: We conducted a comprehensive search in PubMed, Embase, and Web of Science databases for articles which comparing the treatment outcomes of AVF with 2 mm as vein diameter threshold. Fixed and random effect model were used for synthesis of results. Subgroup analysis was designed to assess the risk of bias. Result: Eight high-quality articles were included finally. Among a total of 1,075 patients (675 males and 400 females), 227 and 809 patients possessed <2 mm and ≥2 mm vein respectively. Apart from gender and coronary artery disease (P < 0.05), there was no significant difference in age, diabetes, hypertension or radial artery between maturation and non-maturation groups. The functional maturation rate was lower in patients with <2 mm vein according to fixed effect model [OR = 0.19, 95% CI (0.12, 0.30), P < 0.01]. There was no significant difference in primary [OR = 0.63, 95% CI (0.12, 3.25), P = 0.58] or cumulative patency rates [OR = 0.40, 95% CI (0.13, 1.19), P = 0.10]. Conclusion: Vein diameter less than 2 mm has a negative impact on the functional maturation rate of AVF, while it does not affect the primary and cumulative patency rates (12 months).