Long-term warming increased carbon sequestration capacity in a humid subtropical forest.

Tropical and subtropical forests play a crucial role in global carbon (C) pools, and their responses to warming can significantly impact C-climate feedback and predictions of future global warming. Despite earth system models projecting reductions in land C storage with warming, the magnitude of this response varies greatly between models, particularly in tropical and subtropical regions. Here, we conducted a field ecosystem-level warming experiment in a subtropical forest in southern China, by translocating mesocosms (ecosystem composed of soils and plants) across 600 m elevation gradients with temperature gradients of 2.1°C (moderate warming), to explore the response of ecosystem C dynamics of the subtropical forest to continuous 6-year warming. Compared with the control, the ecosystem C stock decreased by 3.8% under the first year of 2.1°C warming; but increased by 13.4% by the sixth year of 2.1°C warming. The increased ecosystem C stock by the sixth year of warming was mainly attributed to a combination of sustained increased plant C stock due to the maintenance of a high plant growth rate and unchanged soil C stock. The unchanged soil C stock was driven by compensating and offsetting thermal adaptation of soil microorganisms (unresponsive soil respiration and enzyme activity, and more stable microbial community), increased plant C input, and inhibitory C loss (decreased C leaching and inhibited temperature sensitivity of soil respiration) from soil drying. These results suggest that the humid subtropical forest C pool would not necessarily diminish consistently under future long-term warming. We highlight that differential and asynchronous responses of plant and soil C processes over relatively long-term periods should be considered when predicting the effects of climate warming on ecosystem C dynamics of subtropical forests.

Climate change-related biodiversity fluctuations and composition changes in an old-growth subtropical forest: A 26-yr study.

The detection and attribution of biodiversity change is of great scientific interest and central to policy effects aimed at meeting biodiversity targets. Yet, how such a diverse climate scenarios influence forest biodiversity and composition dynamics remains unclear, particularly in high diversity systems of subtropical forests. Here we used data collected from the permanent sample plot spanning 26 years in an old-growth subtropical forest. Combining various climatic events (extreme drought, subsequent drought, warming, and windstorm), we analyzed long-term dynamics in multiple metrics: richness, turnover, density, abundance, reordering and stability. We did not observe consistent and directional trends in species richness under various climatic scenarios. Still, drought and windstorm events either reduced species gains or increased species loss, ultimately increased species turnover. Tree density increased significantly over time as a result of rapid increase in smaller individuals due to mortality in larger trees. Climate events caused rapid changes in dominant populations due to a handful of species undergoing strong increases or declines in abundance over time simultaneously. Species abundance composition underwent significant changes, particularly in the presence of drought and windstorm events. High variance ratio and species synchrony weaken community stability under various climate stress. Our study demonstrates that all processes underlying forest community composition changes often occur simultaneously and are equally affected by climate events, necessitating a holistic approach to quantifying community changes. By recognizing the interconnected nature of these processes, future research should accelerate comprehensive understanding and predicting of how forest vegetation responds to global climate change.

Effect of fire and post-fire management on soil microbial communities in a lower subtropical forest ecosystem after a mountain fire.

Wildfires and post-fire management exert profound effects on soil properties and microbial communities in forest ecosystems. Understanding microbial community recovery from fire and what the best post-fire management should be is very important but needs to be sufficiently studied. In light of these gaps in our understanding, this study aimed to assess the short-term effects of wildfire and post-fire management on both bacteria and fungi community composition, diversity, structure, and co-occurrence networks, and to identify the principal determinants of soil processes influencing the restoration of these communities. Specifically, we investigated soil bacterial and fungal community composition, diversity, structure, and co-occurrence networks in lower subtropical forests during a short-term (<3 years) post-fire recovery period at four main sites in Guangdong Province, southern China. Our results revealed significant effects of wildfires on fungal community composition, diversity, and co-occurrence patterns. Network analysis indicated reduced bacterial network complexity and connectivity post-fire, while the same features were enhanced in fungal networks. However, post-fire management effects on microbial communities were negligible. Bacterial diversity correlated positively with soil microbial biomass nitrogen, soil organic carbon, and soil total nitrogen. Conversely, based on the best random forest model, fungal community dynamics were negatively linked to nitrate-nitrogen and soil water content. Spearman's correlation analysis suggested positive associations between bacterial networks and soil factors, whereas fungal networks exhibited predominantly negative associations. This study elucidates the pivotal role of post-fire management in shaping ecological outcomes. Additionally, it accentuates the discernible distinctions between bacterial and fungal responses to fire throughout a short-term recovery period. These findings contribute novel insights that bear significance in evaluating the efficacy of environmental management strategies.

Climate change reshapes plant trait spectrum to explain biomass dynamics in an old-growth subtropical forest.

Climate change leads to novel species interactions and continues to reshuffle ecological communities, which significantly declines carbon accumulation rates in mature forests. Still, little is known about the potential influence of multiple global change factors on long-term biomass dynamics and functional trait combinations. We used temporal demographic records spanning 26 years and extensive databases of functional traits to assess how old-growth subtropical forest biomass dynamics respond to various climatic change scenarios (extreme drought, subsequent drought, warming, elevated CO2 concentrations, and windstorm). We found that the initial severe drought, subsequent drought and windstorm events increased biomass loss due to tree mortality, which exceeded the biomass gain produced by survivors and recruits, ultimately resulting in more negative net biomass balances. These drought and windstorm events caused massive biomass loss due to tree mortality that tended towards acquisition species with high hydraulic efficiency, whereas biomass growth from survivors and recruits tended to consist of acquisition species with high hydraulic safety. Compensatory growth in this natural forest provided good explanation for the increase in biomass growth after drought and windstorm events. Notably, these dominant-species transitions reduced carbon storage and residence time, forming a positive carbon-climate feedback loop. Our findings suggest that climate changes could alter functional strategies and cause shifts in new dominant species, which could greatly reduce ecological functions and carbon gains of old-growth subtropical forests.

Acidity of Soil and Water Decreases in Acid-Sensitive Forests of Tropical China.

Acid deposition in China has been declining since the 2000s. While this may help mitigate acidification in forest soils and water, little is known about the recovery of soils and water from previous severe acidification in tropical China. Here, we assessed the chemistry of mineral soils, water, and acid gases (SO2 and NOx) from three successional forest types in tropical China from 2000 to 2022. Our results showed that soil pH increased synchronously from 3.9 (2000-2015) to 4.2 (2016-2022) across all three forest types, with exchangeable acid initially decreasing and thereafter stabilizing. Surface and ground water pH also gradually increased throughout the monitoring period. Soil pH recovery was stronger in the primary than in the planted forest. However, soil pH recovery lagged behind the increase in rainfall pH by approximately a decade. The recovery of soil pH was likely related to the positive effects of the dissolution of Al/Fe-hydroxysulfate mineral and subsequent sulfur desorption on soil acid-neutralizing capacity, increased soil organic matter, and climate warming, but was likely moderated by increased exchangeable aluminum and potentially proton-producing hydroxysulfate mineral dissolution that caused the lagged soil pH recovery. Surface and ground water pH recovery was attributed to increased water acid-neutralizing capacity. Our study reports the potential for the recovery of acidified soil and water following decreased acid deposition and provides new insights into the functional recovery of acid-sensitive forests.

Can leaf drought tolerance predict species abundance and its changes in tropical-subtropical forests?

Climate change has resulted in an increase in drought severity in the species-rich tropical and subtropical forests of southern China. Exploring the spatiotemporal relationship between drought-tolerance trait and tree abundance provides a means to elucidate the impact of droughts on community assembly and dynamics. In this study, we measured the leaf turgor loss point (πtlp) for 399 tree species from three tropical forest plots and three subtropical forest plots. The plot area was 1 ha and tree abundance was calculated as total basal area per hectare according to the nearest community census data. The first aim of this study was to explore πtlp abundance relationships in the six plots across a range of precipitation seasonality. Additionally, three of the six plots (two tropical forests and one subtropical forest) had consecutive community censuses data (12-22 years) and the mortality ratios and abundance year slope of tree species were analyzed. The second aim was to examine whether πtlp is a predictor of tree mortality and abundance changes. Our results showed that tree species with lower (more negative) πtlp were more abundant in the tropical forests with relative high seasonality. However, πtlp was not related to tree abundance in the subtropical forests with low seasonality. Moreover, πtlp was not a good predictor of tree mortality and abundance changes in both humid and dry forests. This study reveals the restricted role of πtlp in predicting the response of forests to increasing droughts under climate change.

An Interannual Comparative Study on Ecosystem Carbon Exchange Characteristics in the Dinghushan Biosphere Reserve, a Dominant Subtropical Evergreen Forest Ecosystem.

Compared with other forest systems, research interest in the potential for a stronger ecosystem carbon sequestration of evergreen forests throughout subtropical China has greatly increased. The eddy covariance technique is widely employed to determine accurate forest-atmosphere carbon dioxide (CO2) flux, which is subsequently used to determine forest ecosystem carbon exchange characteristics. The Dinghushan Biosphere Reserve, a subtropical monsoon evergreen broad-leaved forest, is a suitable study area due to its warm and humid climate (compared with other regions within the same latitude), consequently playing a role in the carbon cycle in the region. For this study, we hypothesized that the forest land in this region generally acts as a carbon sink, and that its carbon sequestration capacity increases over time despite the influence of climatic factors. Here, we compared net CO2 flux data derived from the eddy covariance technique over an 8-year study window. Additionally, we ascertained the effects of various environmental factors on net CO2 flux, while also using the Michaelis-Menten model and a physiologically based process model to track and report on ecosystem carbon exchange characteristics. We observed seasonal trends in daily ecosystem flux, indicative of sensitivity to climatic factors, such as air temperature, precipitation, and sunlight. The carbon sequestration capacity of the region exhibited seasonal variability, increasing from October to March (-264 g C m-2 year-1, i.e., 48.4%) while weakening from April to September (-150 g C m-2 year-1, i.e., 40.4%) on average. The net ecosystem exchange (NEE) rate varied from -518 to -211 g C m-2 year-1; ecosystem respiration (Re) varied from 1,142 to 899 g C m-2 year-1; and gross primary production (GPP) varied from 1,552 to 1,254 g C m-2 year-1. This study found that even though the Dinghushan Biosphere Reserve generally acts as a carbon sink, its carbon sequestration capacity did not increase significantly throughout the study period. The techniques (models) used in this study are suitable for application in other ecosystems globally, which can aid in their management and conservation. Finally, the Dinghushan Biosphere Reserve is both an exemplary and a model forest system useful in exploring CO2 absorption and sequestration from the atmosphere.

Receptor activator of NF-κB mediates podocyte injury in diabetic nephropathy.

Receptor activator of NF-κB (RANK) expression is increased in podocytes of patients with diabetic nephropathy. However, the relevance of RANK to diabetic nephropathy pathobiology remains unclear. Here, to evaluate the role of podocyte RANK in the development of diabetic nephropathy, we generated a mouse model of podocyte-specific RANK depletion (RANK-/-Cre T), and a model of podocyte-specific RANK overexpression (RANK TG), and induced diabetes in these mice with streptozotocin. We found that podocyte RANK depletion alleviated albuminuria, mesangial matrix expansion, and basement membrane thickening, while RANK overexpression aggravated these indices in streptozotocin-treated mice. Moreover, streptozotocin-triggered oxidative stress was increased in RANK overexpression but decreased in the RANK depleted mice. Particularly, the expression of NADPH oxidase 4, and its obligate partner, P22phox, were enhanced in RANK overexpression, but reduced in RANK depleted mice. In parallel, the transcription factor p65 was increased in the podocyte nuclei of RANK overexpressing mice but decreased in the RANK depleted mice. The relevant findings were largely replicated with high glucose-treated podocytes in vitro. Mechanistically, p65 could bind to the promoter regions of NADPH oxidase 4 and P22phox, and increased their respective gene promoter activity in podocytes, dependent on the levels of RANK. Taken together, these findings suggested that high glucose induced RANK in podocytes and caused the increase of NADPH oxidase 4 and P22phox via p65, possibly together with the cytokines TNF- α, MAC-2 and IL-1 ß, resulting in podocyte injury. Thus, we found that podocyte RANK was induced in the diabetic milieu and RANK mediated the development of diabetic nephropathy, likely by promoting glomerular oxidative stress and proinflammatory cytokine production.

Mapping forest type and age in China's plantations.

Forest age serves as an essential factor in determining the accuracy of historical and future carbon (C) uptake quantifications, which is especially critical for China since the forest C stock dynamics are sensitive to the fast-growing, young-age plantations. However, a spatially explicit forest age maps with specific focus on forest plantations is not available yet. In this study, we developed a 1-km resolution age and type maps of forest plantations, and quantified their uncertainties spatially using field-measured data, national forest inventory data, digitalized forest maps, and remote sensing-based forest height maps. Simulation results showed forest plantations were 16.5 years old at national scale in 2005, which is close to the age of 16.6 years old derived from the 7th national inventory data using medium age in each forest plantation group with weighted area. Interestingly, we found that human management played an important role in forest age map reconstruction, which has not yet been considered in former studies. We also suggest that forest age and type maps should be used consistently in C stock simulations to avoid biases from mismatch information. Large uncertainty found in this study suggests further endeavors are required for improving the forest age and type maps.

Levels and Clinical Significances of Glypican-5 in Urine of Type 2 Diabetic Nephropathy Cases.

INTRODUCTION: Increased glypican-5 expression in podocytes induces podocyte injury. Glypican-5 is shed into the urine, but its value in predicting progression of diabetic nephropathy (DN) has not been investigated. METHODS: Glypican-5 was determined in spot urine from 20 type 2 diabetes mellitus (T2DM) patients, and 37 type 2 DN patients, and 20 healthy controls by enzyme-linked immunosorbent assay. The association of urinary glypican-5 with markers of renal function was evaluated. RESULTS: Urinary glypican-5 was significantly higher in DN patients than in both DM patients and controls. Glypican-5 level was not associated with baseline 24-hour urine protein/albumin excretion, serum creatinine, estimated glomerular filtration rate (eGFR), systolic blood pressure (SBP), or hemoglobin (Hb) A1c values in the DN patients. After 52 weeks follow-up, urinary glypican-5 level was associated with significant increases in urine protein and albumin excretion and a significant decline in eGFR in the DN patients. The decline in eGFR was independent of changes in urine protein and albumin excretion, SBP, or HbA1c. The results indicate that urinary glypican-5 was not only a biomarker but also contributed to the pathogenesis of DN in these patients. CONCLUSION: Urinary glypican-5 was specifically elevated in type 2 diabetes patients with DN and it was associated with disease progression. Urinary glypican-5 may serve as a useful non-invasive marker for the progression of DN.

Climate and litter C/N ratio constrain soil organic carbon accumulation.

Soil organic carbon (SOC) plays critical roles in stabilizing atmospheric CO2 concentration, but the mechanistic controls on the amount and distribution of SOC on global scales are not well understood. In turn, this has hampered the ability to model global C budgets and to find measures to mitigate climate change. Here, based on the data from a large field survey campaign with 2600 plots across China's forest ecosystems and a global collection of published data from forested land, we find that a low litter carbon-to-nitrogen ratio (C/N) and high wetness index (P/PET, precipitation-to-potential-evapotranspiration ratio) are the two factors that promote SOC accumulation, with only minor contributions of litter quantity and soil texture. The field survey data demonstrated that high plant diversity decreased litter C/N and thus indirectly promoted SOC accumulation by increasing the litter quality. We conclude that any changes in plant-community composition, plant-species richness and environmental factors that can reduce the litter C/N ratio, or climatic changes that increase wetness index, may promote SOC accumulation. The study provides a guideline for modeling the carbon cycle of various ecosystem scales and formulates the principle for land-based actions for mitigating the rising atmospheric CO2 concentration.

RANK Deficiency Ameliorates Podocyte Injury by Suppressing Calcium/Calcineurin/ NFATc1 Signaling.

BACKGROUND/AIMS: Podocyte injury and loss contribute to proteinuria, glomerulosclerosis and eventually kidney failure. Receptor activator of NF-κB (RANK) belongs to the TNF receptor superfamily, which plays a key role in the pathogenesis of podocyte injury. However, the mechanism underlying the effect of RANK in podocyte injury remains unclear. Here, we sought to explore the possible molecular mechanisms involved in podocyte injury caused by RANK. METHODS: Immortalized mouse podocytes were treated with siRNA targeting RANK for 48 h or ionomycin for 24 h before harvest. Western blot, quantitative RT-PCR and immunofluorescence staining were used to evaluate the expression and function of RANK, nuclear factor of activated T cells c1 (NFATc1), transient receptor potential cation channel, subfamily C, member 6 (TRPC6) and calcineurin in podocytes. The Calcineurin Cellular Activity Assay kit was used to detect the phosphatase activity of calcineurin in cultured podocytes. A Ca2+ influx assay was performed to analyze alterations in Ca2+ entry under different conditions. Co-immunoprecipitation assays were used to observe the relationship between RANK and TRPC6. RESULTS: RANK mRNA and protein expression were markedly increased in injured podocytes (ionomycin stimulation). Further study found that translocation of NFATc1 to the nucleus was significantly reduced after knocking down RANK by siRNA. Meanwhile, we also demonstrated that loss of RANK suppressed the phosphatase activity of calcineurin and attenuated the ionomycin-induced increase in Ca2+ influx. In addition, we showed that RANK knockdown in cultured podocytes decreased TRPC6 protein expression. Co-immunoprecipitation experiments suggested that RANK binds to TRPC6 and that ionomycin enhanced the binding of RANK to TRPC6. CONCLUSION: Our findings demonstrated that RANK deficiency ameliorates podocyte injury by suppressing calcium/calcineurin/NFATc1 signaling, which may present a promising target for therapeutic intervention.

Advanced glycation end-products suppress autophagic flux in podocytes by activating mammalian target of rapamycin and inhibiting nuclear translocation of transcription factor EB.

Insufficient autophagy in podocytes is related to podocyte injury in diabetic nephropathy (DN). Advanced glycation end-products (AGEs) are major factors of podocyte injury in DN. However, the role and mechanism of AGEs in autophagic dysfunction remain unknown. We investigated autophagic flux in AGE-stimulated cultured podocytes using multiple assays: western blotting, reverse transcription-quantitative PCR, immunofluorescence staining, and electron microscopy. We also utilized chloroquine and a fluorescent probe to monitor the formation and turnover of autophagosomes. Mice of the db/db strain were used to model diabetes mellitus (DM) with high levels of AGEs. To mimic DM with normal levels of AGEs as a control, we treated db/db mice with pyridoxamine to block AGE formation. AGEs impaired autophagic flux in the cultured podocytes. Compared with db/db mice with normal AGEs but high glucose levels, db/db mice with high AGEs and high glucose levels exhibited lower autophagic activity. Aberrant autophagic flux was related to hyperactive mammalian target of rapamycin (mTOR), a major suppressor of autophagy. Pharmacologic inhibition of mTOR activity restored impaired autophagy. AGEs inhibited the nuclear translocation and activity of the pro-autophagic transcription factor EB (TFEB) and thus suppressed transcription of its several autophagic target genes. Conversely, TFEB overexpression prevented AGE-induced autophagy insufficiency. Attenuating mTOR activity recovered TFEB nuclear translocation under AGE stimulation. Co-immunoprecipitation assays further demonstrated the interaction between mTOR and TFEB in AGE-stimulated podocytes and in glomeruli from db/db mice. In conclusion, AGEs play a crucial part in suppressing podocyte autophagy under DM conditions. AGEs inhibited the formation and turnover of autophagosomes in podocytes by activating mTOR and inhibiting the nuclear translocation of TFEB. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Integrating Two Efficient and Specific Bioorthogonal Ligation Reactions with Natural Metabolic Incorporation in One Cell for Virus Dual Labeling.

Though techniques in bioorthogonal chemistry and metabolic incorporation have been developed over the past decade, it remains difficult to integrate different bioorthogonal reactions or metabolic incorporations into one system. In this report, the protein and DNA metabolic incorporations were combined with two bioorthogonal reactions in one cell to develop a facile and universal method for virus dual labeling. Azide and vinyl groups were introduced into the proteins or genomes of viruses, respectively, through the intrinsic biosynthesis of biomolecules, which were subsequently fluorescently labeled via copper-free click chemistry or alkene-tetrazine ligation reactions during natural propagation process in host cells. Both the envelope viruses and the capsid viruses could be labeled, and the dual labeling efficiency was more than 80%. The labeled progeny virions were structurally intact and fully infectious, and their fluorescence was strong enough to track single virions.

WWC1 promotes podocyte survival via stabilizing slit diaphragm protein dendrin.

Previous studies have indicated that glomerular podocyte injury serves a crucial role in proteinuria during the process of chronic kidney disease. The slit diaphragm of podocytes forms the final barrier to proteinuria. Dendrin, a constituent of the slit diaphragm protein complex, has been observed to relocate from the slit diaphragm to the nuclei in injured podocytes and promote podocyte apoptosis. However, the exact mechanism for nuclear relocation of dendrin remains unclear. The expression of WWC1 in podocyte injury induced by lipopolysaccharides (LPS) or adriamycin (ADR) was detected by reverse transcription­quantitative polymerase chain reaction (RT­qPCR), western blotting and the immunofluorescence assay. The role of WWC1 in podocyte apoptosis was detected by knockdown of WWC1 and flow cytometry. The mRNA and protein expression levels of apoptosis­associated genes Bcl­2­associated X (Bax) and Bcl­2 were measured by RT­qPCR and western blotting. The impact of WWC1 on dendrin nucleus relocation in vitro in podocytes was further evaluated by knockdown of WWC1. Expression of WWC1 significantly decreased in injured podocytes in vitro. The loss­of­function assay indicated that knockdown of WWC1 gene in vitro promoted podocyte apoptosis, accompanied with increased levels of the pro­apoptotic protein Bax and decreased levels of the anti­apoptotic protein Bcl­2. Furthermore, the relocation of dendrin protein was significantly promoted by knockdown of the WWC1 gene. In conclusion, the study indicated that loss of WWC1 may contribute to podocyte apoptosis by inducing nuclear relocation of dendrin protein, which provided novel insight into the molecular events in podocyte apoptosis.

Biomimetic Magnetosomes as Versatile Artificial Antigen-Presenting Cells to Potentiate T-Cell-Based Anticancer Therapy.

Adoptive T-cell transfer for cancer therapy relies on both effective ex vivo T-cell expansion and in vivo targeting performance. One promising but challenging method for accomplishing this purpose is to construct multifunctional artificial antigen-presenting cells (aAPCs). We herein developed biomimetic magnetosomes as versatile aAPCs, wherein magnetic nanoclusters were coated with azide-engineered leucocyte membranes and then decorated with T-cell stimuli through copper-free click chemistry. These nano aAPCs not only exhibited high performance for antigen-specific cytotoxic T-cell (CTL) expansion and stimulation but also visually and effectively guided reinfused CTLs to tumor tissues through magnetic resonance imaging and magnetic control. The persisting T cells were able to delay tumor growth in a murine lymphoma model, while the systemic toxicity was not notable. These results together demonstrated the excellent potential of this "one-but-all" aAPC platform for T-cell-based anticancer immunotherapy.

High sensitive detection method for protein by combining the magnetic separation with cation exchange based signal amplification.

PSA is a member of low abundance proteins and serves as a critical indicator of the development and therapy efficacy for prostate cancer. In this study, a facile and high sensitive method was developed for serum PSA detection by integrating the immunomagnetic separation and cation exchange based signal amplification. On the basis of nanoparticle preparation and immunoprobe construction, PSA in serum was captured, separated by the immunomagnetic probe and then interacted with the quantum dots (QDs) based immunofluorescence probe; Zn2+ inside QDs was replaced by Ag+ within seconds, after which fluorescence signal was amplified by Fluozin-3, the Zn2+ responsive dye. Under optimized conditions, low detection limit (1.56pg/mL), wide linear range (1.56-25ng/mL) and good repeatability (intra-coefficient variation=3.18%) were achieved, which is superior to commercialized ELISA kit. These results demonstrated the potential of our high sensitive method for PSA detection in clinical.

DNA methyltransferase 1 may be a therapy target for attenuating diabetic nephropathy and podocyte injury.

The contribution of DNA methylation to diabetic nephropathy, especially the effect on podocyte integrity, is not clarified. Here we found that albuminuria in a db/db mouse model was markedly attenuated after treatment with a DNA methylation inhibitor. This was accompanied by alleviation of glomerular hypertrophy, mesangial matrix expansion, and podocyte injury. The expression of DNA methyltransferase 1 (Dnmt1), nuclear factor Sp1, and nuclear factor kappa B (NFκB)-p65 markedly increased in podocytes in vivo and in vitro under the diabetic state. The increased expression of Dnmt1 was attenuated after treatment with 5-azacytidine or 5-aza-2'-deoxycytidine or Dnmt1 knockdown, accompanied by restored decreased podocyte slit diaphragm proteins resulting from hypermethylation and improved podocyte motility. Further studies found that increased Sp1 and NFκB-p65 interacted in the nucleus of podocytes incubated with high glucose, and Sp1 bound to the Dnmt1 promoter region. The involvement of the Sp1/NFκB-p65 complex in Dnmt1 regulation was confirmed by the observation that Sp1 knockdown using mithramycin A or siRNA decreased Dnmt1 protein levels. The luciferase reporter assay further indicated that Dnmt1 was a direct target of Sp1. Thus, inhibition of DNA methylation may be a new therapeutic avenue for treating diabetic nephropathy. Hence, the Sp1/NFκB p65-Dnmt1 pathway may be exploited as a therapeutic target for protecting against podocyte injury in diabetic nephropathy.

Water-use efficiency of an old-growth forest in lower subtropical China.

Carbon and water fluxes are key properties of ecosystem processes and functions. A better understanding of their temporal dynamics and coupling mechanism between these fluxes will help us improve ecosystem management for mitigation as well as adaption to future climatic change. From 2003 to 2009, carbon and water flux data were obtained by the eddy covariance method over an old-growth forest in the lower subtropical China. The 7 years of observational data indicated that the water-use efficiency (WUE) of the old-growth forest exhibited weak inter-annual variability. The mean annual WUE ranged from 1.70 to 1.98 g C kg-1 H2O. An analysis of the effects of environmental variables on the monthly gross primary productivity (GPP) and evapotranspiration (ET) indicated that solar radiation, air temperature, precipitation and vapor pressure deficit (VPD) produced similar effects on the monthly GPP and ET, which suggests that photosynthesis and ET were similarly driven by the climatic variables. At the monthly scale, the WUE decreased significantly as the precipitation and soil moisture content increased. However, a significant correlation was not detected between the WUE and the VPD at the monthly scale. Moisture conditions tend to be major drivers of the ecosystem WUE.

RhoA deficiency disrupts podocyte cytoskeleton and induces podocyte apoptosis by inhibiting YAP/dendrin signal.

BACKGROUND: Podocyte apoptosis is a major mechanism that leads to proteinuria in many kidney diseases. However, the concert mechanisms that cause podocyte apoptosis in these kidney diseases are not fully understood. RhoA is one of Rho GTPases that has been well studied and plays a key role in regulating cytoskeletal architecture. Previous study showed that insufficient RhoA could result in rat aortic smooth muscle cell apoptosis. However, whether RhoA is involved in podocyte apoptosis remains unknown. METHODS: Culture podocytes were treated with LPS, ADR or siRNA for 48 h before harvest. Subcellular immunoblotting, qRT-PCR, immunofluorescence and flow cytometry were used to exam the expression and function of RhoA or YAP in podocytes. RESULTS: We found that the expression of RhoA and its activity were significantly decreased in LPS or ADR-injured podocytes, accompanying loss of stress fibers and increased cell apoptosis. Knocking down RhoA or its downstream effector mDia expression by siRNA also caused loss of stress fibers and podocyte apoptosis. Moreover, our results further demonstrated that RhoA deficiency could reduce the mRNA and protein expression of YAP, which had been regarded as an anti-apoptosis protein in podocyte. Silenced dendrin expression significantly abolished RhoA, mDia or YAP deficiency-induced podocyte apoptosis. CONCLUSION: RhoA deficiency could disrupt podocyte cytoskeleton and induce podocyte apoptosis by inhibiting YAP/dendrin signal. RhoA/mDia/YAP/dendrin signal pathway may potentially play an important role in regulating podocyte apoptosis. Maintaining necessary RhoA would be one potent way to prevent proteinuria kidney diseases.