Podocyte-specific deletion of ubiquitin carboxyl-terminal hydrolase L1 causes podocyte injury by inducing endoplasmic reticulum stress.

Ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) is a unique component of the ubiquitin-proteasome system (UPS), which has multiple activities in maintaining intracellular ubiquitin levels. We previously reported the aberrant low expression of UCHL1 in podocytes of non-immune complex-mediated glomerulonephritis, and recent studies indicate that anti-UCHL1 antibody was responsible for the refractory minimal change disease (MCD), but the specific effect of UCHL1 to the podocytopathy has not been determined. Therefore, we generated podocyte-specific UCHL1 gene knockout (UCHL1cre/cre) rats model. Podocyte-specific UCHL1 knockout rats exhibited severe kidney damage, including segmental/global glomerulosclerosis, kidney function damage and severe proteinuria, compared with littermate control. Subsequently, by carrying out mass spectrometry analysis of isolated glomeruli of rats, abnormal protein accumulation of ECM-receptor Interaction was found in UCHL1cre/cre rats. Mechanistic studies in vivo and in vitro revealed that aberrant protein accumulation after UCHL1 deficiency induced endoplasmic reticulum (ER) stress, unfolded protein reaction (UPR) to reduce the protein level of podocyte skeleton proteins, and CHOP mediated apoptosis as well, which related to the dysfunction of the ubiquitin-proteasome system with decreased free monomeric ubiquitin level, thereby affecting protein ubiquitination and degradation. In addition, inhibition of ER stress by 4-PBA could attenuate the degree of ER stress and podocyte dysfunction. Our study indicates that UCHL1 is a potential target for preventing podocytes injury in some non-immune complex-mediated glomerulopathy.

Lipid droplet accumulation in Wdr45-deficient cells caused by impairment of chaperone-mediated autophagic degradation of Fasn.

BACKGROUND: ß-Propeller protein-associated neurodegeneration (BPAN) is a genetic neurodegenerative disease caused by mutations in WDR45. The impairment of autophagy caused by WDR45 deficiency contributes to the pathogenesis of BPAN; however, the pathomechanism of this disease is largely unknown. Lipid dyshomeostasis is involved in neurogenerative diseases, but whether lipid metabolism is affected by Wdr45 deficiency and whether lipid dyshomeostasis contributes to the progression of BPAN are unclear. METHODS: We generated Wdr45 knockout SN4741 cell lines using CRISPR‒Cas9-mediated genome editing, then lipid droplets (LDs) were stained using BODIPY 493/503. Chaperone-mediated autophagy was determined by RT-qPCR and western blotting. The expression of fatty acid synthase (Fasn) was detected by western blot in the presence or absence of the lysosomal inhibitor NH4Cl and the CMA activator AR7. The interaction between Fasn and HSC70 was analyzed using coimmunoprecipitation (Co-IP) assay. Cell viability was measured by a CCK-8 kit after treatment with the Fasn inhibitor C75 or the CMA activator AR7. RESULTS: Deletion of Wdr45 impaired chaperone-mediated autophagy (CMA), thus leading to lipid droplet (LD) accumulation. Moreover, Fasn can be degraded via CMA, and that defective CMA leads to elevated Fasn, which promotes LD formation. LD accumulation is toxic to cells; however, cell viability was not rescued by Fasn inhibition or CMA activation. Inhibition of Fasn with a low concentration of C75 did not affect cell viability but decreases LD density. CONCLUSIONS: These results suggested that Fasn is essential for cell survival but that excessive Fasn leads to LD accumulation in Wdr45 knockout cells.

Cepharanthine Exerts Antioxidant and Anti-Inflammatory Effects in Lipopolysaccharide (LPS)-Induced Macrophages and DSS-Induced Colitis Mice.

Cepharanthine (CEP), a biscoclaurine alkaloid extracted from Stephania cepharantha Hayata, has been widely used for the treatment of various acute and chronic diseases, including leukopenia, and snake bites. Here, our objective was to investigate the anti-oxidative stress and anti-inflammatory response effects of CEP in lipopolysaccharide (LPS)-induced macrophages as well as dextran sulfate sodium (DSS)-induced colitis mice. Our findings demonstrated that supplementation with CEP effectively mitigates body weight loss and elevation of disease activity index (DAI), reduces the malondialdehyde (MDA) content to 2.45 nM/mL while increasing the reduced glutathione (GSH) content to 35.53 µg/mL, inhibits inflammatory response, and maintains proper intestinal epithelium tight junctions in DSS-induced wild type (WT) mice. However, it failed to provide protective effects in DSS-induced transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) knockout (NRF2-/-) mice. GSH content decreased to 10.85 µg/106 cells following LPS treatment, whereas supplementation with CEP increased the GSH content to 12.26 µg/106 cells. Moreover, CEP effectively attenuated ROS production in LPS-induced macrophages. Additionally, CEP exhibited inhibitory effects on pro-inflammatory cytokines and mediators in LPS-induced macrophages. Furthermore, we observed that supplementation with CEP promoted the expression of NRF2/heme oxygenase 1 (HO-1)/NADPH quinone oxidoreductase-1 (NQO-1) as well as the phosphorylation of the adenosine monophosphate-activated protein kinase alpha 1 (AMPK-α1)/protein kinase B (AKT)/glycogen synthase kinase-3 beta (GSK-3ß) signaling pathway in macrophages while inhibiting the phosphorylation of the extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK), and nuclear factor-kappa B p65 (NF-κB p65) signaling pathway in LPS-induced macrophages. Although CEP did not demonstrate inhibitory effects on oxidative stress or promote the expression of HO-1/NQO-1, it effectively activated the phosphorylation of the AMPK-α1/AKT/GSK-3ß signaling pathway which is an upstream regulator of NRF2 in LPS-induced primary peritoneal macrophages from NRF2-/- mice. In summary, our findings suggest that CEP exerts protective effects against oxidative stress and inflammatory response by activating the AMPK-α1/AKT/GSK-3ß/NRF2 signaling pathway while concurrently inhibiting the activation of mitogen activated protein kinases (MAPKs) and the NF-κB p65 signaling pathway. These results not only elucidate the mechanisms underlying CEP's protective effects on colon oxidative stress and inflammation but also provide evidence supporting NRF2 as a potential therapeutic target for IBD treatment.

Effects of different colors of film mulch on soil temperature and rice growth in a non-flooded condition.

BACKGROUND: Rice cultivation under film mulching with no flooding is widely used as an effective water-saving technology. Different colors of film mulch have different effects on the soil hydrothermal environment and crop growth because of their different optical properties. However, the effects of different colors of film mulch on soil temperature and rice physiological growth are not clearly understood. RESULTS: Field experiments were conducted in 2019 and 2020 to investigate the effects of different color mulches on soil temperature and rice growth in a non-flooded condition. Transparent film (TM), black film (BM), two-color film (BWM, silver on the front and black on the back), and no film (NM) in a non-flooded condition were designed. Soil temperature variation at different soil depths of 0-0.25 m and rice plant height, stem thickness, dry matter, yield and quality were monitored. The results showed that compared to no mulching, the mulching treatment effectively increased the average soil temperature during the whole rice growth stage with the soil temperature ranked TM > BM > BWM. Compared with NM, the BM and BWM treatments increased rice yield by 12.1-17.7% and 6.4-14.4% in 2019 and 2020, respectively. The BWM had 18.2% and 6.8% greater gel consistency than NM in 2019 and 2020, respectively. CONCLUSION: Transparent film should be applied with care because of the high soil temperature stress. Black film and two-color film (silver on the front and black on the back) could be better option for rice yield, increasing and quality improving in a non-flooded condition. © 2023 Society of Chemical Industry.

Prophylactic cranial irradiation (PCI) versus active surveillance in patients with limited-stage small cell lung cancer: a retrospective, multicentre study.

BACKGROUND: The recommendation of PCI for limited-stage small cell lung cancer (LS-SCLC) is primarily based on evidence from the pre-magnetic resonance imaging (MRI) era. However, as MRI accuracy improves and stereotactic radiosurgery advances, the role of PCI for LS-SCLC has become uncertain. This study aims to compare the contemporary survival outcomes of patients with LS-SCLC treated with PCI versus active surveillance. METHODS: We conducted a retrospective cohort study in which 1068 patients with LS-SCLC who achieved a good response to first-line chemoradiotherapy were consecutively enrolled from 5 tertiary medical centres between June 2009 and June 2019. Of these patients, 440 received PCI, while 628 received surveillance without PCI. Propensity score matching with a 1:1 ratio was performed to balance the baseline characteristics of the two cohorts. The endpoints were overall survival (OS) and the incidence of brain metastasis (BM). RESULTS: In total, 648 patients were matched. The baseline characteristics were generally well balanced. At a median follow-up of 64.5 months (range 2-190), patients who underwent PCI had a significantly lower risk for BM than those who underwent surveillance. The 3-year cumulative incidence rate of BM was 28.2% (95% CI 22.5-33.8%) in the PCI cohort and 38.5% (32.6-44.5%) in the surveillance cohort (Gray's p = 0.002). However, the lower incidence of BM in the PCI cohort did not translate into a significant extension of OS. The median OS was 35.8 months (95% CI 27.6-44.0 months) in the PCI cohort versus 32 months (26.4-37.6 months) in the surveillance cohort (HR 0.90, 95% CI 0.74-1.10, p = 0.29). Multivariable analysis showed that disease stage, chemoradiotherapy sequence, and response to chemoradiotherapy were independent prognostic factors for BM or OS. CONCLUSIONS: Overall, PCI reduces the risk for BM but does not substantially prolong OS compared with active surveillance. A phase 3, prospective clinical trial (NCT04829708) we initiated is currently underway, which is expected to corroborate our results.

Surprising Hydrophobic Polymer Surface with a High Content of Hydrophilic Polar Groups.

The wetting property of a solid surface has been a hotspot for centuries, and many studies suggest that the hydrophobicity is highly related to the polar components. However, the underlying mechanism of polar moieties on the hydrophobicity remains unclear. Here, we tailor the surface polar moieties of epoxy resin (EP) by ozone modification and assess their wetting properties. Our results show that, for the modified EP with more (60.54%) polar moieties, the polar effect on hydrophobicity cannot be empirically observed. To reveal the underlying mechanism, the absorption parameters, including equilibrium distance, adsorption radius, and effective adsorption sites for water on EP before and after ozone treatment, are calculated on the basis of molecular simulations. After ozone modification, the equilibrium distance (from 1.95 to 1.70 Å), adsorption radius (from 3.80 to 4.50 Å), and effective adsorption sites (from 1 to 2) change slightly and the EP surface remains hydrophobic, although the polar groups significantly increase. Therefore, it is concluded that the wetting properties of solid surfaces are dominated by the equilibrium distance, adsorption radius, and effective adsorption sites for water on solids, and the nonlinear relationship between polar groups and hydrophilicity is clarified.

Molecular characterization of a novel virga-like virus associated with wheat.

In this work, we report the detection of a novel single-strand RNA virus from wheat, tentatively named "Triticum aestivum-associated virga-like virus 1" (TaAVLV1). Further characterization revealed that the complete genome of TaAVLV1 is divided into two segments, RNA1 and RNA2, which are 3530 and 3466 nt in length, excluding their respective polyA tails, and each contains only one open reading frame (ORF). The ORF of RNA1 encodes an RNA-dependent RNA polymerase (RdRp), while the ORF of RNA2 encodes a putative protein with methyltransferase and helicase domains. Phylogenetic analysis showed that the RdRp of TaAVLV1 is closely related to those of members of the unclassified virga-like virus group in the family Virgaviridae. Thus, we have identified TaAVLV1 as a putative novel virga-like virus belonging to the family Virgaviridae.

EP300/CBP is crucial for cAMP-PKA pathway to alleviate podocyte dedifferentiation via targeting Notch3 signaling.

Podocyte injury is the hallmark of proteinuric glomerular diseases. Notch3 is neo-activated simultaneously in damaged podocytes and podocyte's progenitor cells of FSGS, indicating a unique role of Notch3. We previously showed that activation of cAMP-PKA pathway alleviated podocyte injury possibly via inhibiting Notch3 expression. However, the mechanisms are unknown. In the present study, Notch3 signaling was significantly activated in ADR-induced podocytes in vitro and in PAN nephrosis rats and patients with idiopathic FSGS in vivo, concomitantly with podocyte dedifferentiation. In cultured podocytes, pCPT-cAMP, a selective cAMP-PKA activator, dramatically blocked ADR-induced activation of Notch3 signaling as well as inhibition of cAMP-PKA pathway, thus alleviating the decreased cell viability and podocyte dedifferentiation. Bioinformatics analysis revealed EP300/CBP, a transcriptional co-activator, as a central hub for the crosstalk between these two signaling pathways. Additionally, CREB/KLF15 in cAMP-PKA pathway competed with RBP-J the major transcriptional factor of Notch3 signaling for binding to EP300/CBP. EP300/CBP siRNA significantly inhibited these two signaling transduction pathways and disrupted the interactions between the above major transcriptional factors. These data indicate a crucial role of EP300/CBP in regulating the crosstalk between cAMP-PKA pathway and Notch3 signaling and modulating the phenotypic change of podocytes, and enrich the reno-protective mechanisms of cAMP-PKA pathway.

NAD+ Anabolism Disturbance Causes Glomerular Mesangial Cell Injury in Diabetic Nephropathy.

The homeostasis of NAD+ anabolism is indispensable for maintaining the NAD+ pool. In mammals, the mainly synthetic pathway of NAD+ is the salvage synthesis, a reaction catalyzed by nicotinamide mononucleotide adenylyltransferase (NAMPT) and nicotinamide mononucleotide adenylyltransferase (NMNATs) successively, converting nicotinamide (NAM) to nicotinamide mononucleotide (NMN) and NMN to NAD+, respectively. However, the relationship between NAD+ anabolism disturbance and diabetic nephropathy (DN) remains elusive. Here our study found that the disruption of NAD+ anabolism homeostasis caused an elevation in both oxidative stress and fibronectin expression, along with a decrease in Sirt1 and an increase in both NF-κB P65 expression and acetylation, culminating in extracellular matrix deposition and globular fibrosis in DN. More importantly, through constitutively overexpressing NMNAT1 or NAMPT in human mesangial cells, we revealed NAD+ levels altered inversely with NMN levels in the context of DN and, further, their changes affect Sirt1/NF-κB P65, thus playing a crucial role in the pathogenesis of DN. Accordingly, FK866, a NAMPT inhibitor, and quercetin, a Sirt1 agonist, have favorable effects on the maintenance of NAD+ homeostasis and renal function in db/db mice. Collectively, our findings suggest that NMN accumulation may provide a causal link between NAD+ anabolism disturbance and diabetic nephropathy (DN) as well as a promising therapeutic target for DN treatment.

Nuclear exclusion of YAP exacerbates podocyte apoptosis and disease progression in Adriamycin-induced focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is a chronic glomerular disease with poor clinical outcomes. Podocyte loss via apoptosis is one important mechanism underlying the pathogenesis of FSGS. Recently, Yes-associated-protein (YAP), a key downstream protein in the Hippo pathway, was identified as an activator for multiple gene transcriptional factors in the nucleus to control cell proliferation and apoptosis. To investigate the potential role of YAP in the progression of FSGS, we examined kidney samples from patients with minimal change disease or FSGS and found that increases in podocyte apoptosis is positively correlated with the cytoplasmic distribution of YAP in human FSGS. Utilizing an established mT/mG transgenic mouse model and primary cultured podocytes, we found that YAP was distributed uniformly in nucleus and cytoplasm in the podocytes of control animals. Adriamycin treatment induced gradual nuclear exclusion of YAP with enhanced phospho-YAP/YAP ratio, accompanied by the induction of podocyte apoptosis both in vivo and in vitro. Moreover, we used verteporfin to treat an Adriamycin-induced FSGS mouse model, and found YAP inhibition by verteporfin induced nuclear exclusion of YAP, thus increasing podocyte apoptosis and accelerating disease progression. Therefore, our findings suggest that YAP nuclear distribution and activation in podocytes is an important endogenous anti-apoptotic mechanism during the progression of FSGS.

Wnt8B, transcriptionally regulated by ZNF191, promotes cell proliferation of hepatocellular carcinoma via Wnt signaling.

Dysregulation of wingless-type (Wnt) signaling is implicated in hepatocellular carcinoma (HCC). Wnt family member 8B (Wnt8B), one of the canonical Wnt ligands, is implicated in oncogenesis. However, the role of Wnt8B in human HCCs and its transcriptional regulation mechanism are presently unknown . Here, we report that Wnt8B expression was frequently increased in HCCs and was significantly associated with poorer patient prognosis. Wnt8B knockdown suppresses HCC cell growth both in vitro and in vivo via inhibiting the canonical Wnt signaling. Zinc finger transcription factor 191 (ZNF191) can positively regulate Wnt8B mRNA and protein expression, and promoter luciferase assay indicated that ZNF191 can increase the transcription activity of the 2-Kbps WNT8B promoter. Chromatin immunoprecipitation-qPCR and electrophoretic mobility shift assay showed that ZNF191 protein directly binds to the WNT8B promoter, and the binding sites are at nt-1491(ATTAATT) and nt-1178(ATTCATT). Moreover, Wnt8B contributes to the effect of ZNF191 on cell proliferation, and Wnt8B expression correlates positively with ZNF191 in human HCCs. Our findings suggested that Wnt8B, directly transcriptionally regulated by ZNF191, plays a pivotal role in HCC proliferation via the canonical Wnt pathway and may serve as a new prognostic biomarker and a potential therapeutic target for HCC patients.

The biological pump effects of phytoplankton on the occurrence and benthic bioaccumulation of hydrophobic organic contaminants (HOCs) in a hypereutrophic lake.

The distribution of hydrophobic organic contaminants (HOCs) in eutrophic ecosystems has been widely studied, but how phytoplankton blooms affect their occurrence and benthic bioaccumulation is poorly understood. To fill this knowledge gap, the biological pump effects of phytoplankton on the fate of organochlorine pesticides (OCPs) and polycyclic aromatic hydrocarbons (PAHs) in sediments and benthos (Corbicula fluminea) from Lake Taihu, a hypereutrophic lake in China, were identified. The spatial-temporal distribution of HOCs suggests that higher phytoplankton biomass, coupled with sediment organic matter (SOM) content, greatly increased the concentration of HOCs in sediments in both winter and summer seasons. This could be attributed to the biological pump effects sequestering more HOCs from water to sediments with settling phytoplankton, especially during the summer. The biological pump effects further promoted the uptake of sediment-bound HOCs by benthos. The significant positive relationships between concentrations of HOCs in sediments and benthos were observed during the winter dormancy phase of benthos. Furthermore, the benthic bioaccumulation of HOCs could be strengthened by phytoplankton, due to their contribution to SOM and the following increased bioavailability of HOCs in sediments. Further research is needed to elucidate the phytoplankton biological pump effects on the fate of HOCs in benthic food chain, especially for hypereutrophic waters.

Weighting of toilet assessment scheme in China implementing analytic hierarchy process.

Advancing toilet technologies to address public health and sanitation issues are a concern of governments and organizations. This article mainly studies the assessment methods for the public toilets and some rural toilets considering from design to demolition to assist for the innovation of toilet technologies. The Analytic Hierarchy Process (AHP) and Life Cycle Assessment (LCA) methods were adopted to identify the assessment indicators and rank the weight. The outcome of Toilet Assessment Scheme (TAS), which includes a set of weightings and a classification system for the selected assessment indicators and sub-indicators. The weight calculation result showed that water resources, ecology, and indoor environmental quality are relatively high, which indicates that saving water, protecting the environment and optimizing the toilet environment should be given priority at the current stage. The individual questionnaire experts from the perspective of gender, profession, and generation, have different emphases on the evaluation scheme. This study can improve the comprehensiveness of toilet evaluation under the distinct background conditions, and will play a relevant role in the promotion of new toilet technology. The TAS can accelerate the toilet revolution in areas where toilets are scarce, and thus will improve the sanitary and health conditions of these populations.

Plakoglobin is involved in cytoskeletal rearrangement of podocytes under the regulation of UCH-L1.

UCH-L1 is a de-ubiquitination enzyme comprehensively distributed in neural cells and podocytes, which is involved in several kinds of nervous system and kidney related diseases. Our previous studies have demonstrated the aberrant up-regulation of UCH-L1 in podocytes of renal diseases, but how dose podocytes are injured by up-regulated UCH-L1 is waiting to be elucidated. Here, we observed the cytoskeleton rearrangement in podocytes with over-expression of UCH-L1, accompanied with a down-regulation of synaptopodin and RhoA, which are closely related to cytoskeletal stabilization. However, we did not see any alteration of RhoA ubiquitination level under the stimulation of UCH-L1 in podocytes. Subsequently, mass spectrum was applied in UCH-L1-flag immunoprecipitation and plakoglobin was screened out, which was among the UCH-L1-combined proteins and most likely related to cytoskeleton rearrangement. Our experiment demonstrates UCH-L1 may not injure podocytes cytoskeleton through a direct regulation on RhoA/Synaptopodin, but through the regulation of plakoglobin, which could be a promising target for treatment of renal disease in the future.

Cumulative live birth rates according to the number of oocytes retrieved following the "freeze-all" strategy.

BACKGROUND: In recent years, some studies have shown that there is a positive association between the number of oocytes retrieved and the cumulative live birth rate (CLBR) after fresh and frozen cycles of one oocyte retrieval. However, almost no studies have examined the association between the number of oocytes retrieved and the CLBR when using the "freeze-all" strategy. We performed this study to investigate the effects of an extreme oocyte yield during the first "freeze-all" cycle on the cumulative live birth rate among patients younger than 35 years old. METHODS: This was a retrospective cohort study performed in a university-affiliated reproductive medicine centre. Data obtained from 3276 women aged younger than 35 years who underwent their first "freeze-all" cycle (IVF/ICSI) were collected between January 2009 and December 2016. In all, 5025 frozen cycles took place during the follow-up period from January 2009 to December 2018. Patients were divided into five groups according to oocytes retrieved (group 1: 4-10 oocytes; group 2: 11-20 oocytes; group 3: 21-30 oocytes; group 4: 31-40 oocytes; group 5: > 40 oocytes). The primary outcome was the cumulative live birth rate. RESULTS: Unadjusted results showed that the cumulative live birth rate significantly increased as the number of oocytes retrieved increased and reached up to 93.82% in cases with yields of 21-30 oocytes (P < 0.05), after which it did not have a significant increase (P > 0.05). After adjusting for confounders, our results showed that the number of oocytes retrieved is an independent positive predictor of cumulative live birth rate when using a "freeze-all" strategy. (P < 0.001). In addition, the fertilization rate and the gonadotropin dose also influenced the cumulative live birth rate (P<0.05). CONCLUSIONS: Among women younger than 35 years old who underwent the "freeze-all" strategy, the number of oocytes retrieved positively correlated with the cumulative live birth rate. Taking both efficacy and safety into account, ovarian stimulation should be rational, and the upper limit of the oocyte yield should be no more than 30.

Hypoxia imaging in living cells, tissues and zebrafish with a nitroreductase-specific fluorescent probe.

Hypoxia in solid tumors is directly linked to the elevated levels of endogenous nitroreductase (NTR). We present a novel fluorescent probe, namely NTNO, for nitroreductase-specific detection based on the NTR-catalyzed reduction of the nitro unit to an amine functionality, and demonstrated its application for hypoxia imaging. NTNO was designed by incorporating a nitro unit as the NTR response site into a benzothiazole derivative. Upon reacting with NTR in the presence of reduced nicotinamide adenine dinucleotide (NADH), the fluorescence of the probe was strongly and sensitively turned on, with a good linearity in the NTR concentration range of 0.5-8.0 µg mL-1 and a detection limit of 48 ng mL-1. Most notably, NTNO has been successfully used for imaging hypoxia levels in living cells, tumor tissues and zebrafish, making it of great potential to monitor NTR in biological systems.

TGF-ß1 inhibits the autophagy of podocytes by activating mTORC1 in IgA nephropathy.

IgA nephropathy (IgAN) is a mesangial proliferative glomerulonephritis which often shows proteinuria, an indicator for podocyte damage. TGF-ß1 has been known to contribute to podocyte injury by inducing apoptosis, cytoskeleton relocation or cytoskeleton loss. And Decorin, a small proteoglycan known to neutralize TGF-ß1, was reported to induce autophagy in vascular endothelial cells. However, it remains unknown how TGF-ß1 and Decorin can affect podocyte autophagy in mesangial proliferative glomerulonephritis. In this study, we used in vivo and in vitro models to find out the effect of TGF-ß1 and Decorin on podocyte autophagy. P-rpS6 and p-ULK1 were detected by Western blot to show the activation of mTORC1 pathway following TGF-ß1 treatment. Also, we collected serum from IgAN patients and anti-Thy1.1 nephritis, and quantified TGF-ß1 and Decorin using ELISA. Together, we showed that TGF-ß1 could activate mTORC1 and inhibit autophagy, while Decorin has precisely the opposite effect. As the mesangial cells (MCs) proliferate, TGF-ß1 increases and Decorin decreases in the serum of IgAN and anti-Thy1.1 nephritis. This finding deepened our understanding regarding how MC proliferation could finally result in podocyte dysfunction.

Podocyte infolding glomerulopathy with undifferentiated connective tissue disease: a case report.

Podocyte infolding glomerulopathy (PIG) is a special type of glomerular disease that has been proposed in recent years and has attracted considerable attention. PIG is characterized by the formation of microspheres and microtubules in thickened glomerular basement membrane (GBM) on electron microscopy (EM), which is recognized as podocyte cytoplasmic infolding to the GBM. However, to date, only a few cases of PIG have been reported. Herein, we report a case of a 33-year-old female with PIG with undifferentiated connective tissue disease (UCTD) in China and review the literature.

LDPC-Coded CAP with Spatial Diversity for UVLC Systems over Generalized-Gamma Fading Channel.

In this paper, low-density parity-check (LDPC)-coded carrierless amplitude and phase (CAP) modulation with spatial diversity is proposed to mitigate turbulence-induced fading in an underwater visible-light communication (UVLC) channel. Generalized-gamma (GG) distribution was used to model the fading, as this model is valid for weak- and strong-turbulence regimes. On the basis of the characteristic function (CHF) of GG random variables, we derived an approximated bit-error rate (BER) for the CAP modulation scheme with spatial diversity and equal-gain combining (EGC). Furthermore, we simulated the performance of the CAP system with diversity and LDPC for various turbulence conditions and validated the analysis. Obtained results showed that the combination of LDPC and spatial diversity is effective in mitigating turbulence-induced fading, especially when turbulence strength is strong.

Hedgehog signalling.

The Hedgehog (Hh) signalling pathway is one of the key regulators of metazoan development. Hh proteins have been shown to play roles in many developmental processes and have become paradigms for classical morphogens. Dysfunction of the Hh pathway underlies a number of human developmental abnormalities and diseases, making it an important therapeutic target. Interest in Hh signalling thus extends across many fields, from evo-devo to cancer research and regenerative medicine. Here, and in the accompanying poster, we provide an outline of the current understanding of Hh signalling mechanisms, highlighting the similarities and differences between species.