Valence-Change MnO2-Coated Arsenene Nanosheets as a Pin1 Inhibitor for Hepatocellular Carcinoma Treatment.

The heterogeneity of hepatocellular carcinoma (HCC) can prevent effective treatment, emphasizing the need for more effective therapies. Herein, we employed arsenene nanosheets coated with manganese dioxide and polyethylene glycol (AMPNs) for the degradation of Pin1, which is universally overexpressed in HCC. By employing an "AND gate", AMPNs exhibited responsiveness toward excessive glutathione and hydrogen peroxide within the tumor microenvironment, thereby selectively releasing AsxOy to mitigate potential side effects of As2O3. Notably, AMPNs induced the suppressing Pin1 expression while simultaneously upregulation PD-L1, thereby eliciting a robust antitumor immune response and enhancing the efficacy of anti-PD-1/anti-PD-L1 therapy. The combination of AMPNs and anti-PD-1 synergistically enhanced tumor suppression and effectively induced long-lasting immune memory. This approach did not reveal As2O3-associated toxicity, indicating that arsenene-based nanotherapeutic could be employed to amplify the response rate of anti-PD-1/anti-PD-L1 therapy to improve the clinical outcomes of HCC patients and potentially other solid tumors (e.g., breast cancer) that are refractory to anti-PD-1/anti-PD-L1 therapy.

Design Strategies towards Advanced Hydrogen Evolution Reaction Electrocatalysts at Large Current Densities.

Hydrogen (H2), produced by water electrolysis with the electricity from renewable sources, is an ideal energy carrier for achieving a carbon-neutral and sustainable society. Hydrogen evolution reaction (HER) is the cathodic half-reaction of water electrolysis, which requires active and robust electrocatalysts to reduce the energy consumption for H2 generation. Despite numerous electrocatalysts have been reported by the academia for HER, most of them were only tested under relatively small current densities for a short period, which cannot meet the requirements for industrial water electrolysis. To bridge the gap between academia and industry, it is crucial to develop highly active HER electrocatalysts which can operate at large current densities for a long time. In this review, the mechanisms of HER in acidic and alkaline electrolytes are firstly introduced. Then, design strategies towards high-performance large-current-density HER electrocatalysts from five aspects including number of active sites, intrinsic activity of each site, charge transfer, mass transfer, and stability are discussed via featured examples. Finally, our own insights about the challenges and future opportunities in this emerging field are presented.

SMN haploinsufficiency promotes ischemia/ reperfusion-induced AKI-to-CKD transition by endoplasmic reticulum stress activation.

Acute kidney injury (AKI) and chronic kidney disease (CKD) are interconnected syndromes that represent a global public health challenge. Here, we identified a specific role of survival of motor neuron (SMN) in ischemia/reperfusion (I/R)-induced kidney injury and progression of CKD. SMN was an essential protein in all cell type and was reported to play important roles in multiple fundamental cellular homeostatic pathways. However, the function of SMN in experimental models of I/R-induced kidney fibrosis has not extensively studied. Genetic ablation of SMN or small interfering RNA-base knockdown of SMN expression aggravated the tubular injury and interstitial fibrosis. Administration of scAAV9-CB-SMN or epithelial cell overexpression of SMN reduced I/R-induced kidney dysfunction and attenuated AKI-to-CKD transition, indicating that SMN is vital for the preservation and recovery of tubular phenotype. Our data showed that the endoplasmic reticulum stress (ERS) induced by I/R was persistent and became progressively more severe in the kidney without SMN. On the contrary, overexpression of SMN prevented against I/R-induced ERS and tubular cell damage. In summary, our data collectively substantiate a critical role of SMN in regulating the ERS activation and phenotype of AKI-to-CKD transition that may contribute to renal pathology during injury and repair.

Combining lanthanum-modified bentonite and calcium peroxide to enhance phosphorus removal from lake sediments.

Lanthanum-modified bentonite (LMB) and calcium peroxide (CP) are known for their effective removal phosphorus (P) capacities. The present study aims to investigate the effects of the combined use of LMB and CP（LMB + CP）on the sediment P, dissolved organic matter (DOM) and iron (Fe) concentrations through a 90-day incubation experiment. The combined treatment showed strong removal effects on sediment P and DOM. Indeed, the SRP and DOM concentrations in the 0-10 cm sediment layer decreased following the combined application of LMB and CP by 40.67 and 28.95%, respectively, compared to those of the control group (CK). In contrast, the HCl-P in the 0-5 cm sediment layer increased following the combined treatment by 13.28%. In addition, compared with the single application of LMB, the LMB + CP treatment significantly reduced the soluble Fe (Ⅱ) in the sediment pore water and promoted the oxidation of Fe. Therefore, LMB + CP can enhance the removal of internal P from sediments. The DOM removal and Fe oxidation in sediment pore waters are beneficial for enhancing the adsorption of P by LMB. On the other hand, the single and combined applications of LMB and CP increased the richness of the sediment microbial communities while exhibiting slight effects on their diversity. According to the results of this study, the combined use of LMB and oxidizing materials represents a novel method for treating lakes with high internal phosphorus and DOM loads in sediments.

Ten-eleven translocation 2 modulates allergic inflammation by 5-hydroxymethylcytosine remodeling of immunologic pathways.

Allergic rhinitis (AR) is an allergen-specific immunoglobulin E-mediated inflammatory disease. Both genetic and environmental factors could play a role in the pathophysiology of AR. 5-methylcytosine (5mC) can be converted to 5-hydroxymethylcytosine (5hmC) by the ten-eleven translocation (Tet) family of proteins as part of active deoxyribonucleic acid (DNA) demethylation pathway. 5hmC plays an important role in the regulation of gene expression and differentiation in immune cells. Here, we show that loss of Tet protein 2 (Tet2) could impact the severity of AR in the ovalbumin-induced mouse model. Genome-wide 5hmC profiling of both wild-type and Tet2 KO mice in response to AR revealed that the loss of Tet2 could lead to 5hmC alteration at specific immune response genes. Both partial loss and complete loss of Tet2 alters the 5hmC dynamic remodeling for the adaptive immune pathway as well as cytokines. Thus, our results reveal a new role of Tet2 in immunology, and Tet2 may serve as a promising target in regulating the level of immune response.

Computational Screening of Two-Dimensional Metal-Organic Frameworks as Efficient Single-Atom Catalysts for Oxygen Reduction Reaction.

The development of efficient and inexpensive oxygen reduction reaction (ORR) catalysts is crucial for renewable energy technologies. Herein, using density functional theory (DFT) methods and microkinetic simulations, we systematically investigated the ORR catalytic performance of a series of 2D metal-organic frameworks M3 (HADQ)2 (HADQ=2,3,6,7,10,11-hexaamine dipyrazino quinoxaline). It shows that all 2D M3 (HADQ)2 (M=Cr, Mn, Fe, Co, Ni, Cu, Ru, Rh and Pd) monolayers are metallic, due to π-conjugated crystal orbitals centered on the central metals and ligand N atoms. The catalytic activity of M3 (HADQ)2 depends on the binding strength between ORR intermediates and metal species, and can be tuned via changing the central metals. Among these candidates, Rh3 (HADQ)2 and Co3 (HADQ)2 show superior ORR performance to Pt (111) with high half-wave potentials of 0.99 and 0.93 V, respectively. Moreover, the screened two catalysts have excellent intermediate-tolerance ability for dynamic coverage of oxygenated species on the active sites. Our work provides a new path towards developing efficient ORR electrocatalysts.

Self-Supported Ru-Incorporated NiSe2 for Ampere-Level Current Density Hydrogen Evolution.

To meet the requirements for industrial water splitting to generate hydrogen, it is urgent, but still quite challenging to develop highly active and stable electrocatalysts for large-current-density hydrogen evolution reaction (HER). Herein, Ru-incorporated NiSe2 (Ru-NiSe2 ) was designed and synthesized. The introduction of Ru results in the formation of hierarchically structured Ru-NiSe2 with large electrochemical active surface area, and well-modified electronic structure. As expected, the as-fabricated Ru-NiSe2 displays impressive HER activity in 1.0 M KOH, with a low overpotential of 180.8 mV to reach the current density of 1000 mA cm-2 . Ru-NiSe2 also presents outstanding long-term stability at high current densities, owing to its high intrinsic chemical stability, and strong catalyst-support interface. Notably, when performed at a certain current density of 1000 mA cm-2 , the overpotential increase after 90 h is only 13 mV. Such excellent HER performance of Ru-NiSe2 demonstrates its great potential for practical use in industrial water splitting.

A Decade of Pathogenesis Advances in Non-Type 2 Inflammatory Endotypes in Chronic Rhinosinusitis: 2012-2022.

Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by localized inflammation of the upper airways. CRS includes two main phenotypes, namely, CRS with nasal polyps and CRS without nasal polyps. The phenotype-based classification method cannot reflect the pathological mechanism. The endotype-based classification method has been paid more and more attention by researchers. It is mainly divided into type 2 and non-type 2 endotypes. The mechanism driving the pathogenesis of non-type 2 inflammation is currently unknown. In this review, the PubMed and Web of Science databases were searched to conduct a critical analysis of representative literature works on the pathogenesis of non-type 2 inflammation in CRS published in the past decade. This review summarizes the latest evidence that may lead to the pathogenesis of non-type 2 inflammation. It is the main method that analyzing the pathogenesis from the perspective of immunology. Genomics and proteomics technique provide new approaches to the study of the pathogenesis. Due to differences in race, environment, geography, and living habits, there are differences in the occurrence of non-type 2 inflammation, which increase the difficulty of understanding the pathogenesis of non-type 2 inflammation in CRS. Studies have confirmed that non-type 2 endotype is more common in Asian patients. The emergence of overlap and unclassified endotypes has promoted the study of heterogeneity in CRS. In addition, as the source of inflammatory cells and the initiation site of the inflammatory response, microvessels and microlymphatic vessels in the nasal mucosal subepithelial tissue participate in the inflammatory response and tissue remodeling. It is uncertain whether CRS patients affect the risk of infection with SARS-CoV-2. In addition, the pathophysiological mechanism of non-type 2 CRS combined with COVID-19 remains to be further studied, and it is worth considering how to select the befitting biologics for CRS patients with non-type 2 inflammation.

Surface Adsorption of Amorphous Phosphate on RuNi-Doped Molybdate for the Hydrogen Evolution Reaction.

Developing highly active and cost-effective electrocatalysts is critical for enhancing the intrinsic performance of electrocatalytic water splitting. Oxoanion-based compounds, such as phosphates and molybdates, have emerged as promising electrocatalysts owing to their advantageous properties of nontoxicity, low price, and strong water adsorption ability. However, their relatively inferior activity has impeded extensive investigation into electrochemical applications. Herein, an amorphous phosphate-adsorbed and RuNi-doped molybdate (RuNiMo-P) composite is synthesized on nickel foam (NF) support by using a simple two-step method. Significantly, an acidic solution of phosphomolybdic acid (PMo12), containing a low concentration of Ru, can etch the NF, contributing to the in situ growth of the RuNi-doped molybdate precursor. Subsequent phosphating ensures the surface formation of the amorphous phosphate layer due to abundant oxygen in the precursor. The strong structural interaction between RuNi-doped molybdate and amorphous phosphate in RuNiMo-P prompts an enhanced hydrogen evolution reaction (HER) performance, delivering an overpotential of 38 mV at a current density of -10 mA cm-2, a Tafel slope of 53 mV dec-1, and good stability in an alkaline medium. Characterizations after HER reveal that RuNi doping, partial dissolution of phosphate and molybdate species, and newly formed NiOOH nanosheets can expose active sites, facilitate charge transfer, and modify electronic structures, thereby improving the HER performance effectively.

Ni-Doped MnO2 Nanosheet Arrays for Efficient Urea Oxidation.

Urea oxidation reaction (UOR), with a low thermodynamic potential, offers great promise for replacing anodic oxygen evolution reaction of electrolysis systems such as water splitting, carbon dioxide reduction, etc., thus reducing the overall energy consumption. To promote the sluggish kinetics of UOR, highly efficient electrocatalysts are required, and Ni-based materials have been widely investigated. However, most of these reported Ni-based catalysts suffer from large overpotentials, as they generally undergo self-oxidation to form NiOOH species at high potentials, which act as catalytically active sites for UOR. Herein, Ni-doped MnO2 (Ni-MnO2) nanosheet arrays were successfully prepared on nickel foam. The as-fabricated Ni-MnO2 shows distinct UOR behavior with most of the previously reported Ni-based catalysts, as urea oxidation on Ni-MnO2 proceeds before the formation of NiOOH. Notably, a low potential of 1.388 V vs reversible hydrogen electrode was required to achieve a high current density of 100 mA cm-2 on Ni-MnO2. It is suggested that both Ni doping and nanosheet array configuration are responsible for the high UOR activities on Ni-MnO2. The introduction of Ni modifies the electronic structure of Mn atoms, and more Mn3+ species are generated in Ni-MnO2, contributing to its outstanding UOR performance.

Causal role of immune cells in schizophrenia: Mendelian randomization (MR) study.

BACKGROUND: Complex immune-brain interactions that affect neural development, survival and function might have causal and therapeutic implications for psychiatric illnesses. However, previous studies examining the association between immune inflammation and schizophrenia (SCZ) have yielded inconsistent findings. METHODS: Comprehensive two-sample Mendelian randomization (MR) analysis was performed to determine the causal association between immune cell signatures and SCZ in this study. Based on publicly available genetic data, we explored causal associations between 731 immune cell signatures and SCZ risk. A total of four types of immune signatures (median fluorescence intensities (MFI), relative cell (RC), absolute cell (AC), and morphological parameters (MP)) were included. Comprehensive sensitivity analyses were used to verify the robustness, heterogeneity, and horizontal pleiotropy of the results. RESULTS: After FDR correction, SCZ had no statistically significant effect on immunophenotypes. It was worth mentioning some phenotypes with unadjusted low P-values, including FSC-A on NKT (ß = 0.119, 95% CI = 0.044 ~ 0.194, P = 0.002), DN (CD4-CD8-) NKT %T cell (ß = 0.131, 95% CI = 0.054 ~ 0.208, P = 9.03 × 10- 4), and SSC-A on lymphocytes (ß = 0.136, 95% CI = 0.059 ~ 0.213, P = 5.43 × 10- 4). The causal effect of SCZ IgD on transitional was estimated to 0.127 (95% CI = 0.051 ~ 0.203, P = 1.09 × 10- 3). SCZ also had a causal effect on IgD+ %B cell (ß = 0.130, 95% CI = 0.054 ~ 0.207, P = 8.69 × 10- 4), and DP (CD4+CD8+) %T cell (ß = 0.131, 95% CI = 0.054 ~ 0.207, P = 8.05 × 10- 4). Furthermore, four immunophenotypes were identified to be significantly associated with SCZ risk: naive CD4+ %T cell (OR = 0.986, 95% CI = 0.979 ~ 0.992, P = 1.37 × 10- 5), HLA DR on CD14- CD16- (OR = 0.738 (95% CI = 0.642 ~ 0.849, P = 2.00 × 10- 5), CD33dim HLA DR+ CD11b- AC (OR = 0.631, 95% CI = 0.529 ~ 0.753, P = 3.40 × 10- 7) and activated & resting Treg % CD4 Treg (OR = 0.937, 95% CI = 0.906 ~ 0.970, P = 1.96 × 10- 4). CONCLUSIONS: Our study has demonstrated the close connection between immune cells and SCZ by genetic means, thus providing guidance for future clinical research.

Ultrasonographic Findings and Prognosis of Metastases to the Thyroid Gland.

Metastases to the thyroid gland (MTT) are uncommon in clinical practice. The ultrasound (US) features are easily confused with primary thyroid malignancy, Hashimoto's thyroiditis, and other thyroid diseases. Therefore, this study aimed to assess the role of US and analysis of prognosis of MTT. A total of 45 patients with MTT in the database between July 2009 and February 2022 at the Fujian Cancer Hospital were reviewed. US examinations were performed only on 20 patients, who were finally included in our study. Among the 20 patients, nine were male, and eleven were female. According to US characteristics, metastases to the thyroid gland were divided into nodular and diffuse types (17 and 3 cases, respectively). Three lesions (17.6%) had circumscribed margins, and 14 (82.4%) were uncircumscribed. Three lesions (17.6%) were regular in shape, and 14 (82.4%) were irregular. Nine metastases (52.9%) were a taller-than-wide shape, and eight (47.1%) were not a taller-than-wide shape. Ten lesions (58.8%) had rich vascularity, and seven (41.2%) had absence/not rich vascularity. The mean overall survival (OS) from the time of MTT diagnosis was 22 months (95% confidence interval: 5.95-38.05). The 1-, 3-, and 5-year OS after metastasis was 68.1%, 25.5%, and 17%, respectively. The prognosis of MTT was poor, which is closely related to the characteristics of the primary tumor and metastatic disease. The US findings and US-guided core needle biopsy may be useful in diagnosing MTT in patients with a history of the malignant tumors.

The Role of Small Extracellular Vesicles and MicroRNAs in the Diagnosis and Treatment of Allergic Rhinitis and Nasal Polyps.

Allergic rhinitis and nasal polyps are common otorhinolaryngological diseases. Small extracellular vesicles and microRNAs have recently become major research topics of interest due to their key regulatory roles in cancer, inflammation, and various diseases. Although very detailed and in-depth studies on the pathogenesis and pathophysiology of allergic rhinitis and nasal polyps have been conducted, few studies have assessed the regulatory effects of exosomes and microRNAs on allergic rhinitis and nasal polyps. This paper reviews the studies on small extracellular vesicles and microRNAs in allergic rhinitis and nasal polyps conducted in recent years and focuses on the regulation of small extracellular vesicles and microRNAs in allergic rhinitis and nasal polyps with the aim of providing insights for the future diagnosis and treatment of allergic rhinitis and nasal polyps.

Spherical nucleic acids with tailored DNA conformation via bromide backfilling for the detection of kanamycin.

The improper conformation of oligonucleotides on gold nanoparticle surfaces is caused by unintended base adsorption, which hinders DNA hybridization and lowers colloidal stability. In this work, we treated spherical nucleic acids with Br- , which serves as an efficient backfilling agent, to adjust the DNA conformation by displacing bases from the gold surface. To investigate the effect of DNA conformation on interfacial recognition, a kanamycin fluorescent aptasensor was constructed with bromide backfilled-treated spherical nucleic acids. In the presence of kanamycin, the anchored aptamer binds with the target and the partially complementary reporter strand is dissociated from the surface of the gold nanoparticles, resulting in the fluorescence recovery of labelled fluorophore on the reporter strand. Under optimum conditions, the apparent binding affinity of the aptasensor with bromide backfilling was 2.2-fold that without backfilled one. The proposed aptasensor exhibited a good liner relationship between the concentration of kanamycin and fluorescence intensity change in the range 200 nM to 10 µM and the limit of detection was calculated to be 71.53 nM. Moreover, this aptasensor was also successfully applied in a spiked milk sample assay and the satisfactory recoveries were obtained in the range 96.94-101.57%, which demonstrated its potential in practical applications.

Poly-adenine-mediated spherical nucleic acids for interfacial recognition of kanamycin.

Kanamycin fluorescence aptasensors were created using a series of di-block oligonucleotide modified gold nanoparticles with various lengths of poly-adenine. In the presence of kanamycin, the double strand structure of the aptamer-reporter strand complex is disrupted, and the dye-labelled reporter strand detaches from the surface of gold nanoparticles, resulting in fluorescence recovery (Ex/Em = 485/520 nm). By adjusting the number of consecutive adenines, the programable aptamer density can be implemented on the gold nanoparticle surface, and the conformation of nucleic acid changed from lying-down to up-right. The apparent binding constant, binding kinetics, and limit of detection of the prepared aptasensors were carefully examined to explore the influence of surface density. Under the optimum condition, the aptasensor had a tenfold lower limit of detection than the thiolated aptamer modified one, as low as 23.6 nM, when a di-block oligonucleotide with twenty consecutive adenines tailed. In addition, satisfactory recoveries ranging from 96.33 to 99.47% were achieved in spiked milk samples with relative standard deviation of 1.2-6.9% (n = 3). This surface density regulation strategy holds great promise in other aptamer-based interfacial recognition and sensing. Schematic presentation of di-block oligonucleotide modified gold nanoparticle with different surface densities and its kanamycin sensing application.

Structure Engineering of MoS2 via Simultaneous Oxygen and Phosphorus Incorporation for Improved Hydrogen Evolution.

Oxygen and phosphorus dual-doped MoS2 nanosheets (O,P-MoS2 ) with porous structure and continuous conductive network are fabricated using a one-pot NaH2 PO2 -assisted hydrothermal approach. By simply changing the precursor solution, the chemical composition and resulting structure can be effectively controlled to obtain desired properties toward the hydrogen evolution reaction (HER). Thanks to the beneficial structure and strong synergistic effects between the incorporated oxygen and phosphorus, the optimal O,P-MoS2 exhibit superior electrocatalytic performances compared with those of oxygen single-doped MoS2 nanosheets (O-MoS2 ). Specifically, a low HER onset overpotential of 150 mV with a small Tafel slope of 53 mV dec-1 , excellent conductivity, and long-term durability are achieved by the structural engineering of MoS2 via O and P co-doping, making it an efficient HER electrocatalyst for water electrocatalysis. This work provides an alternative strategy to manipulate transition metal dichalcogenides as advanced materials for electrocatalytic and related energy applications.

Electrical transport in amorphous nanofilms embedded with crystalline grains at low temperatures.

Amorphous and ferromagnetic Al-Ni nanofilms have been grown by the magnetron-sputtering method with some nanosized crystalline grains embedded therein. Resistivity is demonstrated to transit from a positive temperature coefficient to a negative temperature coefficient (NTC) with increasing the fraction of Ni atoms in the Al-Ni nanofilms. The lattice disorder is deduced to induce the Anderson localization of electrons and the formation of polarons so that the NTC of the resistivity is driven in the Al-Ni nanofilms, different from that in the elemental Al and Ni nanofilms. The electron transport in the Al-Ni nanofilms is dominated by polaron hopping while it is also determined by electron-magnon and electron-phonon scatterings. The electron-magnon scatterings are further revealed to have a more important contribution to the electron transport at low temperatures than electron-phonon scatterings in the amorphous Al-Ni nanofilms. A so-called polaron-metal physical model has thus been proposed to well explain the electron transport in disorder lattices with crystalline grains embedded therein. This study may help to optimize the design of nano-engineered devices.

Role of A20/TNFAIP3 deficiency in lupus nephritis in MRL/lpr mice.

BACKGROUND: The activation of the nuclear factor-κB (NF-κB) signaling pathway gives rise to inflammation in the pathogenesis of lupus nephritis (LN), with A20 serving as a negative feedback regulator and ubiquitin C­terminal hydrolase L1 (UCH-L1) acting as a downstream target protein. However, their roles in the mechanism of LN remain undetermined. METHODS: In the present study, the expression of A20 and UCH-L1, the activity of NF-κB and ubiquitin-proteasome system (UPS) were measured in MRL/lpr mice and A20 gene silenced podocytes. The severity of podocyte injury and immune complex deposits were detected by transmission electron microscopy. RESULTS: The in vivo experiments revealed that A20 failed to terminate the activation of NF-κB, which was accompanied by UCH-L1 overexpression, ubiquitin accumulation, and glomerular injury in LN mice. Immunosuppression therapy did improve LN progression by attenuating A20 deficiency. In vitro experiments confirmed that tumor necrosis factor-α induced NF-κB activation, which led to UCH-L1 overexpression, UPS impairment, the upregulation of desmin and the downregulation of synaptopodin in A20 gene silenced podocytes. CONCLUSION: Thus, the results of the present study suggest that A20 regulates UCH-L1 expression via the NF-κB signaling pathway and A20 deficiency might play an important role in LN pathogenesis. Therefore, the A20 protein may serve as a promising therapeutic target for LN.

A20 overexpression exerts protective effects on podocyte injury in lupus nephritis by downregulating UCH-L1.

Lupus nephritis (LN), an autoimmune kidney disease caused by systemic lupus erythematosus (SLE), is the inflammation of the kidney. Although the treatment of LN is still a therapeutic challenge for many practitioners, the present study aims to provide a new insight for the treatment and management. The study aims to explore the effect of A20 on LN in relation to the nuclear factor-kappa B (NF-κB) signaling pathway. MRL/lpr mice were used as the LN mouse model. Next, A20, UCH-L1, and NF-κB expression in LN patients and MRL/lpr mice was determined. A20 was upregulated in podocytes to assess biological functions of A20 in LN. Furthermore, to further investigate the pivotal role of the NF-κB pathway in LN, the NF-κB pathway was blocked in podocytes. Next, UCH-L1 was downregulated in MRL/lpr mice to assess biological functions of UCH-L1 in LN. A20 was downregulated, whereas UCH-L1 was upregulated in LN. Overexpressed A20 declined NF-κB, UCH-L1 expression, and the extent of p65 phosphorylation. A20 overexpression or UCH-L1 inhibition increased expression of synaptoporin and nephrin but decreased desmin expression and ubiquitin accumulation level in podocytes. Moreover, A20 overexpression or UCH-L1 inhibition increased the podocyte number but decreased protein level of cleaved caspase-3, podocyte lesion improvement, decreased foot process width, glomerulus basement membrane, and foot process fusion rate. In addition, urine protein, blood urea nitrogen, serum creatinine, and ds-DNA antibody levels decreased with elevated A20 or depleted UCH-L1. Collectively, it could be concluded that A20 protects against podocyte injury in LN via UCH-L1 by inactivating the NF-κB signaling pathway.

Engineering 2D Metal-Organic Framework/MoS2 Interface for Enhanced Alkaline Hydrogen Evolution.

2D metal-organic frameworks (MOFs) have been widely investigated for electrocatalysis because of their unique characteristics such as large specific surface area, tunable structures, and enhanced conductivity. However, most of the works are focused on oxygen evolution reaction. There are very limited numbers of reports on MOFs for hydrogen evolution reaction (HER), and generally these reported MOFs suffer from unsatisfactory HER activities. In this contribution, novel 2D Co-BDC/MoS2 (BDC stands for 1,4-benzenedicarboxylate, C8 H4 O4 ) hybrid nanosheets are synthesized via a facile sonication-assisted solution strategy. The introduction of Co-BDC induces a partial phase transfer from semiconducting 2H-MoS2 to metallic 1T-MoS2 . Compared with 2H-MoS2 , 1T-MoS2 can activate the inert basal plane to provide more catalytic active sites, which contributes significantly to improving HER activity. The well-designed Co-BDC/MoS2 interface is vital for alkaline HER, as Co-BDC makes it possible to speed up the sluggish water dissociation (rate-limiting step for alkaline HER), and modified MoS2 is favorable for the subsequent hydrogen generation step. As expected, the resultant 2D Co-BDC/MoS2 hybrid nanosheets demonstrate remarkable catalytic activity and good stability toward alkaline HER, outperforming those of bare Co-BDC, MoS2 , and almost all the previously reported MOF-based electrocatalysts.