Diabetic nephropathy (DN) is one of the most common complications in diabetes mellitus and the leading cause of end-stage renal disease. TGF-β is a pleiotropic cytokine and has been recognized as a ...key mediator of DN. However, anti-TGF-β treatment for DN remains controversial due to the diverse role of TGF-β1 in DN. Thus, understanding the regulatory role and mechanisms of TGF-β in the pathogenesis of DN is the initial step towards the development of anti-TGF-β treatment for DN. In this review, we first discuss the diverse roles and signaling mechanisms of TGF-β in DN by focusing on the latent versus active TGF-β1, the TGF-β receptors, and the downstream individual Smad signaling molecules including Smad2, Smad3, Smad4, and Smad7. Then, we dissect the regulatory mechanisms of TGF-β/Smad signaling in the development of DN by emphasizing Smad-dependent non-coding RNAs including microRNAs and long-non-coding RNAs. Finally, the potential therapeutic strategies for DN by targeting TGF-β signaling with various therapeutic approaches are discussed.
Metallic lithium affords the highest theoretical capacity and lowest electrochemical potential and is viewed as a leading contender as an anode for high-energy-density rechargeable batteries. ...However, the poor wettability of molten lithium does not allow it to spread across the surface of lithiophobic substrates, hindering the production and application of this anode. Here we report a general chemical strategy to overcome this dilemma by reacting molten lithium with functional organic coatings or elemental additives. The Gibbs formation energy and newly formed chemical bonds are found to be the governing factor for the wetting behavior. As a result of the improved wettability, a series of ultrathin lithium of 10-20 μm thick is obtained together with impressive electrochemical performance in lithium metal batteries. These findings provide an overall guide for tuning the wettability of molten lithium and offer an affordable strategy for the large-scale production of ultrathin lithium, and could be further extended to other alkali metals, such as sodium and potassium.
The uncontrolled growth of Li dendrites upon cycling might result in low coulombic efficiency and severe safety hazards. Herein, a lithiophilic binary lithium–aluminum alloy layer, which was ...generated through an in situ electrochemical process, was utilized to guide the uniform metallic Li nucleation and growth, free from the formation of dendrites. Moreover, the formed LiAl alloy layer can function as a Li reservoir to compensate the irreversible Li loss, enabling long‐term stability. The protected Li electrode shows superior cycling over 1700 h in a Li|Li symmetric cell.
Dendrite‐free anodes: An efficient lithium–aluminum alloy medium with increased affinity for Li and generated through an in situ electrochemical process is engineered to guide uniform Li nucleation and suppress the growth of Li dendrites.
Unstable electrode/solid‐state electrolyte interfaces and internal lithium dendrite penetration hamper the applications of solid‐state lithium‐metal batteries (SSLMBs), and the underlying mechanisms ...are not well understood. Herein, in situ optical microscopy provides insights into the lithium plating/stripping processes in a gel polymer electrolyte and reveals its dynamic evolution. Spherical lithium deposits evolve into moss‐like and branch‐shaped lithium dendrites with increasing current densities. Remarkably, the on‐site‐formed solid electrolyte interphase (SEI) shell on the lithium dendrite is distinctly captured after lithium stripping. Inducing an on‐site‐formed SEI shell with an enhanced modulus to wrap the lithium precipitation densely and uniformly can regulate dendrite‐free behaviors. An in‐depth understanding of lithium dendrite evolution and its functional SEI shell will aid in the optimization of SSLMBs.
In situ optical microscopy combined with atomic force microscopy studies show that the on‐site‐formed solid electrolyte interphase (SEI) shells on deposited lithium can be distinctly captured in gel polymer electrolyte based, quasi‐solid‐state lithium‐metal batteries (SSLMBs). Direct visualization of interfacial evolution of the Li dendrites and their SEI shells provides deep insights into the surface degradation and optimization in SSLMBs.
In this paper, we study the lepton flavor violating decays of the lj→liγγ (j=2, 3; i=1, 2) processes under the U(1)XSSM. The U(1)XSSM is the addition of three singlet new Higgs superfields and ...right-handed neutrinos to the minimal supersymmetric standard model (MSSM). Based on the latest experimental constraints of lj→liγγ, we analyze the effects of different sensitive parameters on the results and made reasonable predictions for future experimental development. Numerical analysis shows that many parameters have a greater or lesser effect on lepton flavor violation (LFV), but the main sensitive parameters and sources leading to LFV are the non-diagonal elements involving the initial and final leptons. This work could provide a basis for the discovery of the existence of new physics (NP).
Boron‐doped fused heterocycles have shown great potential in the field of functional materials. This study reports on the synthesis of a new class of bis‐diazidoboranes and the discovery of their ...cycloaddition reaction with isonitriles. Triply fused boron‐doped heterocyclic compounds were constructed in a one‐pot process through a domino cycloaddition, providing an effective route for constructing complex boron‐doped heterocyclic systems.
The room temperature domino cyclization reaction of bis‐diazidoboranes with isonitriles was reported for the first time. This one‐step reaction leads to complex boron‐doped fused heterocycles and provides a new strategy for the construction of boron‐doped heterocyclic systems.
Food allergies are a serious food safety and public health issue. Soybean, dairy, aquatic, poultry, and nut products are common allergens inducing allergic reactions and adverse symptoms such as ...atopic dermatitis, allergic eczema, allergic asthma, and allergic rhinitis. Probiotics are assumed as an essential ingredient in maintaining intestinal microorganisms' composition. They have unique physiological roles and therapeutic effects in maintaining the mucosal barrier, immune function, and gastrointestinal tract, inhibiting the invasion of pathogenic bacteria, and preventing diarrhea and food allergies. Multiple pieces of evidence reveal a significant disruptive effect of probiotics on food allergy pathology and progression mechanisms. Thus, this review describes the allergenic proteins as an entry point and briefly describes the application of probiotics in allergenic foods. Then, the role of probiotics in preventing and curing allergic diseases by regulating human immunity through intestinal flora and intestinal barrier, modulating host immune active cells, and improving host amino acid metabolism are described in detail. The anti-allergic role of probiotics in the function and metabolism of the gastrointestinal tract has been comprehensively explored to furnish insights for relieving food allergy symptoms and preventing food allergy.
Cross-species transmission of viruses from wildlife animal reservoirs poses a marked threat to human and animal health
. Bats have been recognized as one of the most important reservoirs for emerging ...viruses and the transmission of a coronavirus that originated in bats to humans via intermediate hosts was responsible for the high-impact emerging zoonosis, severe acute respiratory syndrome (SARS)
. Here we provide virological, epidemiological, evolutionary and experimental evidence that a novel HKU2-related bat coronavirus, swine acute diarrhoea syndrome coronavirus (SADS-CoV), is the aetiological agent that was responsible for a large-scale outbreak of fatal disease in pigs in China that has caused the death of 24,693 piglets across four farms. Notably, the outbreak began in Guangdong province in the vicinity of the origin of the SARS pandemic. Furthermore, we identified SADS-related CoVs with 96-98% sequence identity in 9.8% (58 out of 591) of anal swabs collected from bats in Guangdong province during 2013-2016, predominantly in horseshoe bats (Rhinolophus spp.) that are known reservoirs of SARS-related CoVs. We found that there were striking similarities between the SADS and SARS outbreaks in geographical, temporal, ecological and aetiological settings. This study highlights the importance of identifying coronavirus diversity and distribution in bats to mitigate future outbreaks that could threaten livestock, public health and economic growth.
Recent studies have shown that the performance of single-image super-resolution methods can be significantly boosted by using deep convolutional neural networks. In this study, we present a novel ...single-image super-resolution method by introducing dense skip connections in a very deep network. In the proposed network, the feature maps of each layer are propagated into all subsequent layers, providing an effective way to combine the low-level features and high-level features to boost the reconstruction performance. In addition, the dense skip connections in the network enable short paths to be built directly from the output to each layer, alleviating the vanishing-gradient problem of very deep networks. Moreover, deconvolution layers are integrated into the network to learn the upsampling filters and to speedup the reconstruction process. Further, the proposed method substantially reduces the number of parameters, enhancing the computational efficiency. We evaluate the proposed method using images from four benchmark datasets and set a new state of the art.
In the snake-infested mountainous regions of China, Saxifraga stolonifera L. Meeb is widely utilized as an immediate remedy for venomous snake bites. However, the scientific understanding of S. ...stolonifera's efficacy in snakebite treatment remains limited and requires further investigation.
The aim of this study was to assess the inhibitory effects of Saxifraga stolonifera phenolic extracts (SSPE) on Deinagkistrodon acutus venom (DAV) and explore the potential of S. stolonifera as a valuable candidate for antivenom development.
We employed our previously optimized extraction conditions to obtain SSPE. In vitro experiments utilizing diverse models were conducted to assess the inhibitory effects of the extracted phenolic compounds on DAV, specifically targeting phospholipase A2 (PLA2), proteolytic, fibrinolytic, and hyaluronidase enzymes. Furthermore, in vivo investigations were conducted to evaluate the inhibitory potential of the extracted compounds against DAV-induced hemorrhagic and edematogenic activity. To elucidate the chemical composition of the phenolic extracts, Ultra Performance Liquid Chromatography-mass spectrometry (UPLC-MS) analysis was performed.
Our in vitro inhibition study showed that S. stolonifera was able to inhibit the activities of PLA2 enzyme, proteolytic enzyme, hyaluronidase and fibrinogenolytic. The median effective dose (ED50) values of SSPE for inhibiting PLA2 enzyme, proteolytic enzyme and hyaluronidase activities were 0.115 mg/mL, 0.026 mg/mL and 0.238 mg/mL, respectively. The DAV-induced hemorrhagic and edematogenic effects of the SSPE were also successfully inhibited in vivo, and the high SSPE concentration was able to completely inhibit the hemorrhage and edema. It is noteworthy that the mice suffered no harm from the high SSPE concentration. The composition analysis showed that the phenolic substances contained in SSPE are gallic acid, protocatechuic acid, chlorogenic acid, rutin, kaempferol-3-O-ɑ-L-rhamnoside, kaempferol-3-O-β-D-glucopyranoside, quercetin and kaempferol.
This study provides scientific validation of the inhibitory efficacy of S. stolonifera as an emergency treatment for venomous snake bites, offering a theoretical foundation for future drug development strategies targeting snakebite.
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•Inhibitory effect of S. stolonifera on Deinagkistrodon acutus venom was evaluated.•Phenolics were found to be significant contributors to anti-venom activity.•Analyze qualitatively the phenolic composition of the S. stolonifera extract.•Saxifraga stolonifera is a promising natural antivenom source.
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