Synergistic Effects of PtRhNiFeCu High Entropy Alloy Nanocatalyst for Hydrogen Evolution and Oxygen Reduction Reactions.

The unique properties of high entropy alloy (HEA) catalysts, particularly their severe lattice distortion and the synergistic effect of multiple components, endow them with exceptional multifunctional catalytic performance. Herein, it is revealed for the first time, that the ultrasmall PtRhNiFeCu HEA nanoparticles catalyst shows outstanding catalytic activity for both hydrogen evolution reaction (HER) and oxygen reduction reaction (ORR). The catalyst exhibits an impressively low overpotential of 13 mV at 10 mA cm-2 , a Tafel slope of 29.6 mV dec-1, and high mass activity of 7.6 A mgPt -1 at -50 mV in alkaline media, and long-term stability of at least 20 h. Moreover, the catalyst also demonstrates effective catalytic activity for acidic ORR with a commendable performance of 1.23 A mgPt -1 , much exceeding the commercial Pt/C catalyst. Density functional theory (DFT) calculations unveil that the efficient electrocatalytic performance for HER and ORR can be primarily attributed to the synergistic effect between components tailors and optimizes the electronic structure of PtRhNiFeCu/C HEA, which not only enhances the HER activity through increasing water capture capability, decreasing energetic barrier for water dissociation, and optimizing hydrogen absorption but also initiates non-platinum active sites with high ORR activity, achieving the improved ORR performance.

Discovery and exploration of novel somatostatin receptor subtype 5 (SSTR5) antagonists for the treatment of cholesterol gallstones.

The shortage of cholesterol gallstones treatment intensifies the need to discover of effective small molecule drugs. Clinical follow-up and studies have found that activation of somatostatin receptor subtype 5 (SSTR5) reduce gallbladder contraction and thus increase the risk of cholesterol gallstones, implying that antagonizing SSTR5 may promote gallbladder emptying and reduce the formation of gallstones. Herein, we discovered novel SSTR5 antagonists and firstly investigated its effects on cholesterol gallstone. From loperamide, a reported seed structure with micromole activity, we identified optimal compound 23 as an SSTR5 antagonist exhibiting single-digit nanomolar potency, low hERG inhibition and oral availability. Further in vivo evaluation revealed that 23 significantly promoted gallbladder emptying. Moreover, in a mouse cholesterol gallstone model, 23 (3 mg/kg) effectively reduced the cholesterol gallstones formation, showing better efficacy than the clinical first-line drug UDCA (60 mg/kg), providing a new insight into the development of anti-gallstone drugs.

Challenging the Status Quo: Debunking the Necessity of 5-Year to 10-Year Patient-Reported Outcome Measures in Total Hip and Knee Arthroplasties.

BACKGROUND: In the current shift toward value-based healthcare, patient-reported outcome measures (PROMs) have become essential to assess the effectiveness of medical interventions. However, elucidation of the optimal timeframe for PROMs evaluation remains crucial. This study aimed to (1) determine the proportion of patients who experienced clinically meaningful improvements in PROMs scores at each follow-up visit after total hip arthroplasty (THA) and total knee arthroplasty (TKA) and (2) calculate and apply the clinical relevance ratio (CRR) for these long-term PROM collections postoperatively. METHODS: A total of 12 independent studies reporting THA (n = 8 studies) and TKA (n = 4 studies) postoperative PROM data with up to 10 years of follow-up in Europe or the United States were aggregated. A distribution-based minimal clinically important difference threshold and CRR were used to determine which patients had clinically meaningful improvements in PROMs at 1, 5, and 10 years. RESULTS: The proportion of patients who had clinically meaningful improvements in PROM scores stabilized after 1 year following both THA and TKA. Overall, the CRR decreased over time for all PROMs, with the CRR beginning to decrease at 1-year follow-up, bringing into question the robustness and clinical relevance of long-term PROMs data. CONCLUSIONS: The present study challenges the utility of requiring PROMs with a minimum follow-up of 2 years for THA and TKA. Research efforts should be focused on registries evaluating implant survivorship at longer-term follow-up, while PROMs should be better assessed up to 1-year follow-up. Reconsidering the long-term PROMs assessment would lead to more efficient and cost-effective research in orthopedic outcomes, without compromising data quality.

Discovery of a novel GPR35 agonist with high and equipotent species potency for oral treatment of IBD.

The G protein-coupled receptor 35 (GPR35) has been identified as a potential target in the treatment of inflammatory bowel disease (IBD). However, the lack of high and equipotent agonists on both human and mouse GPR35 has limited the in vivo study of GPR35 agonists in mouse models of IBD. In this study, structural modifications to lodoxamide provides a series of high and equivalent agonists on human, mouse, and rat GPR35. These molecules eliminate the species selectivity of human to mouse and rat orthologs that have been prevalent with GPR35 agonists including lodoxamide. The cLogP properties are also optimized to make the compounds more obedient to drug-like rules, yielding compound 4b (cLogP = 2.41), which activates human, mouse or rat GPR35 with EC50 values of 76.0, 63.7 and 77.8 nM, respectively. Oral administration of compound 4b at 20 mg/kg alleviates clinical symptoms of DSS-induced IBD in mice, and is slightly more effective than 5-ASA at 200 mg/kg. In summary, it can serve as a new start point for exploiting more potent GPR35 agonists without species differences for the treatment of IBD, and warrants further study.

Rh-dispersed Cu nanowire catalyst for boosting electrocatalytic hydrogenation of 5-hydroxymethylfurfural.

Electrocatalytic conversion of biomass-derived 5-hydroxymethylfurfural (HMF) to 2,5-bis(hydroxymethyl)furan (BHMF) presents a compelling strategy for the production of premium chemicals via the utilization of renewable energy sources. Exploring efficient catalytic systems to obtain highly selective BHMF has remained a giant challenge. A design strategy is proposed here to regulate active hydrogen (Hads) production in rhodium (Rh) nanoparticles grown on Cu nanowires (RhCu NWs) catalyst, which achieves a faradaic efficiency (FE) of 92.6% in the electrocatalytic reduction of HMF to BHMF at -20 mA cm-2 with no degradation in performance after 8 cycles. Kinetic investigations and electron spin resonance (ESR) spectroscopy reveal that the incorporation of Rh accelerates the water dissociation and facilitates the generation of Hads. In situ attenuated total reflection surface enhanced infrared absorption spectroscopy (ATR-SEIRAS) further demonstrates that the Rh component boosts the proportion of ordered weakly hydrogen-bonded water molecules on the catalyst surface, which is much easier to dissociate. The construction of an interfacial Hads-rich environment promotes the HMF intermediates binding with Hads to BMHF, thereby suppressing the formation of undesired dimers. This work demonstrates the promise of altering the interfacial water environment as a strategy to boost the electrosynthetic properties of biomass-derived products toward value-added outcomes.

Improved Stability Criteria for Delayed Neural Networks via Time-Varying Free-Weighting Matrices and S-Procedure.

This brief investigates the stability of neural networks with time-varying delays. Novel stability conditions are derived by employing free-matrix-based inequality and introducing the variable-augmented-based free-weighting matrices in the estimation of the derivative of the Lyapunov-Krasovskii functionals (LKFs). Both techniques avoid the appearance of the nonlinear terms of the time-varying delay. Especially, the time-varying free-weighting matrices associated with the derivative of the delay and the time-varying S-Procedure related to the delay and its derivative are combined to improve the presented criteria. Finally, numerical examples are given to illustrate the benefits of the presented methods.

Conserved class B GPCR activation by a biased intracellular agonist.

Class B G-protein-coupled receptors (GPCRs), including glucagon-like peptide 1 receptor (GLP1R) and parathyroid hormone 1 receptor (PTH1R), are important drug targets1-5. Injectable peptide drugs targeting these receptors have been developed, but orally available small-molecule drugs remain under development6,7. Here we report the high-resolution structure of human PTH1R in complex with the stimulatory G protein (Gs) and a small-molecule agonist, PCO371, which reveals an unexpected binding mode of PCO371 at the cytoplasmic interface of PTH1R with Gs. The PCO371-binding site is totally different from all binding sites previously reported for small molecules or peptide ligands in GPCRs. The residues that make up the PCO371-binding pocket are conserved in class B GPCRs, and a single alteration in PTH2R and two residue alterations in GLP1R convert these receptors to respond to PCO371. Functional assays reveal that PCO371 is a G-protein-biased agonist that is defective in promoting PTH1R-mediated arrestin signalling. Together, these results uncover a distinct binding site for designing small-molecule agonists for PTH1R and possibly other members of the class B GPCRs and define a receptor conformation that is specific only for G-protein activation but not arrestin signalling. These insights should facilitate the design of distinct types of class B GPCR small-molecule agonist for various therapeutic indications.

Discovery of Novel 5,6-Dihydro-1,2,4-triazine Derivatives as Efficacious Glucagon-Like Peptide-1 Receptor Agonists.

Danuglipron is the most representative small-molecule agonist of the glucagon-like peptide-1 receptor (GLP-1R) and has received considerable attention due to positive results in the treatment of type 2 diabetes mellitus (T2DM) and obesity in clinical trials. However, hERG inhibition, lower activity than endogenous GLP-1, and a short action time represent limitations in terms of feasible application. In this study, we report a new class of 5,6-dihydro-1,2,4-triazine derivatives that serve to eliminate potential hERG inhibition caused by the piperidine ring of danuglipron. Applying systematic in vitro to in vivo screening, we have identified compound 42 as a highly potent and selective GLP-1R agonist, which delivers improved (7-fold) efficacy in stimulating cAMP accumulation compared with danuglipron and which exhibits acceptable drug-like properties. Furthermore, 42 significantly reduces glucose excursion and inhibits food intake of hGLP-1R Knock-In mice. These effects are longer-lasting than that shown by danuglipron, demonstrating feasibility in the treatment of T2DM and obesity.

Cu Single-Atom Catalysts for High-Selectivity Electrocatalytic Acetylene Semihydrogenation.

The site isolation strategy has been employed in thermal catalytic acetylene semihydrogenation to inhibit overhydrogenation and C-C coupling. However, there is a dearth of analogous investigations in electrocatalytic systems. In this work, density functional theory (DFT) simulations demonstrate that isolated Cu metal sites have higher energy barriers on overhydrogenation and C-C coupling. Following this result, we develop Cu single-atom catalysts highly dispersed on nitrogen-doped carbon matrix, which exhibit high ethylene selectivity (>80 % Faradaic efficiency for ethylene, <1 % Faradaic efficiency for C4 , and no ethane) at high concentrations of acetylene. The superior performance observed in the electrocatalytic selective hydrogenation of acetylene can be attributed to the weak adsorption of ethylene intermediates and highly energy barriers on C-C coupling at isolated sites, as confirmed by both DFT calculations and experimental results. This study provides a comprehensive understanding of the isolated sites inhibiting the side reactions of electrocatalytic acetylene semihydrogenation.

Ni-CeO2 Heterostructure Promotes Hydrogen Evolution Reaction via Tuning of the O-H Bond Length of Adsorbed Water at the Electrolyte/Electrode Interface.

Understanding the properties and structure of reactant water molecules at the electrolyte solution/electrode interface is relevant to know the mechanisms of hydrogen evolution reaction (HER). However, this approach has rarely been implemented due to the elusive local microenvironment in the vicinity of the catalyst. Taking the Ni-CeO2 heterostructure immobilized onto carbon paper (Ni-CeO2 /CP) as a model, the dynamic behavior of adsorbed intermediates during the reaction was measured by in situ surface-enhanced infrared absorption spectroscopy with attenuated total reflection configuration (ATR-SEIRAS). Theoretical calculations are used in combination to comprehend the potential causes of increased HER activity. The results show that the O-H bond of adsorbed water at the electrolyte solution/electrode interface becomes longer for promoting the dissociation of water and accelerating the kinetically slow Volmer step. In addition, forming the Ni-CeO2 heterostructure interface optimizes the hydrogen adsorption Gibbs free energy, thus increasing HER activity. Therefore, the Ni-CeO2 /CP electrode exhibits remarkably low HER overpotentials of 37 and 119 mV at 10 and 100 mA cm-2 , which are close to commercial Pt/C (16 and 102.6 mV, respectively).

Magnesium lithospermate B ameliorates diabetic nephropathy by suppressing the uremic toxin formation mediated by gut microbiota.

Diabetic nephropathy (DN) is a major cause of renal failure and urgently necessitates new therapeutic strategies. Magnesium lithospermate B (MLB) showed a good protective effect on kidney injure by oral administration, despite its extremely low bioavailability. The current study aimed to investigate its gut microbiota-targeted mechanism to explain the paradoxical properties of pharmacodynamics and pharmacokinetics. Here we show that MLB alleviated DN by recovering the dysfunction of gut microbiota and their associated metabolites in colon content, such as short-chain fatty acids and amino acids. Moreover, MLB significantly decreased uremic toxin levels in plasma, especially the p-cresyl sulfate. We further discovered that MLB could affect the metabolism of p-cresyl sulfate by suppressing the formation of its intestinal precursors, i.e. the microbiota-mediated conversion from 4-hydroxyphenylacetate to p-cresol. In addition, the inhibition effects of MLB were confirmed. MLB and its metabolite danshensu exhibited inhibitory effects on p-cresol formation mediated by three strains belonging to the genus Clostridium, Bifidobacterium, and Fusobacterium, respectively. Meanwhile, MLB decreased the levels of p-cresyl sulfate in plasma and p-cresol in feces caused by rectal administration of tyrosine in mice. To summarize, the results indicated that MLB ameliorated DN through modulating gut microbiota-associated p-cresyl sulfate metabolism. Together, this study provides new insights on the microbiota-targeted mechanism of MLB in intervening DN and a new strategy in lowering plasma uremic toxins by blocking the formation of their precursors in intestine.

TGR5 agonist inhibits intestinal epithelial cell apoptosis via cAMP/PKA/c-FLIP/JNK signaling pathway and ameliorates dextran sulfate sodium-induced ulcerative colitis.

Excessive apoptosis of intestinal epithelial cell (IEC) is a crucial cause of disrupted epithelium homeostasis, leading to the pathogenesis of ulcerative colitis (UC). The regulation of Takeda G protein-coupled receptor-5 (TGR5) in IEC apoptosis and the underlying molecular mechanisms remained unclear, and the direct evidence from selective TGR5 agonists for the treatment of UC is also lacking. Here, we synthesized a potent and selective TGR5 agonist OM8 with high distribution in intestinal tract and investigated its effect on IEC apoptosis and UC treatment. We showed that OM8 potently activated hTGR5 and mTGR5 with EC50 values of 202 ± 55 nM and 74 ± 17 nM, respectively. After oral administration, a large amount of OM8 was maintained in intestinal tract with very low absorption into the blood. In DSS-induced colitis mice, oral administration of OM8 alleviated colitis symptoms, pathological changes and impaired tight junction proteins expression. In addition to enhancing intestinal stem cell (ISC) proliferation and differentiation, OM8 administration significantly reduced the rate of apoptotic cells in colonic epithelium in colitis mice. The direct inhibition by OM8 on IEC apoptosis was further demonstrated in HT-29 and Caco-2 cells in vitro. In HT-29 cells, we demonstrated that silencing TGR5, inhibition of adenylate cyclase or protein kinase A (PKA) all blocked the suppression of JNK phosphorylation induced by OM8, thus abolished its antagonizing effect against TNF-α induced apoptosis, suggesting that the inhibition by OM8 on IEC apoptosis was mediated via activation of TGR5 and cAMP/PKA signaling pathway. Further studies showed that OM8 upregulated cellular FLICE-inhibitory protein (c-FLIP) expression in a TGR5-dependent manner in HT-29 cells. Knockdown of c-FLIP blocked the inhibition by OM8 on TNF-α induced JNK phosphorylation and apoptosis, suggesting that c-FLIP was indispensable for the suppression of OM8 on IEC apoptosis induced by OM8. In conclusion, our study demonstrated a new mechanism of TGR5 agonist on inhibiting IEC apoptosis via cAMP/PKA/c-FLIP/JNK signaling pathway in vitro, and highlighted the value of TGR5 agonist as a novel therapeutic strategy for the treatment of UC.

Phenotypic screening-based drug discovery of furan-2-carboxylic acid derivatives for the amelioration of type 2 diabetes mellitus (T2DM).

Phenotypic screening still plays an important role in discovering new drugs, especially for diseases with complex pathogenesis, such as diabetes. As excessive gluconeogenesis is considered an important factor in the occurrence of hyperglycemia in T2DM, we previously screened our compounds library for active molecules which inhibit gluconeogenesis, resulting in the discovery of SL010110 with a unique mechanism, different from metformin and a thienopyridine derivative (DMT). The SARs study of SL010110 led to the discovery of 10v. Compared with SL010110, 10v showed improved anti-gluconeogenesis potency and pyruvate tolerance. A further pharmacokinetic study demonstrated that 10v displayed a relatively short half-life, moderate volume of distribution, and moderate to high oral bioavailability. In vivo chronic experiments showed an improved capability of 10v in ameliorating hyperglycemia as the 5 mg/kg 10v treatment greatly reduced non-fasting and fasting blood glucose levels, making it a promising candidate for the treatment of T2DM. The progression from in vitro screening to in vivo testing of the derivatized compounds provided a useful phenotypic screening drug discovery strategy based on the inhibition of gluconeogenesis.

Coronarin A modulated hepatic glycogen synthesis and gluconeogenesis via inhibiting mTORC1/S6K1 signaling and ameliorated glucose homeostasis of diabetic mice.

Promotion of hepatic glycogen synthesis and inhibition of hepatic glucose production are effective strategies for controlling hyperglycemia in type 2 diabetes mellitus (T2DM), but agents with both properties were limited. Herein we report coronarin A, a natural compound isolated from rhizomes of Hedychium gardnerianum, which simultaneously stimulates glycogen synthesis and suppresses gluconeogenesis in rat primary hepatocytes. We showed that coronarin A (3, 10 µM) dose-dependently stimulated glycogen synthesis accompanied by increased Akt and GSK3ß phosphorylation in rat primary hepatocytes. Pretreatment with Akt inhibitor MK-2206 (2 µM) or PI3K inhibitor LY294002 (10 µM) blocked coronarin A-induced glycogen synthesis. Meanwhile, coronarin A (10 µM) significantly suppressed gluconeogenesis accompanied by increased phosphorylation of MEK, ERK1/2, ß-catenin and increased the gene expression of TCF7L2 in rat primary hepatocytes. Pretreatment with ß-catenin inhibitor IWR-1-endo (10 µM) or ERK inhibitor SCH772984 (1 µM) abolished the coronarin A-suppressed gluconeogenesis. More importantly, we revealed that coronarin A activated PI3K/Akt/GSK3ß and ERK/Wnt/ß-catenin signaling via regulation of a key upstream molecule IRS1. Coronarin A (10, 30 µM) decreased the phosphorylation of mTOR and S6K1, the downstream target of mTORC1, which further inhibited the serine phosphorylation of IRS1, and subsequently increased the tyrosine phosphorylation of IRS1. In type 2 diabetic ob/ob mice, chronic administration of coronarin A significantly reduced the non-fasting and fasting blood glucose levels and improved glucose tolerance, accompanied by the inhibited hepatic mTOR/S6K1 signaling and activated IRS1 along with enhanced PI3K/Akt/GSK3ß and ERK/Wnt/ß-catenin pathways. These results demonstrate the anti-hyperglycemic effect of coronarin A with a novel mechanism by inhibiting mTORC1/S6K1 to increase IRS1 activity, and highlighted coronarin A as a valuable lead compound for the treatment of T2DM.

Design and exploration of gut-restricted bifunctional molecule with TGR5 agonistic and DPP4 inhibitory effects for treating ulcerative colitis.

Ulcerative colitis (UC) is a gastrointestinal disease with complex etiology, and the shortage of the treatment further intensifies the need to discover new therapies based on novel mechanisms and strategies. TGR5 and DPP4 are beneficial to treat UC through multiple mechanisms, notably increasing GLP-2 levels by promoting secretion and inhibiting degradation respectively. However, some unwanted systemic effects caused by systemic exposure hinder development, especially the gallbladder-filling effects. Herein, we firstly reported a series of high-potency gut-restricted TGR5-DPP4 bifunctional molecules by gut-restriction and multitarget strategies to utilize the positive impacts of TGR5 and DPP4 on UC and avoid unwanted systemic effects. In particularly, racemic compound 15, a high-potency TGR5-DPP4 bifunctional molecule, showed favorable intestinal distribution, preferable efficacy in mice colitis model and good gallbladder safety. Therefore, the feasibility of gut-restricted TGR5-DPP4 bifunctional molecule was confirmed for the treatment UC, providing a new insight into the development of anti-UC drugs.

Highly stable halide perovskites for photocatalysis via multi-dimensional structure design and in situ phase transition.

Lead halide perovskite CsPbBr3 quantum dots (QDs) possess several desirable features which enable them to be promising candidates for photocatalysis. However, the instability caused by their inherent liquid-like ionic properties hampers their further development. Herein, this work employs the surficial molecular modification strategy and a multi-dimensional structure design to ease the instability issue. The additive 2-phenylethanamine bromide (PEABr) can serve as a ligand to compensate for stripping the amine ligands and passivate the surficial bromide vacancy defects of CsPbBr3 QDs in photocatalysis. In addition, PEABr acts as a reactant to form 2D and quasi-2D perovskite nanosheets. The addition of a small amount of these nanosheets into QDs can enhance their general stability due to their unique layered structures. Moreover, PEABr can trigger the phase transition of cubic CsPbBr3 into tetragonal CsPb2Br5. The newly formed Z-scheme homologous heterojunctions further improve the catalytic performance. Simulated photocatalytic dynamics reveals that our multi-dimensional structure favors decreasing the reaction barrier energy and then facilitating the photocatalytic reaction. Therefore, the electron consumption rate of our multi-dimensional perovskites doubles that of pristine CsPbBr3 QDs and also has superior long-term stability.

A derivatization strategy for comprehensive identification of 2- and 3-hydroxyl fatty acids by LC-MS.

2/3-Hydroxy fatty acids (2/3-OHFAs) are a class of important biological molecules closely related to many diseases, of which the unsaturated ones (2/3-OHUFAs) obtain special recognition for their bioactivities. However, the comprehensive identification of 2/3-OHFAs has been a daunting task due to the similarity of isomeric structures and lack of authentic standards. Herein, we report a strategy for the 2/3-OHUFA identification by using an in-house synthesized derivatization reagent, 4-amino-1,1-dimethylpiperidin-1-ium iodide hydrochloride (ADMI). Through ADMI derivatization, the diagnostic ion m/z 155.1 or 171.1 were produced by liquid chromatography-mass spectrometry (LC-MS) analysis, which could distinguish the 2-OH or 3-OH group, respectively. Then the meta-chloroperoxybenzoic acid (mcpba) was used to resolve the locations of double bonds in 2/3-OHUFAs by the characteristic cleavage of the newly formed epoxides. Thus, the identification of 2/3-OHUFAs was enabled by all these characteristics. Moreover, in order to simplify the whole analysis, an isotope-labeled ADMI was designed to quickly pick out the low-abundant 2/3-OHFAs from complex biological matrices. Finally, a combined derivatization strategy was established to analyze mouse lung tissues with melanoma metastasis. Different long-chain 2-OHFAs and 3-OHFAs were identified, including FA 12:0-3OH, FA 12:1(Δ9)-3OH, FA 14:0-3OH, FA 14:1(Δ5)-3OH, FA 16:0-2/3OH, and FA 18:0-2/3OH. The results showed that the contents of most identified 2/3-OHFAs were lower in the cancer group than in the control group, suggesting the plausible role of 2/3-OHFAs in cancer development. In summary, the new derivatization method provides a powerful analysis strategy for 2/3-OHUFAs, which sheds light on a better understanding of the biological functions of 2/3-OHUFAs.

Synthesis of AC1903 analogs as potent transient receptor potential canonical channel 4/5 inhibitors and biological evaluation.

Transient receptor potential canonical (TRPC) channels are a class of non-selective cation channels expressed in a variety of tissues and organ systems where they functionally regulate physiological and pathological processes. TRPC5 has been shown to be a promising target for focal segmental glomerulosclerosis treatment. In this study, we report the synthesis and biological evaluation of a novel series of benzimidazole-based TRPC5 inhibitors. One compound, 8b, is 100-fold more potent than the parent compound, AC1903, in the suppression of TRPC5 channel activity. Interestingly, both AC1903 and 8b also suppressed TRPC4 channel activity with similar potency. Compound 8b also significantly blunts protamine sulfate-induced reorganization of podocyte cytoskeleton, interleukin (IL)-17-induced cell proliferation, and the expression of proinflammatory mediators in human keratinocyte HaCaT cells.

Polyacrylic acid-b-polystyrene-passivated CsPbBr3 perovskite quantum dots with high photoluminescence quantum yield for light-emitting diodes.

We report a novel strategy for the preparation of CsPbBr3 perovskite quantum dots by polyacrylic acid-b-polystyrene ligands, which exhibited high stability and photoluminescence quantum yields. The fabricated white light-emitting diodes exhibited luminescence performance with the colour rendering index of 65.5, and a correlated colour temperature of 5464 K.

Discovery of pyrroledione analogs as potent transient receptor potential canonical channel 5 inhibitors.

A deepening understanding of the relationship between transient receptor potential canonical channel 5 (TRPC5) and chronic kidney disease (CKD), has led to the emergence of several types of TRPC5 inhibitors displaying clear therapeutic effect. Herein, we report the synthesis and biological evaluation of a series of pyrroledione TRPC5 inhibitors, culminating in the discovery of compound 16g with subtype selectivity. Compared with GFB-8438, a potent TRPC5 inhibitor (Goldfinch Bio), compound 16g showed improved inhibition of TRPC5 and enhanced protective effect against protamine sulfates (PS)-induced podocyte injury in vitro. In addition, compound 16g did not induce cell death in primary cultured hepatocytes and immortalized podocytes in a preliminary toxicity assessment, indicating its utility as a potent and safe inhibitor for studying the function of TRPC5.