A Self-Delivery Nanodrug Simultaneously Inhibits COX-2/PGE2 Mediated Inflammation and Downregulates PD-L1 to Boost Photoimmunotherapy.

Phototherapy promotes anti-tumor immunity by inducing immunogenic cell death (ICD), However, the accompanying inflammatory responses also trigger immunosuppression, attenuating the efficacy of photo-immunotherapy. Herein, they co-assembled a cell-membrane targeting chimeric peptide C16-Cypate-RRKK-PEG8-COOH (CCP) and anti-inflammatory diclofenac (DA) to develop a nanodrug (CCP@DA) that both enhances the immune effect of phototherapy and weakens the inflammation-mediated immunosuppression. CCP@DA achieves cell membrane-targeting photodynamic and photothermal synergistic therapies to damage programmed death ligand 1 (PD-L1) and induce a strong ICD to activate anti-tumor response. Simultaneously, the released DA inhibits the cycoperoxidase-2 (COX-2)/prostaglandin E2 (PGE2) pathway in tumor cells to inhibit pro-tumor inflammation and further down-regulate PD-L1 expression to relieve the immunosuppressive microenvironment. CCP@DA significantly inhibited tumor growth and inflammation both in vitro and in vivo, while maintaining a potent anti-tumor immune response. Additionally, it exhibits excellent anti-metastatic capabilities and prolongs mouse survival time with a single dose and low levels of near-infrared (NIR) light exposure. This work provides a valuable strategy to control the therapy-induced inflammation for high-efficiency photoimmunotherapy.

Efficacy of Lenvatinib Combined with Anti-PD-1 Antibodies plus Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Retrospective, Multicenter Study.

Purpose: The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) is extremely poor, and systemic therapy is currently the mainstream treatment. This study aimed to assess the efficacy and safety of lenvatinib combined with anti-PD-1 antibodies and transcatheter arterial chemoembolization (triple therapy) in patients with HCC and PVTT. Materials and Methods: This retrospective multicenter study included patients with HCC and PVTT who received triple therapy, were aged between 18 and 75 years, classified as Child Pugh class A or B, and had at least one measurable lesion. The overall survival (OS), progression-free survival (PFS), objective response rates, and disease control rates were analyzed to assess efficacy. Treatment-related adverse events were analyzed to assess safety profiles. Results: During a median follow-up of 11.23 months (range, 3.07-34.37 months), the median OS was greater than 24 months, and median PFS was 12.53 months. The two-year OS rate was 54.9%. The objective response rate and disease control rate were 69.8% (74/106) and 84.0% (89/106), respectively; 20.8% (22/106) of the patients experienced grade 3/4 treatment-related adverse events and no treatment-related deaths occurred. The conversion rate to liver resection was 31.1% (33/106), with manageable postoperative complications. The median OS was not reached in the surgery group, but was 19.08 months in the non-surgery group. The median PFS in the surgery and non-surgery groups were 20.50 and 9.00 months, respectively. Conclusion: Triple therapy showed promising survival benefits and high response rates in patients with HCC and PVTT, with manageable adverse effects.

Machine Learning Models Identify Inhibitors of New Delhi Metallo-ß-lactamase.

The worldwide spread of the metallo-ß-lactamases (MBL), especially New Delhi metallo-ß-lactamase-1 (NDM-1), is threatening the efficacy of ß-lactams, which are the most potent and prescribed class of antibiotics in the clinic. Currently, FDA-approved MBL inhibitors are lacking in the clinic even though many strategies have been used in inhibitor development, including quantitative high-throughput screening (qHTS), fragment-based drug discovery (FBDD), and molecular docking. Herein, a machine learning-based prediction tool is described, which was generated using results from HTS of a large chemical library and previously published inhibition data. The prediction tool was then used for virtual screening of the NIH Genesis library, which was subsequently screened using qHTS. A novel MBL inhibitor was identified and shown to lower minimum inhibitory concentrations (MICs) of Meropenem for a panel of E. coli and K. pneumoniae clinical isolates expressing NDM-1. The mechanism of inhibition of this novel scaffold was probed utilizing equilibrium dialyses with metal analyses, native state electrospray ionization mass spectrometry, UV-vis spectrophotometry, and molecular docking. The uncovered inhibitor, compound 72922413, was shown to be 9-hydroxy-3-[(5-hydroxy-1-oxa-9-azaspiro[5.5]undec-9-yl)carbonyl]-4H-pyrido[1,2-a]pyrimidin-4-one.

Biochemical Characterization of a Novel Thermostable Ulvan Lyase from Tamlana fucoidanivorans CW2-9.

Ulvan is a complex sulfated polysaccharide extracted from Ulva, and ulvan lyases can degrade ulvan through a ß-elimination mechanism to obtain oligosaccharides. In this study, a new ulvan lyase, EPL15085, which belongs to the polysaccharide lyase (PL) 28 family from Tamlana fucoidanivorans CW2-9, was characterized in detail. The optimal pH and salinity are 9.0 and 0.4 M NaCl, respectively. The Km and Vmax of recombinant EPL15085 toward ulvan are 0.80 mg·mL-1 and 11.22 µmol·min -1 mg-1·mL-1, respectively. Unexpectedly, it is very resistant to high temperatures. After treatment at 100 °C, EPL15085 maintained its ability to degrade ulvan. Molecular dynamics simulation analysis and site-directed mutagenesis analysis indicated that the strong rigidity of the disulfide bond between Cys74-Cys102 in the N-terminus is related to its thermostability. In addition, oligosaccharides with disaccharides and tetrasaccharides were the end products of EPL15085. Based on molecular docking and site-directed mutagenesis analysis, Tyr177 and Leu134 are considered to be the crucial residues for enzyme activity. In conclusion, our study identified a new PL28 family of ulvan lyases, EPL15085, with excellent heat resistance that can expand the database of ulvan lyases and provide the possibility to make full use of ulvan.

Comparative long-term outcomes of airway resection and functional reconstruction for papillary thyroid cancer.

INTRODUCTION: The surgical management of patients diagnosed with papillary thyroid carcinoma (PTC) and tracheal invasion has been a subject of ongoing discussion, particularly regarding the approach to tracheal functional reconstruction. The objective of this study was to examine the surgical technique and prognosis of PTC patients with tracheal invasion. MATERIALS AND METHODS: This study employed both univariate and multivariate Cox proportional hazard models to determine predictive factors that affect the progression-free survival (PFS) of PTC patients with tracheal invasion. Cox regression analysis was conducted by using R software version 4.3.1. RESULTS: In our study, we included 247 patients with T4a PTC. Among them, 146 patients (59.1 %) were classified as Shin I, 57 patients (23.1 %) as Shin II-III, and 44 patients (17.8 %) as Shin IV. Patients in the Shin I group underwent shaving of the tumours in the airway. The preferred surgical methods in the Shin II, III and IV groups were window resection (66.7 %), sleeve resection (34.8 %) and partial tracheal resection and skin fistula (61.8 %), respectively. Multivariate analysis demonstrated that neither tracheal surgery nor reconstruction procedures had an impact on PFS in T4a PTC patients with tracheal invasion. The 5-year DSS rate for patients receiving radioiodine (RAI) therapy was 87.3 % (p = 0.033). CONCLUSION: This study confirmed that tracheal surgery and reconstruction methods had no impact on PFS in T4a PTC patients with tracheal invasion in different Shin groups. Furthermore, RAI therapy has the potential to increase the survival rate of patients with preoperative distant metastasis of T4a PTC.

Error-controlled algorithm for the cumulative distribution function of doubly non-central F distribution.

The doubly non-central F distribution is a widely applied probability distribution. The cumulative distribution function (CDF) of the doubly non-central F distribution can be expressed using the infinite doubly series. In this paper, a CDF calculation method that allows for controlled precision is derived through the study of the infinite doubly series. By setting parameters, this method can provide an upper limit of error for the computed results, thereby allowing for precision control in the calculations. Experimental results demonstrate that this method achieves a good balance between computational precision and speed.

Lead-induced liver fibrosis and inflammation in mice by the AMPK/MAPKs/NF-κB and STAT3/TGF-ß1/Smad2/3 pathways: the role of Isochlorogenic acid a.

Lead (Pb) is a nonessential heavy metal, which can cause many health problems. Isochlorogenic acid A (ICAA), a phenolic acid present in tea, fruits, vegetables, coffee, plant-based food products, and various medicinal plants, exerts multiple effects, including anti-oxidant, antiviral, anti-inflammatory and antifibrotic functions. Thus, the purpose of our study was to determine if ICAA could prevent Pb-induced hepatotoxicity in ICR mice. An evaluation was performed on oxidative stress, inflammation and fibrosis, and related signaling. The results indicate that ICAA attenuates Pb-induced abnormal liver function. ICAA reduced liver fibrosis, inflammation and oxidative stress caused by Pb. ICAA abated Pb-induced fibrosis and decreased inflammatory cytokines interleukin-1ß (IL-1ß) and tumor necrosis factor-alpha (TNF-α). ICAA abrogated reductions in activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Masson staining revealed that ICAA reduced collagen fiber deposition in Pb-induced fibrotic livers. Western blot and immunohistochemistry analyses showed ICAA increased phosphorylated AMP-activated protein kinase (p-AMPK) expression. ICAA also reduced the expression of collagen I, α-smooth muscle actin (α-SMA), phosphorylated extracellular signal-regulated kinase (p-ERK), phosphorylated c-jun N-terminal kinase (p-JNK), p-p38, phosphorylated signal transducer and phosphorylated activator of transcription 3 (p-STAT3), transforming growth factor ß1 (TGF-ß1), and p-Smad2/3 in livers of mice. Overall, ICAA ameliorates Pb-induced hepatitis and fibrosis by inhibiting the AMPK/MAPKs/NF-κB and STAT3/TGF-ß1/Smad2/3 pathways.

Protease SfpB plays an important role in cell membrane stability and immune system evasion in Streptococcus agalactiae.

Bacteria possess the ability to develop diverse and ingenious strategies to outwit the host immune system, and proteases are one of the many weapons employed by bacteria. This study sought to identify S. agalactiae additional serine protease and determine its role in virulence. The S. agalactiae THN0901 genome features one S8 family serine peptidase B (SfpB), acting as a secreted and externally exposed entity. A S8 family serine peptidase mutant strain (ΔsfpB) and complement strain (CΔsfpB) were generated through homologous recombination. Compared to the wild-type strain THN0901, the absorption of EtBr dyes was significantly reduced (P<0.01) in ΔsfpB, implying an altered cell membrane permeability. In addition, the ΔsfpB strain had a significantly lower survival rate in macrophages (P<0.01) and a 61.85% lower adhesion ability to the EPC cells (P<0.01) compared to THN0901. In the in vivo colonization experiment using tilapia as a model, 210 fish were selected and injected with different bacterial strains at a concentration of 3 x 106 CFU/tail. At 6, 12, 24, 48, 72 and 96 hours post-injection, three fish were randomly selected from each group and their brain, liver, spleen, and kidney tissues were isolated. Subsequently, it was demonstrated that the ΔsfpB strain exhibited a markedly diminished capacity for colonization in tilapia. Additionally, the cumulative mortality of ΔsfpB in fish after intraperitoneal injection was reduced by 19.92-23.85%. In conclusion, the findings in this study have demonstrated that the SfpB plays a significant role in S. agalactiae cell membrane stability and immune evasion. The immune evasion is fundamental for the development and transmission of invasive diseases, the serine protease SfpB may be a promising candidate for the development of antimicrobial agents to reduce the transmission of S. agalactiae.

Molecular Engineering for Modulating Photocatalytic Hydrogen Evolution of Fully Conjugated 3D Covalent Organic Frameworks.

Covalent organic frameworks (COFs) have recently shown great potential for photocatalytic hydrogen production. Currently almost all reports are focused on two-dimensional (2D) COFs, while the 3D counterparts are rarely explored due to their non-conjugated frameworks derived from the sp3 carbon based tetrahedral building blocks. Here, we rationally designed and synthesized a series of fully conjugated 3D COFs by using the saddle-shaped cyclooctatetrathiophene derivative as the building block. Through molecular engineering strategies, we thoroughly discussed the influences of key factors including the donor-acceptor structure, hydrophilicity, specific surface areas, as well as the conjugated/non-conjugated structures on their photocatalytic hydrogen evolution properties. The as-synthesized fully conjugated 3D COFs could generate the hydrogen up to 40.36 mmol h-1 g-1. This is the first report on intrinsic metal-free 3D COFs in photocatalytic hydrogen evolution application. Our work provides insight on the structure design of 3D COFs for highly-efficient photocatalysis, and also reveals that the semiconducting fully conjugated 3D COFs could be a useful platform in clear energy-related fields.

Arene Reduction by Rh/Pd or Rh/Pt under 1 atm Hydrogen Gas and Room Temperature.

Current methods for arene hydrogenation generally need either harsh reaction conditions or complex catalyst preparation. Here we describe a mild and convenient protocol that only utilizes commercially available catalysts. Using [Rh(nbd)Cl]2 and Pd/C together as catalysts, arenes bearing various functional groups can be hydrogenated under 1 atm of H2 at room temperature. This arene hydrogenation can also be achieved using catalysts of [Rh(cod)Cl]2 and PtO2, thus avoiding glovebox manipulations and simplifying the reaction procedure.

Combining brief recall and ketamine treatment prevents stress-primed methamphetamine memory reinstatement via heightening mPFC GABA activity.

This study aimed to assess whether brief recall of methamphetamine (MA) memory, when combined with ketamine (KE) treatment, may prevent stress-primed MA memory reinstatement. Combining 3-min recall and KE facilitated MA memory extinction and resistance to subsequent stress-primed reinstatement. Such combination also produced glutamate metabotropic receptor 5 (mGluR5) upregulation in animals' medial prefrontal cortex (mPFC) γ-amino-butyric acid (GABA) neuron. Accordingly, chemogenetic methods were employed to bi-directionally modulate mPFC GABA activity. Following brief recall and KE-produced MA memory extinction, intra-mPFC mDlx-Gi-coupled-human-muscarinic-receptor 4 (hM4Di)-infused mice receiving compound 21 (C21) treatment showed eminent stress-primed reinstatement, while their GABA mGluR5 expression seemed to be unaltered. Intra-mPFC mDlx-Gq-coupled-human-muscarinic-receptor 3 (hM3Dq)-infused mice undergoing C21 treatment displayed MA memory extinction and resistance to stress-provoked reinstatement. These results suggest that combining a brief recall and KE treatment and exciting mPFC GABA neuron may facilitate MA memory extinction and resistance to stress-primed recall. mPFC GABA neuronal activity plays a role in mediating brief recall/KE-produced effects on curbing the stress-provoked MA seeking.

Inhibitory effects of glutathione peroxidase on microbial spoilage of crayfish (Procambarus clarkii) during refrigerated storage.

The variety of enzyme-based biological preservatives is limited. This study evaluated the effects of glutathione peroxidase (GSH-Px) on the quality of crayfish during refrigerated storage by measuring the pH, total volatile basic nitrogen, trimethylamine, and microbial contamination in crayfish muscle simulation system. The results revealed that 0.3% GSH-Px (CK3) not only suppressed the degradation of nitrogenous substances but also decreased the contamination levels of total viable, Enterobacteriaceae, and Pseudomonas counts (P < 0.05). Furthermore, the populations of Lactococcus, Aeromonas, and Massilia differed in the CK3 group compared to the other groups (P < 0.05) at the end of the storage (day 15). Moreover, the principal coordinate analysis showed that the colony composition of CK3 stored for 15 days was similar to that of the control group stored for 10 days. Therefore, GSH-Px exhibits antibacterial activity against Gram-negative bacteria and has good application potential in freshwater aquatic product preservation.

Ultra-Low Thermal Conductivity and Improved Thermoelectric Performance in Tungsten-Doped GeTe.

Compared to SnTe and PbTe base materials, the GeTe matrix exhibits a relatively high Seebeck coefficient and power factor but has garnered significant attention due to its poor thermal transport performance and environmental characteristics. As a typical p-type IV-VI group thermoelectric material, W-doped GeTe material can bring additional enhancement to thermoelectric performance. In this study, the introduction of W, Ge1-xWxTe (x = 0, 0.002, 0.005, 0.007, 0.01, 0.03) resulted in the presence of high-valence state atoms, providing additional charge carriers, thereby elevating the material's power factor to a maximum PFpeak of approximately 43 µW cm-1 K-2, while slightly optimizing the Seebeck coefficient of the solid solution. Moreover, W doping can induce defects and promote slight rhombohedral distortion in the crystal structure of GeTe, further reducing the lattice thermal conductivity κlat to as low as approximately 0.14 W m-1 K-1 (x = 0.002 at 673 K), optimizing it to approximately 85% compared to the GeTe matrix. This led to the formation of a p-type multicomponent composite thermoelectric material with ultra-low thermal conductivity. Ultimately, W doping achieves the comprehensive enhancement of the thermoelectric performance of GeTe base materials, with the peak ZT value of sample Ge0.995W0.005Te reaching approximately 0.99 at 673 K, and the average ZT optimized to 0.76 in the high-temperature range of 573-723 K, representing an increase of approximately 17% compared to pristine GeTe within the same temperature range.

Decreased Ubiquitination and Acetylation of Histones 3 and 4 Are Associated with Obesity-Induced Disorders of Spermatogenesis in Mice.

BACKGROUND: Obesity, a chronic metabolic disorder, is related to cardiovascular diseases, diabetes, cancer, and reproductive disorders. The relationship between obesity and male infertility is now well recognized, but the mechanisms involved are unclear. We aimed to observe the effect of obesity on spermatogenesis and to investigate the role of histone ubiquitination and acetylation modifications in obesity-induced spermatogenesis disorders. METHODS: Thirty male C57BL/6J mice were randomly divided into two groups. The control group was fed with a general maintenance diet (12% fat), while a high-fat diet (HFD) group was fed with 40% fat for 10 weeks; then, they were mated with normal females. The fertility of male mice was calculated, testicular and sperm morphology were observed, and the expression levels of key genes and the levels of histone acetylation and ubiquitination modification during spermatogenesis were detected. RESULTS: The number of sperm was decreased, as well as the sperm motility, while the number of sperm with malformations was increased. In the testes, the mRNA and protein expression levels of gonadotropin-regulated testicular RNA helicase (GRTH/DDX25), chromosome region maintenance-1 protein (CRM1), high-mobility group B2 (HMGB2), phosphoglycerate kinase 2 (PGK2), and testicular angiotensin-converting enzyme (tACE) were decreased. Furthermore, obesity led to a decrease in ubiquitinated H2A (ubH2A) and reduced levels of histone H3 acetylation K18 (H3AcK18) and histone H4 acetylation K5, K8, K12, and K16 (H4tetraAck), which disrupted protamine 1 (Prm1) deposition in testis tissue. CONCLUSION: These results suggest that low levels of histone ubiquitination and acetylation are linked with obesity-induced disorders during spermatogenesis, contributing to a better understanding of obesity-induced damage to male reproduction.

Neuroimage analysis using artificial intelligence approaches: a systematic review.

In the contemporary era, artificial intelligence (AI) has undergone a transformative evolution, exerting a profound influence on neuroimaging data analysis. This development has significantly elevated our comprehension of intricate brain functions. This study investigates the ramifications of employing AI techniques on neuroimaging data, with a specific objective to improve diagnostic capabilities and contribute to the overall progress of the field. A systematic search was conducted in prominent scientific databases, including PubMed, IEEE Xplore, and Scopus, meticulously curating 456 relevant articles on AI-driven neuroimaging analysis spanning from 2013 to 2023. To maintain rigor and credibility, stringent inclusion criteria, quality assessments, and precise data extraction protocols were consistently enforced throughout this review. Following a rigorous selection process, 104 studies were selected for review, focusing on diverse neuroimaging modalities with an emphasis on mental and neurological disorders. Among these, 19.2% addressed mental illness, and 80.7% focused on neurological disorders. It is found that the prevailing clinical tasks are disease classification (58.7%) and lesion segmentation (28.9%), whereas image reconstruction constituted 7.3%, and image regression and prediction tasks represented 9.6%. AI-driven neuroimaging analysis holds tremendous potential, transforming both research and clinical applications. Machine learning and deep learning algorithms outperform traditional methods, reshaping the field significantly.

UTRN as a potential biomarker in breast cancer: a comprehensive bioinformatics and in vitro study.

Utrophin (UTRN), known as a tumor suppressor, potentially regulates tumor development and the immune microenvironment. However, its impact on breast cancer's development and treatment remains unstudied. We conducted a thorough examination of UTRN using both bioinformatic and in vitro experiments in this study. We discovered UTRN expression decreased in breast cancer compared to standard samples. High UTRN expression correlated with better prognosis. Drug sensitivity tests and RT-qPCR assays revealed UTRN's pivotal role in tamoxifen resistance. Furthermore, the Kruskal-Wallis rank test indicated UTRN's potential as a valuable diagnostic biomarker for breast cancer and its utility in detecting T stage of breast cancer. Additionally, our results demonstrated UTRN's close association with immune cells, inhibitors, stimulators, receptors, and chemokines in breast cancer (BRCA). This research provides a novel perspective on UTRN's role in breast cancer's prognostic and therapeutic value. Low UTRN expression may contribute to tamoxifen resistance and a poor prognosis. Specifically, UTRN can improve clinical decision-making and raise the diagnosis accuracy of breast cancer.

Combined diagnosis for Parkinson's disease via gait and eye movement disorders.

BACKGROUND AND OBJECTIVES: With the discovery of the potential role of gait and eye movement disorders in Parkinson's disease (PD) recognition, we intend to investigate the combined diagnostic value of gait and eye movement disorders for PD. METHODS: We enrolled some Chinese PD patients and healthy controls and separated them into the training and validation sets based on enrollment time. Performance in five oculomotor paradigms and in one gait paradigm was examined using an infrared eye tracking device and a wearable gait analysis device. We developed and validated a combined model for PD diagnosis via multivariate stepwise logistic regression analysis. Furthermore, subgroup comparisons and multi-model comparison were performed to assess its applicability and advantages. RESULTS: A total of 145 PD patients and 80 healthy controls in China were recruited. The pro-saccade velocity, the trunk-sway max, and the turn mean angular velocity were finally screened out for the model development. Incorporating age factor, the ternary model demonstrated more satisfactory performance on ROC (AUC of 0.953 in the training set and AUC of 0.972 in the validation set), calibration curve, and decision curve. A nomogram was drawn to visualize the model. The combined model outperforms individual models with a broad application and the unique diagnostic value for early detection of PD patients, especially TD-PD patients. CONCLUSION: We demonstrated the presence of gait and eye movement disorders, as well as the feasibility, applicability, and superiority of employing them together to diagnose PD.

Xanthine oxidase inhibitory constituents from the roots of Ampelopsis japonica.

Bioassay-guided purification of the xanthine oxidase (XOD) inhibitory extract of the roots of Ampelopsis japonica resulted in the isolation of two new triterpenoids (1-2), designated Ampejaponoside A and B, along with sixteen known compounds (3-18). The structures of Ampejaposide A and B were elucidated by comprehensive analysis of spectroscopic data with the structures of the known compounds 3-18 confirmed by comparison the spectral data with corresponding values reported in literatures. All the isolates were evaluated for their XOD inhibitory activity in vitro. As a result, compounds 2, 8, and 14-16 displayed significant XOD inhibitory effect, particularly 16 being the most potent with an IC50 value of 0.21 µM, superior to positive substance allopurinol (IC50 1.95 µM). Molecular docking uncovered a unique interaction mode of 16 with the active site of XOD. The current study showed that the triterpenoids and polyphenols from A. japonica could serve as new lead compounds with the potential to speed up the development of novel XOD inhibitors with clinical potential to treat hyperuricaemia and gout.

[Evaluation of chemical constituents of Draconis Sanguis and its protective effect on renal tubular injury in diabetic kidney disease].

The chemical constituents of Draconis Sanguis were preliminarily studied by macroporous resin, silica gel, dextran gel, and high-performance liquid chromatography. One retro-dihydrochalcone, four flavonoids, and one stilbene were isolated. Their chemical structures were identified as 4-hydroxy-2,6-dimethoxy-3-methyldihydrochalcone(1), 4'-hydroxy-5,7-dimethoxy-8-methylflavan(2), 7-hydroxy-4',5-dimethoxyflavan(3),(2S)-7-hydroxy-5-methoxy-6-methylflavan(4),(2S)-7-hydroxy-5-methoxyflavan(5), and pterostilbene(6) by modern spectroscopy, physicochemical properties, and literature comparison. Compound 1 was a new compound. Compounds 2 and 6 were first found in the Arecaceae family. Compound 5 had the potential to prevent and treat diabetic kidney disease.