In situ spectroelectrochemical probing of CO redox landscape on copper single-crystal surfaces.

Electrochemical reduction of CO(2) to value-added chemicals and fuels is a promising strategy to sustain pressing renewable energy demands and to address climate change issues. Direct observation of reaction intermediates during the CO(2) reduction reaction will contribute to mechanistic understandings and thus promote the design of catalysts with the desired activity, selectivity, and stability. Herein, we combined in situ electrochemical shell-isolated nanoparticle-enhanced Raman spectroscopy and ab initio molecular dynamics calculations to investigate the CORR process on Cu single-crystal surfaces in various electrolytes. Competing redox pathways and coexistent intermediates of CO adsorption (*COatop and *CObridge), dimerization (protonated dimer *HOCCOH and its dehydrated *CCO), oxidation (*CO2- and *CO32-), and hydrogenation (*CHO), as well as Cu-Oad/Cu-OHad species at Cu-electrolyte interfaces, were simultaneously identified using in situ spectroscopy and further confirmed with isotope-labeling experiments. With AIMD simulations, we report accurate vibrational frequency assignments of these intermediates based on the calculated vibrational density of states and reveal the corresponding species in the electrochemical CO redox landscape on Cu surfaces. Our findings provide direct insights into key intermediates during the CO(2)RR and offer a full-spectroscopic tool (40-4,000 cm-1) for future mechanistic studies.

CD38 deficiency prevents diabetic nephropathy by inhibiting lipid accumulation and oxidative stress through activation of the SIRT3 pathway.

Diabetic nephropathy (DN) is one of the most common complications of diabetes. Our previous study showed that CD38 knockout (CD38KO) mice had protective effects on many diseases. However, the roles and mechanisms of CD38 in DN remain unknown. Here, DN mice were generated by HFD feeding plus streptozotocin (STZ) injection in male CD38KO and CD38flox mice. Mesangial cells (SV40 MES 13 cells) were used to mimic the injury of DN with palmitic acid (PA) treatment in vitro. Our results showed that CD38 expression was significantly increased in kidney of diabetic CD38flox mice and SV40 MES 13 cells treated with PA. CD38KO mice were significantly resistant to diabetes-induced renal injury. Moreover, CD38 deficiency markedly decreased HFD/STZ-induced lipid accumulation, fibrosis and oxidative stress in kidney tissue. In contrast, overexpression of CD38 aggravated PA-induced lipid accumulation and oxidative stress. CD38 deficiency increased expression of SIRT3, while overexpression of CD38 decreased its expression. More importantly, 3-TYP, an inhibitor of SIRT3, significantly enhanced PA-induced lipid accumulation and oxidative stress in CD38 overexpressing cell lines. In conclusion, our results demonstrated that CD38 deficiency prevented DN by inhibiting lipid accumulation and oxidative stress through activation of the SIRT3 pathway.

Convolutional Neural Network-Driven Impedance Flow Cytometry for Accurate Bacterial Differentiation.

Impedance flow cytometry (IFC) has been demonstrated to be an efficient tool for label-free bacterial investigation to obtain the electrical properties in real time. However, the accurate differentiation of different species of bacteria by IFC technology remains a challenge owing to the insignificant differences in data. Here, we developed a convolutional neural networks (ConvNet) deep learning approach to enhance the accuracy and efficiency of the IFC toward distinguishing various species of bacteria. First, more than 1 million sets of impedance data (comprising 42 characteristic features for each set) of various groups of bacteria were trained by the ConvNet model. To improve the efficiency for data analysis, the Spearman correlation coefficient and the mean decrease accuracy of the random forest algorithm were introduced to eliminate feature interaction and extract the opacity of impedance related to the bacterial wall and membrane structure as the predominant features in bacterial differentiation. Moreover, the 25 optimized features were selected with differentiation accuracies of >96% for three groups of bacteria (bacilli, cocci, and vibrio) and >95% for two species of bacilli (Escherichia coli and Salmonella enteritidis), compared to machine learning algorithms (complex tree, linear discriminant, and K-nearest neighbor algorithms) with a maximum accuracy of 76.4%. Furthermore, bacterial differentiation was achieved on spiked samples of different species with different mixing ratios. The proposed ConvNet deep learning-assisted data analysis method of IFC exhibits advantages in analyzing a huge number of data sets with capacity for extracting predominant features within multicomponent information and will bring about progress and advances in the fields of both biosensing and data analysis.

Tomatidine activates autophagy to improve lung injury and inflammation in sepsis by inhibiting NF-κB and MAPK pathways.

Sepsis-induced acute lung injury (ALI) is a life-threatening medical condition with high mortality and morbidity. Autophagy is involved in the pathophysiological process of sepsis-induced ALI, including inflammation, which indicates that regulating autophagy may be beneficial for this disease. Tomatidine, a natural compound abundant in unripe tomatoes, has been reported to have anti-inflammatory, anti-tumorigenic, and lipid-lowering effects. However, the biological functions and mechanisms of tomatidine in sepsis-induced ALI remain unknown. The principal objective of this study was to investigate the effect of tomatidine on sepsis-induced ALI. Cecal ligation and puncture (CLP) was used to induce septic lung injury in mice, and 10 mg/kg tomatidine was intraperitoneally injected into mice 2 h after the operation. The results of hematoxylin and eosin staining and assessment of lung edema and total protein levels in bronchoalveolar lavage fluid (BALF) demonstrated that tomatidine alleviated CLP-induced severe lung injuries such as hemorrhage, infiltration of inflammatory cells, and interstitial and alveolar edema in mice. Additionally, the levels of proinflammatory cytokines in BALF and lung tissues were measured by enzyme-linked immunosorbent assay (ELISA), and the results showed that tomatidine inhibited CLP-induced inflammatory damage to lungs. Moreover, the results of western blotting showed that tomatidine promoted autophagy during CLP-induced ALI. Mechanistically, immunofluorescence staining and western blotting were used to measure the protein levels of TLR4, phosphorylated NF-κB, phosphorylated IκBα, and phosphorylated MAPKs, showing that tomatidine inactivated NF-κB and MAPK signaling in lung tissues of CLP-induced ALI mice. In conclusion, tomatidine exerts protective effects against sepsis-induced severe damage to the lungs by inhibiting inflammation and activating autophagy in CLP-treated mice through inactivating the NF-κB and MAPK pathways, which may be an effective candidate for treating septic ALI.

Ultra-Small Copper-Based Multienzyme-Like Nanoparticles Protect Against Hepatic Ischemia-Reperfusion Injury Through Scavenging Reactive Oxygen Species in Mice.

Hepatic ischemia-reperfusion injury (IRI) is a severe complication that occurs in the process of liver transplantation, hepatectomy, and other end-stage liver disease surgery, often resulting in the failure of surgery operation and even patient death. Currently, there is no effective way to prevent hepatic IRI clinically. Here, it is reported that the ultra-small copper-based multienzyme-like nanoparticles with catalase-like (CAT-like) and superoxide dismutase-like (SOD-like) catalytic activities significantly scavenge the surge-generated endogenous reactive oxygen species (ROS) and effectively protects hepatic IRI. Density functional theory calculations confirm that the nanoparticles efficiently scavenge ROS through their synergistic effects of the ultra-small copper SOD-like activity and manganese dioxides CAT-like activity. Furthermore, the results show that the biocompatible CMP NPs significantly protected hepatocytes from IRI in vitro and in vivo. Importantly, their therapeutic effect is much stronger than that of N-acetylcysteamine acid (NAC), an FDA-approved antioxidative drug. Finally, it is demonstrated that the protective effects of CMP NPs on hepatic IRI are related to suppressing inflammation and hepatocytic apoptosis and maintaining endothelial functions through scavenging ROS in liver tissues. The study can provide insight into the development of next-generation nanomedicines for scavenging ROS.

Stress granules affect the dual PI3K/mTOR inhibitor response by regulating the mitochondrial unfolded protein response.

Drug resistance remains a challenge in ovarian cancer. In addition to aberrant activation of relevant signaling pathways, the adaptive stress response is emerging as a new spotlight of drug resistance in cancer cells. Stress granules (SGs) are one of the most important features of the adaptive stress response, and there is increasing evidence that SGs promote drug resistance in cancer cells. In the present study, we compared two types of ovarian cancer cells, A2780 and SKOV3, using the dual PI3K/mTOR inhibitor, PKI-402. We found that SGs were formed and SGs could intercept the signaling factor ATF5 and regulate the mitochondrial unfolded protein response (UPRmt) in A2780 cells. Therefore, exploring the network formed between SGs and membrane-bound organelles, such as mitochondria, which may provide a new insight into the mechanisms of antitumor drug functions.

Quercetin Protects Against Hypertensive Renal Injury by Attenuating Apoptosis: An Integrated Approach Using Network Pharmacology and RNA Sequencing.

ABSTRACT: Quercetin is known for its antihypertensive effects. However, its role on hypertensive renal injury has not been fully elucidated. In this study, hematoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, and Annexin V staining were used to assess the pathological changes and cell apoptosis in the renal tissues of angiotensin II (Ang II)-infused mice and Ang II-stimulated renal tubular epithelial cell line (NRK-52E). A variety of technologies, including network pharmacology, RNA-sequencing, immunohistochemistry, and Western blotting, were performed to investigate its underlying mechanisms. Network pharmacology analysis identified multiple potential candidate targets (including TP53, Bcl-2, and Bax) and enriched signaling pathways (including apoptosis and p53 signaling pathway). Quercetin treatment significantly alleviated the pathological changes in renal tissues of Ang II-infused mice and reversed 464 differentially expressed transcripts, as well as enriched several signaling pathways, including those related apoptosis and p53 pathway. Furthermore, quercetin treatment significantly inhibited the cell apoptosis in renal tissues of Ang II-infused mice and Ang II-stimulated NRK-52E cells. In addition, quercetin treatment inhibited the upregulation of p53, Bax, cleaved-caspase-9, and cleaved-caspase-3 protein expression and the downregulation of Bcl-2 protein expression in both renal tissue of Ang II-infused mice and Ang II-stimulated NRK-52E cells. Moreover, the molecular docking results indicated a potential binding interaction between quercetin and TP53. Quercetin treatment significantly attenuated hypertensive renal injury and cell apoptosis in renal tissues of Ang II-infused mice and Ang II-stimulated NRK-52E cells and by targeting p53 may be one of the potential underlying mechanisms.

Role of hepatitis B core-related antigen in predicting the occurrence and recurrence of hepatocellular carcinoma in patients with chronic hepatitis B: A systemic review and meta-analysis.

BACKGROUND AND AIM: The purpose of the current study was to investigate the predictive value of hepatitis B core-related antigen (HBcrAg) on the occurrence and recurrence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). METHODS: We searched PubMed, Embase, Scopus, and Web of Science from database inception to April 6, 2023. Pooled hazard ratio (HR) or odds ratio (OR) with 95% confidence interval (CI) was calculated for the occurrence and recurrence of HCC. RESULTS: Of the 464 articles considered, 18 articles recruiting 10 320 patients were included. The pooled results showed that high serum HBcrAg level was an independent risk factor for the occurrence of HCC in CHB patients (adjusted HR = 3.12, 95% CI: 2.40-4.06, P < 0.001, I2 = 43.2%, P = 0.043; OR = 5.65, 95% CI: 3.44-5.82, P < 0.001, I2 = 0.00%, P = 0.42). Further subgroup analysis demonstrated that the predictive ability of HBcrAg for the occurrence of HCC is not influenced by the hepatitis B e antigen (HBeAg) status or the use of nucleoside/nucleotide analogs (NAs). In addition, our meta-analysis also suggests that HBcrAg is a predictor of HCC recurrence (adjusted HR = 1.71, 95% CI: 1.26-2.32, P < 0.001, I2 = 7.89%, P = 0.031). CONCLUSIONS: For patients with CHB, serum HBcrAg may be a potential predictive factor for the occurrence of HCC, regardless of HBeAg status or NA treatment. It may also serve as a novel prognostic biomarker for the recurrence of HCC. More studies are needed to confirm our conclusions.

Presumed atypical late-onset toxic anterior segment syndrome after implantable collamer lens implantation: a case report.

BACKGROUND: Toxic anterior segment syndrome (TASS) is a rare, noninfectious inflammation that occurs after anterior segment surgery. We report a case herein that developed presumed atypical late-onset TASS after V4c implantable collamer lens (ICL) implantation surgery. CASE PRESENTATION: A 26-year-old man underwent ICL implantation surgeries of both eyes on two separate days. The 1-day and 7-day postoperative routine follow-up visits revealed no abnormalities. However, one month after surgery, dense white spots attached to the posterior surface and scattered ones to the anterior surface of ICL in the left eye were noted on anterior segment examination. His uncorrected distance visual acuity (UDVA) was 20/16 in both eyes and the fundus examination was normal. Despite the absence of typical clinical manifestations, late-onset TASS was suspect and intense topical steroid was administered. After 6 weeks of tapering topical steroid therapy, the white spots disappeared and the patient had no subjective complains throughout the treatment period. CONCLUSIONS: This case suggested that the traditionally considered acute and serious TASS could also present as delayed and insidious onset after ICL implantation surgery. Due to its variabilities, the awareness of TASS should be raised to ophthalmologists and regular follow-up visits should be emphasized to patients. Once TASS was suspected, intensive steroid therapy should be implemented in time.

Lightweight Detection Method for X-ray Security Inspection with Occlusion.

Identifying the classes and locations of prohibited items is the target of security inspection. However, X-ray security inspection images with insufficient feature extraction, imbalance between easy and hard samples, and occlusion lead to poor detection accuracy. To address the above problems, an object-detection method based on YOLOv8 is proposed. Firstly, an ASFF (adaptive spatial feature fusion) and a weighted feature concatenation algorithm are introduced to fully extract the scale features from input images. In this way, the model can learn further details in training. Secondly, CoordAtt (coordinate attention module), which belongs to the hybrid attention mechanism, is embedded to enhance the learning of features of interest. Then, the slide loss function is introduced to balance the simple samples and the difficult samples. Finally, Soft-NMS (non-maximum suppression) is introduced to resist the conditions containing occlusion. The experimental result shows that mAP (mean average precision) achieves 90.2%, 90.5%, 79.1%, and 91.4% on the Easy, Hard, and Hidden sets of the PIDray and SIXray public test set, respectively. Contrasted with original model, the mAP of our proposed YOLOv8n model increased by 2.7%, 3.1%, 9.3%, and 2.4%, respectively. Furthermore, the parameter count of the modified YOLOv8n model is roughly only 3 million.

Assessing the effects of drought on rainfed maize water footprints based on remote sensing approaches.

BACKGROUND: Drought affects the characteristics of water use during crop production and so quantitatively evaluating the impacts is important. However, it remains unclear how crop water use responds to drought. To address this gap, water footprint (WF) and standardized precipitation evapotranspiration index (SPEI) were calculated by remote sensing approaches to assess the effects of drought on crop water use. Rainfed maize is the most important crop in Jilin Province, and its growth and water use are more susceptible to drought. The present study explored not only the impact of growing season drought on the maize WF values in Jilin Province, but also the response of WF values to drought at different time scales. RESULTS: Spatially, 72.94% of the WFblue pixels showed a non-significant increase, and the WFgreen in 68% pixels decreased significantly, being mainly concentrated in the middle region. Furthermore, the pixels affected by monthly time scale drought were mainly in the middle region, whereas the pixels affected by annual time scale drought were mainly in the western region. CONCLUSION: Drought not only affected on the source and structure of agricultural water consumption, but also had different effects on WF values at different time scale. These effects had obvious spatial differences. The present study systematically explored the effects of drought on the WF values for rainfed maize in different climate regions and a consideration of these effects could provide valuable information on rainfed maize growth and the agricultural water use response to a changing climate. © 2023 Society of Chemical Industry.

Comprehensive measurement of the near-infrared refractive index of GaAs at cryogenic temperatures.

The refractive index is a critical parameter in optical and photonic device design. However, due to the lack of available data, precise designs of devices working in low temperatures are still frequently limited. In this work, we have built a homemade spectroscopic ellipsometer (SE) and measured the refractive index of GaAs at a matrix of temperatures (4 K < T < 295 K) and photon wavelengths (700 nm < λ < 1000 nm) with a system error of ∼0.04. We verified the credibility of the SE results by comparing them with afore-reported data at room temperature and with higher precision values measured by vertical GaAs cavity at cryogenic temperatures. This work makes up for the lack of the near-infrared refractive index of GaAs at cryogenic temperatures and provides accurate reference data for semiconductor device design and fabrication.

Height-Switching Dynamics of Mixed Polymer Brushes with Polymers of Different Stiffnesses.

Mixed brushes consisting of flexible and semiflexible polymers of the same chain length exhibit a height-switching phenomenon because of rigidity-dependent critical adsorption [Yang et al. Macromolecules 2020, 53, 7369]. Semiflexible polymers stand higher at weak surface attraction (high temperature), but they close to the attractive surface at strong attraction (low temperature). In this work, the height-switching dynamics of the mixed polymer brushes is studied by Metropolis Monte Carlo simulation. The height-switching time is calculated by a sudden change in the surface attraction. Two surface attraction change modes, i.e., the weak-to-strong mode where the attraction is changed from weak to strong and the strong-to-weak mode where it is changed from strong to weak, are investigated. Simulation results show that the height-switching time is related to the grafting density, the polymer stiffness, and surface attraction change mode. We find that the height-switching time is significantly decreased for the strong-to-weak mode. And our results also show that the height switching in the mixed polymer brushes is reversible.

Azobenzene-Functionalized UiO-66-NH2: Solid Base Catalysts with Photocontrollable Activity.

Heterogeneous solid base catalysts are highly expected due to their high activity and environmentally friendly nature in a variety of reactions. However, the catalytic activity of traditional solid base catalysts is controlled by external factors (such as temperature and pressure), and regulation of the activity by in situ changing their own properties has never been reported. Herein, we report a smart solid base catalyst by chemically anchoring the photoresponsive azobenzene derivative p-phenylazobenzoyl chloride (PAC) onto the metal-organic framework UiO-66-NH2 (UN) for the first time, which can regulate the catalytic activity through remote control of external light. The prepared catalysts have a regular crystal structure and photoresponsive properties. It is fascinating that the configuration of PAC can be isomerized easily during UV- and visible-light irradiation and resulted in regulation of the catalytic activity. In the Knoevenagel condensation of 1-naphthaldehyde and ethyl cyanoacetate to ethyl 2-cyano-3-(1-naphthalenyl)acrylate, the optimal catalyst shows up to 56.2% of change after trans/cis isomerization, while the change of the yield over UN is negligible. The regulated catalytic behavior can be assigned to the steric hindrance change of the catalysts under external light irradiation. This work may shed light on the design and construction of smart solid base catalysts with tailorable properties for various reactions.

Design, synthesis, and biological evaluation of quinoxalinone derivatives as potent BRD4 inhibitors.

The bromodomain-containing protein 4 (BRD4) has gained growing interest as an effective drug target for the treatment of hepatocellular carcinoma (HCC). Herein, we designed and synthesized a series of quinoxalinone derivatives as BRD4 inhibitors via scaffold hopping. The representative compound X9 showed potent BRD4 inhibitory activity (with IC50 = 82.3 nM), and preferable antiproliferative activity against HepG2 cells (with IC50 = 1.13 ± 0.07 µM), as well as less toxicity against GES-1 cells (with IC50 = 57.24 ± 5.46 µM). Furthermore, compound X9 dose-dependently inhibited colony formation and blocked the migration of HepG2 cells by down-regulating the expression of Snail and MMP-9 while up-regulating the E-cadherin and Occludin. Besides, compound X9 efficiently down-regulated the expression of c-Myc in HepG2 cells, induced apoptosis, and arrested at G0/G1 phase. In total, quinoxalinone was a potential core as BRD4 inhibitor and compound X9 might be effective for liver cancer therapy.

Lateralized Decrease of Parvalbumin+ Cells in the Somatosensory Cortex of ASD Models Is Correlated with Unilateral Tactile Hypersensitivity.

Inhibitory control of excitatory networks contributes to cortical functions. Increasing evidence indicates that parvalbumin (PV+)-expressing basket cells (BCs) are a major player in maintaining the balance between excitation (E) and inhibition (I). Disruption of E/I balance in cortical networks is believed to be a hallmark of autism spectrum disorder (ASD). Here, we report a lateralized decrease in the number of PV+ BCs in L2/3 of the somatosensory cortex in the dominant hemisphere of Shank3-/- and Cntnap2-/- mouse models of ASD. The dominant hemisphere was identified during a reaching task to establish each animal's dominant forepaw. Double labeling with anti-PV antibody and a biotinylated lectin (Vicia villosa lectin [VVA]) showed that the number of BCs was not different but rather, some BCs did not express PV (PV-), resulting in an elevated number of PV- VVA+ BCs. Finally, we showed that dominant hindpaws had higher mechanical sensitivity when compared with the other hindpaws. This mechanical hypersensitivity in the dominant paw strongly correlated with the decrease in the number of PV+ interneurons and reduced PV expression in the corresponding cortex. Together, these results suggest that the hypersensitivity in ASD patients could be due to decreased inhibitory inputs to the dominant somatosensory cortex.

Characterization of an efficient CRISPR-iCas9 system in Yarrowia lipolytica for the biosynthesis of carotenoids.

The application of clustered regularly interspaced short palindromic repeats-Cas (CRISPR-Cas9) technology in the genetic modification of Yarrowia lipolytica is challenged by low efficiency and low throughput. Here, a highly efficient CRISPR-iCas9 (with D147Y and P411T mutants) genetic manipulation tool was established for Y. lipolytica, which was further utilized to integrate carotene synthetic key genes and significantly improve the target product yield. First, CRISPR-iCas9 could shorten the time of genetic modification and enable the rapid knockout of nonsense suppressors. iCas9 can lead to more than 98% knockout efficiency for NHEJ-mediated repair after optimal target disruption of a single gene, 100% knockout efficiency for a single gene-guided version, and more than 80% knockout efficiency for multiple genes simultaneously in Y. lipolytica. Subsequently, this technology allowed for rapid one-step integration of large fragments (up to 9902-bp) of genes into chromosomes. Finally, YL-ABTG and YL-ABTG2Z were further constructed through CRISPR-iCas9 integration of key genes in a one-step process, resulting in a maximum ß-carotene and zeaxanthin content of 3.12 mg/g and 2.33 mg/g dry cell weight, respectively. Therefore, CRISPR-iCas9 technology provides a feasible approach to genetic modification for efficient biosynthesis of biological compounds in Y. lipolytica. KEY POINTS: • iCas9 with D147Y and P411T mutants improved the CRISPR efficiency in Y. lipolytica. • CRISPR-iCas9 achieved efficient gene knockout and integration in Y. lipolytica. • CRISPR-iCas9 rapidly modified Y. lipolytica for carotenoid bioproduction.

CD38 deficiency promotes skeletal muscle and brown adipose tissue energy expenditure through activating NAD+-Sirt1-PGC1α signaling pathway.

Obesity is a metabolic syndrome characterized by abnormal lipid deposition and energy imbalance. CD38 is a single-chain transmembrane glycoprotein widely expressed in a variety of cell types. The roles of skeletal muscle and brown fat in CD38 deficiency under HFD-induced obesity remain unknown. In this study, we established obesity model with HFD and examined the changes in metabolites with metabonomics. Our results showed that CD38 expression was increased in muscle and brown fat after HFD treatment. Moreover, the results of metabonomics showed that CD38 deficiency significantly altered the metabolites in energy metabolism, cofactor generation, and redox homeostasis. Furthermore, CD38 deficiency reduced the expressions of NADPH oxidase 2 and FASN in mRNA level. We found that the expressions of Sirt1, Sirt3, and PGC1α were upregulated in CD38-deficient muscle tissue. In brown fat, the Sirt1-3, cell death inducing DFFA-like effector A, ELOVL3, and Dio2 expressions were increased in CD38-deficient mice. Our results showed the uncoupling protein 1 expression was upregulated. And NAD+ supplementation increased the expression of Sirt1 and PGC1α after palmitic acid treatment. Taken together, our results demonstrated that the protection of CD38 deficiency on HFD-induced obesity was related to the inhibition of oxidative stress and increasing energy expenditure via activating NAD+/Sirtuins signaling pathways in muscle and brown fat.

Aspergetherins A-D, New Chlorinated Biphenyls with anti-MRSA Activity from the Marine Sponge Symbiotic Fungus Aspergillus terreus 164018.

Aspergetherins A-D (1-4), four new chlorinated biphenyls, were isolated from the rice fermentation of a marine sponge symbiotic fungus Aspergillus terreus 164018, along with seven known biphenyl derivatives (5-11). The structures of four new compounds were determined by a comprehensive analysis of the spectroscopic data, including HR-ESI-MS and 2D NMR data. All 11 isolates were evaluated for their anti-bacterial activity against two strains of methicillin-resistant Staphylococcus aureus (MRSA). Among them, compounds 1, 3, 8 and 10 showed anti-MRSA activity with MIC values of 1.0-128 µg/mL. Preliminary structure-activity relationship analysis unveiled that both chlorinated substitution and esterification of 2-carboxylic acid could impact the antibacterial activity of biphenyls.

CD38 Deficiency Alleviates Diabetic Cardiomyopathy by Coordinately Inhibiting Pyroptosis and Apoptosis.

Diabetic cardiomyopathy is one of the diabetes mellitus-induced cardiovascular complications that can result in heart failure in severe cases, which is characterized by cardiomyocyte apoptosis, local inflammation, oxidative stress, and myocardial fibrosis. CD38, a main hydrolase of NAD+ in mammals, plays an important role in various cardiovascular diseases, according to our previous studies. However, the role of CD38 in diabetes-induced cardiomyopathy is still unknown. Here, we report that global deletion of the CD38 gene significantly prevented diabetic cardiomyopathy induced by high-fat diet plus streptozotocin (STZ) injection in CD38 knockout (CD38-KO) mice. We observed that CD38 expression was up-regulated, whereas the expression of Sirt3 was down-regulated in the hearts of diabetic mice. CD38 deficiency significantly promoted glucose metabolism and improved cardiac functions, exemplified by increased left ventricular ejection fraction and fractional shortening. In addition, we observed that CD38 deficiency markedly decreased diabetes or high glucose and palmitic acid (HG + PA)-induced pyroptosis and apoptosis in CD38 knockout hearts or cardiomyocytes, respectively. Furthermore, we found that the expression levels of Sirt3, mainly located in mitochondria, and its target gene FOXO3a were increased in CD38-deficient hearts and cardiomyocytes with CD38 knockdown under diabetic induction conditions. In conclusion, we demonstrated that CD38 deficiency protected mice from diabetes-induced diabetic cardiomyopathy by reducing pyroptosis and apoptosis via activating NAD+/Sirt3/FOXO3a signaling pathways.