Gypenosides Synergistically Reduce the Extracellular Matrix of Hepatic Stellate Cells and Ameliorate Hepatic Fibrosis in Mice.

Liver fibrosis resulting from chronic liver damage is becoming one of the major threats to health worldwide. Active saponin constituents isolated from Gynostemma pentaphyllum were found to possess a protective effect in liver diseases. Here, we obtained a naturally abundant gypenoside, XLVI, and evaluated its liver protection activity in both animal and cellular models. The results showed that it ameliorated acute and chronic liver injuries and lightened the process of fibrogenesis in vivo. XLVI can inhibit TGF-ß-induced activation of hepatic stellate cells and ECM deposition in vitro. The underlying mechanism study verified that it upregulated the protein expression of protein phosphatase 2C alpha and strengthened the vitality of the phosphatase together with a PP2Cα agonist gypenoside NPLC0393. These results shed new light on the molecular mechanisms and the potential therapeutic function of the traditional herb Gynostemma pentaphyllum in the treatment of liver fibrosis.

Endophytic Microbes from Medicinal Plants in Fenghuang Mountain as a Source of Antibiotics.

One of the largest concerns with world health today is still antibiotic resistance, which is making it imperative to find efficient alternatives as soon as possible. It has been demonstrated that microbes are reliable sources for the creation of therapeutic antibiotics. This research intends to investigate the endophytic microorganisms from several medicinal plants in Fenghuang Mountain (Jiangsu Province, China) and to discover new antibiotics from their secondary metabolites. A total of 269 endophytic strains were isolated from nine distinct medicinal plants. Taxonomic analysis revealed that there were 20 distinct species among these endophytes, with Streptomyces being the most common genus. Three of the target strains were chosen for scale-up fermentation after preliminary screening of antibacterial activities and the metabolomics investigation using LC-MS. These strains were Penicillium sp. NX-S-6, Streptomyces sp. YHLB-L-2 and Streptomyces sp. ZLBB-S-6. Twenty-three secondary metabolites (1-23), including a new sorbicillin analogue (1), were produced as a result of antibacterial activity-guided isolation. Through spectroscopic analysis using MS and NMR, the structures of yield compounds were clarified. According to antibacterial data, S. aureus or B. subtilis were inhibited to varying degrees by sorrentanone (3), emodic acid (8), GKK1032 B (10), linoleic acid (14), toyocamycin (17) and quinomycin A (21). The most effective antimicrobial agent against S. aureus, B. subtilis, E. coli and A. baumannii was quinomycin A (21). In addition, quinomycin A showed strong antifungal activity against Aspergillus fumigatus, Cryptococcus neoformans, and two clinical isolated strains Aspergillus fumigatus #176 and #339, with MIC as 16, 4, 16 and 16 µg/mL, respectively. This is the first time that bioprospecting of actinobacteria and their secondary metabolites from medicinal plants in Fenghuang Mountain was reported. The finding demonstrates the potential of endophytic microbes in medical plants to produce a variety of natural products. Endophytic microbes will be an important source for new antibiotics.

Photonic Spin Lattices: Symmetry Constraints for Skyrmion and Meron Topologies.

Symmetry and topology govern many electronic, magnetic, and photonic phenomena in condensed matter physics and optics, resulting in counterintuitive skyrmion, meron, and other phenomena important for modern technologies. Here we demonstrate photonic spin lattices as a new topological construct governed by the spin-orbit coupling in an optical field. The symmetry of the electromagnetic field in the presence of the spin-orbit interaction may result in only two types of photonic spin lattices: either hexagonal spin-skyrmion or square spin-meron lattices. We show that these spin structures correspond to the lowest energy of the electromagnetic field configuration, therefore, energetically stable. We further show that in the absence of spin-orbit coupling these spin topologies are degenerated in dynamic field skyrmions, unifying the description of electromagnetic field topologies. The results provide a new understanding of electromagnetic field topology and its transformations as well as new opportunities for applications in quantum technologies, spin optics, and topological photonics.

Surface plasmon coupled nano-probe for near field scanning optical microscopy.

Near-field scanning optical microscopy (NSOM) is a powerful tool for study of the nanoscale information of objects by measuring their near-field electric field distributions. The near-field probe, which determines NSOM system performance, can be either a scattering-type or an aperture-type. Both types have strengths and weaknesses. Here we propose and study a surface plasmon-coupled type nano-probe, which works as a hybrid scheme and could potentially combine the advantages of the two NSOM probe types. The key element of the proposed probe is a nanoparticle-on-film structure designed on a tapered fiber tip. On the one hand, the probe can yield the signals scattered in the near field by a nanoparticle with a scattering mechanism; on the other hand, the scattered signals can be transmitted by the metal film and coupled into the fiber via surface plasmon coupled emission, thus providing a collection mode similar to an aperture-type NSOM. This will lead to signal enhancement, while greatly suppressing background noise. This surface plasmon-coupled nano-probe thus has great potential for near-field optical microscopy applications.

Selective magnetic responses of silicon nanoparticles modulated by waveguide structures.

High-refractive-index nanoparticles (NPs), such as silicon NPs, were considered as effective carriers in their response to a magnetic field at optical frequencies. Such NPs play an important role in many state-of-the-art technologies in nano-optics. Although the resonance properties of these NPs when varying their structural parameters have been studied intensely in the past few years, their interaction with the underlying substrate has seldom been discussed, in particular, when the substrate is a waveguide structure that significantly modulates the optical responses of the NPs. We proposed and studied a selective magnetic coupling system comprising a Si-NP on a metal-dielectric waveguide (MDW). The MDW structure supports either a transverse electric (TE) or a transverse magnetic (TM) mode that induces a large polarization dependence in the magnetic resonance. A new manifestation of the optical spin Hall effect was demonstrated in which a vertical rotating magnetic dipole excites a TE-type waveguide mode with a specific unidirectional emission. Making use of this polarization response, we developed a scanning imaging system that can selectively map the transverse or longitudinal magnetic field component of a focused beam depending on the type of MDW used in the system. This selective magnetic resonance coupling system is expected to be valuable for studying the fundamental interactions between the magnetic field and matter and for developing related nano-applications.

Mental health status of patients with coronavirus disease 2019 in Changsha. / 长沙地区2019å† çŠ¶ç— æ¯’ç— æ‚£è€ çš„å¿ƒç†å¥åº·çŠ¶å†µ.

OBJECTIVES: The epidemic of coronavirus disease 2019 (COVID-19) brought psychological stress to the public, especially to patients. This study aims to investigate the mental health of patients with COVID-19 in Changsha. METHODS: We took cross-section investigation for the mental health of 112 patients with COVID-19 via questionnaires. Mann-Whitney U test, Chi-square test, and Fisher's exact test were performed to compare general and clinical data between the slight-ordinary patients and severe patients. Single sample t-tests were used to compare the difference between the factor scores of the Symptom Check-List 90 (SCL-90) in COVID-19 patients with the norm of 2015 and factor scores of SCL-90 in patients with the severe acute respiratory syndrome (SARS). RESULTS: The obsessive-compulsive, depression, sleep and eating disorders had the highest frequency among the positive symptoms of SCL-90 in patients with COVID-19 in Changsha. The factor scores of somatization, depression, anxiety, phobia anxiety, sleep and eating disorders in patients with COVID-19 were higher than those of the norm (P≤0.001 or P<0.05). Slight-ordinary patients with COVID-19 in Changsha showed lower factor scores of somatization, depression, anxiety, and hostility compared with the patients with SARS (P<0.001 or P<0.05). There was no difference in factor scores of SCL-90 between the patients with severe COVID-19 and those with SARS(P>0.05). CONCLUSIONS: The levels of somatization, depression, anxiety, phobia anxiety, sleep and eating disorders in patients with COVID-19 in Changsha are higher than those of the norm. However, the mental health of slight-ordinary patients with COVID-19 is better than that of patients with SARS. It needs to provide targeting psychological interventions depending on the severity of patients.

Long noncoding RNA C21orf121/bone morphogenetic protein 2/microRNA-140-5p gene network promotes directed differentiation of stem cells from human exfoliated deciduous teeth to neuronal cells.

Previous studies have revealed that long noncoding RNA (lncRNA) and microRNA play a crucial role in autism, which is a childhood neurodevelopmental disorder with complicated genetic origins. Hence, the study concerns whether lncRNA C21orf121/bone morphogenetic proteins 2 (BMP2)/miR-140-5p gene network affects directed differentiation of stem cells from human exfoliated deciduous teeth (SHED) to neuronal cells in rats with autism. Autism models were successfully established. The neuron cells that differentiated from SHED cell were identified. The expression of lncRNA C21orf121, miR-140-5p, BMP2, Nestin, ßIII-tubulin, and microtubule-associated protein 2 (MAP2) and the expression of neuron-specific enolase (NSE) were examined. Besides, the gap junction (GJ) function of SHED, the intracellular free Ca 2+ concentration, and the social behavior and repetitive stereotyped movements of rats in autism were detected. The target relationship between lncRNA C21orf121 and miR-140-5p and that between miR-140-5p and BMP2 were also verified. Firstly, we successfully isolated SHED and identified the differentiated neurons of SHED. Besides, the expression of BMP2, MAP2, Nestin, ßIII-tubulin, NSE positive rate, GJ function, and intracellular free Ca 2+ concentration were increased with the upregulation of C21orf121 and downregulation of miR-140-5p, and accumulated time of repetitive stereotyped movements decreased and the frequency of social behavior increased. The results indicate that lncRNA C21orf121 as a competing endogenous RNA competes with BMP2 binding to miR-140-5p, thereby promoting SHED to differentiate into neuronal cells via upregulating BMP2 expression.

Low-loss metal-dielectric waveguide mode enabled structured illumination microscopy with 0.18λ0 resolution.

Structured illumination microscopy (SIM) is a powerful super-resolved imaging technique which enables to perform fast and in vivo imaging of bio-samples. In order to achieve a better resolution of a SIM system, evanescent waves with larger in-plane wave-vector are preferred for SIM, among which the total internal reflection (TIRF-SIM) and the plasmonic SIM (pSIM) configurations are widely studied. Here, we demonstrated a metal-dielectric waveguide (MDW) based SIM system - termed as MDW-SIM, which can achieve a good compromise between TIRF-SIM and pSIM. The MDW can support a low-loss waveguide mode at an aqueous environment, with an evanescent tail existing above the water/dielectric interface for SIM. A proof-of-concept imaging experiment was performed on fluorescent beads, where a spatial resolution of 86nm was achieved at a 473nm illumination wavelength and a 1.45 numerical aperture objective lens. The proposed MDW-SIM has a great potential for the bio-imaging applications.

Mapping the weak plasmonic transverse field by a dielectric-nanoparticle-on-film structure with ultra-high precision.

Highly confined electromagnetic fields play a significant role in modern nano-optics, among which surface plasmon polaritons (SPPs) are outstanding because of their subwavelength and enhancement nature. While many state-of-the-art methods have been proposed to uncover the field distribution of SPPs, it still faces challenge to map the weak transverse field component (the field tangential to the interface) of SPPs with high contrast and precision. We propose a direct imaging technique, which employs a dielectric-nanoparticle-on-metal-film (DNP-MF) structure as a near-field probe, to overcome this difficulty. The angular distribution of the scattering radiation from the structure is strongly polarization dependent. By extracting the scattering signals that are mainly induced by the horizontal polarization, the imaging of the weak plasmonic transverse field with high precision can be achieved. The mappings of SPPs distributions excited by various vector beams were performed in experiment, which accord excellent with theory. This technique provides a new approach for near-field imaging with high contrast and reliability, which is expected to be valuable for studying the vectorial features of SPPs such as transverse spin, spin-orbit interactions, etc.

MRI features and differential diagnoses of congenital vaginal atresia.

Objective: To investigate the MRI manifestations of congenital vaginal atresia, analyze its imaging features, and improve the understanding of the disease. Methods: MRI findings and clinical data of 12 patients with congenital vaginal atresia confirmed by hysteroscopy and laparoscopic surgery were retrospectively analyzed. Vaginal atresia was classified according to vaginal dysplasia in AFS female genital malformation classification system. Results: In this study, 12 cases of congenital vaginal atresia were diagnosed by combined preoperative MRI with operative diagnosis. Among them, 10 patients all had type-I congenital vaginal atresia, and their uterus and cervix were normal (1 patient had ectopic renal malformation combined with left ovarian endometriosis cyst and 1 patient with uterine empyema). The other two cases were diagnosed congenital vaginal atresia type II (1 case merged with residual uterus, 1 case with cervical dysplasia). MRI mainly manifested as dilatation and hemorrhage in the uterine cavity, cervical canal and vaginal upper segment. T1WI showed high signal, T2WI showed slightly lower and slightly higher signal. The dilated vagina was above the perineal level. Conclusion: MRI features of congenital vaginal atresia have certain characteristics. MRI cannot only accurately assess the type of vaginal dysplasia and its associated complications, but also make objective evaluation and diagnosis, so it can be used as the best effective preoperative image evaluation.

A study of single nucleotide polymorphisms in CD157, AIM2 and JARID2 genes in Han Chinese children with autism spectrum disorder.

PURPOSE: Autism spectrum disorder (ASD) is a group of developmental brain disorders caused by genetic and environmental factors. The objective of this study was to investigate whether single nucleotide polymorphisms (SNPs) in genes related to immune function were associated with ASD in Chinese Han children. MATERIALS AND METHODS: A total of 201 children with ASD and 200 age- and gender-matched healthy controls were recruited from September 2012 to June 2106. A TaqMan probe-based approach was used to genotype SNPs corresponding to rs28532698 and rs4301112 in CD157, rs855867 in AIM2, and rs2237126 in JARID2. Case-control and case-only studies were performed to determine the contribution of SNPs to the predisposition of disease and its severity, respectively. RESULTS: Our results revealed that the genotypes and allele frequencies of these SNPs were not significantly associated with childhood ASD and its severity in this population. CONCLUSIONS: Results of our study suggest that these SNPs are not predictors of childhood ASD in the Chinese Han population. The discrepant results suggest the predictor roles of SNPs have to be determined in different ethnic populations due to genetic heterogeneity of ASD.

Neutrophil CD64 combined with PCT, CRP and WBC improves the sensitivity for the early diagnosis of neonatal sepsis.

BACKGROUND: The aim of this study was to determine whether neutrophil CD64 (nCD64) combined with procalcitonin (PCT), C-reactive protein (CRP) and white blood cell count (WBC) can increase the sensitivity and accuracy of neonatal sepsis diagnosis. METHODS: The serum levels of nCD64, CRP, PCT and WBC were detected in 60 patients with neonatal sepsis and 60 patients with non-sepsis. Sensitivity, specificity, positive and negative predictive values, receiver operating characteristic (ROC) area under the curve (AUC), and logistic regression analysis were performed to evaluate the diagnostic value of these markers on neonatal sepsis. RESULTS: Serum levels of nCD64, PCT, CRP and WBC were higher in the sepsis group than non-sepsis group (p<0.001). The sensitivities of nCD64, PCT, CRP and WBC at the recommended cut-off level for all infants were 79.5%, 68.2%, 38.6% and 52.3%, respectively. The best combination was nCD64 and PCT, which obtained sensitivity of 90.9%, largest AUC of 0.922, and a negative predictive value of 89.2%. However by using an optimal cut-off value, the sensitivities of all four biomarkers for the diagnosis of neonatal sepsis were increased to 95.5%. Except for WBC, the birth weight and gestational age had no effects on the diagnostic value of these serum biomarkers. CONCLUSIONS: nCD64 and PCT are better diagnostic biomarkers for early diagnosis of neonatal sepsis as compared to CRP. With the help of optimal cut-off value based on ROC curve and logistic regression analysis, the combination of these biomarkers could improve the sensitivity for the diagnosis of suspected late-onset neonatal sepsis based on common serum biomarkers.

Electronic spill-out induced spectral broadening in quantum hydrodynamic nanoplasmonics.

The hydrodynamic theory is a powerful tool to study the nonlocal effects in metallic nanostructures that are too small to obey classical electrodynamics while still too large to be handled with a full quantum-mechanical theory. The existing hydrodynamic model can give accurate quantitative predictions for the plasmonic resonance shifts in metallic nanoplasmonics, yet is not able to predict the spectral width which is usually taken as a pre-set value instead. By taking account the fact that due to electron density spill-out from a surface, the Coulomb interaction screening is less efficient close the surface thus leads to a higher electron-electron scattering rate in this paper, we study how the electron-density-related damping rate induced by such Coulomb interaction will affect the plasmonic spectral broadening. We perform the simulation on a Na nanowire, which shows that the absorption spectra width is wider when the size of the nanowire becomes smaller. This result is consistent well with the reported experiment. Therefore, our theoretical model extends the existing hydrodynamic model and can provide much more quantum insight about nonlocal effects in metallic nanostructures.

Association between genetic variants in SLC25A12 and risk of autism spectrum disorders: An integrated meta-analysis.

The solute carrier family 25 (aspartate/glutamate carrier), member 12 gene (SLC25A12) has been strongly posed as a candidate gene for autism spectrum disorder (ASD) given its important role in mitochondrial function and adenosine triphosphate (ATP) synthesis. Evidence is mounting for the association between SLC25A12 variants (rs2056202 and rs2292813) and ASD risk, but the results are inconsistent. To clarify the effect of these two variants on ASD, a meta-analysis integrating case-control and transmission disequilibrium test (TDT) studies was performed. The PubMed, Embase, Cochrane Library, Web of Science, Chinese BioMedical Literature (CBM), Wanfang, and Chinese National Knowledge Infrastructure (CNKI) databases were systematically searched to identify relevant studies published up to May 2014. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated to assess the strength of association. A total of 775 cases, 922 controls, and 1289 families available from 8 studies concerning rs2056202, and 465 cases, 450 controls, and 1516 families available from 7 studies concerning rs2292813 were finally included. In the overall meta-analysis, the rs2056202 T allele and rs2292813 T allele were both significantly associated with a decreased risk of ASD (rs2056202: OR = 0.809, P = 0.001, 95%CI: 0.713-0.917, I(2) = 0.0%, and P(heterogeneity) = 0.526; rs2292813: OR = 0.752, P < 0.001, 95%CI: 0.649-0.871, I(2) = 0.0%, P(heterogeneity) = 0.486). Besides, subjects with T-T haplotype of rs2056202-rs2292813 had a significantly reduced risk of ASD (OR = 0.672, P < 0.001, 95%CI: 0.564-0.801, I(2) = 0.0%, P(heterogeneity) = 0.631). Sensitivity analysis, cumulative meta-analysis, and publication bias diagnostics confirmed the reliability and stability of our results. Our meta-analysis suggests that rs2056202 and rs2292813 in SLC25A12 may contribute significantly to ASD risk.

Integration of molecular docking and molecular dynamics simulations with subtractive proteomics approach to identify the novel drug targets and their inhibitors in Streptococcus gallolyticus.

Streptococcus gallolyticus (Sg) is a non-motile, gram-positive bacterium that causes infective endocarditis (inflammation of the heart lining). Because Sg has gained resistance to existing antibiotics and there is currently no drug available, developing effective anti-Sg drugs is critical. This study combined core proteomics with a subtractive proteomics technique to identify potential therapeutic targets for Sg. Several bioinformatics approaches were used to eliminate non-essential and human-specific homologous sequences from the bacterial proteome. Then, virulence, druggability, subcellular localization, and functional analyses were carried out to specify the participation of significant bacterial proteins in various cellular processes. The pathogen's genome contained three druggable proteins, glucosamine-1phosphate N-acetyltransferase (GlmU), RNA polymerase sigma factor (RpoD), and pantetheine-phosphate adenylyltransferase (PPAT) which could serve as effective targets for developing novel drugs. 3D structures of target protein were modeled through Swiss Model. A natural product library containing 10,000 molecules from the LOTUS database was docked against therapeutic target proteins. Following an evaluation of the docking results using the glide gscore, the top 10 compounds docked against each protein receptor were chosen. LTS001632, LTS0243441, and LTS0236112 were the compounds that exhibited the highest binding affinities against GlmU, PPAT, and RpoD, respectively, among the compounds that were chosen. To augment the docking data, molecular dynamics simulations and MM-GBSA binding free energy were also utilized. More in-vitro research is necessary to transform these possible inhibitors into therapeutic drugs, though computer validations were employed in this study. This combination of computational techniques paves the way for targeted antibiotic development, which addresses the critical need for new therapeutic strategies against S. gallolyticus infections.

Proteomics-based vaccine targets annotation and design of multi-epitope vaccine against antibiotic-resistant Streptococcus gallolyticus.

Streptococcus gallolyticus is a non-motile, gram-positive bacterium that causes infective endocarditis. S. gallolyticus has developed resistance to existing antibiotics, and no vaccine is currently available. Therefore, it is essential to develop an effective S. gallolyticus vaccine. Core proteomics was used in this study together with subtractive proteomics and reverse vaccinology approach to find antigenic proteins that could be utilized for the design of the S. gallolyticus multi-epitope vaccine. The pipeline identified two antigenic proteins as potential vaccine targets: penicillin-binding protein and the ATP synthase subunit. T and B cell epitopes from the specific proteins were forecasted employing several immunoinformatics and bioinformatics resources. A vaccine (360 amino acids) was created using a combination of seven cytotoxic T cell lymphocyte (CTL), three helper T cell lymphocyte (HTL), and five linear B cell lymphocyte (LBL) epitopes. To increase immune responses, the vaccine was paired with a cholera enterotoxin subunit B (CTB) adjuvant. The developed vaccine was highly antigenic, non-allergenic, and stable for human use. The vaccine's binding affinity and molecular interactions with the human immunological receptor TLR4 were studied using molecular mechanics/generalized Born surface area (MMGBSA), molecular docking, and molecular dynamic (MD) simulation analyses. Escherichia coli (strain K12) plasmid vector pET-28a ( +) was used to examine the ability of the vaccine to be expressed. According to the outcomes of these computer experiments, the vaccine is quite promising in terms of developing a protective immunity against diseases. However, in vitro and animal research are required to validate our findings.

Stress mitigation mechanism of rice leaf microbiota amid atmospheric deposition of heavy metals.

Leaf microbiota have been extensively applied in the biological control of plant diseases, but their crucial roles in mitigating atmospheric heavy metal (HM) deposition and promoting plant growth remain poorly understood. This study demonstrates that elevated atmospheric HM deposition on rice leaves significantly shapes distinct epiphytic and endophytic microbiota across all growth stages. HM stress consistently leads to the dominance of epiphytic Pantoea and endophytic Microbacterium in rice leaves, particularly during the booting and filling stages. Leaf-bound HMs stimulate the differentiation of specialized microbial communities in both endophytic and epiphytic compartments, thereby regulating leaf microbial interactions. Metagenomic binning retrieved high-quality genomes of keystone leaf microorganisms, indicating their potential for essential metabolic functions. Notably, Pantoea and Microbacterium show significant HM resistance, plant growth-promoting capabilities, and diverse element cycling functions. They possess genes associated with metal(loid) resistance, such as ars and czc, suggesting their ability to detoxify arsenic(As) and cadmium(Cd). They also support carbon, nitrogen, and sulfur cycling, with genes linked to carbon fixation, nitrogen fixation, and sulfur reduction. Additionally, these bacteria may enhance plant stress resistance and growth by producing antioxidants, phytohormones, and other beneficial compounds, potentially improving HM stress tolerance and nutrient availability in rice plants. This study shows that atmospheric HMs affect rice leaf microbial communities, prompting plants to seek microbial help to combat stress. The unique composition and metabolic potential of rice leaf microbiota offer a novel perspective for mitigating adverse stress induced by atmospheric HM deposition. This contributes to the utilization of leaf microbiota to alleviate the negative impact of heavy metal deposition on rice development and food security.

Evaluation of perceptual interactions between key aldehydes in Kung Pao Chicken.

Aldehydes are the strongest and most abundant aromatic compounds in Kung Pao Chicken. However, the perceptual interactions between these aldehydes are not fully understood. Therefore, the flavor contribution of nine key aldehydes was estimated by determining thresholds. Except for benzaldehyde, the thresholds of all aldehydes measured in tasteless chicken matrices (TM) were significantly larger than their comparable values in water. Based on these results, the perceptual interactions of nine aldehydes were evaluated using S-curves and σ-τ plots. The interactions indicated that 31 of their 36 binary mixtures exhibited additive effects, three had masking effects, while two had synergistic effects. Recombination experiments showed that the addition of aldehydes lowered the odor threshold of aldehyde reconstitution (AR), thereby enhancing the aroma intensity of AR. These findings contribute to a better understanding of Kung Pao Chicken's aroma and can be used to improve its aroma quality.

Integrating network pharmacology, molecular docking and simulation approaches with machine learning reveals the multi-target pharmacological mechanism of Berberis integerrima against diabetic nephropathy.

Diabetic nephropathy (DN) is one of the most feared complications of diabetes and key cause of end-stage renal disease (ESRD). Berberis integerrima has been widely used to treat diabetic complications, but exact molecular mechanism is yet to be discovered. Data on active ingredients of B. integerrima and target genes of both diabetic nephropathy and B.integerrima were obtained from public databases. Common results between B. integerrima and DN targets were used to create protein-protein interaction (PPI) network using STRING database and exported to Cytoscape software for the selection of hub genes based on degree of connectivity. Future, PPI network between constituents and overlapping targets was created using Cytoscape to investigate the network pharmacological effects of B. integerrima on DN. KEGG pathway analysis of core genes exposed their involvement in excess glucose-activated signaling pathway. Then, expression of core genes was validated through machine learning classifiers. Finally, PyRx and AMBER18 software was used for molecular docking and simulation. We found that Armepavine, Berberine, Glaucine, Magnoflorine, Reticuline, Quercetin inhibits the growth of diabetic nephropathy by affecting ICAM1, PRKCB, IKBKB, KDR, ALOX5, VCAM1, SYK, TBXA2R, LCK, and F3 genes. Machine learning revealed SYK and PRKCB as potential genes that could use as diagnostic biomarkers against DN. Furthermore, docking and simulation analysis showed the binding affinity and stability of the active compound with target genes. Our study revealed that B. integerrima has preventive effect on DN by acting on glucose-activated signaling pathways. However, experimental studies are needed to reveal biosafety profiles of B. integerrima in DN.Communicated by Ramaswamy H. Sarma.

Sinoflavonoids NJ and NK, anti-inflammatory prenylated flavonoids from the fruits of Podophyllum hexandrum Royle.

Two new prenylated flavonoids named sinoflavonoids NJ and NK (1-2), along with ten known compounds were isolated from the fruits of Podophyllum hexandrum Royle. The chemical structures were determined through NMR spectroscopic data and MS analysis. Sinoflavonoid NJ (1) with an unusual 5,11-dioxabenzo[b]fluoren-10-one skeleton was firstly reported from Berberidaceae. The isolated flavonoids were tested with LPS-induced RAW 264.7 mouse macrophages model for their anti-inflammatory activity. Sinoflavonoid NJ (1) showed the most potent inhibition on nitric oxide production with IC50 value as 0.06 µM.