Structure-Guided Discovery of Diverse Cytotoxic Dimeric Xanthones/Chromanones from Penicillium chrysogenum C-7-2-1 and Their Interconversion Properties.

Xanthone-chromanone homo- or heterodimers are regarded as a novel class of topoisomerase (Topo) inhibitors; however, limited information about these compounds is currently available. Here, 14 new (1-14) and 6 known tetrahydroxanthone chromanone homo- and heterodimers (15-20) are reported as isolated from Penicillium chrysogenum C-7-2-1. Their structures and absolute configurations were unambiguously demonstrated by a combination of spectroscopic data, single-crystal X-ray diffraction, modified Mosher's method, and electronic circular dichroism analyses. Plausible biosynthetic pathways are proposed. For the first time, it was discovered that tetrahydroxanthones can convert to chromanones in water, whereas chromone dimerization does not show this property. Among them, compounds 5, 7, 8, and 16 exhibited significant cytotoxicity against H23 cell line with IC50 values of 6.9, 6.4, 3.9, and 2.6 µM, respectively.

Cerina litoralis gen. nov., sp. nov., a novel potential polysaccharide degrading bacterium of the family Flavobacteriaceae, isolated from marine sediment.

The Gram-strain-negative, facultative anaerobic, chemoheterotrophic, short-rod-shaped, non-motile, forming yellow colonies strain, designated F89T, was isolated from marine sediment of Xiaoshi Island, Weihai. Strain F89T grew at 15-37 °C (optimally at 28 °C), at pH 6.0-8.5 (optimally at pH 7.0) and in the presence of 1-5% (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequence showed that strain F89T was related to the family Flavobacteriaceae. F89T had highest 16S rRNA gene sequence similarity to Maribacter cobaltidurans MCCC 1K03318T (93.3%). The predominant cellular fatty acids of F89T were iso-C15:0, iso-C15:0 G and Summed Feature 3. The main respiratory quinone of F89T was menaquinone 6 (MK-6), consistent with that observed for all related strains. The polar lipid profile of strain F89T contained phosphatidylethanolamine, two aminolipids and three unidentified polar lipids. The genomic DNA G + C content of strain F89T was 42.7%. Strain F89T encoded 121 glycoside hydrolases and was a potential polysaccharide degrading bacterium. Differential phenotypic and genotypic characteristics of the strain showed that F89T should be classified as a novel genus in Flavobacteriaceae, for which the name Cerina litoralis is proposed. The type strain is F89T (= MCCC 1H00510T = KCTC 92203T).

Chondrogenic differentiation of ChM-I gene transfected rat bone marrow-derived mesenchymal stem cells on 3-dimensional poly (L-lactic acid) scaffold for cartilage engineering.

We have explored the role of Chondromodulin-I (ChM-I) in chondrogenesis of bone marrow-derived mesenchymal stem cells (BMSCs) in 3-dimensional (3D) scaffold for cartilage tissue engineering. BMSCs of Sprague Dawley (SD) rats were cultured on poly-(L-lactic acid) [PLLA] scaffolds with different pore sizes (80-200 µm, 200-450 µm) with or without surface modification by chitosan. Cell viability, proliferation, and morphology were measured using confocal microscope and the CCK-8 method. Untransfected BMSCs, BMSCs expressing pcDNA3.1(+), BMSCs expressing plasmid pcDNA3.1 (+)/ChM-I were cultured on 3D scaffolds in standard growth medium or transforming growth factor-ß1 (TGF-ß1) supplemented chondrogenic induction medium in vitro for 3 weeks and the expression of collagen type II was determined. Cell-scaffolds constructs were implanted subcutaneously for 3 months in vivo. BMSCs had a higher viability and proliferation in PLLA scaffolds of pore size 200-450 µm than that of 80-200 µm, and surface modification with chitosan did not enhance cell attachment. The ChM-I gene enhanced chondrogenesis and increased collagen type II synthesis. Immunohistochemistry from in vivo study showed enhanced cartilage regeneration in BMSCs expressing pcDNA3.1 (+)/ChM-I on 3D PLLA scaffolds. It also demonstrated that TGF-ß1 might promote chondrogenesis of rat BMSCs by synergizing with the ChM-I gene. ChM-I could be beneficial to future applications in cartilage repair.

Tuning interfacial oxygen vacancy level of bismuth oxybromide to enhance photocatalytic degradation of bisphenol A.

Oxygen vacancies (OVs) have garnered significant interest for their role as active sites, enhancing the catalytic efficiency of various catalysts. Despite their widespread application in environmental purification processes, the generation of OVs conventionally depends on high-temperature conditions and strong reducing agents for the extraction of surface partial oxygen atoms from catalysts. In this work, bismuth oxybromide (BiOBr) nanosheets with varying levels of OVs were synthesized via a simple and effective solvothermal method. This novel method affords precise control over the conduction band (CB) and valence band (VB) positions of BiOBr. The presence of different OVs exhibited varying photocatalytic efficiencies in the degradation of bisphenol A (BPA) under visible light irradiation, with higher levels of OVs resulting in superior photocatalytic performance. Furthermore, radical scavenger experiments demonstrated that superoxide oxides (O2•-) and holes (h+) were the primary reactive oxygen species for BPA degradation. Additionally, BiOBr-OVs exhibited excellent anti-interference and stability in water matrices containing diverse inorganic anions and organic compounds. This work provides a simple and effective approach for the fine-regulating of catalysts through interfacial defect engineering, paving the way for their practical application in environmental decontamination.

Effects of Germination on the Structure, Functional Properties, and In Vitro Digestibility of a Black Bean (Glycine max (L.) Merr.) Protein Isolate.

The utilization of black beans as a protein-rich ingredient presents remarkable prospects in the protein food industry. The objective of this study was to assess the impact of germination treatment on the physicochemical, structural, and functional characteristics of a black bean protein isolate. The findings indicate that germination resulted in an increase in both the total and soluble protein contents of black beans, while SDS-PAGE demonstrated an increase in the proportion of 11S and 7S globulin subunits. After germination, the particle size of the black bean protein isolate decreased in the solution, while the absolute value of the zeta potential increased. The above results show that the stability of the solution was improved. The contents of ß-sheet and ß-turn gradually decreased, while the content of α-helix increased, and the fluorescence spectrum of the black bean protein isolate showed a red shift phenomenon, indicating that the structure of the protein isolate and its polypeptide chain were prolonged, and the foaming property, emulsification property and in vitro digestibility were significantly improved after germination. Therefore, germination not only improves functional properties, but also nutritional content.

Antifungal bioactivity of Sarcococca hookeriana var. digyna Franch. against fluconazole-resistant Candida albicans in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Sarcococca hookeriana var. digyna Franch. has been widely utilized in folk medicine by the Miao people in the southwestern region of China for treating skin sores which may be associated with microbial infection. AIM OF THE STUDY: To investigate the antifungal bioactivity of S. hookeriana var. digyna against fluconazole-resistant Candida albicans in vitro and in vivo, as well as its underlying mechanism and the key bioactive component. MATERIALS AND METHODS: The antifungal bioactivity of 80% ethanol extract of S. hookeriana var. digyna (SHE80) was investigated in vitro using the broth microdilution method, time-growth curve, and time-kill assay. Its key functional component and antifungal mechanism were explored with combined approaches including UPLC-Q-TOF-MS, network pharmacology and metabolomics. The antifungal pathway was further supported via microscopic observation of fungal cell morphology and examination of its effects on fungal biofilm and cell membranes using fluorescent staining reagents. In vivo assessment of antifungal bioactivity was conducted using a mouse model infected with C. albicans on the skin. RESULTS: S. hookeriana var. digyna suppressed fluconazole-resistant C. albicans efficiently (MIC = 16 µg/mL, MFC = 64 µg/mL). It removed fungal biofilm, increased cell membrane permeability, induced protein leakage, reduced membrane fluidity, disrupted mitochondrial membrane potential, induced the release of reactive oxygen species, promoted cell apoptosis, and inhibited the transformation of fungi from the yeast state to the hyphal state significantly. In terms of mechanism, it affected sphingolipid metabolism and signaling pathway. Moreover, the predicted bioactive component, sarcovagine D, was supported by antifungal bioactivity evaluation in vitro (MIC = 4 µg/mL, MFC = 16 µg/mL). Furthermore, S. hookeriana var. digyna promoted wound healing, reduced the number of colony-forming units, and reduced inflammation effectively in vivo. CONCLUSIONS: The traditional use of S. hookeriana var. digyna for fungal skin infections was supported by antifungal bioactivity investigated in vitro and in vivo. Its mechanism and bioactive component were predicted and confirmed by experiments, which also provided a new antifungal agent for future research.

Single Dispersion of Fe(H2O)2-Based Polyoxometalate on Polymeric Carbon Nitride for Biomimetic CH4 Photooxidation.

Direct methane conversion to value-added oxygenates under mild conditions with in-depth mechanism investigation has attracted wide interest. Inspired by methane monooxygenase, the K9Na2Fe(H2O)2{[γ-SiW9O34Fe(H2O)]}2·25H2O polyoxometalate (Fe-POM) with well-defined Fe(H2O)2 sites is synthesized to clarify the key role of Fe species and their microenvironment toward CH4 photooxidation. The Fe-POM can efficiently drive the conversion of CH4 to HCOOH with a yield of 1570.0 µmol gPOM -1 and 95.8% selectivity at ambient conditions, much superior to that of [Fe(H2O)SiW11O39]5- with Fe(H2O) active site, [Fe2SiW10O38(OH)]2 14- and [P8W48O184Fe16(OH)28(H2O)4]20- with multinuclear Fe-OH-Fe active sites. Single-dispersion of Fe-POM on polymeric carbon nitride (PCN) is facilely achieved to provide single-cluster functionalized PCN with well-defined Fe(H2O)2 site, the HCOOH yield can be improved to 5981.3 µmol gPOM -1. Systemic investigations demonstrate that the (WO)4-Fe(H2O)2 can supply Fe═O active center for C-H activation via forming (WO)4-Fea-Ot···CH4 intermediate, similar to that for CH4 oxidation in the monooxygenase. This work highlights a promising and facile strategy for single dispersion of ≈1-2 Å metal center with precise coordination microenvironment by uniformly anchoring nanoscale molecular clusters, which provides a well-defined model for in-depth mechanism research.

Discovery of Novel Ortho-Aminophenol Derivatives Targeting Lipid Peroxidation with Potent Antiferroptotic Activities.

The concept of ferroptosis inhibition has gained growing recognition as a promising therapeutic strategy for addressing a wide range of diseases. Here, we present the discovery of four series of ortho-aminophenol derivatives as potential ferroptosis inhibitors beginning with the endogenous substance 3-hydroxyanthranilic acid (3-HA) by employing quantum chemistry techniques, in vitro and in vivo assays. Our findings reveal that these ortho-aminophenol derivatives exhibit unique intra-H bond interactions, compelling ortho-amines to achieve enhanced alignment with the aromatic π-system, thereby expanding their activity. Notably, compounds from all four series display remarkable activity against RSL3-induced ferroptosis, showcasing an activity 100 times more than that of 3-HA. Furthermore, these compounds also demonstrate robust in vivo efficacy in protecting mice from kidney ischemia-reperfusion injury and acetaminophen-induced hepatotoxicity. In summary, we provide four distinct series of active scaffolds that significantly expand the chemical space of ferroptosis inhibitors, serving as valuable insights for future structural modifications.

Oral bacteriome and mycobiome of patients with idiopathic membranous nephropathy with different tongue coatings treated with a Chinese herbal formula.

ETHNOPHARMACOLOGICAL RELEVANCE: Moshen Fuyuan Formula (MSFY) is one of the representative Chinese medicine compound for Idiopathic membranous nephropathy (IMN), that originate from Fang Ji Huang Qi decoction in the Han dynasty. IMN is usually accompanied by different tongue coatings in traditional Chinese medicine (TCM), and tongue microorganisms are important factors affecting the formation of the tongue coating. Recently, oral microbiomes, including bacteria and fungi, have been identified as pivotal factors that contribute to disease development. However, the regulation of oral microbiomes by MSFY has not been defined. AIM OF THE STUDY: In this work, we explore the characteristics of oral bacteria and fungi in IMN patients with different tongue coatings, and clarify the therapeutic effect of MSFY based on oral microbiome. MATERIALS AND METHODS: We enrolled 24 patients with IMN, including 11 with white tongue (IMN-W) and 13 with yellow tongue (IMN-Y), and recruited an additional 10 healthy individuals. Patients with IMN were treated with the MSFY. The oral bacteriome and fungi before and after treatment were detected using full-length 16S rRNA and internal transcribed spacer gene sequencing. RESULTS: The therapeutic effect of MSFY on patients with yellow tongue coating was more significant than that on patients with white tongue coating. In terms of oral bacteriome, Campylobacter bacteria were enriched in patients with yellow tongue and could be a promising biomarker for yellow coating. Enrichment of Veillonella parvula_A may partially account for the therapeutic effect of MSFY. As for oral fungi, Malassezia globosa was enhanced in patients with IMN-W and reduced in patients with IMN-Y. Notably, it was reduced by MSFY. We also found that mycobiome-bacteriome interactions were highly complex and dynamic in patients with IMN. CONCLUSION: The regulation of the dynamic balance between oral fungi and bacteria by MSFY contributes to the treatment of IMN. This study determined the oral bacteriome and mycobiome of patients with IMN with different tongue coatings before and after MSFY treatment, which aids in promoting personalized treatment in clinical TCM and provides direction for investigating the mechanism of Chinese herbal medicines.

Successful treatment of patients with refractory idiopathic membranous nephropathy with low-dose Rituximab: A single-center experience.

BACKGROUND: The recognition of idiopathic membranous nephropathy (IMN) as an autoimmune disease has paved the way for the use of B-cell-depleting agents, such as Rituximab (RTX), which is now a first-line drug for treating IMN with proven safety and efficacy. Nevertheless, the usage of RTX for the treatment of refractory IMN remains controversial and challenging. AIM: To evaluate the efficacy and safety of a new low-dose RTX regimen for the treatment of patients with refractory IMN. METHODS: A retrospective study was performed on refractory IMN patients that accepted a low-dose RTX regimen (RTX, 200 mg, once a month for five months) in the Xiyuan Hospital of Chinese Academy of Chinese Medical Sciences' Department of Nephrology from October 2019 to December 2021. To assess the clinical and immune remission data, we performed a 24 h urinary protein quantification (UTP) test and measured the serum albumin (ALB) and serum creatinine (SCr) levels, phospholipase A2 receptor (PLA2R) antibody titer, and CD19+ B-cell count every three months. RESULTS: A total of nine refractory IMN patients were analyzed. During follow-up conducted twelve months later, the results from the 24 h UTP decreased from baseline [8.14 ± 6.05 g/d to 1.24 ± 1.34 g/d (P < 0.05)] and the ALB levels increased from baseline [28.06 ± 8.42 g/L to 40.93 ± 5.85 g/L (P < 0.01)]. Notably, after administering RTX for six months, the SCr decreased from 78.13 ± 16.49 µmol/L to 109.67 ± 40.87 µmol/L (P < 0.05). All of the nine patients were positive for serum anti-PLA2R at the beginning, and four patients had normal anti-PLA2R titer levels at six months. The level of CD19+ B-cells decreased to 0 at three months, and CD19+ B-cell count remained at 0 up until six months of follow-up. CONCLUSION: Our low-dose RTX regimen appears to be a promising treatment strategy for refractory IMN.

Electrochemical sensor for sensitive detection of bisphenol A based on molecularly imprinted TiO2 with oxygen vacancy.

Bisphenol A (BPA) is an endocrine disrupting chemical and broadly used in plastics. The leakage of BPA in food and water cycles poses a significant risk to the environment and human health. Thus, monitoring the concentration of BPA to avoid its potential risk is highly important. In this work, a simple and efficient oxygen deficient molecularly imprinted TiO2 electrochemical sensor was proposed for the detection of BPA. The introduction both oxygen vacancies and molecular imprinting evidently enhanced the electrochemical oxidation signal of BPA. The sensor had a good linear response ranging from 0.01 µM to 20 µM with a limit of detection of 3.6 nM. Additionally, the sensor showed remarkable stability, reproducibility and interference resistant ability. It also exhibits excellent recovery during the detection of real water. These findings suggested that the sensor has the potential to be developed as a simple, efficient and low-cost monitoring system for the monitoring of BPA in water.

Mechanism of Yiqi Yangying Heluo Formula in the Treatment of IgA Nephropathy by Affecting Gd-IgA1 Based on BAFF Molecular Level and T Lymphocyte Immunity.

Background: Galactose-deficient IgA1 (Gd-IgA1) is a critical initiating factor in the pathogenesis of IgA nephropathy (IgAN), which plays an important role in the diagnosis and evaluation of this disease. Moreover, the whole pathogenesis process has an intimate association with the immune response of T and B lymphocytes and their inflammatory factors. There is no specific therapy for IgAN at present. Yiqi Yangyin Formula can significantly reduce urinary protein and hematuria in patients with IgAN. Yiqi Yangying Heluo Formula (YYHF) is optimized on the basis of the above prescription, but its specific mechanism remains to be further studied. Methods: The effect of YYHF on urinary protein and urinary red blood cell count in patients with IgAN was observed by a self-controlled clinical study before and after treatment. On this basis, flow cytometry was used to detect the proportion of T lymphocyte subsets in peripheral blood of patients with IgAN before and after treatment and healthy controls. Meanwhile, the levels of Gd-IgA1, B cell activation factor (BAFF), and their cytokines (IL-4, IL-6, and IL-17) in peripheral blood were detected by enzyme-linked immunosorbent assay. The changes in mechanism-related indicators of the two groups were observed and subject to correlation analysis. Results: (1) Compared with the levels before treatment, 24-hour urinary protein content decreased by 47.7% and urinary red blood cell number decreased by 67% in patients with IgAN intervened by YYHF after 48 weeks of follow-up. (2) Compared with the healthy control group, patients with IgAN showed a significantly increased proportion of Th1 cells, Th17 cells, Th1/Th2, Th1/Treg, Th2/Treg, and Th17/Treg, obviously reduced proportion of Th2 cells and Treg cells, and evidently elevated levels of Gd-IgA1, BAFF, and their cytokines (IL-4, IL-6, and IL-17) in the peripheral blood. (3) Following 48 weeks of follow-up after intervention treatment with YYHF, the levels of Gd-IgA1, BAFF, IL-6, and IL-17 were significantly lower, but the level of IL-4 was higher in peripheral blood of patients with IgAN than those before treatment and after 24 weeks of treatment; simultaneously, the proportion of Th1 cells, Th17 cells, Th1/Th2, Th1/Treg, Th2/Treg, and Th17/Treg decreased while that of Th2 cells and Treg cells increased after 48 weeks of follow-up compared with that before treatment in peripheral blood of patients with IgAN. (4) The results of correlation analysis revealed that the level of Gd-IgA1 in peripheral blood of patients with IgAN was positively correlated with the level of BAFF, as well as the proportion of Th1 cells, Th17 cells, Th1/Th2, IL-6, and IL-17 levels, and negatively correlated with the proportion of Treg cells. In addition, the level of Gd-IgA1 in peripheral blood was positively correlated with proteinuria, yet without correlation with hematuria. Conclusion: YYHF can reduce the quantitative level of 24 h urinary protein and urinary red blood cell count in patients with IgAN. Patients with IgAN have obvious T cell immune imbalance. YYHF can significantly reduce the level of Gd-IgA1 in patients with IgAN, and its mechanism may be explained by the reduced level of BAFF in peripheral blood and improved immune balance of T cells.

Supplementary Feeding of Grazing Inner Mongolian Cashmere Goats during Pregnancy-Based on "Nutrient Requirements of Cashmere Goats".

This study aimed to conduct precise supplementation for pregnant cashmere goats under grazing based on the feeding standard. Eight Inner Mongolian pregnant cashmere goats of near-average body weight were selected at early gestation (44.41 ± 4.03 kg) and late gestation (46.54 ± 4.02 kg) to measure their nutrient intake. Then, two pregnant cashmere goat flocks, No. 10 (control group, on-farm supplement) and No. 11 (supplemented group, supplement based on standard), with the same goat herd structure and grassland type, were chosen to conduct the supplemental feeding experiment. The results showed that pregnant cashmere goats lacked daily the intake of dry matter, digestive energy, crude protein and most essential mineral elements under grazing. After supplemental feeding, the supplementation based on the feeding standard increased the cashmere length and cashmere length growth volume and decreased the cashmere fineness, with no statistical significance. The goat cashmere yield, goat weight after shearing, single and twin-birth kid weight and kids' mature secondary hair follicle density were significantly higher in the supplemented group (p < 0.05). In conclusion, supplementation in accordance with "Nutrient Requirements of Cashmere Goats" can enhance pregnant cashmere goats' fiber production, growth performance, fertility and kids' secondary hair follicles development, which is of great importance for the healthy and precise nutrition and management of cashmere goats.

Diagnostic and prognostic value of galactose-deficient IgA1 in patients with IgA nephropathy: an updated systematic review with meta-analysis.

Objectives: Galactose-deficient IgA1 (Gd-IgA1) is a critical effector molecule in the pathogenesis of IgA nephropathy (IgAN), a leading renal disease without noninvasive assessment options. This updated systematic review aimed to determine the diagnostic and prognostic value of Gd-IgA1 assessment in biological fluids in patients with IgAN. Methods: PRISMA guidelines were followed in this review. We searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, China Biology Medicine disc, VIP Information/China Science and Technology Journal Database, and WANFANG for studies published between database inception and January 31, 2023. Eligible studies that evaluated aberrant IgA1 glycosylation in IgAN patients relative to controls were identified, and random effects meta-analyses were used to compare Gd-IgA1 levels in different groups. The quality of the evidence was assessed using the Newcastle-Ottawa Scale. This study was registered on PROSPERO (CRD42022375246). Findings: Of the 2727 records identified, 50 were eligible and had available data. The mean Newcastle-Ottawa Scale score was 7.1 (range, 6-8). Data synthesis suggested that IgAN patients had higher levels of blood and/or urine Gd-IgA1 compared with healthy controls (standard mean difference [SMD]=1.43, 95% confidence interval [CI]=1.19-1.68, P<0.00001), IgA vasculitis patients (SMD=0.58, 95% CI=0.22-0.94, P=0.002), and other kidney disease patients (SMD=1.06, 95% CI=0.79-1.33, P<0.00001). Moreover, patients with IgAN had similar levels of serum Gd-IgA1 compared to first-degree relatives (SMD=0.38, 95% CI= -0.04-0.81, P=0.08) and IgA vasculitis with nephritis patients (SMD=0.12, 95% CI= -0.04-0.29, P=0.14). In addition, ten studies demonstrated significant differences in serum Gd-IgA1 levels in patients with mild and severe IgAN (SMD= -0.37, 95% CI= -0.64--0.09, P=0.009). Conclusions: High serum and urine Gd-IgA1 levels suggest a diagnosis of IgAN and a poor prognosis for patients with this immunological disorder. Future studies should use more reliable and reproducible methods to determine Gd-IgA1 levels. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022375246, identifier CRD42022375246.

Thiolated Mesoporous Silica Nanoparticles as an Immunoadjuvant to Enhance Efficacy of Intravesical Chemotherapy for Bladder Cancer.

The characteristics of global prevalence and high recurrence of bladder cancer has led numerous efforts to develop new treatments. The spontaneous voiding and degradation of the chemodrug hamper the efficacy and effectiveness of intravesical chemotherapy following tumor resection. Herein, the externally thiolated hollow mesoporous silica nanoparticles (MSN-SH(E)) is fabricated to serve as a platform for improved bladder intravesical therapy. Enhanced mucoadhesive effect of the thiolated nanovector is confirmed with porcine bladder. The permeation-enhancing effect is also verified, and a fragmented distribution pattern of a tight junction protein, claudin-4, indicates the opening of tight junction. Moreover, MSN-SH(E)-associated reprogramming of M2 macrophages to M1-like phenotype is observed in vitro. The antitumor activity of the mitomycin C (MMC)-loaded nanovector (MMC@MSN-SH(E)) is more effective than that of MMC alone in both in vitro and in vivo. In addition, IHC staining is used to analyze IFN-γ, TGF-ß1, and TNF-α. These observations substantiated the significance of MMC@MSN-SH(E) in promoting anticancer activity, holding the great potential for being used in intravesical therapy for non-muscle invasive bladder cancer (NMIBC) due to its mucoadhesivity, enhanced permeation, immunomodulation, and prolonged and very efficient drug exposure.

SORL1 genetic variants and cerebrospinal fluid biomarkers of Alzheimer's disease.

The neuronal sortilin-related receptor with A-type repeats (SORL1, also called LR11 or sorLA) is involved in amyloidogenesis, and the SORL1 gene is a major risk factor for Alzheimer's disease (AD). We investigated AD-related CSF biomarkers for associations with SORL1 genetic variants in 105 German patients with mild cognitive impairment (MCI) and AD. The homozygous CC-allele of single nucleotide polymorphism (SNP) 4 was associated with increased Tau concentrations in AD, and the minor alleles of SNP8, SNP9, and SNP10 and the haplotype CGT of these SNPs were associated with increased SORL1 concentrations in MCI. SNP22 and SNP23, and the haplotypes TCT of SNP19-21-23, and TTC of SNP22-23-24 were correlated with decreased Ab42 levels in AD. These results strengthen the functional role of SORL1 in AD.

Effects of goal-oriented nursing intervention on postpartum depression.

This retrospective study aimed to explore the effects of goal-oriented nursing intervention (GONI) on postpartum depression (PPD). We retrospectively analyzed the medical records of 72 women with PPD. They were allocated to a treatment group (n = 36, exercise plus GONI) or a control group (n = 36, exercise). Patients in both groups received a total of 3 months of treatment. Outcomes included the 17-item Hamilton Rating Scale for Depression (HAMD-17) total score, HAMD-17 response rate (≥50% score reduction), HAMD-17 remission rate (score ≤ 7), and adverse events. Outcomes were analyzed before and after 3-month of treatment. After treatment, patients in the treatment group achieved more effective outcomes in the HADM-17 total score (P < .01), HADM-17 response rate (P < .01), HADM-17 remission rate (P < .01) than those in the control group. Regarding safety, the medical records of both the groups did not report any adverse events. The results of this study showed that GONI and exercise had more effects in patients with PPD. Further prospective studies are required to validate our findings.

Structural modulation of gut microbiota during alleviation of experimental passive Heymann nephritis in rats by a traditional Chinese herbal formula.

BACKGROUND: Jianpi-Qushi-Heluo formula (JQHF) has been used to treat idiopathic membranous nephropathy (IMN) in hospitals for many years. PURPOSE: Elucidating the protective effect and exploring the potential mechanism of JQHF against IMN. METHODS: Passive Heymann nephritis (PHN) was induced in rats by a single tail vein injection of anti-Fx1A antiserum. Then, the animals were treated with JQHF at 16.2 g/kg or 32.4 g/kg, with benzepril (10 mg/kg) as a positive control. Renal function was evaluated by biochemical measurements and pathological testing. Fecal samples were collected before and after treatment to analyze the gut microbiota composition by shotgun whole metagenome sequencing. RESULTS: JQHF exhibited potent efficacy in ameliorating PHN at both doses, as revealed by decreasing the deposition of IgG and C5b-9, relieving podocyte injury, and reducing glomerular and tubular cell apoptosis. The lower dose was corresponding to the clinical dosage and showed better therapeutic effects than the higher dose. Metagenomic analysis showed that gavage with 16.2 g/kg of JQHF shifted the structure of the gut microbiota in PHN rats and significantly increased the relative abundances of Prevotella copri, Lactobacillus vaginalis and Subdoligranulum variabile. Particularly, S. variabile was strongly negatively correlated with serum levels of TC and TG, the deposition of IgG and C5b-9, and apoptosis of glomerular cells. CONCLUSIONS: The JQHF is an effective agent for the treatment of experimental PHN. The PHN-allevating effect of JQHF is associated with specific alternation of gut microbiota.

Traditional Chinese Medicine in Treating IgA Nephropathy: From Basic Science to Clinical Research.

IgA nephropathy (IgAN) is a major cause of chronic kidney disease (CKD) and end-stage renal disease worldwide. Currently, clinical interventions for IgAN are limited, and many patients seek out alternative therapies such as traditional Chinese medicine (TCM). In the last several years, TCM has accumulated ample application experiences and achieved favorable clinical effects. This article summarizes high-quality research from basic science to clinical applications aimed to provide more evidence-based medicine proof for the clinical treatment of IgAN. In summary, qi and yin deficiency accounted for the largest proportion in IgAN patients, and the treatment of IgAN should be based on supplementing qi and nourishing yin. Further, for patients with severe IgAN, the treatment combination of Chinese and Western medicines is better than pure Chinese medicine or hormone therapy. In addition, the pharmacological mechanism of Chinese herbal medicines is mostly based on restoring the immune function, relieving the inflammation damage, and inhibiting proliferation of the glomerular mesangial cells.

Effect of hybridized local and charge transfer molecules rotation in excited state on exciton utilization.

The fluorescent molecules utilizing hybridized local and charge-transfer (HLCT) state as potential organic light-emitting diodes materials attract extensive attention due to their high exciton utilization. In this work, we have performed the density functional theory method on three HLCT-state molecules to investigate their excited-state potential energy surface (PES). The calculated results indicate the T1 and T2 energy gap is quite large, and the T2 is very close to S1 in the energy level. The large gap is beneficial for inhibiting the internal conversion between T1 and T2, and quite closed S1 and T2 energies are favor for activating the T2 → S1 reverse intersystem crossing path. However, considering the singlet excited-state PES by twisting the triphenylamine (TPA) or diphenylamine (PA) group, it can be found that the TPA or PA group almost has no influence on T1 and T2 energy levels. However, the plots of S1 PES display two kinds of results that the S1 emissive state is dominated by charge-transfer (CT) or HLCT state. The CT emission state formation would decrease the S1 energy level, enlarge the S1 and T2 gap, and impair the triplet exciton utilization. Therefore, understanding the relationship between the S1 PES and molecular structures is important for designing high-performance luminescent materials utilizing HLCT state.