Palladium-Catalyzed Intermolecular Dehydrogenative C-2 Pentenylation of Indoles with 2-Methyl-2-butene.

Five-carbon (C5) units are the fundamental building blocks that constitute a multitude of natural products. Herein we report an unprecedented unusual C5 functionalization of indole regioselectively at the C-2-position enabled by a (2-pyridyl)sulfonyl-directing palladium-catalyzed dehydrogenative strategy with a bulk chemical 2-methyl-2-butene as a C5 source. Compared to typical C5 functionalization using pentenyl alcohols, carbonates, borates, or halides as the C5 source, the protocol not only has a low cost advantage but also is of atom and step economy.

Combination of DCE-MRI and NME-DWI via Deep Neural Network for Predicting Breast Cancer Molecular Subtypes.

BACKGROUND: To explore whether the combination of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and nonmono-exponential (NME) model-based diffusion-weighted imaging (DWI) via deep neural network (DNN) can improve the prediction of breast cancer molecular subtypes compared to either imaging technique used alone. PATIENTS AND METHODS: This prospective study examined 480 breast cancers in 475 patients undergoing DCE-MRI and NME-DWI at 3.0 T. Breast cancers were classified as follows: human epidermal growth factor receptor 2 enriched (HER2-enriched), luminal A, luminal B (HER2-), luminal B (HER2+), and triple-negative subtypes. A total of 20% cases were withheld as an independent test dataset, and the remaining cases were used to train DNN with an 80% to 20% training-validation split and 5-fold cross-validation. The diagnostic accuracies of DNN in 5-way subtype classification between the DCE-MRI, NME-DWI, and their combined multiparametric-MRI datasets were compared using analysis of variance with least significant difference posthoc test. Areas under the receiver-operating characteristic curves were calculated to assess the performances of DNN in binary subtype classification between the 3 datasets. RESULTS: The 5-way classification accuracies of DNN on both DCE-MRI (0.71) and NME-DWI (0.64) were significantly lower (P < .05) than on multiparametric-MRI (0.76), while on DCE-MRI was significantly higher (P < .05) than on NME-DWI. The comparative results of binary classification between the 3 datasets were consistent with the 5-way classification. CONCLUSION: The combination of DCE-MRI and NME-DWI via DNN achieved a significant improvement in breast cancer molecular subtype prediction compared to either imaging technique used alone. Additionally, DCE-MRI outperformed NME-DWI in differentiating subtypes.

Leaf Spot caused by Alternaria tenuissima on Rhamnella franguloides in China.

The small tree species Rhamnella franguloides, belonging to the genus Rhamnella in the tribe Rhamneae Hook. f. of Rhamnaceae (Hauenschild et al. 2016), is an important medicinal plant commonly used for making tea in China. In August 2023, leaf spot symptoms were observed on R. franguloides in Shangyao county, Yantai, Shandong, China, with a disease incidence of 45-65%. Initially appearing as small dark brown spots on the tip lesions, they later expanded and merged into irregular-shaped brown necrotic lesions with yellowish halos. To isolate pathogen, 20 symptomatic tissue fragments (5 × 5 mm) from ten sampling randomly plants were surface sterilized, placed on potato dextrose agar (PDA) plates, and incubated at 25°C in darkness for 3 days to obtain colonies.10 purified isolates with similar morphological characteristics were obtained by single-spore isolation from the colonies. The representative isolate MR13 was chosen for morphological and molecular analysis. The colonies On PDA medium initially appear as a circular yellow-brown ring with white round margins, ultimately turning into olive green with fluffy aerial hyphae. The conidiophores displayed brown pigmentation, solitary or branched, producing abundant short chains of conidia. The conidia were typically obclavate to obpyriform or ellipsoid in shape, 22.5-64.5 × 12.5-23.6µm in size, with a short conical beak at the apex, zero to three longitudinal septa and one to five transverse septa. Based on cultural and morphological characteristics, the fungus was identified as Alternaria spp (Simmons 2007). Due to morphological traits, five genes (the internal transcribed spacer [ITS], actin [ACT], plasma membrane ATPase [ATP], Alternaria major allergen [Alt a1] and histone 3 [H3]) form MR13 were amplified using primer pairs ITSI / ITS4, ACTDF1/R1, ATPDF1 / ATPDRI, Alt-for / Alt-rev, and H3-1a/1b, respectively (Hong et al. 2005; Lawrence et al. 2013; Lousie and Donaldson 1995). BLASTn analysis failed to confirm the identification of MR13 species based on ITS, ACT, ATP and Alt a1(ITS, OR668512; ACT, OR676918; ATP, OR676917; Alt a1, OR676919). The phylogenetic tree showed that it was closely related to Alternaria alternate, A. tenuissima, and A. destruens. The H3 sequence (OR676920) exhibited 100% similarity to A. tenuissima (OR485421). The phylogenetic tree constructed solely with H3 further confirmed MR13 as A. tenuissima. Pathogenicity tests were conducted by introducing the fungus onto healthy R. franguloides leaves in the field. Fifty leaves (five per plant) were treated with a 20ml suspension containing around 1x10^4 spores/ml, while an equal number of control samples were sprayed with distilled water. Transparent plastic bags were used to cover the treated leaves for 48 hours and maintain humidity. After fourteen days of inoculation, consistent leaf spotting symptoms were observed. In contrast, the control leaves showed no sign of infection. The fungal pathogen was successfully reisolated and identified as A. tenuissima through morphological and sequence analysis, fulfilling Koch's postulates. To our knowledge, this is the first report of A. tenuissima causing leaf spot disease on R. franguloides in China. Identifying the disease's causal agent is crucial for developing effective management strategies.

Hydrogen sulfide inhibits alveolar type II cell senescence and limits pulmonary fibrosis via promoting MDM2-mediated p53 degradation.

AIM: Senescence of alveolar type II (AT2) cells is an important driver of pulmonary fibrosis. This study aimed to investigate whether and how dysregulation of hydrogen sulfide (H2 S) production affected AT2 cell senescence, and then explored the effect of H2 S on the communication between AT2 and fibroblasts. METHODS: ICR mice were intratracheally administered with bleomycin (3 mg/kg). Sodium hydrosulfide (NaHS, 28 µmol/kg/d) was intraperitoneally injected for 2 weeks. The H2 S-generating enzyme cystathionine-ß-synthase (CBS) knockout heterozygous (CBS+/- ) mice were used as a low H2 S production model. RESULTS: Analysis of microarray datasets revealed downregulation of H2 S-generating enzymes in lung tissues of patients with pulmonary fibrosis. Decreased H2 S production was correlated with higher levels of cell senescence markers p53 and p21 in bleomycin-induced lung fibrosis. CBS+/- mice exhibited increased levels of p53 and p21. The numbers of AT2 cells positive for p53 and p21 were increased in CBS+/- mice as compared to control mice. H2 S donor NaHS attenuated bleomycin-induced AT2 cell senescence both in vivo and in vitro. H2 S donor suppressed bleomycin-induced senescence-associated secretory phenotype (SASP) of AT2 cells via inhibiting p53/p21 pathway, consequently suppressing proliferation and myofibroblast transdifferentiation of fibroblasts. Mechanically, H2 S suppressed p53 expression by enhancing the mouse double-minute 2 homologue (MDM2)-mediated ubiquitination and degradation of p53. CONCLUSION: H2 S inactivated p53-p21 pathway, consequently suppressing AT2 cell senescence as well as cell communication between senescent AT2 cells and fibroblasts. Aberrant H2 S synthesis may contribute to the development of pulmonary fibrosis through promoting the activation loop involving senescent AT2 cells and activated fibroblasts.

Enhancement of the viability of T cells electroporated with DNA via osmotic dampening of the DNA-sensing cGAS-STING pathway.

Viral delivery of DNA for the targeted reprogramming of human T cells can lead to random genomic integration, and electroporation is inefficient and can be toxic. Here we show that electroporation-induced toxicity in primary human T cells is mediated by the cytosolic pathway cGAS-STING (cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase-stimulator of interferon genes). We also show that an isotonic buffer, identified by screening electroporation conditions, that reduces cGAS-STING surveillance allowed for the production of chimaeric antigen receptor (CAR) T cells with up to 20-fold higher CAR T cell numbers than standard electroporation and with higher antitumour activity in vivo than lentivirally generated CAR T cells. The osmotic pressure of the electroporation buffer dampened cGAS-DNA interactions, affecting the production of the STING activator 2'3'-cGAMP. The buffer also led to superior efficiencies in the transfection of therapeutically relevant primary T cells and human haematopoietic stem cells. Our findings may facilitate the optimization of electroporation-mediated DNA delivery for the production of genome-engineered T cells.

A Channel-Dimensional Feature-Reconstructed Deep Learning Model for Predicting Breast Cancer Molecular Subtypes on Overall b-Value Diffusion-Weighted MRI.

BACKGROUND: Dynamic contrast-enhanced (DCE) MRI commonly outperforms diffusion-weighted (DW) MRI in breast cancer discrimination. However, the side effects of contrast agents limit the use of DCE-MRI, particularly in patients with chronic kidney disease. PURPOSE: To develop a novel deep learning model to fully exploit the potential of overall b-value DW-MRI without the need for a contrast agent in predicting breast cancer molecular subtypes and to evaluate its performance in comparison with DCE-MRI. STUDY TYPE: Prospective. SUBJECTS: 486 female breast cancer patients (training/validation/test: 64%/16%/20%). FIELD STRENGTH/SEQUENCE: 3.0 T/DW-MRI (13 b-values) and DCE-MRI (one precontrast and five postcontrast phases). ASSESSMENT: The breast cancers were divided into four subtypes: luminal A, luminal B, HER2+, and triple negative. A channel-dimensional feature-reconstructed (CDFR) deep neural network (DNN) was proposed to predict these subtypes using pathological diagnosis as the reference standard. Additionally, a non-CDFR DNN (NCDFR-DNN) was built for comparative purposes. A mixture ensemble DNN (ME-DNN) integrating two CDFR-DNNs was constructed to identify subtypes on multiparametric MRI (MP-MRI) combing DW-MRI and DCE-MRI. STATISTICAL TESTS: Model performance was evaluated using accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). Model comparisons were performed using the one-way analysis of variance with least significant difference post hoc test and the DeLong test. P < 0.05 was considered significant. RESULTS: The CDFR-DNN (accuracies, 0.79 ~ 0.80; AUCs, 0.93 ~ 0.94) demonstrated significantly improved predictive performance than the NCDFR-DNN (accuracies, 0.76 ~ 0.78; AUCs, 0.92 ~ 0.93) on DW-MRI. Utilizing the CDFR-DNN, DW-MRI attained the predictive performance equal (P = 0.065 ~ 1.000) to DCE-MRI (accuracies, 0.79 ~ 0.80; AUCs, 0.93 ~ 0.95). The predictive performance of the ME-DNN on MP-MRI (accuracies, 0.85 ~ 0.87; AUCs, 0.96 ~ 0.97) was superior to those of both the CDFR-DNN and NCDFR-DNN on either DW-MRI or DCE-MRI. DATA CONCLUSION: The CDFR-DNN enabled overall b-value DW-MRI to achieve the predictive performance comparable to DCE-MRI. MP-MRI outperformed DW-MRI and DCE-MRI in subtype prediction. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 1.

[Common diseases and drug use characteristics of Chinese herbal medicines and suggestions].

Based on the data of 56 kinds of diseases and drug use in 100 kinds of cultivated Chinese herbal medicines, this paper used frequency analysis method to count the types of diseases and their drug use characteristics, and systematically analyzed the status of drug registration and monitoring standards for disease prevention and control of Chinese herbal medicines. The results showed that 14 diseases such as root rot, powdery mildew, and drooping disease were common in the production of Chinese herbal medicines. Among the 99 pesticides reported, 67.68% were chemically synthesized, 23.23% were biological pesticides, and 9.09% were mineral pesticides. Among the reported pesticides, 92.93% of them were low toxic, with relative safety. However, 70% of the production drugs were not registered in Chinese herbal medicines, and the phenomenon of overdose was serious. The current pesticide residue monitoring standards does not match well with production drugs in China. Although the matching degree between Maximum Residue Limit of Pesticide in Food Safety National Standard(GB 2763-2021) and production drugs is more than 50%, there are few varieties of Chinese herbal medicines covered. The matching degree between Chinese Pharmacopoeia(2020 edition), Green Industry Standard of Medicinal Plants and Preparations(WM/T2-2004), and production drugs is only 1.28%. It is suggested to speed up the research and registration of Chinese herbal medicine production and further improve the pesticide residue limit standard combined with the actual production, so as to promote the high-quality development of Chinese herbal medicine industry.

[Common diseases and drug use of Pseudostellaria heterophylla].

Pseudostellaria heterophylla in large-scale cultivation needs to apply pesticides to control diseases, and non-standard use of pesticide may cause excessive pesticide residues in medicinal materials, increasing the risk of clinical medication. To accurately monitor the residual pesticides, this paper investigated the drug use during the process of P. heterophylla disease prevention in 25 P. he-terophylla planting enterprises or individual households in Guizhou province. It was found that there were 8 common diseases in P. he-terophylla planting, including leaf spot, downy mildew, virus disease, root rot, dropping disease, purple feather disease, white silk disease, and damping-off disease. Twenty-three kinds of pesticides were used in disease control, mainly chemical synthetic pesticides, accounting for 78.3%, followed by biological pesticides and mineral pesticides, accounting for 13.0% and 8.7%, respectively. The disease prevention and control drugs were all low-toxic pesticides, and there were no varieties banned in the Chinese Pharmacopoeia(2020 edition). However, the pesticides used have not been registered on P. heterophylla, and the excessive use of drugs was serious. The present monitoring of pesticide residues in P. heterophylla is mainly based on traditional pesticides such as organochlorine, organophosphorus, and carbamate, which does not effectively cover the production of drugs and had certain safety risks. It is suggested to speed up the research and registration of drug use in the production of P. heterophylla, increase the use of biological pesticides, and further improve the monitoring indicators of pesticide residues in combination with the actual production of drugs, so as to promote the high-quality development of P. heterophylla industry.

Cas12a-based one-pot SNP detection with high accuracy.

CRISPR-Cas12a based one-pot detection system has been used in nucleic acid detection and diagnosis. However, it is not sensitive enough to distinguish single nucleotide polymorphisms (SNP), which has greatly restricted its application. To overcome these limitations, we engineered a LbCas12a variant with enhanced sensitivity against SNP, named seCas12a (sensitive Cas12a). SeCas12a-based one-pot SNP detection system is a versatile platform that could use both canonical and non-canonical PAM, and was almost not limited by mutation types to distinguish SNPs located between position 1 to 17. The use of truncated crRNA further improved SNP specificity of seCas12a. Mechanistically, we found only when the cis-cleavage was at low level between 0.01min-1 and 0.0006 min-1, a good signal-to-noise ratio can be achieved in one-pot test. SeCas12a-based one-pot SNP detection system was applied to detect pharmacogenomic SNPs in human clinical samples. Of thirteen donors tested in two different SNPs, the seCas12a mediated one-pot system could faithfully detect the SNPs in 30 min with 100% accuracy.

Regioselective Dehydrogenative Reverse Prenylation of Indoles with 2-Methyl-2-butene.

Bulk chemical 2-methyl-2-butene, one of the main C5 distillates of the petrochemical industry, has scarcely been utilized directly in synthesizing high-value-added fine chemicals. Herein, we use 2-methyl-2-butene as the starting material to develop a palladium-catalyzed highly site- and regio-selective C-3 dehydrogenation reverse prenylation of indoles. This synthetic method features mild reaction conditions, a broad substrate scope, atom- and step-economies.

Pearl-Structure-Enhanced NASICON Cathode toward Ultrastable Sodium-Ion Batteries.

Based on the favorable ionic conductivity and structural stability, sodium superionic conductor (NASICON) materials especially utilizing multivalent redox reaction of vanadium are one of the most promising cathodes in sodium-ion batteries (SIBs). To further boost their application in large-scale energy storage production, a rational strategy is to tailor vanadium with earth-abundant and cheap elements (such as Fe, Mn), reducing the cost and toxicity of vanadium-based NASICON materials. Here, the Na3.05 V1.03 Fe0.97 (PO4 )3 (NVFP) is synthesized with highly conductive Ketjen Black (KB) by ball-milling assisted sol-gel method. The pearl-like KB branch chains encircle the NVFP (p-NVFP), the segregated particles possess promoted overall conductivity, balanced charge, and modulated crystal structure during electrochemical progress. The p-NVFP obtains significantly enhanced ion diffusion ability and low volume change (2.99%). Meanwhile, it delivers a durable cycling performance (87.7% capacity retention over 5000 cycles at 5 C) in half cells. Surprisingly, the full cells of p-NVFP reveal a remarkable capability of 84.9 mAh g-1 at 20 C with good cycling performance (capacity decay rate is 0.016% per cycle at 2 C). The structure modulation of the p-NVFP provides a rational design on the superiority of others to be put into practice.

[Contamination status and exposure risk of mycotoxins in Coicis Semen].

By investigating the contamination status and predicting the exposure risk of mycotoxin in Coicis Semen, we aim to provide guidance for the safety supervision of Chinese medicinal materials and the formulation(revision) of mycotoxin limit standards. The content of 14 mycotoxins in the 100 Coicis Semen samples collected from five major markets of Chinese medicinal materials in China was determined by UPLC-MS/MS. The probability evaluation model based on Monte Carlo simulation method was established after Chi-square test and One-way ANOVA of the sample contamination data. Health risk assessment was performed on the basis of margin of exposure(MOE) and margin of safety(MOS). The results showed that zearalenone(ZEN), aflatoxin B_1(AFB_1), deoxynivalenol(DON), sterigmatocystin(ST), and aflatoxin B_2(AFB_2) in the Coicis Semen samples had the detection rates of 84%, 75%, 36%, 19%, and 18%, and the mean contamination levels of 117.42, 4.78, 61.16, 6.61, and 2.13 µg·kg~(-1), respectively. According to the limit standards in the Chinese Pharmacopoeia(2020 edition), AFB_1, AFs and ZEN exceeded the standards to certain extents, with the over-standard rates of 12.0%, 9.0%, and 6.0%, respectively. The exposure risks of Coicis Semen to AFB_1, AFB2, ST, DON, and ZEN were low, while 86% of the samples were contaminated with two or more toxins, which needs more attention. It is suggested that the research on the combined toxicity of different mycotoxins should be strengthened to accelerate the cumulative exposure assessment of mixed contaminations and the formulation(revision) of toxin limit standards.

Synthesis of 5,6-Dihydrophenanthridines via Palladium-Catalyzed Intramolecular Dehydrogenative Coupling of Two Aryl C-H Bonds.

5,6-Dihydrophenanthridines are common aza heterocycle frameworks of natural products and pharmaceuticals. Herein, we reported the first palladium-catalyzed intramolecular C-H/C-H dehydrogenative coupling reaction of two simple arenes to generate 5,6-dihydrophenanthridines. The approach features a broad substrate scope and good tolerance of functional groups, offering an efficient alternative synthesis route for important 5,6-dihydrophenanthridine compounds.

Comparison of Dynamic Contrast-Enhanced MRI and Non-Mono-Exponential Model-Based Diffusion-Weighted Imaging for the Prediction of Prognostic Biomarkers and Molecular Subtypes of Breast Cancer Based on Radiomics.

BACKGROUND: Dynamic contrast-enhanced (DCE) MRI and non-mono-exponential model-based diffusion-weighted imaging (NME-DWI) that does not require contrast agent can both characterize breast cancer. However, which technique is superior remains unclear. PURPOSE: To compare the performances of DCE-MRI, NME-DWI and their combination as multiparametric MRI (MP-MRI) in the prediction of breast cancer prognostic biomarkers and molecular subtypes based on radiomics. STUDY TYPE: Prospective. POPULATION: A total of 477 female patients with 483 breast cancers (5-fold cross-validation: training/validation, 80%/20%). FIELD STRENGTH/SEQUENCE: A 3.0 T/DCE-MRI (6 dynamic frames) and NME-DWI (13 b values). ASSESSMENT: After data preprocessing, high-throughput features were extracted from each tumor volume of interest, and optimal features were selected using recursive feature elimination method. To identify ER+ vs. ER-, PR+ vs. PR-, HER2+ vs. HER2-, Ki-67+ vs. Ki-67-, luminal A/B vs. nonluminal A/B, and triple negative (TN) vs. non-TN, the following models were implemented: random forest, adaptive boosting, support vector machine, linear discriminant analysis, and logistic regression. STATISTICAL TESTS: Student's t, chi-square, and Fisher's exact tests were applied on clinical characteristics to confirm whether significant differences exist between different statuses (±) of prognostic biomarkers or molecular subtypes. The model performances were compared between the DCE-MRI, NME-DWI, and MP-MRI datasets using the area under the receiver-operating characteristic curve (AUC) and the DeLong test. P < 0.05 was considered significant. RESULTS: With few exceptions, no significant differences (P = 0.062-0.984) were observed in the AUCs of models for six classification tasks between the DCE-MRI (AUC = 0.62-0.87) and NME-DWI (AUC = 0.62-0.91) datasets, while the model performances on the two imaging datasets were significantly poorer than on the MP-MRI dataset (AUC = 0.68-0.93). Additionally, the random forest and adaptive boosting models (AUC = 0.62-0.93) outperformed other three models (AUC = 0.62-0.90). DATA CONCLUSION: NME-DWI was comparable with DCE-MRI in predictive performance and could be used as an alternative technique. Besides, MP-MRI demonstrated significantly higher AUCs than either DCE-MRI or NME-DWI. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 2.

Benefits of Hydroxychloroquine Combined with Low-Dose Aspirin on Pregnancy Outcomes and Serum Cytokines in Pregnant Women with Systemic Lupus Erythematosus.

BACKGROUND AND OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease, with hydroxychloroquine being the main therapeutic agent for the treatment of SLE. This research explored the effects of hydroxychloroquine combined with low-dose aspirin on maternal and infant outcomes and cytokines of pregnant women with SLE. METHODS: Ninety pregnant women with SLE were divided into the hydroxychloroquine (HCQ) group (45 cases) and the hydroxychloroquine combined with low-dose aspirin (HCQASP) group (45 cases) by random number table. Patients in the HCQ group were treated with oral administration of hydroxychloroquine, while patients in the HCQASP group were treated with low-dose aspirin based on oral administration of hydroxychloroquine. Pregnancy outcomes, fetal outcomes, and cytokine levels were statistically analyzed. RESULTS: The HCQASP group had a significantly higher proportion of full-term pregnancies and a significantly lower proportion of hypertension, prematurity, and pregnancy loss than the HCQ group. Neonates in the HCQASP group also had significantly higher birth weights and Apgar scores and a significantly lower proportion of neonatal asphyxia than the HCQ group. After treatment, the HCQASP group had significantly higher interleukin (IL-2) and interferon (IFN)-γ levels and significantly lower IL-4 and IL-10 levels than the HCQ group. CONCLUSION: Hydroxychloroquine combined with low-dose aspirin can effectively improve the pregnancy outcomes of pregnant women with SLE by affecting the levels of T helper (Th) 2 and Th1 cytokines.

Experience in management of cesarean scar pregnancy and outcomes in a single center.

OBJECTIVE: This study aimed to describe our experience of managing cesarean scar pregnancy (CSP) and outcomes depending on ultrasound imaging features. METHODS: A retrospective, cohort observational study was performed on 31 consecutive patients with CSP at 6 to 9 weeks of gestation from April 2015 to January 2021. All patients were evaluated for the residual myometrial thickness (RMT), growth direction of the gestational sac (GS), blood flow, and chorionic parenchyma using ultrasonography. Patients underwent curettage or methotrexate (MTX) combined with curettage in CSP depending on the age of the GS. Blood loss of >500 mL with curettage was considered major bleeding. RESULTS: Twenty-five (80.6%) patients had successful treatment, and six (19.4%) patients had major bleeding. The incidence of major bleeding was significantly higher in patients with >7 weeks of gestation, types II and III CSP, mixed and exogenous types of the growth direction of the GS, an RMT < 2 mm, and multiple lacunae formation in thickened chorionic parenchyma. CONCLUSIONS: The exogenous and mixed types of the GS, an RMT < 2 mm, and multiple lacunae in thickened chorionic parenchyma may be high-risk factors for major hemorrhage by curettage in CSP.

Relationship Between Serum Vitamin D and Perirenal Fat Thickness in Patients with Metabolic Syndrome in Community.

Background: Visceral obesity is independently associated with hypovitaminosis D. Perirenal fat is a visceral fat type active in performing endocrine functions. However, the relationship between perirenal fat thickness (PrFT) and serum 25-hydroxy vitamin D [25(OH)D] is unclear. The aim of this study is to investigate the relationship between serum 25(OH)D and PrFT in patients with metabolic syndrome (MS) in the community. Methods: From May to September 2020, 332 MS subjects in Qinfengyuan and Dongfang communities in Taiyuan City, China were enrolled in an MS survey. All the participants completed the questionnaire survey and physical examination, and their fasting blood samples were collected for biochemical examination. Abdominal ultrasonography was performed to measure the perirenal fat thickness. Results: The mean serum 25(OH)D level for the 332 MS subjects was 13.5 ng/mL, the proportions of vitamin D deficiency [serum 25(OH)D < 20 ng/mL] and insufficiency [serum 25(OH)D = 20-29.9 ng/mL] were 60.8% (202) and 24.4% (81), respectively. Among the hypovitaminosis D [serum 25(OH)D < 30 ng/mL] subjects, the prevalence of abdominal obesity (waist circumference ≥ 90cm for men and ≥ 80cm for women) is 61.1%. Pearson correlation analysis showed that lg25(OH)D was significantly and negatively associated with body mass index (BMI), waist circumference (W), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), insulin resistance index (HOMA-IR), uric acid (UA)) and PrFT (all P<0.05), and positively correlated with high-density lipoprotein cholesterol (HDL-C) (P<0.05). Multivariate analysis showed that PrFT and HOMA-IR were independently correlated with 25(OH)D. Conclusion: In screening MS patients, approximately 85% of the community MS patients in Taiyuan had hypovitaminosis D; in which 3/5 is abdominal obesity. PrFT is an independent risk factor for hypovitaminosis D in MS subjects.

[Effect of Danlou Tablets on alleviating hepatic adipogenesis, inflammatory response, and insulin resistance in db/db mice].

This study explored the effect and potential mechanism of Danlou Tablets(DLT) on insulin resistance in db/db mice with type 2 diabetic mellitus(T2 DM). The db/db male mice were randomly assigned into model control(MC) group, metformin(MET, tablet, 100 mg·kg~(-1)) group, and DLT(1 g·kg~(-1)) group, and C57 BL/6 J mice were taken as normal control(NC) group. The mice in the MET group and DLT group were given corresponding drugs by gavage once a day for 16 weeks. The fasting blood glucose, glucose tolerance, and insulin tolerance were measured to evaluate the effect of DLT on blood glucose and insulin resistance in diabetic mice. The serum free fatty acid, triacylglycerol, and total cholesterol levels were determined to evaluate the effect of DLT on blood lipids in diabetic mice. The liver index and perirenal fat index were calculated to measure the effect of DLT on lipid accumulation in non-adipose tissue and adipose tissue. Western blot was performed to determine the protein levels of insulin receptor-ß(IRß), phospho-IRß(p-IRß), phosphatidylinositol 3-kinase(PI3 K), and insulin receptor substrate-1(IRS-1) involved in IRS-1/PI3 K/Akt signaling pathway in the livers of mice to reveal the mechanism of DLT in alleviating insulin resistance in diabetic mice. The protein levels of sterol regulatory element binding protein-1(SREBP-1) and the mRNA levels of sterol regulatory element binding protein-1 c(SREBP-1 c), fatty acid synthase(FAS), acetyl-CoA carboxylase(ACC), diacylglycerol acyltransferase-1(Dgat1), and diacylglycerol acyltransferase-2(Dgat2) involved in the SREBP-1/FAS signaling pathway were detected to evaluate the effect of DLT on lipid metabolism in diabetic mice. Real-time quantitative PCR was employed to determine the mRNA levels of galectin-3(Gal-3), interleukin-6(IL-6), and monocyte chemoattractant protein-1(MCP-1) in mouse liver to evaluate the effect of DLT on inflammatory response in diabetic mice. The results showed that DLT significantly reduced the blood glucose and lipid levels and alleviated the insulin resistance in diabetic mice. Compared with the MC group, DLT significantly up-regulated the protein levels of p-IRß, PI3 K, and IRS-1(P<0.05 or P<0.01), and down-regulated the protein level of SREBP-1 in liver tissues of diabetic mice(P<0.05). DLT lowered the mRNA levels of SREBP-1 c, FAS, ACC, Dgat1, and Dgat2 related to lipid metabolism as well as those of Gal-3, IL-6, and MCP-1 associated with inflammation in the livers of diabetic mice(P<0.05 or P<0.01). The findings of this study suggest that DLT may alleviate insulin resistance in diabetic mice by regulating IRS-1/PI3 K/Akt signaling pathway and SREBP-1/FAS signaling pathway to reduce lipid production and inhibit inflammatory response.

Synthesis of Acyl Hydrazides via a Radical Chemistry of Azocarboxylic tert-Butyl Esters.

A new chemistry of azo compounds, that is, addition of free radicals generated in situ to access various acyl hydrazides, has been developed. The protocol provides a novel strategy for the synthesis of valuable acyl hydrazides. The transformation features mild reaction conditions, good tolerance of functional groups, and a broad substrate scope. In view of the importance of acyl hydrazides in functional materials and medicinal chemistry, this approach would find broad applications.

Effects of Astragalus membranaceus on systemic lupus erythematosus in a mouse model of pregnancy.

BACKGROUND: This study used astragalus membranaceus (AM) to treat systemic lupus erythematosus (SLE) model mice during pregnancy, aiming to explore the role of AM in Helper T cell 17 (Th17) differentiation and SLE during pregnancy. METHODS: We used lipopolysaccharide to constructed the SLE mouse model. AM decoction given by intragastric administration lasted from the eighth week of the mouse age until the mouse was killed. We estimated the messenger RNA  levels of IL-17a and Rorc, counted the Th17 cell number and examined the levels of cytokines including interleukin (IL)-12, tumor necrosis factor α, interferon gamma, IL-17A in mouse serum. Periodic acid-Schiff staining and renal glomerular/tubulointerstitial (TI) score were used to evaluate the progression of lupus nephritis (LN). RESULTS: AM treatment improved the conception rate and increased the number and average weight of fetuses in SLE mice. It significantly decreased the urinary albumin/creatinine ratios and reduced the glomerular scores and TI scores in the pregnant SLE mice. AM gavage significantly decreased the weight of spleen, mesenteric lymph node, total splenocytes and T cells, and the expression of proinflammatory factors. Furthermore, AM treatment reduced the ratio of Th17 cells and the expression levels of RORγt and IL-17A. CONCLUSION: AM significantly improved pregnancy outcomes and inhibited lupus nephritis during pregnancy in SLE mice.