Elevated Interleukin-37 Associated with Dengue Viral Load in Patients with Dengue Fever.

Dengue remains a public health issue worldwide. Similar to chronic infectious diseases, stimulation of cytokine production is not enough to drive immune effector cells for effective virus clearance. One possible mechanism is the virus induces a large number of negative stimulatory cytokines inhibiting immune response. Interleukin 37 (IL-37) plays a crucial regulatory role in infection and immunity, inhibits innate and adaptive immunity as an anti-inflammatory cytokine by inhibiting proinflammatory mediators and pathways. To date, there are few studies reporting correlations between dengue fever (DF) and IL-37. In this study we found that the serum IL-37b and IL-37b-producing monocytes in patients were significantly increased in DF patients. A majority of the IL-37b produced by DF patients was produced by monocytes, not lymphocytes. Increased levels of IL-6, IL-10, and IFN-α were also found in DF patients. However, we failed to detect IL-1ß, IL-17A and TNF-α in plasma, because of off-target. In our study, there was no relation between IL-6, IL-10, and IFN-α expressions and IL-37b in serum (P > 0.05). The IL-37b-producing monocytes were negatively correlated with the level of IFN-α in serum and platelet count, and positively correlated with lymphocytes percentage (P < 0.05, respectively). Additionally, serum DENV nonstructural protein 1 levels were positively correlated with monocytes percentages (P < 0.05). Our data represents findings for IL-37b expression and its potential mechanisms in DF patients' immune response.

Association of Sugar-Sweetened, Artificially Sweetened, and Unsweetened Coffee Consumption With All-Cause and Cause-Specific Mortality : A Large Prospective Cohort Study.

BACKGROUND: Previous observational studies have suggested an association between coffee intake and reduced risk for death, but these studies did not distinguish between coffee consumed with sugar or artificial sweeteners and coffee consumed without. OBJECTIVE: To evaluate the associations of consumption of sugar-sweetened, artificially sweetened, and unsweetened coffee with all-cause and cause-specific mortality. DESIGN: Prospective cohort study. SETTING: Data were extracted from the UK Biobank. PARTICIPANTS: A total of 171 616 participants (mean age, 55.6 years [SD, 7.9]) without cardiovascular disease (CVD) or cancer at baseline were eligible. Baseline demographic, lifestyle, and dietary data from the UK Biobank were used, with follow-up beginning in 2009 and ending in 2018. MEASUREMENTS: Dietary consumption of sugar-sweetened, artificially sweetened, and unsweetened coffee was self-reported. All-cause, cancer-related, and CVD-related mortality were estimated. RESULTS: During a median follow-up of 7.0 years, 3177 deaths were recorded (including 1725 cancer deaths and 628 CVD deaths). Cox models with penalized splines showed U-shaped associations of unsweetened coffee, sugar-sweetened coffee, and artificially sweetened coffee with mortality. Compared with nonconsumers, consumers of various amounts of unsweetened coffee (>0 to 1.5, >1.5 to 2.5, >2.5 to 3.5, >3.5 to 4.5, and >4.5 drinks/d) had lower risks for all-cause mortality after adjustment for lifestyle, sociodemographic, and clinical factors, with respective hazard ratios of 0.79 (95% CI, 0.70 to 0.90), 0.84 (CI, 0.74 to 0.95), 0.71 (CI, 0.62 to 0.82), 0.71 (CI, 0.60 to 0.84), and 0.77 (CI, 0.65 to 0.91); the respective estimates for consumption of sugar-sweetened coffee were 0.91 (CI, 0.78 to 1.07), 0.69 (CI, 0.57 to 0.84), 0.72 (CI, 0.57 to 0.91), 0.79 (CI, 0.60 to 1.06), and 1.05 (CI, 0.82 to 1.36). The association between artificially sweetened coffee and mortality was less consistent. The association of coffee drinking with mortality from cancer and CVD was largely consistent with that with all-cause mortality. U-shaped associations were also observed for instant, ground, and decaffeinated coffee. LIMITATION: Exposure assessed at baseline might not capture changes in intake over time. CONCLUSION: Moderate consumption of unsweetened and sugar-sweetened coffee was associated with lower risk for death. PRIMARY FUNDING SOURCE: National Natural Science Foundation of China, Young Elite Scientist Sponsorship Program by CAST, and Project Supported by Guangdong Basic and Applied Basic Research Foundation.

Diagnostic value of circulating microRNAs for esophageal cancer: a meta-analysis based on Asian data.

BACKGROUND AND OBJECTIVE: esophageal cancer (EC) is one of the most common gastrointestinal malignant diseases. We conducted a comprehensive meta-analysis to explore the clinical applicability of circulating microRNA for the diagnosis of EC. METHODS: as of September 10, 2021, a comprehensive literature search was conducted on PubMed, Embase, Web of Science, Cochrane Library, Wanfang Database, and China National Knowledge Infrastructure (CNKI) to identify eligible studies. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were pooled to evaluate the test performance. The potential sources of heterogeneity were analyzed by subgroup analysis. Deeks' funnel plot was used to assess publication bias. RESULTS: 85 studies from 50 articles were included in the current meta-analysis. The overall pooled sensitivity was 0.82 (95 % CI, 0.79-0.84), specificity was 0.84 (95 % CI, 0.81-0.86), PLR was 4.9 (95 % CI, 4.2-5.9), NLR was 0.22 (95 % CI, 0.19-0.25), DOR was 22 (95 % CI, 17-29) and AUC was 0.89 (95 % CI, 0.86-0.92), respectively. Subgroup analysis suggested that miRNA clusters with a large sample size showed better diagnostic accuracy. Publication bias was not found. CONCLUSIONS: circulating miRNAs can be used as a potential non-invasive biomarker for the diagnosis of EC in Asian populations.

Diagnostic accuracy of circulating microRNA in hepatitis B virus-related hepatocellular carcinoma: a meta-analysis based on Asian data.

BACKGROUND AND AIM: hepatitis B virus (HBV) is the main risk factor for hepatocellular carcinoma (HCC). We performed a meta-analysis based on Asian data to evaluate the diagnostic accuracy of circulating microRNA as a non-invasive biomarker in the diagnosis of HBV-related HCC. METHODS: a comprehensive literature search (updated to May 12, 2021) in PubMed, Embase, Web of Science, Wanfang Database, and China National Knowledge Infrastructure (CNKI) was performed to identify eligible studies. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) for diagnosing HBV-related HCC were pooled in this meta-analysis. A subgroup analysis was performed to explore heterogeneity, and Deeks' funnel plot was used to assess publication bias. RESULTS: a total of 19 articles including 32 studies were included in the current meta-analysis. The overall sensitivity, specificity, PLR, NLR, DOR and AUC were 0.83 (95 % CI: 0.79 to 0.87), 0.78 (95 % CI: 0.73 to 0.83), 3.9 (95 % CI: 3.0 to 4.9), 0.21 (95 % CI: 0.16 to 0.27), 18 (95 % CI: 12 to 27) and 0.88 (95 % CI: 0.85 to 0.91), respectively. Subgroup analysis shows that miRNA clusters with a large sample size showed better diagnostic accuracy. Although there is no publication bias, the research still has some limitations. CONCLUSIONS: circulating miRNAs could serve as a potential non-invasive biomarker in diagnosing HBV-related HCC in Asian populations.

Association of asymmetric dimethylarginine with the pathological process of persistent pulmonary hypertension of the newborn. / ä¸å¯¹ç§°äºŒç”²åŸºç²¾æ°¨é ¸ä¸Žæ–°ç”Ÿå„¿æŒç»­æ€§è‚ºåŠ¨è„‰é«˜åŽ‹ç— ç†è¿›ç¨‹çš„ç›¸å ³æ€§ç ”ç©¶.

OBJECTIVES: To study the change in asymmetric dimethylarginine (ADMA) in the circulation system of full-term infants with persistent pulmonary hypertension of the newborn (PPHN) and its association with treatment response, as well as the possibility of ADMA as a therapeutic target and a marker for treatment response. METHODS: A prospective study was performed. A total of 30 full-term neonates who were diagnosed with PPHN within 3 days after birth were enrolled as the PPHN group, and the neonates without PPHN, matched for gestational age and age, who were treated or observed in the department of neonatology were enrolled as the control group. Serum samples were collected on days 1, 7, and 14 of treatment. The high-performance liquid chromatography-tandem mass spectrometry was used to measure the serum concentrations of L-arginine, ADMA, and its isomer symmetric dimethylarginine (SDMA). RESULTS: For the neonates in the control group, the serum concentrations of ADMA and L-arginine continuously increased and the serum concentration of SDMA continuously decreased within the first 14 days of treatment. On days 1 and 14, there was no significant difference in the serum concentration of ADMA between the control and PPHN groups (P>0.05). On day 7, the PPHN group had a significantly higher serum concentration of ADMA than the control group (P<0.05), while there were no significant differences in serum concentrations of SDMA or L-arginine (P>0.05). Moreover, after 7 days of treatment, the PPHN neonates with a systolic pulmonary arterial pressure (sPAP) of >35 mmHg had a significantly higher serum concentration of ADMA than those with an sPAP of ≤35 mm Hg. CONCLUSIONS: There are continuous increases in the ADMA concentration and the ADMA/SDMA ratio in the circulation system of full-term infants within the first 2 weeks after birth, and this process is accelerated by the pathological process of PPHN, suggesting that ADMA may be involved in the pathologic process of PPHN. A high level of ADMA is associated with the resistance to PPHN treatment, suggesting that inhibition of ADMA might be a potential target of drug intervention to improve the treatment response of PPHN.

[Clinical features of intestinal polyps and risk factors for secondary intussusception in children: an analysis of 2 669 cases]. / 2 669ä¾‹å„¿ç«¥è‚ æ¯è‚‰çš„ä¸´åºŠç‰¹å¾åŠç»§å‘è‚ å¥—å çš„å±é™©å› ç´ åˆ†æž.

OBJECTIVES: To study the clinical features of intestinal polyps and the risk factors for secondary intussusception in children. METHODS: A retrospective analysis was performed for the medical data of 2 669 children with intestinal polyps. According to the presence or absence of secondary intussusception, they were divided into two groups: intussusception (n=346) and non-intussusception (n=2 323). Related medical data were compared between the two groups. The multivariate logistic regression analysis was used to identify the risk factors for secondary intussusception. RESULTS: Among the children with intestinal polyps, 62.42% were preschool children, and the male/female ratio was 2.08∶1; 92.66% had hematochezia as disease onset, and 94.34% had left colonic polyps and rectal polyps. There were 346 cases of secondary intussusception, with an incidence rate of 12.96% (346/2 669). Large polyps (OR=1.644, P<0.001), multiple polyps (≥2) (OR=6.034, P<0.001), and lobulated polyps (OR=93.801, P<0.001) were the risk factors for secondary intussusception. CONCLUSIONS: Intestinal polyps in children often occur in preschool age, mostly in boys, and most of the children have hematochezia as disease onset, with the predilection sites of the left colon and the rectum. Larger polyps, multiple polyps, and lobulated polyps may increase the risk of secondary intussusception, and endoscopic intervention is needed as early as possible to improve prognosis.

Simple non-invasive scoring systems and histological scores in predicting mortality in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND AND AIM: There is debate among the hepatology community regarding the simple non-invasive scoring systems and histological scores (even it was developed for histological classification) in predicting clinical outcomes in patients with non-alcoholic fatty liver disease (NAFLD). This study aimed to determine whether the presence of simple non-invasive scoring systems and histological scores could predict all-cause mortality, liver-related mortality, and liver disease decompensation (liver failure, cirrhosis, hepatocellular carcinoma, or decompensated liver disease). METHODS: The pooled hazard ratio of prognostic factors and incidence rate per 1000 person-years in patients with NAFLD was calculated and further adjusted by two different models of handling the duplicated data. RESULTS: A total of 19 longitudinal studies were included. Most simple non-invasive scoring systems (Fibrosis-4 Score, BARD, and aspartate aminotransferase-to-platelet ratio index ) and histological scores (NAFLD activity score, Brunt, and "steatosis, activity, and fibrosis" ) failed in predicting mortality, and only the NAFLD fibrosis score > 0.676 showed prognostic ability to all-cause mortality (four studies, 7564 patients, 118 352 person-years followed up, pooled hazard ratio 1.44, 95% confidence interval [CI] 1.05-1.96). The incidence rate per 1000 person-years of all-cause mortality, liver-related mortality, cardiovascular-related mortality, and liver disease decompensation resulted in a pooled incidence rate per 1000 person-years of 22.65 (14 studies, 95% CI 9.62-53.31), 3.19 (7 studies, 95% CI 1.14-8.93), 6.02 (6 studies, 95% CI 4.69-7.74), and 11.46 (4 studies, 95% CI 5.33-24.63), respectively. CONCLUSION: Non-alcoholic fatty liver disease fibrosis score showed promising prognostic value to all-cause mortality. Most present simple non-invasive scoring systems and histological scores failed to predict clinical outcomes.

[Clostridium difficile infection and its susceptibility factors in children with inflammatory bowel disease].

OBJECTIVE: To investigate the incidence rates of Clostridium difficile colonization and Clostridium difficile infection (CDI) in children with inflammatory bowel disease (IBD) and the susceptibility factors for CDI in children with IBD. METHODS: A total of 62 children diagnosed with IBD were enrolled as the IBD group. Forty-two children who attended the hospital due to persistent or chronic diarrhea and were excluded from IBD were enrolled as the non-IBD group. The incidence rate of CDI was compared between the two groups. According to the presence or absence of CDI, the IBD group was subdivided into two groups:IBD+CDI (n=12) and non-CDI IBD (n=50), and the clinical data were collected from the two groups to analyze the susceptibility factors for CDI. RESULTS: The IBD group had a significantly higher incidence rate of CDI[19% (12/62) vs 2% (1/42); P < 0.05] than the non-IBD group (P < 0.05). Compared with the non-CDI IBD group, the IBD+CDI group had a significantly longer disease course (P < 0.05), and a significantly higher proportion of children with fever, diarrhea, or abdominal pain (P < 0.05). The IBD+CDI group had significantly higher activity indices of pediatric Crohn's disease, C-reactive protein levels and erythrocyte sedimentation rate than the non-CDI IBD group (P < 0.05). The univariate analysis showed that compared with the non-CDI IBD group, the IBD+CDI group had a significantly higher proportion of children with moderate-to-severe disease, use of glucocorticoids, or treatment with broad-spectrum antibiotics for more than 14 days before diagnosis (P < 0.05). CONCLUSIONS: The children with IBD have a higher incidence of CDI than those without IBD. Severe disease conditions and use of broad-spectrum antibiotics or glucocorticoids may be associated with an increased incidence of CDI in children with IBD.

[Ingredients changes in Rehmanniae Radix processing based by HPLC-ELSD specific chromatogram].

To establish the HPLC-ELSD specific chromatogram analysis method of Rehmanniae Radix and Rehmanniae Radix Prae-parata, and analyze and compare their chemical compositions, so as to reveal the change regularity of compositions during the proces-sing. By HPLC-ELSD method, the chromatographic column for Prevail Carbohydrate ES(4.6 mm ×250 mm, 5 µm) was adopted, with acetonitrile(A)-water(B) as mobile phase for gradient elution, and the evaporative light-scattering detector was used. A total of 23 batches of Rehmannia Radix samples, and 25 batches of Rehmanniae Radix Praeparata samples and processing dynamic samples were compared. The established method had a great repeatability, precision and stability. Eight common chromatographic peaks were extracted from 23 batches of Rehmanniae Radix samples, 8 common peaks were extracted from 25 Rehmanniae Radix Praeparata, and 7 chromatographic peaks were identified. The composition ratio of Rehmannia Radix was changed greatly during the processing. When the simila-rity≥0.95 and the fructose peak area was more than 2 times of stachyose tetrahydrate or more than 20 times of raffinose, the processing degree conformed to the requirements of empirical identification. The three main oligosaccharides of Rehmanniae Radix were sucrose that was heated to generate fructose and glucose, stachyose tetrahydrate that was heated to generate melibiose, sucrose and fructose, and stachyose tetrahydrate that was heated to generate manninotriose. The change in the index of proportion between monosaccharides and oligosaccharides can be used as the quantitative criterion for the processing quality of Rehmanniae Radix Praeparata.

Purification and the secondary structure of a novel angiotensin I-converting enzyme (ACE) inhibitory peptide from the alcalase hydrolysate of seahorse protein.

Bioactive peptides with blood pressure-lowering functions have received increasing attention. In recent years, many ACE-inhibiting peptides have been widely purified from various food-derived proteins and have received considerable interest owing to their potential role in cardiovascular diseases and in the reduction of side effects. In this study, we hydrolyzed a three-spot seahorse (Hippocampus trimaculatus Leach) protein by alcalase to obtain a hydrolysate containing angiotensin I-converting enzyme (ACE) inhibitory peptide. Then, the hydrolysate was fractionated by dialysis, Sephadex G-25 gel filtration chromatography, and reverse-phase high performance liquid chromatography. After consecutive purification, a potent ACE-inhibiting peptide composed of 8 amino acids (Pro-Ala-Gly-Pro-Arg-Gly-Pro-Ala; MW: 721.39 Da; IC50 value: 7.90 µM) was successfully isolated from three-spot seahorse protein. For the first time, a novel ACE-inhibiting peptide (PAGPRGPA) was isolated from the seahorse. Circular dichroism (CD) analyses suggested that the secondary structure of the purified peptide was mainly composed of random coil. Therefore, the peptide from seahorse protein may be used as a favorable ingredient in nutraceuticals, medicines, and functional foods against antihypertensive and related diseases.

Pentatricopeptide repeat protein DEK40 is required for mitochondrial function and kernel development in maize.

Pentatricopeptide repeat (PPR) proteins are one of the largest protein families, which consists of >400 members in most species. However, the molecular functions of many PPR proteins are still uncharacterized. Here, we isolated a maize mutant, defective kernel 40 (dek40). Positional cloning, and genetic and molecular analyses revealed that DEK40 encodes a new E+ subgroup PPR protein that is localized in the mitochondrion. DEK40 recognizes and directly binds to cox3, nad2, and nad5 transcripts and functions in their processing. In the dek40 mutant, abolishment of the C-to-U editing of cox3-314, nad2-26, and nad5-1916 leads to accumulated reactive oxygen species and promoted programmed cell death in endosperm cells due to the dysfunction of mitochondrial complexes I and IV. Furthermore, RNA sequencing analysis showed that gene expression in some pathways, such as glutathione metabolism and starch biosynthesis, was altered in the dek40 mutant compared with the wild-type control, which might be involved in abnormal development of the maize mutant kernels. Thus, our results provide solid evidence on the molecular mechanism underlying RNA editing by DEK40, and extend our understanding of PPR-E+ type protein in editing functions and kernel development in maize.

[Clinical and fundamental research Yinhua Miyanling Tablets in treating urinary tract infection].

As the famous Chinese patent medicine, Yinhua Miyanling Tablets, which was derived from ancient prescription denominated Bazhengsan, has not only the effects in clearing away heat and purging pathogenic fire, removing dampness and relieving stranguria, but also have the functions of detoxifying and tonifying. A great number of scientific studies have demonstrated that Yinhua Mi-yanling Tablets played significant roles in destroying harmful microbes and resisting inflammatory and diuresis. Compared with antibiotics, traditional antibacterial Chinese patent medicine Yinhua Miyanling Tablets has the advantage in bacterial resistance in long-term use. Fundamental studies about the content of pharmaceutical ingredients and the modern pharmacology of Yinhua Miyanling Tablets were collected and summarized, which conduces to indicating the active ingredients of Yinhua Miyanling Tablets with the medicinal efficacy from the molecular level and the internal mechanism of Yinhua Miyanling Tablets in the treatment of urinary tract infection(UTI) from the scientific perspective. In the field of clinical research, literatures associated with Yinhua Miyanling Tablets for the treatment of UTI were summarized and analyzed in terms of treatment type, administration mode, dosage, frequency of medication, course, efficiency, side effects and whether combined with healthy lifestyle. These literatures confirmed the medicinal values and the application prospect of Yinhua Miyanling Tablets in treating UTI, especially acute UTI, which provides a scientific theoretical foundation and a correct direction for the clinical application of Yinhua Miyanling Tablets. In conclusion, this article contributes to the standardization of Yinhua Miyanling Tablets in the treatment of UTI, in the expectation of giving the scientific guidance for clinical practice.

[Construction of rat interleukin-10 adenoviral vector and its expression in bone marrow mesenchymal stem cells].

OBJECTIVE: To construct the recombinant adenoviral vector carrying the rat interleukin-10 (rIL-10) gene, and to investigate whether it is stably expressed in bone marrow mesenchymal stem cells. METHODS: The rIL-10 gene was amplified by PCR from template rIL-10 cDNA, and the recovered 656 bp rIL-10 DNA fragment was cloned into pcDNA3.1 to construct pcDNA3.1-IL-10. Then HEK293 cells were transfected with pcDNA3.1-IL-10 and adenoviral vector for homologous recombination, and sequencing and PCR were used to evaluate whether recombination was successful. HEK293 cells were lysed by repeated freeze-thaw cycles, and bone marrow mesenchymal stem cells were infected with the virus solution containing the rIL-10 gene. Western blot was used to measure the expression of rIL-10 in bone marrow mesenchymal stem cells. RESULTS: Sequencing and PCR verified that the rIL-10 adenoviral vector was successfully constructed, with a virus titer of 4×109 PFU/mL. The expression of IL-10 was detected after bone marrow mesenchymal stem cells were infected by the virus solution containing the rIL-10 gene. CONCLUSIONS: The constructed rIL-10 recombinant adenovirus can mediate the stable expression of rIL-10 gene in bone marrow mesenchymal stem cells, which provides a basis for gene transplantation therapy of inflammatory bowel disease.

[Study on original plant species and geographical distribution of Fructus Aurantii].

The original plant species of Fructus Aurantii are multitudinous and complex, and their requirements to the growing environment is strict. In order to clarify the original plant species and geographical distribution of Fructus Aurantii which recorded in the standards and circulated, used in commodity. The national and local standards of Chinese medicinal materials were collected and the original plants of Fructus Aurantii recoded in standards were found. Ten original plant species of Fructus Aurantii (including varieties of cultivars, the same below) were recorded in the Chinese pharmacopoeia and six local standards of Zhejiang, Yunnan and Guizhou etc. The producing areas and commodity in markets of Fructus Aurantii were investigated. The growth environment and geographical distribution of them were analyzed. There are six types of Fructus Aurantii i.e., Fructus Aurantii Chuan, Fructus Aurantii Xiang, Fructus Aurantii Jiang, Fructus Aurantii Qu, Fructus Aurantii Su, Fructus Aurantii Wen, and nineteen species of original plants in the practical commodities. There are four major Fructus Aurantii producing areas: Sichuan Basin, Dongting Lake Plain, Poyang Lake Plain, Jinqu Basin and its surrounding hilly areas. All of them are located in the area of the east longitude 104° to 121° and the northern latitudes 27° to 31°. There is a certain difference between the actual commodity and the standards of medicinal materials. It is suggested that the traditional mainstream types of Fructus Aurantii with fine quality should be accepted into Chinese Pharmacopoeia, and the types with poor quality should be withdrawn from Chinese Pharmacopoeia.

RhoGDIß Inhibits Bone Morphogenetic Protein 4 (BMP4)-induced Adipocyte Lineage Commitment and Favors Smooth Muscle-like Cell Differentiation.

The integration of signals involved in deciding the fate of mesenchymal stem cells is largely unknown. We used proteomics profiling to identify RhoGDIß, an inhibitor of the small G-protein Rho family, as a component that regulates commitment of C3H10T1/2 mesenchymal stem cells to the adipocyte or smooth muscle cell lineage in response to bone morphogenetic protein 4 (BMP4). RhoGDIß is notably down-regulated during BMP4-induced adipocytic lineage commitment of C3H10T1/2 mesenchymal stem cells, and this involves the cytoskeleton-associated protein lysyl oxidase. Excess RhoGDIß completely prevents BMP4-induced commitment to the adipocyte lineage and simultaneously stimulates smooth muscle cell commitment by suppressing the activation of Rac1. Overexpression of RhoGDIß induces stress fibers of F-actin by a process involving phosphomyosin light chain, indicating that cytoskeletal tension regulated by RhoGDIß contributes to determining adipocyte versus myocyte commitment. Furthermore, the overexpression of RacV12 (constitutively active form of Rac1) totally rescues the inhibition of adipocyte commitment by RhoGDIß, simultaneously preventing formation of the smooth muscle-like phenotype and disrupting the stress fibers in cells overexpressing RhoGDIß. Collectively, these results indicate that RhoGDIß functions as a novel BMP4 signaling target that regulates adipogenesis and myogensis.

[Analysis of Volatile Components of Polypodium hastatum by GC-MS].

OBJECTIVE: To further reveal the chemical constituents of Polypodium hastatum, volatile components from this plant were investigated. METHODS: The volatile components were extracted under reflux from the whole plant of Polypodium hastatum, and then analyzed qualitatively and quantitatively by GC-MS. RESULTS: 60 volatile components were detected and of all components detected, the structures and relative contents of 34 volatile compounds were elucidated. CONCLUSION: In the volatile components identified, most are fatty acid esters, especially methyl and ethyl esters, which compose the major volatile chemical constituents of Polypodium hastatum.

CuI-catalyzed C-N bond formation and cleavage for the synthesis of benzimidazo[1,2-a]quinazoline derivatives.

A copper(I)-catalyzed domino reaction of N-(2-benzimidazolyl)-2-aminobenzamide and 2-halogenated benzaldehyde has been studied. The procedure is based on a sequential CuI-catalyzed Ullmann reaction (C-N bond formation) and two bond cleavage reactions and provides an efficient strategy for the synthesis of benzimidazo[1,2-a]quinazolines catalyzed by CuI/L-proline.

Enantioselective separation of mirtazapine and its metabolites by capillary electrophoresis with acetonitrile field-amplified sample stacking and its application.

A simple, rapid and sensitive chiral capillary zone electrophoresis coupled with acetonitrile-field-amplified sample stacking method was developed that allows the simultaneous enantioselective separation of the mirtazapine, N-demethylmirtazapine, 8-hydroxymirtazapine and mirtazapine-N-oxide. The separation was achieved on an uncoated 40.2 cm×75 µM fused silica capillary with an applied voltage of 16 kV. The electrophoretic analyses were carried out in 6.25 mM borate-25 mM phosphate solution at pH 2.8 containing 5.5 mg/mL carboxymethyl-ß-cyclodextrin. The detection wavelength was 200 nm. Under these optimized conditions, satisfactory chiral separations of four pair enantiomers were achieved in less than 7 min in vitro. After one step clean-up liquid-liquid extraction using 96-well format, sample was introduced capillary zone electrophoresis with acetonitrile-field-amplified sample stacking to enhance the sensitivity of enantiomers. The method was validated with respect to specificity, linearity, lower limit of quantitation, accuracy, precision, extraction recovery and stability. The lower limit of quantification was 0.5 ng/mL with linear response over the 0.5-50 ng/mL concentration range for each mirtazapine, N-demethylmirtazapine and 8-hydroxymirtazapine enantiomer. The developed and validated method has been successfully applied to the enantioselective pharmacokinetic studies in 12 healthy volunteers after oral administration of rac- mirtazapine.

Avicularin Attenuated Lead-Induced Ferroptosis, Neuroinflammation, and Memory Impairment in Mice.

Lead (Pb) is a common environmental neurotoxicant that results in abnormal neurobehavior and impaired memory. Avicularin (AVL), the main dietary flavonoid found in several plants and fruits, exhibits neuroprotective and hepatoprotective properties. In the present study, the effects of AVL on Pb-induced neurotoxicity were evaluated using ICR mice to investigate the molecular mechanisms behind its protective effects. Our study has demonstrated that AVL treatment significantly ameliorated memory impairment induced by lead (Pb). Furthermore, AVL mitigated Pb-triggered neuroinflammation, ferroptosis, and oxidative stress. The inhibition of Pb-induced oxidative stress in the brain by AVL was evidenced by the reduction in malondialdehyde (MDA) levels and the enhancement of glutathione (GSH) and glutathione peroxidase (GPx) activities. Additionally, in the context of lead-induced neurotoxicity, AVL mitigated ferroptosis by increasing the expression of GPX4 and reducing ferrous iron levels (Fe2+). AVL increased the activities of glycogenolysis rate-limiting enzymes HK, PK, and PYG. Additionally, AVL downregulated TNF-α and IL-1ß expression while concurrently enhancing the activations of AMPK, Nrf2, HO-1, NQO1, PSD-95, SNAP-25, CaMKII, and CREB in the brains of mice. The findings from this study suggest that AVL mitigates the memory impairment induced by Pb, which is associated with the AMPK/Nrf2 pathway and ferroptosis.

A novel antidepressant homogeneous polysaccharide YLP-1 from Millettia pulchra ameliorates tryptophan metabolism and SCFAs through modulating gut microbiota.

The root of Millettia pulchra (YLS) has been traditionally used as a folk medicine for the treatment of depression and insomnia in the Zhuang nationality of China, and its polysaccharides have potential antidepressant effect. In this study, a novel homogeneous polysaccharide (YLP-1) was purified from the crude polysaccharides of YLS, and it is mainly composed of glucose, arabinose and mannose with molar ratio of 87.25%, 10.77%, and 1.98%, respectively. YLP-1 is a novel α-glucan with the backbone of 1,4-Glcp and branched at C6 of 1,4,6-Glcp to combine 1,4-Manp and 1,5-Araf. The microstructure of YLP-1 displayed a uniform ellipsoidal-like chain morphology and dispersed uniformly in solution. YLP-1 effectively ameliorated depression-like ethological behaviors and restored the decreased catecholamine levels in chronic variable stress (CVS)-induced depression rats. Additionally, it significantly improved the disturbance of gut microbiota induced by CVS stimuli, particularly affecting bacteria that produce short-chain fatty acids (SCFAs), such as bacteria species Lactobacillus spp.. In vitro fermentation study further confirmed that YLP-1 intake could promote SCFAs production by Lactobacillus spp. YLP-1 also mitigated the disruption of tryptophan metabolites in urine and serum. These findings provide evidences for the further development of YLP-1 as a macromolecular antidepressant drug.