Screening of active components in Astragalus mongholicus Bunge and Panax notoginseng formula for anti-fibrosis in CKD: nobiletin inhibits Lgals1/PI3K/AKT signaling to improve renal fibrosis.

The Astragalus mongholicus Bunge and Panax notoginseng formula (A&P) has been clinically shown to effectively slow down the progression of chronic kidney disease (CKD) and has demonstrated significant anti-fibrosis effects in experimental CKD model. However, the specific active ingredients and underlying mechanism are still unclear. The active ingredients of A&P were analyzed by Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-HR-MS). A mouse model of CKD was constructed by 5/6 nephrectomy. Renal function was assessed by creatinine and urea nitrogen. Real-time PCR and Western Blot were performed to detect the mRNA and protein changes in kidney and cells. An in vitro fibrotic cell model was constructed by TGF-ß induction in TCMK-1 cells. The results showed that thirteen active ingredients of A&P were identified by UPLC-HR-MS, nine of which were identified by analysis with standards, among which the relative percentage of NOB was high. We found that NOB treatment significantly improved renal function, pathological damage and reduced the expression level of fibrotic factors in CKD mice. The results also demonstrated that Lgals1 was overexpressed in the interstitial kidney of CKD mice, and NOB treatment significantly reduced its expression level, while inhibiting PI3K and AKT phosphorylation. Interestingly, overexpression of Lgals1 significantly increased fibrosis in TCMK1 cells and upregulated the activity of PI3K and AKT, which were strongly inhibited by NOB treatment. NOB is one of the main active components of A&P. The molecular mechanism by which NOB ameliorates renal fibrosis in CKD may be through the inhibition of Lgals1/PI3K/AKT signaling pathway.

Untargeted metabonomics and TLR4/ NF-κB signaling pathway analysis reveals potential mechanism of action of Dendrobium huoshanense polysaccharide in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is marked by hepatic steatosis accompanied by an inflammatory response. At present, there are no approved therapeutic agents for NAFLD. Dendrobium Huoshanense polysaccharide (DHP), an active ingredient extracted from the stems of Dendrobium Huoshanense, and exerts a protective effect against liver injury. However, the therapeutic effects and mechanisms of action DHP against NAFLD remain unclear. DHP was extracted, characterized, and administered to mice in which NAFLD had been induced with a high-fat and high-fructose drinking (HFHF) diet. Our results showed that DHP used in this research exhibits the characteristic polysaccharide peak with a molecular weight of 179.935 kDa and is composed primarily of Man and Glc in a molar ratio of 68.97:31.03. DHP treatment greatly ameliorated NAFLD by significantly reducing lipid accumulation and the levels of liver function markers in HFHF-induced NAFLD mice, as evidenced by decreased serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC) and total triglyceride (TG). Furthermore, DHP administration reduced hepatic steatosis, as shown by H&E and Oil red O staining. DHP also inhibited the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway expression, thereby reducing levels of hepatic proinflammatory cytokines. Besides, untargeted metabolomics further indicated that 49 metabolites were affected by DHP. These metabolites are strongly associated the metabolism of glycine, serine, threonine, nicotinate and nicotinamide, and arachidonic acid. In conclusion, DHP has a therapeutic effect against NAFLD, whose underlying mechanism may involve the modulation of TLR4/NF-κB, reduction of inflammation, and regulation of the metabolism of glycine, serine, threonine, nicotinate and nicotinamide metabolism, and arachidonic acid metabolism.

Analysis of age-specified and genotype distribution of HPV multiple infections in the Chinese population.

Multiple infections are a key component of HPV pathogenesis and have a direct impact on how an infection turns out. It's crucial to look at the associations between HPV multiple infections and both age and HPV genotypes in the Chinese population, searching for the causative factors of multiple infections with a view to providing new ideas for the treatment and prevention of multiple infections. In this study, we retrospectively analyzed the data of HPV infections among outpatients from the 2019 year to the 2021 year of Shandong Maternal and Child Health Hospital. Analyzed the correlation between HPV multiple infections and age using logistic regression. Differences in the percentage of multiple infections between age groups were compared using the chi-square test. The chi-square test compared the differences in the distribution of 15 common HPV genotypes in mono- versus multiple infections. A two-dimensional matrix presented the frequency of HPV genotype combinations. Logistics regression analysis showed that age was significantly associated with the occurrence of multiple infections, with a dominance ratio OR 1.026 (95% CI 1.02-1.04). Interestingly, the proportion of HPV multiple infections among HPV-positive individuals increases with age in people older than 30 years of age. The chi-square test showed there was a difference in the distribution of HPV genotypes between multiple infections and mono- HPV infection (χ2 = 76.4; p = 0.000), a difference in the composition of HPV genotypes for dual versus single infections (χ2 = 90.6; p = 0.000) and a difference in HPV genotypes for triple versus single infections (χ2 = 56.7; p = 0.000). A 2 × 2 matrix showed that the combination of HPV52/HPV58 (30; 6.4%) was the combination of the highest frequency of infection for dual infections; The HPV52/HPV58 (21; 4.8%) combination was the highest frequency of HPV triple infection combination. HPV multiple infections were positively correlated with age; increasing age was positively correlated with the proportion of HPV multiple infections in the total infected population; the distribution of the 15 common genotypes of HPV differed between multiple infections and single infections; and HPV52:58 was a common type of infection combination in the Shandong population.

The novel HLA-B*54:01:12 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-B*54:01:12 differs from HLA-B*54:01:01:01 by one nucleotide in exon 2.

Organocatalytic Enantioselective Functionalization of Cyclic α-Hydroxyamides: Access to Chiral Cyclic Imides and Azapolycyclic Compounds.

A highly efficient enantioselective enamine-catalyzed asymmetric conjugate addition has been developed to directly convert unfunctionalized cyclic α-hydroxyamides into chiral cyclic α-hydroxyamides by reacting with vinyl sulfones, which could be used as versatile azacyclic synthons in the following sequences: (1) as the precursors of cyclic N-acyliminium ions to prepare natural productlike chiral azapolycyclic compounds under acidic conditions and (2) to construct chiral cyclic imides bearing unilateral substituents via oxidation reaction-induced formal desymmetrization.

Analysis of HPV prevalence among individuals with reproductive tract infections in a Chinese population.

The previous research has found that human papillomavirus (HPV) infection is the main cause of cervical cancer, but it is still unclear whether HPV infection, as well as the HPV genotypes, are related to reproductive tract infections in the Chinese population. Patients who underwent HPV screening at Shandong Maternal and Child Health Hospital were selected, and the HPV infection status was analyzed among patients with cervical lesions, bacterial vaginosis, cervical inflammation, fungal vaginitis, and pelvic infections. SPSS 22 statistical analysis was used to analyze the differences in HPV infection types and rates between the control group and the experimental group. The HPV infection rate of bacterial vaginosis (χ2 = 13.4; P < .001) and fungal vaginitis (χ2 = 3.3; P < .045) are both significantly different from the control group. The single HPV infections reveals significant differences from control group in bacterial vaginosis (χ2 = 7.3; P = .004), fungal vaginitis (χ2 = 4.5; P = .023), and cervical lesions (χ2 = 58.8; P < .001). In the bacterial infection group, HPV51 (1.9%; χ2 = 6.0; P = .008) and HPV58 (4.7%; χ2 = 3.3; P = .044) showed significant differences in infection compared to the control group. In the fungal infection group, HPV39 (2.7%; χ2 = 4.7; P = .032) showed a significant difference in infection compared to the control group. Cervical lesions, bacterial vaginosis, fungal vaginitis, and cervical lesions among Chinese population exhibit age-specified distribution. HPV infection rate in bacterial vaginitis, fungal vaginitis and cervical lesions was higher than that in normal group. HPV52 and HPV16 infection are different, and HPV39 is different between bacterial vaginitis and fungal vaginitis.

Heme Oxygenase-1 as a Predictive Marker for Spontaneous Bacterial Peritonitis in Cirrhotic Patients with Ascites.

OBJECTIVE: Identifying a predictive biomarker for spontaneous bacterial peritonitis (SBP) is of crucial importance in cirrhotic patients with ascites. This study was designed to identify the predictive value of serum or ascitic heme oxygenase-1 (HO-1) for SBP in this population. METHODS: In this cohort study, 60 patients with liver cirrhosis and ascites accompanied by SBP (studied cohort, n=26) or not (control cohort, n=34) were retrospectively included. HO-1 levels in the serum and ascites were detected by ELISA. The predictive performance of HO-1 was evaluated by calculating the area under the curve (AUC) in receiver operating characteristic (ROC) curve analysis. RESULTS: The HO-1 level of SBP patients was significantly higher than that of non-SBP patients both in the serum and ascites (p<0.001). Serum, ascites HO-1, and their combination displayed an AUC of 0.897 (95% CI, 0.808-0.986), 0.825 (95% CI, 0.708-0.941), and 0.902 (95% CI, 0.817-0.986) for discriminating SBP from non-SBP patients. HO-1 level between serum and ascites had a higher correlation in patients in a Child-Pugh B stage (R=0.691, p<0.001) than in the Child-Pugh C stage (R=0.475, p=0.014). The correlation between HO-1 level and inflammatory factors or biochemical parameters was observed in SBP patients and presented in a Child-Pugh stage-dependent manner. CONCLUSION: HO-1 level has the ability to predict the occurrence of SBP in cirrhotic patients with ascites which has the potential to be a biomarker for the early prediction of SBP and move into the clinical setting. However, the Child-Pugh stage should be considered when using the HO-1 as a predictive biomarker.

Gold-Catalyzed Divergent N/O-Vinylations of trans-2-Butene-1,4-amino Alcohols with Alkynes and the Cascade Rearrangements/Cyclizations to Dihydropyrroles and Dihydrofurans.

Although the transition-metal-catalyzed vinylations of amines and alcohols via the additions to alkynes have been well developed, the selective vinylations of amino alcohols have been merely investigated. Herein, we report the gold-catalyzed divergent additions of trans-2-butene-1,4-amino alcohols' N-H and O-H groups to alkynes. The allyl enamine and allyl vinyl ether adducts then underwent a cascade (Aza-) Claisen rearrangement/cyclization sequence, furnishing the functionalized dihydropyrrole and dihydrofuran products.

Single-cell transcriptomic characterization of sheep conceptus elongation and implantation.

Bidirectional communication between the developing conceptus and endometrium is essential for pregnancy recognition and establishment in ruminants. We dissect the transcriptomic dynamics of sheep conceptus and corresponding endometrium at pre- and peri-implantation stages using single-cell RNA sequencing. Spherical blastocysts contain five cell types, with 68.62% trophectoderm cells. Strikingly, elongated conceptuses differentiate into 17 cell types, indicating dramatic cell fate specifications. Cell-type-specific gene expression delineates the features of distinctive trophectoderm lineages and indicates that the transition from polar trophectoderm to trophoblast increases interferon-tau expression and likely drives elongation initiation. We identify 13 endometrium-derived cell types and elucidate their molecular responses to conceptus development. Integrated analyses uncover multiple paired transcripts mediating the dialogues between extraembryonic membrane and endometrium, including IGF2-IGF1R, FGF19-FGFR1, NPY-NPY1R, PROS1-AXL, and ADGRE5-CD55. These data provide insight into the molecular regulation of conceptus elongation and represent a valuable resource for functional investigations of pre- and peri-implantation ruminant development.

Comparative transcriptomics provides insights into the pathogenic immune response of brown leaf spots in weeping forsythia.

Weeping forsythia is an important ornamental, ecological and medicinal plant. Brown leaf spots limit the large-scale production of weeping forsythia as a medicinal crop. Alternaria alternata is a pathogen causing brown leaf spots in weeping forsythia; however, its pathogenesis and the immune response mechanisms of weeping forsythia remain unclear. In this study, we identified two mechanisms based on morphological anatomy, physiological indexes and gene expression analyses. Our results showed that A. alternata induced leaf stomata to open, invaded the mesophyll, dissolved the cell wall, destroyed the cell membrane and decreased the number of chloroplasts by up-regulating the expression of auxin-activated signaling pathway genes. Alternaria alternata also down-regulated iron-ion homeostasis and binding-related genes, which caused an increase in the levels of iron ions and reactive oxygen species in leaves. These processes eventually led to programmed cell death, destroying palisade and spongy tissues and causing the formation of iron rust spots. Alternaria alternata also caused defense and hypersensitive responses in weeping forsythia through signaling pathways mediated by flg22-like and elf18-like polypeptides, ethylene, H2O2 and bacterial secretion systems. Our study provides a theoretical basis for the control of brown leaf spots in weeping forsythia.

C-X-C chemokine receptor type 7 antibody enhances neural plasticity after ischemic stroke.

Stromal cell-derived factor-1 and its receptor C-X-C chemokine receptor 4 (CXCR4) have been shown to regulate neural regeneration after stroke. However, whether stromal cell-derived factor-1 receptor CXCR7, which is widely distributed in the developing and adult central nervous system, participates in neural regeneration remains poorly understood. In this study, we established rat models of focal cerebral ischemia by injecting endothelin-1 into the cerebral cortex and striatum. Starting on day 7 after injury, CXCR7-neutralizing antibody was injected into the lateral ventricle using a micro drug delivery system for 6 consecutive days. Our results showed that CXCR7-neutralizing antibody increased the total length and number of sprouting corticospinal tract fibers in rats with cerebral ischemia, increased the expression of vesicular glutamate transporter 1 and growth-related protein 43, markers of the denervated spinal cord synapses, and promoted the differentiation and maturation of oligodendrocyte progenitor cells in the striatum. In addition, CXCR7 antibody increased the expression of CXCR4 in the striatum, increased the protein expression of RAS and ERK1/2 associated with the RAS/ERK signaling pathway, and improved rat motor function. These findings suggest that CXCR7 improved neural functional recovery after ischemic stroke by promoting axonal regeneration, synaptogenesis, and myelin regeneration, which may be achieved by activation of CXCR4 and the RAS/ERK1/2 signaling pathway.

Transcriptome sequencing and metabolite analysis reveal the single and combined effects of microplastics and di-(2-ethylhexyl) phthalate on Peneaus vannamei.

Due to the rising usage of plastics, plastic debris are present throughout marine ecosystems and detrimentally affects marine biota. Additionally, plastics likely result in elusive toxicity effects due to addition of plasticizers. The aim of the present study was to reveal the potential effects and mechanism of microplastics (MPs), di-(2-ethylhexyl) phthalate (DEHP) and copollution of MPs and DEHP (MPs-DEHP) on Peneaus vannamei (P. vannamei) juveniles regarding oxidative stress, transcriptomics and metabolomics. MPs, DEHP and MPs-DEHP significantly induced the activities of superoxide dismutase (SOD) and catalase (CAT); MPs and DEHP have an antagonistic effect for malondialdehyde (MDA); suggesting that disorders of the antioxidant defence systems. 13, 133 and 58 differentially expressed genes and 21, 82 and 39 differentially expressed metabolites were responsible for the distinction of MPs, DEHP and MPs-DEHP groups, respectively. The combination of transcriptomic and metabolomic analyses showed that MPs, DEHP and MPs-DEHP exposure disturbed amino acid and lipid metabolism, and further induced inflammatory responses and dysfunction of purine metabolism. Furthermore, the presence of MPs might alleviate the biotoxicity of DEHP in P. vannamei. These findings provide new insights into the single and combined toxicological effects of MPs and additives for marine biota.

Effect of anemia and erythrocyte indices on hemoglobin A1c levels among pregnant women.

BACKGROUND: Anemia is a common disorder among pregnant women; however, the effect of anemia on hemoglobin A1c (HbA1c) levels has not been adequately explored. We aim to examine the influence of anemia on the HbA1c concentration and investigate the relationship between erythrocyte indices and HbA1c levels during pregnancy. METHODS: We performed a retrospective analysis of 1369 pregnant Chinese women. The clinical and analytical data were collected. Independent t-test and Analysis of Variance were used for comparative studies, and multiple linear regression analysis was used to identify the association between erythrocyte indices and HbA1c. RESULTS: The differences in HbA1c between non-anemia and mild anemia were negligible, and the differences in HbA1c between non-anemia and moderate anemia were well within the allowable variability for clinical practice (≥0.5% absolute changes). Mean corpuscular hemoglobin (MCH) correlated with HbA1c significantly, independent of pregnancy, trimester, and anemia. The distinction of HbA1c levels between grades of Hb became no significant (P = 0.955), while differences between trimesters persisted after adjusting for MCH. CONCLUSION: Mild and moderate anemia should not be the primary concern when using HbA1c to monitor blood glucose in pregnancy. MCH showed negative correlations with HbA1c independently, suggesting a previously unknown mechanism affecting HbA1c levels.

Organophosphate esters in the mariculture ecosystem: Environmental occurrence and risk assessments.

Most investigations on organophosphate esters (OPEs) are conducted predominantly in a separate biological or abiotic medium, and few joint analyses have been performed in the mariculture ecosystem based on yearly sampling. Herein, we investigated the occurrence, load estimation, phase distribution, source diagnostics, and risks of 20 OPEs in seawater, sediment, and aquaculture organisms from a typical mariculture area in China. The total of these OPEs (∑OPEs) ranged within 3.97-1068 ng/L, 0.39-65.5 ng/g (dw), and 4.09-16.3 ng/g (ww) in seawater, sediment and organisms, respectively. Chlorinated OPEs were the predominant congeners detected in seawater, whereas alkyl-OPEs were the leading contributors in sediment and biological samples. Seasonal variations of ∑OPEs in seawater were more distinct than those in sedimentary environments. Load estimation indicated that approximately 70% of the OPEs in the study area existed in the water bodies. Source identification performed using the U.S. EPA positive matrix factorization indicated that polyurethane foam/plastics and hydraulic oil made the greatest contributions in seawater, whereas chemical production was the predominant source in sediment. Indices of ecological and health risks of OPEs were lower than their risk threshold, indicating that the OPEs detected in this study posed a low risk to the aquatic environment and human health.

Evaluation of the diagnostic performance of the EFSUMB CEUS Pancreatic Applications guidelines (2017 version): a retrospective single-center analysis of 455 solid pancreatic masses.

OBJECTIVES: To explore the diagnostic performance of EFSUMB CEUS Pancreatic Applications guidelines (version 2017) before and after the addition of iso-enhancement and very fast/fast washout as supplementary diagnostic criteria for PDAC. METHODS: In this retrospective study, patients diagnosed with solid pancreatic lesions from January 2017 to December 2020 were evaluated. Pancreatic ductal adenocarcinoma (PDAC) is reported to show hypo-enhancement in all phases according to the EFSUMB guidelines. First, based on this definition, all lesions were categorized as PDAC and non-PDAC. Then, iso-enhancement and very fast/fast washout were added as supplementary diagnostic criteria, and all lesions were recategorized. The diagnostic performance was assessed in terms of the accuracy (ACC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), and negative predictive value (NPV). The reference standard consisted of histologic evaluation or composite imaging and clinical follow-up findings. RESULTS: A total of 455 nodules in 450 patients (median age, 58.37 years; 250 men) were included. The diagnostic performance using the EFSUMB CEUS guidelines for PDAC had an ACC of 69.5%, SEN of 65.4%, SPE of 84%, PPV of 93.5%, NPV of 40.6%, and ROC of 0.747. After recategorization according to the supplementary diagnostic criteria, the diagnostic performance for PDAC had an ACC of 95.8%, SEN of 99.2%, SPE of 84%, PPV of 95.7%, NPV of 96.6%, and ROC of 0.916. CONCLUSION: The EFSUMB guidelines and recommendations for pancreatic lesions can effectively identify PDAC via hypo-enhancement on CEUS. However, the diagnostic performance may be further improved by the reclassification of PDAC lesions after adding iso-enhancement and very fast/fast washout mode. KEY POINTS: • In the EFSUMB guidelines, the only diagnostic criterion for PDAC is hypo-enhancement, to which iso-enhancement and very fast/fast washout mode were added in our research. • Using hypo-enhancement/iso-enhancement with very fast/fast washout patterns as the diagnostic criteria for PDAC for solid pancreatic masses on CEUS has high diagnostic accuracy. • The blood supply pattern of PDAC can provide important information, and CEUS has unique advantages in this respect due to its real-time dynamic attenuation ability.

Radiomics analysis of ultrasound to predict recurrence of hepatocellular carcinoma after microwave ablation.

OBJECTIVE: To develop and validate an ultrasonic radiomics model for predicting the recurrence and differentiation of hepatocellular carcinoma (HCC). Convolutional neural network (CNN) ResNet 18 and Pyradiomics were used to analyze gray-scale-ultrasonic images to predict the prognosis and degree of differentiation of HCC. METHODS: This retrospective study enrolled 513 patients with HCC who underwent preoperative grayscale-ultrasonic imaging, and their clinical characteristics were observed. Patients were randomly divided into training (n = 413) and validation (n = 100) cohorts. CNN ResNet 18 and Pyradiomics were used to analyze ultrasonic images of HCC and peritumoral images to develop a prognostic and differentiation model. Clinical characteristics were integrated into the radiomics model and patients were stratified into high- and low-risk groups. The predictive effect was evaluated using the C-index and receiver operating characteristic (ROC) curve. RESULTS: The model combined with ResNet 18 and clinical characteristics achieved a good predictive ability. The C-indices of early recurrence (ER), late recurrence (LR), and recurrence-free survival (RFS) were 0.695 (0.561-0.789), 0.715 (0.623-0.800) and 0.721 (0.647-0.795), respectively, in the validation cohort, which was superior to the clinical model and ultrasonic semantic model. The model could stratify patients into high- and low-risk groups, which showed significant differences (p < 0.001) in ER, LR, and RFS. The area under the curve for predicting the degree of HCC differentiation was 0.855 and 0.709 in the training and validation cohorts, respectively. CONCLUSION: We developed and validated a radiomics model to predict HCC recurrence and HCC differentiation, which could also acquire pathological information in a noninvasive manner.KEY RESULTSA hepatocellular carcinoma (HCC) prognostic prediction model was developed and validated by convolutional neural network (CNN) ResNet 18-based gray-scale ultrasound (US).A differentiation of HCC prediction model was developed for preoperative prediction avoiding invasive operation.Compared with Pyradiomics, CNN ResNet was more suitable for extracting information from US images.

An ethnobotany survey of wild plants used by the Tibetan people of the Yadong River Valley, Tibet, China.

INTRODUCTION: Plant resources gathered from the wild are important sources of livelihood needs, especially for low-income populations living in remote areas, who rely on these plants for food, fuelwood, medicine and building materials. Yadong County is a valley at the border between the China, India and Bhutan in southern Tibet. Yadong is rich in biodiversity and culture, but ethnobotanical knowledge has not been systematically studied. This study aimed to document the ethnobotanical knowledge of Tibetans in Yadong County. METHODS: Ethnobotanical data were documented through free listings, key informant interviews, and semi-structured interviews during fieldwork. The culture importance index (CI) and informant consensus factor index (FIC) were used as the quantitative indices. RESULTS: In total, 163 informants (46 women and 117 men). A total of 3,031 use reports and 121 plant species belonging to 52 families and 91 genera were included. These use reports were then classified into 20 categories belonging to 9 major categories. The utilisation category that containing the most plant species was food, followed by economic, medicine, animal feed, social uses, other uses, environmental uses, materials and fuels. Among the economic plants, 32 medicinal plants are traditionally used in the local region. Plants with high CI included Fritillaria cirrhosa, Neopicrorhiza scrophulariiflora, Betula utilis, Rheum nobile, and Urtica hyperborean. CONCLUSION: This research demonstrates the diversity of the types and functions of Yadong Tibetan traditional plant knowledge. Knowledge of edible and medicinal plants in this area is prominent, reflecting the ability to cope with the lack of fruits and vegetables and basic family medical care. There were exchanges between the traditional plant culture in the study area and its surroundings. With socioeconomic development, the commercial value of medicinal plants has increased, and locals are also seeking ways to adoptsustainable development to cope with the excessive consumption of plant resources.

Design, development and applications of copper-catalyzed regioselective (4 + 2) annulations between diaryliodonium salts and alkynes.

Diaryliodonium salts have been extensively applied in organic synthesis as aryl cation equivalents. However, in the electrophilic reactions with alkenes or alkynes, only the electrophilic carbon of the diaryliodonium salts was involved while the other part of the aryl ring was not utilized. Herein, a reaction pattern of diaryliodonium was reported as oxa-1,4-dipoles to undergo (4 + 2) cycloaddition reactions with alkynes. Broad spectrum of the two reaction partners could be utilized in this protocol, enabling an operationally simple, high yielding, and regioselective synthetic approach to isocoumarins. Particularly, good to excellent regioselectivities were achieved for the sterically unbiased unsymmetrical diaryl acetylenes, which was challenging for other transition metal-catalyzed processes. The reaction could be scaled up with the ideal 1:1 stoichiometry and the isocoumarin type natural products Oospolactone and Thunberginol A could be obtained in one or three steps through this methodology.

Transcranial Magnetic Stimulation Alleviates Levodopa-Induced Dyskinesia in Parkinson's Disease and the Related Mechanisms: A Mini-Review.

After long-term use of levodopa, Parkinson's patients almost inevitably develop dyskinesia, a kind of drug side effect manifesting as uncontrollable choreic movements and dystonia, which could be crippling yet have limited therapeutic options. Transcranial magnetic stimulation is the most widely studied non-invasive neuromodulation technology to treat levodopa-induced dyskinesia. Many studies have shown that transcranial magnetic stimulation has beneficial effects on levodopa-induced dyskinesia and is patient-tolerable, barely with reported adverse effects. Changes in brain connectivity, neuroplasticity, neurotransmitter, neurorestoration, and blood flow modulation could play crucial roles in the efficacy of transcranial magnetic stimulation for levodopa-induced dyskinesia. The appearance of new modes and application for emerging targets are possible solutions for transcranial magnetic stimulation to achieve sustained efficacy. Since the sample size in all available studies is small, more randomized double-blind controlled studies are needed to elucidate the specific treatment mechanisms and optimize treatment parameters.

Prefrontal cortex alterations in major depressive disorder, generalized anxiety disorder and their comorbidity during a verbal fluency task assessed by multi-channel near-infrared spectroscopy.

Major depressive disorder (MDD) and generalized anxiety disorder (GAD) are frequently comorbid with each other, and both associated with substantial cognitive impairments; however, it is still unclear whether their impairments are neurobiologically similar or distinct. This study aims to investigate the cognitive functions of the prefrontal cortex (PFC) in patients with MDD and GAD during the verbal fluency task (VFT) using functional near-infrared spectroscopy (fNIRS). Fifty-two patients with MDD, fifty-one patients with GAD, fifty-two patients with the comorbidity of MDD and GAD (CMG), and forty-seven healthy controls (HC) participated in the study. Significant hypoactivation in the left ventrolateral and the left dorsolateral PFC was common in all patient groups when compared to HCs, suggesting a shared etiology. Furthermore,  MDD patients showed significant hypoactivation at the right frontal pole cortex (FPoC) when compared to HCs and significant hypoactivation at the middle FPoC when compared to the CMG patients. Our work is the first fNIRS study to reveal the shared and unique neurobiological profiles of MDD, GAD and their comorbidity under the same standard experimentation condition, suggesting fNIRS holds promise as an adjutant to assist clinical diagnosis.