IGFBP1a is a nutrient deficient response factor that can inhibit fish reproduction through the hypothalamus-pituitary-ovary axis†.

Reproduction is a high energy consuming process, so long-term malnutrition can significantly inhibit gonadal development. However, little is known about the molecular mechanism by which fasting inhibits reproduction. Our present study found that fasting could dramatically induce insulin-like growth factor binding protein 1 (IGFBP1) expression in the liver, hypothalamus, pituitary and ovaries of grass carp. In addition, IGFBP1a in the hypothalamus-pituitary-gonad axis could inhibit the development of gonads. These results indicated that fasting may participate in the regulation of fish gonadal development through the mediation of IGFBP1a. Further studies found that IGFBP1a could markedly inhibit gonadotropin-releasing hormone 3 expressions in hypothalamus cells. At the pituitary level, IGFBP1a could significantly reduce the gonadotropin hormones (LH and FSH) expression by blocking the action of pituitary insulin-like growth factor 1. Interestingly, IGFBP1a could also directly inhibit the expression of lhr, fshr, and sex steroid hormone synthase genes (cyp11a, cyp17a, and cyp19a1) in the ovary. These results indicated that IGFBP1a should be a nutrient deficient response factor that could inhibit fish reproduction through the hypothalamus-pituitary-ovary axis.

Engineered macrophage-derived cellular vesicles for NIR-II fluorescence imaging-guided precise cancer photo-immunotherapy.

Significant progress has been made in cancer immunotherapy; however, challenges such as interpatient variability, limited treatment response, and severe side effects persist. Although nanoimmunotherapy has emerged as a promising approach, the construction of precise and efficient nanosystems remain formidable challenges. Herein, a multifunctional nanoplatform was developed using macrophage-derived cellular vesicles (MCVs) for NIR-II imaging-guided precise cancer photo-immunotherapy. MCVs exhibited excellent tumor targeting and TAMs re-education effects, serving as both delivery carriers and therapeutic agents. Through amide bond, indocyanine green (ICG) was conjugated to the surface of MCVs, enabling in vivo tracking of MCVs distribution. Notably, ICG exhibited dual functionality as a NIR-II fluorescent agent and possessed photodynamic and photothermal effects, enabling the conversion of light energy into chemical or heat energy to eliminate tumor cells. This precision phototherapy triggered immunogenic cell death (ICD) of tumor, thereby activating the anti-tumor immune response. Additionally, MCVs loaded with R848, a toll-like receptor agonist, augmented the ICD-induced anti-tumor immunity. Animal experiments confirmed that MCVs-mediated photoimmunotherapy promoted T cell infiltration, inhibited tumor growth, and improved survival rates. In conclusion, we have developed a promising precision immunotherapy strategy capable of enhancing the immune response while mitigating off-target effects. These findings offer encouraging prospects for clinical translation.

Ultrasound-assisted extraction of polyphenols from pine needles (Pinus elliottii): Comprehensive insights from RSM optimization, antioxidant activity, UHPLC-Q-Exactive Orbitrap MS/MS analysis and kinetic model.

Extracting polyphenolic bioactive compounds from Pinus elliottii needles, a forestry residue, promises economic and environmental benefits, however, relevant experimental data are lacking. Herein, a comprehensive investigation of the polyphenolic composition of pine needles (PNs) was carried out. Ultrasound-Assisted Extraction (UAE) was applied to extract the polyphenolic compounds of pine needles. The optimal conditions of extracts were determined by Response Surface Methodology (RSM). The maximum total phenolic content (TPC) of 40.37 mg GAE/g PNs was achieved with solid-liquid ratio of 1:20, 60 % ethanol, and 350 W for 25 min at 45 °C. Polyphenolic extracts showed antioxidant activity in scavenging free radicals and reducing power (DPPH, IC50 41.05 µg/mL; FRAP 1.09 mM Fe2+/g PNs; ABTS, IC50 214.07 µg/mL). Furthermore, the second-order kinetic model was also constructed to describe the mechanism of the UAE process, with the extraction activation energy estimated at 12.26 kJ/mol. In addition, 37 compounds in PNs were first identified by UHPLC-Q-Exactive Orbitrap MS/MS, including flavonoids and phenolic acids. The results suggest that Ultrasound-Assisted is an effective method for the extraction of natural polyphenolic compounds from pine needles and this study could serve as a foundation for utilizing phenolics derived from PNs in the food and pharmaceutical industries.

The application of demographic characteristics of Ectropis grisescens (Lepidoptera: Geometridae) in pest risk assessment of IPM.

Ectropis grisescens Warren is one of the most important pests of tea plants. In this study, data on the development, survival, and fecundity of E. grisescens were collected at 15, 22, and 32 °C and analyzed by using the age-stage, two-sex life table. At 15 °C, the duration of the preadult period of E. grisescens was significantly prolonged (81.06 days), with high mortality (69.0%), and the proportion of emerged female adults was extremely low (7.0%). At 32 °C, the preadult period was significantly shortened (29.12 days), with high preadult mortality (74.0%), and a low proportion of emerged female adults (15.0%). At 22 °C, with low preadult mortality (24.0%), and a high proportion of emerged female adults (26.0%). The overall effects of the shorter preadult duration, higher preadult survival rate, higher proportion of emerged female adults, higher fecundity (F = 350.88 eggs/♀), and higher net reproductive rate (R0 = 91.23 offspring/individual) at 22 °C resulted in the highest values of the intrinsic rate of increase (r = 0.1054 days-1) and finite rate of increase (λ = 1.1112 days-1). Computer simulation showed that E. grisescens populations can increase much faster at 22 °C than at 15 and 32 °C. The weighted population size and cumulative weighted insect-days provided the dynamics necessary for estimating the damage potential of E. grisescens in devising economical pest management programs. Our results demonstrate that populations of E. grisescens were able to develop at a broad range of temperatures and adapt to the high temperatures. These finding can be utilized to improve the management of E. grisescens.

The mechanism of Shenlong Jianji treatment of idiopathic pulmonary fibrosis inhibits fibroblast-to-myofibroblast transformation via the TGF-ß1/smads signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Shenlong Jianji (SLJJ) is a Chinese herbal compound composed of traditional medicines for supplementing Qi, nourishing Yin, promoting blood circulation, and removing obstruction in channels. It is widely used to treat idiopathic pulmonary fibrosis (IPF) in China. However, the underlying mechanism of SLJJ remains unclear. AIM OF THIS STUDY: To elucidate the efficacy and mechanisms of SLJJ in the treatment of IPF through in vivo and in vitro experiments. MATERIAL AND METHODS: 84 Wistar rats were randomly and equally divided into 7 groups: the control group (CTRL), the sham operation group (SHAM), the model group (IPF), the low dose of SLJJ group (L-SLJJ), the middle dose of SLJJ group (M-SLJJ), the high dose of SLJJ group (H-SLJJ), and the pirfenidone group (PFD). The rats in the CTRL, SHAM, and IPF groups were given normal saline each time for 28 days; the SLJJ groups were given Shenlong Jianji (9 g kg-1·d-1, 18 g kg-1·d-1, 36 g kg-1·d-1), and pirfenidone was administered as a sequential dose. After 28 days, the general condition of the rats was evaluated, and samples were collected. The lung coefficient was measured. The pathological changes of lung in each group were observed by H&E staining and Masson staining. α-SMA, collagen 1, and E-cadherin proteins were detected by immunohistochemistry. α-SMA, collagen 1, vimentin, E-cadherin, N-cadherin, TGF-ß1, smad2, and smad3 proteins were detected by WB in vivo.In vitro, A scratch test was used to assess the ratio of cell migration. α-SMA, vimentin, E-cadherin, and N-cadherin protein levels were evaluated by a cellular immunofluorescence assay. TGF-ß1/smads signaling pathway was detected by WB. HPLC-Q-TOF/MS analysis was used to identify the active compounds in the SLJJ. Molecular docking determined the free binding energy of the compound with the TGF-ß1 protein. RESULTS: SLJJ significantly improved the respiratory symptoms, heart rate, mental state, and food intake of IPF group rats and decreased the lung coefficient. In the IPF group, inflammatory cells were infiltrated, and the thickened alveoli wall and alveoli collapse were shown, while significantly alleviating pathological changes in the SLJJ and PFD groups. Masson staining showed that SLJJ and PFD decreased the collagen expression. Immunohistochemical results showed that the expressions of α-SMA, collagen 1, and N-cadherin decreased in the SLJJ and PFD groups, while E-cadherin increased significantly compared with the IPF group. SLJJ regulates TGF-ß1/smads signaling pathway proteins in vivo. SLJJ decreased the ratio of migration in HFL-1 cells; SLJJ reduced the fluorescence intensity of α-SMA, vimentin, and N-cadherin and increased the fluorescence intensity of E-cadherin in primary rat lung (PRL) fibroblast cells and HFL-1 cells. WB results showed that SLJJ significantly down-regulated α-SMA, Vimentin, N-cadherin, TGF-ß1, smad2, and p-smad2/3 proteins expression and up-regulated E-cadherin protein expression in vitro, whereas SRI-011381 (a TGF-ß1 agonist) antagonized the effects of SLJJ. CONCLUSION: SLJJ inhibits idiopathic pulmonary fibrosis. The TGF- ß1/Smads signaling pathway can be the target of SLJJ, which inhibits fibroblast-to-myofibroblast transformation and is expected to be a new drug for the treatment of IPF.

The influence of adjunctive traditional Chinese medicine therapy on survival in primary liver cancer: a real-world study based on electronic medical records.

Background: Traditional Chinese medicine (TCM) effectively improves the survival rate and quality of life of primary liver cancer patients, but high-level evidence is lacking. Patients and methods: Patients were selected from 5 tertiary hospitals in Henan Province, China. Two thousand sixty-seven patients with primary liver cancer were included in the study. The electronic medical records (EMRs) of the patients were collected. Patients who received adjunctive TCM treatment and underwent treatment cumulative time for more than 1 month were classified as the TCM intervention cohort. Patients who did not receive adjunctive TCM treatment or underwent treatment cumulative time for less than 1 month were classified as the non-TCM intervention cohort. The main outcome indicators were the survival rate and overall survival time. The propensity score inverse probability weighting method was used to balance the differences between the groups. Results: The primary cohort comprised 2,067 patients, including 462 patients who received adjunctive TCM treatment and 1,605 patients who did not receive adjunctive TCM treatment. The results of the Kaplan‒Meier survival curve indicated that the survival rate and median survival time of the exposure group before and after propensity score weighting were greater than those of the control group (p < 0.0001). Univariate Cox regression analysis after propensity score weighting showed that adjunctive TCM treatment was an independent protective factor for survival [regression coefficient = -0.215, hazard ratio (HR) = 0.8066, 95% confidence interval (CI) (0.6609-0.9844)]. Conclusion: Adjuvant treatment with TCM has a protective effect on the prognosis of patients with primary liver cancer; it can reduce the mortality and prolong the survival time.

Efficacy of mind-body therapies for sleep disturbance in patients with early-stage cancer: A systematic review and network meta-analysis.

OBJECTIVE: To evaluate and compare the efficacy of different mind-body therapies (MBTs) for sleep disturbance in patients with early-stage cancer. METHODS: Randomised controlled trials that included patients (aged ≥18 years) with early stage cancer who underwent MBTs (mindfulness, hypnosis, relaxation, yoga, and qigong) were searched in the CINAHL via the EBSCO Host, Cochrane Library, Embase, MEDLINE, PsycINFO, PubMed, and Scopus databases, from the date of database inception to October 2022. The outcomes were subjective sleep disturbance and objective sleep efficiency. Network meta-analysis (NMA) and comparative effects ranking were performed using STATA (v14.0; STATACorp, College Station, TX, USA). RESULTS: Forty-seven studies investigating five MBTs were included in the NMA. For cancer patients receiving active treatment, mindfulness demonstrated the largest effect size in reducing subjective sleep disturbance (standardised mean difference [SMD]: 0.85; 95% confidence intervals [CI]: 0.20-1.50; Grading of Recommendations Assessment, Development, and Evaluation assessment: moderate), and had the highest cumulative probability compared to usual care or waitlist. For cancer patients who had completed active treatment, qigong demonstrated the largest effect size in reducing subjective sleep disturbance (SMD: 0.99; 95% CI: 0.35-1.63; GRADE: low), followed by hypnosis (SMD: 0.87; 95% CI: 0.32-1.42; GRADE: moderate), and mindfulness (SMD: 0.42; 95% CI: 0.24-0.59; GRADE: moderate). Qigong also demonstrated the largest effect size in improving objective sleep efficiency (weighted mean differences: 10.76; 95% CI: 2.01-19.50; GRADE: low); however, the effect of qigong was tested in only one study in this NMA. Among the eight different treatment conditions, cognitive behavioral therapy (CBT) showed the highest cumulative probability (surface under the cumulative ranking curve: 96.3%) in reducing subjective sleep disturbance and the second highest cumulative probability (SUCRA: 83.3%) in improving objective sleep efficiency. CONCLUSION: There is no evidence supporting the use of MBTs to replace or be comparable to CBT. Mindfulness can be recommended as an optional treatment for reducing sleep disturbance in patients with early-stage cancer. Some support was observed for qigong and hypnosis in reducing sleep disturbances in patients with early-stage cancer who had completed active treatment. More rigorous trials are warranted to confirm whether different forms of MBTs have different effects on sleep in patients with cancer.

Recognize enhanced temporal-spatial-spectral features with a parallel multi-branch CNN and GRU.

Deep learning has been applied to the recognition of motor imagery electroencephalograms (MI-EEG) in brain-computer interface, and the performance results depend on data representation as well as neural network structure. Especially, MI-EEG is so complex with the characteristics of non-stationarity, specific rhythms, and uneven distribution; however, its multidimensional feature information is difficult to be fused and enhanced simultaneously in the existing recognition methods. In this paper, a novel channel importance (NCI) based on time-frequency analysis is proposed to develop an image sequence generation method (NCI-ISG) for enhancing the integrity of data representation and highlighting the contribution inequalities of different channels as well. Each electrode of MI-EEG is converted to a time-frequency spectrum by utilizing short-time Fourier transform; the corresponding part to 8-30 Hz is combined with random forest algorithm for computing NCI; and it is further divided into three sub-images covered by α (8-13 Hz), ß1 (13-21 Hz), and ß2 (21-30 Hz) bands; their spectral powers are further weighted by NCI and interpolated to 2-dimensional electrode coordinates, producing three main sub-band image sequences. Then, a parallel multi-branch convolutional neural network and gate recurrent unit (PMBCG) is designed to successively extract and identify the spatial-spectral and temporal features from the image sequences. Two public four-class MI-EEG datasets are adopted; the proposed classification method respectively achieves the average accuracies of 98.26% and 80.62% by 10-fold cross-validation experiment; and its statistical performance is also evaluated by multi-indexes, such as Kappa value, confusion matrix, and ROC curve. Extensive experiment results show that NCI-ISG + PMBCG can yield great performance on MI-EEG classification compared to state-of-the-art methods. The proposed NCI-ISG can enhance the feature representation of time-frequency-space domains and match well with PMBCG, which improves the recognition accuracies of MI tasks and demonstrates the preferable reliability and distinguishable ability. This paper proposes a novel channel importance (NCI) based on time-frequency analysis to develop an image sequences generation method (NCI-ISG) for enhancing the integrity of data representation and highlighting the contribution inequalities of different channels as well. Then, a parallel multi-branch convolutional neural network and gate recurrent unit (PMBCG) is designed to successively extract and identify the spatial-spectral and temporal features from the image sequences.

Combined Transcriptome and Metabolome Analysis Reveals Adaptive Defense Responses to DON Induction in Potato.

Phytophthora infestans poses a serious threat to potato production, storage, and processing. Understanding plant immunity triggered by fungal elicitors is important for the effective control of plant diseases. However, the role of the potato stress response to Fusarium toxin deoxynivalenol (DON)-induced stress is still not fully understood. In this study, the metabolites of DON-treated potato tubers were studied for four time intervals using UPLC-MS/MS. We identified 676 metabolites, and differential accumulation metabolite analysis showed that alkaloids, phenolic acids, and flavonoids were the major differential metabolites that directly determined defense response. Transcriptome data showed that differentially expressed genes (DEGs) were significantly enriched in phenylpropane and flavonoid metabolic pathways. Weighted gene co-expression network analysis (WGCNA) identified many hub genes, some of which modulate plant immune responses. This study is important for understanding the metabolic changes, transcriptional regulation, and physiological responses of active and signaling substances during DON induction, and it will help to design defense strategies against Phytophthora infestans in potato.

Juglone Inhibits Tumor Metastasis by Regulating Stemness Characteristics and the Epithelial-to-Mesenchymal Transition in Cancer Cells both in Vitro and in Vivo.

BACKGROUND: The stemness characteristics of cancer cells, such as self-renewal and tumorigenicity, are considered to be responsible, in part, for tumor metastasis. Epithelial-to-mesenchymal transition (EMT) plays an important role in promoting both stemness and tumor metastasis. Although the traditional medicine juglone is thought to play an anticancer role by affecting cell cycle arrest, induction of apoptosis, and immune regulation, a potential function of juglone in regulating cancer cell stemness characteristics remains unknown. METHODS: In the present study, tumor sphere formation assay and limiting dilution cell transplantation assays were performed to assess the function of juglone in regulating maintenance of cancer cell stemness characteristics. EMT of cancer cells was assessed by western blot and transwell assay in vitro, and a liver metastasis model was also performed to demonstrate the effect of juglone on colorectal cancer cells in vivo. RESULTS: Data gathered indicates juglone inhibits stemness characteristics and EMT in cancer cells. Furthermore, we verified that metastasis was suppressed by juglone treatment. We also observed that these effects were, in part, achieved by inhibiting Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1). CONCLUSIONS: These results indicate that juglone inhibits maintenance of stemness characteristics and metastasis in cancer cells.

Astragaloside IV mitigates cerebral ischaemia-reperfusion injury via inhibition of P62/Keap1/Nrf2 pathway-mediated ferroptosis.

Cerebral ischaemia-reperfusion injury (CIRI) is a critical component of ischaemic stroke pathogenesis. Ferroptosis contributes to and aggravates CIRI, whereas the P62/Kelch-like ECH-associated protein 1 (Keap1)/NF-E2-related factor 2 (Nrf2) pathway exerts neuroprotective effects. Astragaloside IV (AST IV) is the primary active ingredient of Astragalus, an herb with anti-CIRI properties used in traditional Chinese medicine. However, the mechanism of its anti-CIRI action is unclear. This study examined the mechanisms underlying the anti-CIRI action of AST IV using a combination of in vitro and in vivo approaches. We established an erastin-induced ferroptosis model, oxygen and glucose deprivation/reoxygenation (OGD/R)-induced model in SH-SY5Y cells, and middle cerebral artery occlusion-reperfusion (MCAO/R) model using Sprague-Dawley rats. The extent of cell damage and brain damage in rats, ferroptosis indicator changes, and expression of P62, Keap1, and Nrf2 were investigated. AST IV inhibited erastin-induced ferroptosis, attenuated OGD/R-induced cell damage, and ameliorated sensorimotor dysfunction and injury in the MCAO/R model. Further, AST IV promoted Nrf2 activation, inhibited ferroptosis, and reduced cell damage. Notably, these effects were inhibited by ML385, an Nrf2 inhibitor. AST IV increased the P62 and Nrf2 levels and decreased the Keap1 levels. P62 silencing reduced the effects of AST IV on the P62/Keap1/Nrf2 pathway and ferroptosis. Our findings suggest that AST IV mitigates CIRI by inhibiting ferroptosis via activation of the P62/Keap1/Nrf2 pathway. This study provides an important scientific basis and direction for the application and research of AST IV and provides new potential targets and ideas for the study of the pathological mechanism of CIRI.

Ascophyllum nodosum polysaccharide regulates gut microbiota metabolites to protect against colonic inflammation in mice.

Ascophyllum nodosum polysaccharide (ANP) can protect against colonic inflammation but the underlying mechanism is still unclear. This study has determined the metabolites of gut microbiota regulated by ANP to reveal the mechanism of the anti-inflammation effect of ANP. Using an in vitro colonic fermentation model, the results indicate that gut microbiota could utilize a proportion of ANP to increase the concentrations of short-chain fatty acids (SCFAs) and decrease ammonia content. Metabolomics revealed that 46 differential metabolites, such as betaine, L-carnitine, and aminoimidazole carboxamide ribonucleotide (AICAR), could be altered by ANP. Metabolic pathway analysis showed that ANP mainly up-regulated the phenylalanine, tyrosine, and tryptophan biosynthesis and aminoacyl-tRNA biosynthesis, which were negatively correlated with inflammation progression. Interestingly, these metabolites associated with inflammation were also up-regulated by ANP in colitis mice, including betaine, L-carnitine, AICAR, N-acetyl-glutamine, tryptophan, and valine, which were mainly associated with amino acid metabolism and aminoacyl-tRNA biosynthesis. Furthermore, the metabolites modulated by ANP were associated with the relative abundances of Akkermansia, Bacteroides, Blautia, Coprobacillus, Enterobacter, and Klebsiella. Additionally, based on VIP values, betaine is a key metabolite after the ANP supplement in vitro and in vivo. As indicated by these findings, ANP can up-regulate the production of SCFAs, betaine, L-carnitine, and AICAR and aminoacyl-tRNA biosynthesis to protect against colonic inflammation and maintain intestinal health.

Applying correlation analysis to electrode optimization in source domain.

In brain computer interface-based neurorehabilitation system, a large number of electrodes may increase the difficulty of signal acquisition and the time consumption of decoding algorithm for motor imagery EEG (MI-EEG). The traditional electrode optimization methods were limited by the low spatial resolution of scalp EEG. EEG source imaging (ESI) was further applied to reduce the number of electrodes, in which either the electrodes covering activated cortical areas were selected, or the reconstructed electrodes of EEGs with higher Fisher scores were retained. However, the activated dipoles do not all contribute equally to decoding, and the Fisher score cannot represent the correlations between electrodes and dipoles. In this paper, based on ESI and correlation analysis, a novel electrode optimization method, denoted ECCEO, was developed. The scalp MI-EEG was mapped to cortical regions by ESI, and the dipoles with larger amplitudes were chosen to designate a region of interest (ROI). Then, Pearson correlation coefficients between each dipole of the ROI and the corresponding electrode were calculated, averaged, and ranked to obtain two average correlation coefficient sequences. A small but important group of electrodes for each class were alternately added to the predetermined basic electrode set to form a candidate electrode set. Their features were extracted and evaluated to determine the optimal electrode set. Experiments were conducted on two public datasets, the average decoding accuracies achieved 95.99% and 88.30%, and the reduction of computational cost were 65% and 56%, respectively; statistical significance was examined as well.

Supplement of Caulerpa lentillifera polysaccharide by pre-prandial gavage and free feeding demonstrates differences to prevent obesity and gut microbiota disturbance in mice.

BACKGROUND: Caulerpa lentillifera has received extensive attention regarding expansion of its farming and increasing consumption. In our previous study, the structure of C. lentillifera polysaccharide (CLP) was elucidated. However, little information is available about its health effects. In this study, the anti-obesity effect of CLP was investigated by using a high-fat diet-induced obese mice model with two different supplementation methods. RESULTS: In vitro simulated digestion results showed that CLP significantly decreased the lipid digestibility and induced the lipid droplets aggregation in the intestinal stage to inhibit the absorption of lipids. As revealed by 16S ribosomal RNA sequencing and non-targeted metabolomics, supplement of CLP by both pre-prandial gavage and free feeding patterns effectively prevented mice obesity via ameliorating intestinal flora disturbance and regulating bile acids circulation metabolism. Of note was that CLP administration had no effect on short-chain fatty acids production, suggesting the anti-obesity effect was uncorrelated with their production. Moreover, pre-prandial administration of CLP had a better anti-obesity effect in lowering body weight and serum lipid levels, but the free feeding resulted in a higher α-diversity of gut microbiota. CONCLUSION: The findings of this study indicate that CLP could be a potential anti-obesity nutraceutical and that pre-prandial supplement of CLP may be a better intake method to exhibit its hypolipidemic effect. © 2022 Society of Chemical Industry.

Effects and central mechanism of electroacupuncture and MRI-navigated rTMS for PSD: study protocol for an fMRI-based single-center, randomized, controlled, open-label trial.

Background: Post-stroke depression (PSD) is the most common mental complication after stroke and has a serious impact on functional outcomes and quality of life for stroke patients. Antidepressants are the first-line treatment for PSD; however, many reported side effects remain. Clinical research and practice guidelines have shown that electro-acupuncture (EA) or rTMS have a positive effect on PSD. However, there are few clinical studies on EA and MRI-navigated rTMS for PSD that explore the fMRI-based central mechanism in depression. Methods: In this randomized, controlled, open-label trial, 64 patients with PSD will be randomly allocated into the experiment group (n = 32) or control group (n = 32). The experiment group will receive EA and MRI-navigated rTMS and the control group will receive MRI-navigated rTMS treatment, in 12-20 sessions over 4 weeks. In addition, 10 healthy people for fMRI scanning will be recruited as a healthy control group without any intervention. The primary outcome will be the change from baseline in the Hamilton Depression Scale-24 item (HAMD-24) scores at week 4. The primary analysis of the central mechanism will mainly involve cortical morphology, local spontaneous brain activity, and the default mode network (DMN) functional connectivity based on fMRI at 0 and 4 weeks. Secondary outcomes will include the neuro-patho-physiological and quality of life changes in cortical excitability, determined using the motor evoked potential test (MEP), National Institutes of Health Stroke Scale (NIHSS), EuroQol Five Dimensions Questionnaire (EQ-5D) Scale, Modified Barthel Index (MBI) Scale, and Health Scale of Traditional Chinese Medicine (HSTCM). Additional indicators will include the Acceptability Questionnaire and Health Economics Evaluation (cost-effectiveness analysis) to assess the acceptability and economic practicality of the treatment under study. Outcomes will be assessed at baseline and post intervention. Discussion: EA and MRI-navigated rTMS therapy could become an alternative treatment for PSD, and it is expected that this trial will provide reliable clinical evidence and a potential central mechanism for the future use of EA and MRI-navigated rTMS for PSD. Clinical trial registration: NCT05516680, ClinicalTrials.gov (registered in August 2022).

Non-Isolated Neural Tube Defects with Comorbid Malformations Are Responsive to Population-Level Folic Acid Supplementation in Northern China.

OBJECTIVE: Comorbid congenital malformation of multiple organs may indicate a shared genetic/teratogenic causality. Folic acid supplementation reduces the population-level prevalence of isolated neural tube defects (NTDs), but whether complex cases involving independent malformations are also responsive is unknown. We aimed to describe the epidemiology of NTDs with comorbid malformations in a Chinese population and assess the impact of folic acid supplementation. STUDY DESIGN: Data from five counties in Northern China were obtained between 2002 and 2021 through a population-based birth defects surveillance system. All live births, stillbirths, and terminations because of NTDs at any gestational age were recorded. NTDs were classified as spina bifida, anencephaly, or encephalocele. Isolated NTDs included spina bifida cases with presumed secondary malformations (hydrocephalus, hip dislocation, talipes). Non-isolated NTDs were those with independent concomitant malformations. RESULTS: A total of 296,306 births and 2031 cases of NTDs were recorded from 2002-2021. A total of 4.8% of NTDs (97/2031) had comorbid defects, which primarily affected the abdominal wall (25/97), musculoskeletal system (24/97), central nervous system (22/97), and face (15/97). The relative risk of cleft lip and/or palate, limb reduction defects, hip dislocation, gastroschisis, omphalocele, hydrocephalus, and urogenital system defects was significantly greater in infants with NTDs than in the general population. Population-level folic acid supplementation significantly reduced the prevalence of both isolated and non-isolated NTDs. CONCLUSION: Epidemiologically, non-isolated NTDs follow similar trends as isolated cases and are responsive to primary prevention by folic acid supplementation. Various clinically-important congenital malformations are over-represented in individuals with NTDs, suggesting a common etiology.

Impact of Lycium barbarum arabinogalactan on the fecal metabolome in a DSS-induced chronic colitis mouse model.

Ulcerative colitis (UC) is often accompanied by the dysbiosis of gut microbiota and metabolism. Our previous study indicated that arabinogalactan from Lycium barbarum (LBP-3) could markedly attenuate the symptoms of chronic UC in mice by modulating the structure of gut microbiota. This study explored the impact of LBP-3 on the fecal metabolomic profiling of the same cohort of mice by HPLC-TripleTOF/MS. Untargeted metabolomic analyses indicated that supplementation with LBP-3 markedly reversed 18 of the 48 differential metabolites (mainly belonging to amino acids and organic acids) disturbed by DSS. Targeted metabolomics revealed that the lower levels of tryptophan, lysine, diiodothyronine, kynurenine, and betaine and higher levels of phenylalanine, leucine, glutamine, isoleucine, homoserine, (S)-2-hydroxyglutarate, 2-isopropylmalic acid, ascorbic acid, gluconic acid, and taurine, which were caused by DSS induction, were reversed by LBP-3 treatment. In addition, pathway analysis showed that the pentose phosphate pathway, phenylalanine metabolism, ascorbate and aldarate metabolism, and phenylalanine, tyrosine and tryptophan biosynthesis were strongly affected by LBP-3. More importantly, the above amino acids, organic acids, and metabolic pathways changed by LBP-3 were correlated with the abundance of gut microbiota such as Turicibacter, Lactobacillus, Parasutterella, Odoribacter, Veillonella, Faecalibacterium, and Ruminococcaceae. This study advances our understanding of the interaction between the microbiome and metabolomics in DSS-induced chronic colitis after LBP-3 treatment.

A Review of Traditional Chinese Medicine, Buyang Huanwu Decoction for the Treatment of Cerebral Small Vessel Disease.

Cerebral small vessel disease (CSVD) is often referred to as "collaterals disease" in traditional Chinese medicine (TCM), and commonly includes ischemic and hemorrhagic CSVD. TCM has a long history of treating CSVD and has demonstrated unique efficacy. Buyang Huanwu Decoction (BHD) is a classical TCM formula that has been used for the prevention and treatment of stroke for hundreds of years. BHD exerts its therapeutic effects on CSVD through a variety of mechanisms. In this review, the clinical and animal studies on BHD and CSVD were systematically introduced. In addition, the pharmacological mechanisms, active components, and clinical applications of BHD in the treatment of CSVD were reviewed. We believe that an in-depth understanding of BHD, its pharmacological mechanism, disease-drug interaction, and other aspects will help in laying the foundation for its development as a new therapeutic strategy for the treatment of CSVD.

Fucoxanthin, a Marine Carotenoid, Suppresses Mycoplasma pneumoniae-Triggered Inflammatory Cytokine Production and Promotes Bacterial Clearance in a Murine Model.

Mycoplasma pneumoniae (MP), an atypical bacterium, is a common pathogenetic organism of respiratory infection in children. In the present study, we analyzed the beneficial role of fucoxanthin (Fx), a marine carotenoid, in a murine model of MP. C57BL/6 mice were inoculated once intranasally with 107 CFU of M. pneumoniae, and we found that Fx treatment markedly decreased BAL (quantitative bronchoalveolar lavage) M. pneumoniae concentrations and alleviated airway obstruction in the infected mice. Moreover, the concentrations of proinflammatory cytokines, including IL-6, TNF-α and IL-1ß, were significantly decreased by Fx treatment in the BAL samples of infected mice. In vitro study further indicated that Fx treatment markedly suppressed the production of proinflammatory cytokines in mouse peritoneal macrophages after M. pneumoniae infection. In conclusion, this may be the first study to report the protective role of Fx against M. pneumoniae infection, providing a potential therapeutic agent for MP.

Recent Advances in Application of Computer-Aided Drug Design in Anti-Influenza A Virus Drug Discovery.

Influenza A is an acute respiratory infectious disease caused by the influenza A virus, which seriously threatens global human health and causes substantial economic losses every year. With the emergence of new viral strains, anti-influenza drugs remain the most effective treatment for influenza A. Research on traditional, innovative small-molecule drugs faces many challenges, while computer-aided drug design (CADD) offers opportunities for the rapid and effective development of innovative drugs. This literature review describes the general process of CADD, the viral proteins that play an essential role in the life cycle of the influenza A virus and can be used as therapeutic targets for anti-influenza drugs, and examples of drug screening of viral target proteins by applying the CADD approach. Finally, the main limitations of current CADD strategies in anti-influenza drug discovery and the field's future directions are discussed.