Marine natural products: potential agents for depression treatment.

Depression is a common psychiatric disorder. Due to the disadvantages of current clinical drugs, including poor efficacy and unnecessary side effects, research has shifted to novel natural products with minimal or no adverse effects as therapeutic alternatives. The ocean is a vast ecological home, with a wide variety of organisms that can produce a large number of natural products with unique structures, some of which have neuroprotective effects and are a valuable source for the development of new drugs for depression. In this review, we analyzed preclinical and clinical studies of natural products derived from marine organisms with antidepressant potential, including the effects on the pathophysiology of depression, and the underlying mechanisms of these effects. It is expected to provide a reference for the development of new antidepressant drugs.

Online preconcentration and determination of five alkaloids in Yangxinshi tablet by large-volume sample stacking and micelle to solvent stacking in cyclodextrin-modified electrokinetic chromatography.

The two-step preconcentration technique consisting of large-volume sample stacking (LVSS) and micelle to solvent stacking (MSS) in cyclodextrin-modified electrokinetic chromatography (CDEKC) was developed for the analysis of five cationic alkaloids in complex Chinese herbal prescriptions. Relevant parameters affecting separation and stacking performance were optimized separately. Under the optimal LVSS-MSS-CDEKC conditions, less analysis time and organic solvent were required, and the enhancement factors of analytes ranged from 12 to 15 compared with the normal CDEKC separation mode. Further, all validation results demonstrated good applicability and multiple alkaloids (epiberberine, dehydrocorydaline, jatrorrhizine, coptisine and berberine) in Yangxinshi tablet (YXST) have been simultaneously determined. This approach presents powerful potential for the determination of multiple components in complex preparations of Chinese medicine.

Effect of Graphene on the Performance of Silicon-Carbon Composite Anode Materials for Lithium-Ion Batteries.

(Si/graphite)@C and (Si/graphite/graphene)@C were synthesized by coating asphalt-cracked carbon on the surface of a Si-based precursor by spray drying, followed by heat treatment at 1000 °C under vacuum for 2h. The impact of graphene on the performance of silicon-carbon composite-based anode materials for lithium-ion batteries (LIBs) was investigated. Transmission electron microscopy (TEM) and selected area electron diffraction (SAED) images of (Si/graphite/graphene)@C showed that the nano-Si and graphene particles were dispersed on the surface of graphite, and thermogravimetric analysis (TGA) curves indicated that the content of silicon in the (Si/graphite/graphene)@C was 18.91%. More bituminous cracking carbon formed on the surface of the (Si/graphite/graphene)@C due to the large specific surface area of graphene. (Si/Graphite/Graphene)@C delivered first discharge and charge capacities of 860.4 and 782.1 mAh/g, respectively, initial coulombic efficiency (ICE) of 90.9%, and capacity retention of 74.5% after 200 cycles. The addition of graphene effectively improved the cycling performance of the Si-based anode materials, which can be attributed to the reduction of electrochemical polarization due to the good structural stability and high conductivity of graphene.

Combination of large-volume sample stacking with polarity switching and micelle electrokinetic chromatography for the analysis of anion compounds in Yangxinshi tablets.

INTRODUCTION: Yangxinshi tablet (YXST) is a traditional Chinese medicine preparation characterized by its high efficacy and safety for the treatment of cardiovascular diseases. Anionic compounds have been revealed as potential active components. However, there is currently limited research regarding its quality control. OBJECTIVE: We aimed to establish a strategy for the simultaneous separation and determination of five key anionic compounds in YXST. METHOD: A sensitive and efficient analytical method was developed and applied for the simultaneous separation and determination of five key compounds in YXST using large-volume sample stacking with polarity switching and micelle electrokinetic chromatography (LVSS-PS-MEKC) coupled with diode array detection. Crucial parameters, including sample volume, applied voltage, composition and pH of the running buffer, concentration of organic modifier, and switching time of the polarity, were systematically evaluated and optimized using a single variable method to enhance separation performance. Furthermore, the impact of cyclodextrin and sodium dodecyl sulfate as electrolyte modifiers was also investigated. RESULTS: Under the optimal conditions, baseline separation of the five compounds (daidzein, puerarin, glycyrrhiztinic acid, chlorogenic acid, and salvianolic acid B) was achieved within 20 min. In comparison to the conventional MEKC mode, the constructed LVSS-PS-MEKC method exhibited a more than sixfold increase in the enrichment factor. The method was validated in terms of linearity, precision, accuracy, 24 h stability, and recovery and successfully applied to analyze YXST samples. CONCLUSION: A sensitive strategy was developed for the simultaneous separation and determination of five key anionic components in YXST, offering a robust and efficient strategy for pharmaceutical analysis.

Segmented Template-Directed Self-Assembly of Giant Truncated Triangular Supramolecules.

The template-directed strategy has been extensively employed for the construction of supramolecular architectures. However, with the increase in the size and complexity of these structures, the synthesis difficulty of the templates escalates exponentially, thereby impeding the widespread application of this strategy. In this study, two truncated triangles T1 and T2 were successfully self-assembled through a novel segmented template strategy by segmenting the core triangular template into portions. Two metallo-organic ligands L2 and L3 were designed and synthesized by dividing the central stable triangle into three separate parts and incorporating them into the precursor ligands, which served as templates to guide the self-assembly process with ligands L1 and L4, respectively. The assembled structures were unambiguously characterized by multidimensional and multinuclear NMR (1H, COSY, NOESY), multidimensional mass spectrometry analysis (ESI-MS and TWIM-MS), and transmission electron microscopy (TEM). Moreover, we observed the formation of fiberlike nanotubes from single-molecule triangles by hierarchical self-assembly.

Novel biogenic preparation of gold nanoparticles decorated on sepiolite clay and evaluation of anti-cancer effect on gastric cancer cell and electrochemical sensing of nitrite.

An environmentally friendly strategy was used in this study to synthesize gold nanoparticles decorated on sepiolite clay (GNPs-SC) using Heracleum persicum grass extract. The physicochemical characters of the prepared composite were characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), and X-ray diffraction (XRD). A GNPs-SC modified carbon pate electrode (CPE) was used to study the electrochemical oxidation of nitrite. The proposed nitrite sensor exhibits excellent performance, including a broad linear range (1.0-150 µM), a low limit of detection (0.4 µM), and acceptable reproducibility (RSD = 2.6%). As well, the prepared GNPs-SC was tested for its effectiveness against human gastric adenocarcinoma (AGS) cell line. The MTT assay protocol revealed that the bio-synthesized product displayed significant cytotoxic activity against gastric cancer in human subjects. The findings of this study indicate that GNPs-SC, synthesized using environmentally friendly protocol, exhibit great potential for use in electrochemical sensing and treatment of human cancer.

Dissecting the Imbalance of Synovial Macrophages in Rheumatoid Arthritis.

Objective: This study sought to identify candidate genes of rheumatoid arthritis (RA) synovial macrophages using bioinformatics and to explore their pathways in the pathogenesis of RA. Methods: The microarray datasets GSE10500 and GSE97779 were obtained from the Gene Express Omnibus and analyzed with synovial macrophages of 14 RA patients and 8 healthy donors. The researchers used R software to identify differentially expressed genes and determine functional enrichment pathways. A protein-protein interaction network was then constructed using STRING and Cytoscape. Gene expression was validated with the GSE71370 dataset and RT-qPCR analysis. Results: 102 DEGs were identified in RA synovial macrophages relative to normal samples. Of these, 72 were upregulated; 30 were downregulated. GO and KEGG pathway analyses suggested that DEGs mainly regulated the immune response and signaling pathways associated with inflammatory activation, apoptosis, and cancer. The top five hub genes and top 1 gene module from the PPI network of DEGs were VEGFA, MMP9, FN1, IGF1, CXCL9, ISG20, RSAD2, IFI27, GBP2, and GBP1. The GSE71370 dataset and RT-qPCR analysis showed that CXCL9 and GBP1 were significantly upregulated (P ≤ .05). Conclusions: CXCL9 and GBP1 may contribute to RA pathogenesis and serve as potential biomarkers and therapeutic targets for RA.

Au/TiO2-based molecularly imprinted photoelectrochemical sensor for dibutyl phthalate detection.

A photoelectrochemical molecular imprinting sensor based on Au/TiO2 nanocomposite was constructed for the detection of dibutyl phthalate. Firstly, TiO2 nanorods were grown on fluorine-doped tin oxide substrate by hydrothermal method. Then, gold nanoparticles were electrodeposited on TiO2 to fabricate Au/TiO2. Finally, molecular imprinted polymer was electropolymerized on the Au/TiO2 surface to construct MIP/Au/TiO2 PEC sensor for DBP. The conjugation effect of MIP accelerates the electron transfer between TiO2 and MIP, which can greatly improve the photoelectric conversion efficiency and sensitivity of the sensor. In addition, MIP can also provide sites for highly selective recognition of dibutyl phthalate molecules. Under optimal experimental conditions, the prepared photoelectrochemical sensor was used for the quantitative determination of DBP and the results showed a wide linear range (50 to 500 nM), a low limit of detection (0.698 nM), and good selectivity. The sensor was used in a study of real water samples to show that it has promising applications in environmental analysis.

A Chromosome-level Genome Assembly and Evolution Analysis of Andrena camellia (Hymenoptera: Andrenidae).

Andrena camellia, an effective pollinator of the economicallysignificant crop Camellia oleifera, can withstand the toxic pollen of C. oleifera, making A. camellia a crucial for resource conservation and cultivation of C. oleifera. In this study, the whole genome of A. camellia was sequenced on the Oxford Nanopore platform. The assembled genome size was 340.73 Mb including 50 scaffolds (N50=47.435 Mb) and 131 contigs (N50=17.2 Mb). A total of 11, 258 protein-coding genes were annotated, in addition, 1,104 non-coding RNAs were identified. Further analysis that some chromosomes of A. camellia have a high level of synteny with those of Apis mellifera, Osmia bicornis and Andrena minutula. Thus, our reported genome of A. camellia serves as a valuable resource for studying species evolution, behavioral biology, and adaption to toxic pollen of C. oleifera.

In-capillary screening and quantifying the antioxidants of Yangxinshi Tablet using field-enhanced sample injection-micellar electrokinetic chromatography.

An in-capillary 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) as oxyradicals combining field-enhanced sample injection with micellar electrokinetic chromatography was developed for screening and determination of the major antioxidants in Yangxinshi Tablet. To obtain simultaneous separation and detection of radicals and analytes, relevant factors were optimized separately. Under the optimum conditions, four compounds including salvianolic acid B, hyperoside, puerarin, and caffeic acid were identified as the major antioxidants. All validation results covering recovery, precision, and stability demonstrated good applicability of the method. On this basis, the total antioxidant activity was successfully evaluated in terms of the decreased peak area of radicals. There was a correlation coefficient of 0.8974 between the total contents of major antioxidants and the total antioxidative activity of the sample. Therefore, these four compounds were selected as combinatorial markers for the quality evaluation of Yangxinshi Tablet. It was concluded that the established method presented a powerful potential to screen and quantify active ingredients in the complex preparation of Chinese medicine.

Inhibition of NEMO alleviates arthritis by blocking the M1 macrophage polarization.

The nuclear factor-kappa B (NF-κB) signaling pathway and macrophages are critically involved in the pathogenesis of rheumatoid arthritis (RA). Recent studies have identified NF-κB essential modulator (NEMO), a regulatory subunit of the inhibitor of NF-κB kinase (IKK), as a potential target to inhibit NF-κB signaling pathway. Here, we investigated the interactions between NEMO and M1 macrophage polarization in RA. NEMO inhibition led to the suppression of proinflammatory cytokines secreted from M1 macrophages in collagen-induced arthritis mice. From lipopolysaccharide (LPS)-stimulated RAW264, knocking down NEMO blocked M1 macrophage polarization accompanied by lesser M1 proinflammatory subtype. Our findings link the novel regulatory component of NF-κB signaling and human arthritis pathologies which will pave the way towards the identification of new therapeutic targets and the development of innovative preventive strategies.

Burnout and associative emotional status and coping style of healthcare workers in COVID-19 epidemic control: A cross-sectional study.

Objective: The aim of this study was to evaluate the prevalence of burnout, clinical anxiety, depression, and insomnia and to estimate the associations of adverse emotional status, coping style, and level of self-efficacy with burnout of healthcare workers in the Shenzhen Longgang District Frontline District Headquarters of COVID-19 epidemic control, China. Methods: In this cross-sectional study, 173 staff completed the anonymous questionnaires of the Maslach Burnout Inventory, Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7-item Scale (GAD-7), Insomnia Severity Index (ISI), General Self-efficacy Scale, and Simplified Coping Style Questionnaire electronically (https://www.wjx.cn/) in June 2022. Hierarchical logistic regression was used to explore the associated factors of burnout in this study. Results: The prevalence of burnout in our participants (defined as high emotional exhaustion or high depersonalization) was 47.40%, and reduced personal accomplishment was 92.49%. The prevalence of clinically significant depression (the cutoff score of ≥15), anxiety (the cutoff score of ≥10), and insomnia (the cutoff score of ≥15) was 11.56, 19.08, and 19.08%, respectively. There was a degree of overlap between burnout and other measures of adverse mental status, most notably for anxiety (odds ratio, 27.049; 95% CI, 6.125-117.732; p < 0.001). Hierarchical logistic regression demonstrated that burnout was strongly associated with anxiety (OR = 23.889; 95% CI, 5.216-109.414; p < 0.001) and negative coping style (OR = 1.869; 95% CI, 1.278-2.921; p < 0.01) independently. Conclusion: Medical staff involved in COVID-19 epidemic control in the post-epidemic era were at high risk of burnout, and most of them were in low personal accomplishment. Reducing anxiety and improving coping style by medical management institutions from the system level may be effective in alleviating burnout in healthcare workers.

GATA-binding protein 4 promotes neuroinflammation and cognitive impairment in Aß1-42 fibril-infused rats through small nucleolar RNA host gene 1/miR-361-3p axis.

Aging with dysregulated metabolic and immune homeostasis stimulates pyroptosis, neuroinflammation, and cellular senescence, thus contributing to etiopathogenesis of Alzheimer's disease. GATA-binding protein 4 (GATA4) functions as a transcriptional factor in response to DNA damage, and is associated with neuroinflammation and cellular senescence. The role of GATA4 in Alzheimer's disease was investigated. GATA4 was elevated in hippocampus of Aß1-42 fibril-infused rats. Injection with shRNA targeting GATA4 reduced escape latency with increase of time in target quadrant and number of platform crossings in Aß1-42 fibril-infused rats. Moreover, knockdown of GATA4 ameliorated morphological changes of hippocampus and reduced amyloid plaque deposition in Aß1-42 fibril-infused rats. Silence of GATA4 repressed neuroinflammation and apoptosis in Aß1-42 fibril-infused rats. Loss of GATA4 in Aß1-42 fibril-infused rats reduced the expression of specificity protein 1 (Sp1) to downregulate long noncoding RNA small nucleolar RNA host gene 1 (SNHG1) and upregulated miR-361-3p. Loss of SNHG1 ameliorated learning and memory impairments in Aß1-42 fibril-infused rats. Overexpression of Sp1 attenuated GATA4 silence-induced decrease of escape latency, increase of time in target quadrant, and number of platform crossings in Aß1-42 fibril-infused rats. In conclusion, silence of GATA4 ameliorated cognitive dysfunction and inhibited hippocampal inflammation and cell apoptosis through regulation of Sp1/SNHG1/miR-361-3p.

In-silico evaluation of an artificial pancreas achieving automatic glycemic control in patients with type 1 diabetes.

Artificial pancreas (AP) is a useful tool for maintaining the blood glucose (BG) of patients with type 1 diabetes (T1D) within the euglycemic range. An intelligent controller has been developed based on general predictive control (GPC) for AP. This controller exhibits good performance with the UVA/Padova T1D mellitus simulator approved by the US Food and Drug Administration. In this work, the GPC controller was further evaluated under strict conditions, including a pump with noise and error, a CGM sensor with noise and error, a high carbohydrate intake, and a large population of 100 in-silico subjects. Test results showed that the subjects are in high risk for hypoglycemia. Thus, an insulin on board (IOB) calculator, as well as an adaptive control weighting parameter (AW) strategy, was introduced. The percentage of time spent in euglycemic range of the in-silico subjects was 86.0% ± 5.8%, and the patient group had a low risk of hypoglycemia with the GPC+IOB+AW controller. Moreover, the proposed AW strategy is more effective in hypoglycemia prevention and does not require any personalized data compared with the IOB calculator. Thus, the proposed controller realized an automatic control of the BG of patients with T1D without meal announcements and complex user interaction.

Discovery of a potent allosteric activator of DGKQ that ameliorates obesity-induced insulin resistance via the sn-1,2-DAG-PKCε signaling axis.

sn-1,2-diacylglycerol (sn-1,2-DAG)-mediated activation of protein kinase Cε (PKCε) is a key pathway that is responsible for obesity-related lipid metabolism disorders, which induces hepatic insulin resistance and type 2 diabetes. No small molecules have been previously reported to ameliorate these diseases through this pathway. Here, we screened and identified the phytochemical atractylenolide II (AT II) that reduces the hepatic sn-1,2-DAG levels, deactivates PKCε activity, and improves obesity-induced hyperlipidemia, hepatosteatosis, and insulin resistance. Furthermore, using the ABPP strategy, the diacylglycerol kinase family member DGKQ was identified as a direct target of AT II. AT II may act on a novel drug-binding pocket in the CRD and PH domains of DGKQ to thereby allosterically regulate its kinase activity. Moreover, AT II also increases weight loss by activating DGKQ-AMPK-PGC1α-UCP-1 signaling in adipose tissue. These findings suggest that AT II is a promising lead compound to improve obesity-induced insulin resistance.

Nootkatone Improves Chronic Unpredictable Mild Stress-Induced Depressive-Like Behaviors by Repressing NF-κB/NLRP3-Mediated Neuroinflammation.

OBJECTIVE: To explore the effect of nootkatone (NKT) on chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors and the mechanism underlying NKT improving the depressive-like behaviors. METHODS: The CUMS-induced depression model was established in mice. Fifty mice were randomized into 5 groups (n=10) in accordance with a random number table: control group, CUMS group, CUMS + NKT (6 mg/kg) group, CUMS + NKT (12 mg/kg) group, and CUMS + ketamine group. From the 22th day, NKT (6 or 12 mg/kg) or ketamine (0.5 mg/kg) was given with intragastric administration every day for 21 days. Behavioral tests including forced swimming test (FST), tail suspension test (TST), sucrose preference test (SPT) and open-field test (OFT) were carried out. The mRNA and protein expressions of interleukin (IL)-1ß, IL-18, IL-6, and tumor necrosis factor (TNF)-α in hippocampus were assessed using quantitative realtime polymerase chain reaction (PCR), Western blot analysis, and enzyme linked immunosorbent assay. The nuclear factor-κB (NF-κB)/NOD-like receptor 3 (NLRP3) inflammasome pathway was analyzed using Western blot and immunofluorescence analysis. RESULTS: NKT treatment improved CUMS-induced depressive-like behaviors in mice (P<0.05 or P<0.01). NKT significantly decreased the mRNA and protein levels of IL-1ß, IL-18, IL-6, and TNF-α in hippocampus of CUMS mice (P<0.05 or P<0.01). Furthermore, NKT repressed CUMS-induced activation of NF-κB signaling and NLRP3 inflammasome (P<0.01). More important, Nigericin, a NLRP3 activator, destroyed the effect of NKT on repressing neuroinflammation and improving depressive-like behaviors (P<0.05 or P<0.01). CONCLUSION: NKT ameliorates the depressive-like symptoms, in part by repressing NF-κB/NLRP3-mediated neuroinflammation.

Pregnancy in patients with systemic lupus erythematosus: a systematic review.

Systemic lupus erythematosus (SLE)-a most common disorder in women of reproductive age-has been described to be associated with adverse pregnancy outcomes. Despite the increased health risks for the mother (preeclampsia, lupus flare, arterial hypertension, gestational diabetes mellitus and thrombotic risk when antiphospholipid antibodies are present) and fetus (miscarriage, stillbirth, premature birth, intrauterine growth restriction and neonatal lupus), the majority of patients can deliver healthy neonates. With appropriate management by a multidisciplinary team, composing rheumatologists, obstetricians and neonatologists, women with SLE can achieve better pregnancy outcomes by monitoring associated predictive indicators, raising major concern for severe complications and somewhat early delivery if necessary. In this review, we summarize the latest advances in secondary infertility and pregnancy-related risk perception for lupus patients, with an emphasis on the safety of biological agents (mainly belimumab and rituximab) and traditional therapeutic regimens.

Enhanced Degradation of Levofloxacin through Visible-Light-Driven Peroxymonosulfate Activation over CuInS2/g-C3N4 Heterojunctions.

In this work, the heterojunctions of CuInS2 embedded in the g-C3N4 materials (xCuInS2/g-C3N4, abbreviated as xCIS/GCN) was successfully prepared for peroxymonosulfate (PMS) activation under visible light. The catalysts are characterized by different techniques, such as XRD, FTIR, SEM, TEM, and UV-vis. The unique heterojunction composites can suppress the recombination of photogenerated pairs. The catalytic results showed that the 3CIS/GCN exhibited excellent catalytic levofloxacin (LVF) degradation efficiency, while more than 98.9% of LVF was removed in 60 min over a wide pH range. SO4•-, O2•-, OH•, and 1O2 were verified as the main reactive species for LVF degradation via the quenching experiments and electron paramagnetic resonance technology (EPR). The synergetic effect of xCIS/GCN, PMS, and visible light irradiation was discussed. The possible LVF degradation pathway was proposed through byproducts analysis (LC-MS). Moreover, the 3CIS/GCN/vis-PMS system has very low metal leaching. Owing to xCIS/GCN having good properties for PMS activation, it has potential applications for LVF or other hazardous pollutants degradation.

Berberine increases stromal production of Wnt molecules and activates Lgr5+ stem cells to promote epithelial restitution in experimental colitis.

BACKGROUND: Inflammatory bowel diseases (IBDs) are characterized by sustained inflammation and/or ulcers along the lower digestive tract, and have complications such as colorectal cancer and inflammation in other organs. The current treatments for IBDs, which affect 0.3% of the global population, mainly target immune cells and inflammatory cytokines with a success rate of less than 40%. RESULTS: Here we show that berberine, a natural plant product, is more effective than the frontline drug sulfasalazine in treating DSS (dextran sulfate sodium)-induced colitis in mice, and that berberine not only suppresses macrophage and granulocyte activation but also promotes epithelial restitution by activating Lgr5+ intestinal stem cells (ISCs). Mechanistically, berberine increases the expression of Wnt genes in resident mesenchymal stromal cells, an ISC niche, and inhibiting Wnt secretion diminishes the therapeutic effects of berberine. We further show that berberine controls the expression of many circadian rhythm genes in stromal cells, which in turn regulate the expression of Wnt molecules. CONCLUSIONS: Our findings suggest that berberine acts on the resident stromal cells and ISCs to promote epithelial repair in experimental colitis and that Wnt-ß-Catenin signaling may be a potential target for colitis treatment.