Depression is considered a neuropsychiatric condition which is associated with neuronal injury within specific brain regions. We previously reported that cyclo-oxygenase (COX)-2, a rate-limiting enzyme for prostaglandin E2 (PGE2) synthesis, significantly enhanced depressive-like disorders induced by chronic stress in rats. However, the underlying molecular mechanisms and identification of potential therapeutic targets for preventing neuronal injury associated with depression remain largely uncharacterized. Here, we show that COX-2 inhibition by celecoxib protects against neuronal injury through suppression of oxidative stress and, in this way, mediates its antidepressant effects. COX-2 is highly expressed in the hippocampal dentate gyrus (DG) of rat depression model and its activity is responsible for depression-like behaviors as demonstrated in two independent rat models of depression. Inhibition of COX-2 exerts neuroprotective actions in DG regions, including suppressing neuroinflammatory response, against oxidative stress and neuronal apoptosis, which are the critical risk factors for neuronal injury and pathophysiology of depression. Moreover, the antioxidant, N-acetylcysteine (NAC), significantly attenuates oxidative stress levels and dendritic spine deficiencies resulting from COX-2 overexpression; and, suppression of oxidative stress by NAC also significantly ameliorates depressive behaviors in rats. These findings suggest that selective inhibition of COX-2 ameliorates depression-like behaviors in rat models of depression. This selective inhibition of COX-2 appears to be protective against oxidative stress and neuronal deterioration resulting from chronic stress. Taken together, these findings have potentially important clinical implications with regard to the development of novel therapeutic approaches in the treatment of neuropsychiatric conditions like depression.

Objective: The manuscript aims to explore the relationship between power performance and SNPs of Chinese elite athletes and to create polygenic models. Methods: One hundred three Chinese elite athletes were divided into the power group (n = 60) and endurance group (n = 43) by their sports event. Best standing long jump (SLJ) and standing vertical jump (SVJ) were collected. Twenty SNPs were genotyped by SNaPshot. Genotype distribution and allele frequency were compared between groups. Additional genotype data of 125 Chinese elite athletes were used to verify the screened SNPs. Predictive and identifying models were established by multivariate logistic regression analysis. Results: ACTN3 (rs1815739), ADRB3 (rs4994), CNTFR (rs2070802), and PPARGC1A (rs8192678) were significantly different in genotype distribution or allele frequency between groups (p < 0.05). The predictive model consisted of ACTN3 (rs1815739), ADRB3 (rs4994), and PPARGC1A (rs8192678), the area under curve (AUC) of which was 0.736. The identifying model consisted of body mass index (BMI), standing vertical jump (SVJ), ACTN3, ADRB3, and PPARGC1A, the area under curve (AUC) of which was 0.854. Based on the two models, nomograms were created to visualize the results. Conclusion: Two models can be used for talent identification in Chinese athletes, among which the predictive model can be used in adolescent athletes to predict development potential of power performance and the identifying one can be used in elite athletes to evaluate power athletic status. These can be applied quickly and visually by using nomograms. When the score is more than the 130 or 148 cutoff, it suggests that the athlete has a good development potential or a high level for power performance.

Cancer patients generally has a high risk of thrombotic diseases. However, anticoagulant therapy always aggravates bleeding risks. Rivaroxaban is one of the most widely used direct oral anticoagulants, which is used as anticoagulant treatment or prophylaxis in clinical practice. The present study aimed to systemically estimate the combination safety of rivaroxaban with tyrosine kinase inhibitors (TKIs) based on human cytochrome P450 (CYPs) and efflux transporters and to explore the drug-drug interaction (DDI) mechanisms in vivo and in vitro. In vivo pharmacokinetic experiments and in vitro enzyme incubation assays and bidirectional transport studies were conducted. Imatinib significantly increased the rivaroxaban Cmax value by 90.43% (p < 0.05) and the area under the curve value by 119.96% (p < 0.01) by inhibiting CYP2J2- and CYP3A4-mediated metabolism and breast cancer resistance protein (BCRP)- and P-glycoprotein (P-gp)-mediated efflux transportation in the absorption phase. In contrast, the combination of sunitinib with rivaroxaban reduced the exposure in vivo by 62.32% (p < 0.05) and the Cmax value by 72.56% (p < 0.05). In addition, gefitinib potently inhibited CYP2J2- and CYP3A4-mediated rivaroxaban metabolism with Ki values of 2.99 μΜ and 4.91 μΜ, respectively; however, it almost did not affect the pharmacokinetics of rivaroxaban in vivo. Taken together, clinically significant DDIs were observed in the combinations of rivaroxaban with imatinib and sunitinib. Imatinib increased the bleeding risks of rivaroxaban, while sunitinib had a risk of reducing therapy efficiency. Therefore, more attention should be paid to aviod harmful DDIs in the combinations of rivaroxaban with TKIs.

Due to the natural advantages of spermidine in immunity, we investigated the effects of spermidine pretreatment on nanobody-based CAR-T cells (Nb CAR-T) mediated cytotoxicity and potential mechanism.

A water-soluble and colorimetric fluorescent probe with a large Stokes shift (139 nm) for rapidly detecting Hg2+, namely Hcy-mP, was synthesized by using an indole derivative and 2,4-dihydroxybenzaldehyde as starting materials. This probe demonstrates good selectivity for Hg2+ over other metal ions including Ag+, Pb2+, Cd2+, Cr3+, Zn2+, Fe3+, Co2+, Ni2+, Cu2+, K+, Na+, Mg2+, and Ca2+ in aqueous solution. With the increase in concentration of Hg2+, the color of the solution changed from pale yellow to pink and the fluorescence intensity decreased slightly. When 5-equivalents of EDTA were added to the solution with Hg2+, the fluorescence intensity of this probe was restored. The probe has been applied to the detection of Hg2+ in real water samples. Moreover, this probe was confirmed to have low cytotoxicity and excellent cell membrane permeability. The effect of Hcy-mP-Hg2+ towards living cells by confocal fluorescence was also investigated.

Altered cerebral blood flow (CBF) and amplitude of low-frequency fluctuation (ALFF) have been reported in hemodialysis patients. However, neurovascular coupling impairments, which provide a novel insight into the human brain, have not been reported in hemodialysis patients.

Depression is an inflammatory-related condition, with the progression in neuronal damage resulting in major depression disorder. Ginsenoside-Rg1, a sterol extract from the herb Panax ginseng, has been shown to exert neuroprotective effects upon neurodegeneration disorders. However, whether ginsenoside-Rg1 confers antidepressant-like effects on neuroinflammation as associated with depression, as well as the possible mechanism involved in these neuroprotective effects, is currently unclear. In the present report, we show that treatment with ginsenoside-Rg1 (40 mg/kg, i.p.) significantly ameliorated depressive-like behaviors as induced by chronic unpredictable mild stress (CUMS) in a rat model of depression. Moreover, these CUMS rats treated with ginsenoside-Rg1 showed reductions in the levels of the oxidative stress products and the activity in the antioxidant stress kinase. Furthermore, CUMS rats treated with ginsenoside-Rg1 showed ameliorated neuroinflammation and associated neuronal apoptosis along with a reduction in dendritic spine atrophy and display of depressive behaviors. Taken together, the results of this study suggest that ginsenoside-Rg1 produces antidepressant-like effects in CUMS-exposed rats; and one of the mechanisms for these antidepressant-like effects of ginsenoside-Rg1 appears to involve protection against oxidative stress and thus the neuronal deterioration resulting from inflammatory responses. These findings provide evidence for the therapeutic potential of ginsenoside-Rg1 in the treatment of stress-related depression.

The overexpression of tomato GDP- l -galactose phosphorylase gene enhanced tolerance to chilling stress and reduced photoinhibition of photosystems I and II in transgenic tobacco. Chilling stress is a crucial factor that limits the geographical distribution and yield of chilling-sensitive plants. Ascorbate (AsA) protects plants by scavenging reactive oxygen species and reduces photoinhibition by promoting the conversion of violaxanthin to zeaxanthin in the xanthophyll cycle to dissipate excess excitation energy. Possible mechanisms of AsA for plant photoprotection under chilling stress were investigated by isolating the tomato GDP-L-galactose phosphorylase gene (SlGGP) and producing transgenic tobacco plants with overexpression of SlGGP. The transgenic plants subjected to chilling stress accumulated less H(2)O(2), demonstrated lower levels of ion leakage and malondialdehyde, and acquired higher net photosynthetic rate, higher maximum photochemical efficiency of PSII, and higher D1 protein content compared with the wild-type (WT) plants. The transgenic plants subjected to chilling stress also showed higher GDP-L-galactose phosphorylase activity, increased AsA content as well as ascorbate peroxidase and oxidizable P700 activities than WT plants. Thus, SlGGP overexpression is crucial in promoting AsA synthesis and alleviating photoinhibition of two photosystems.

Asymmetric dimethylarginine (ADMA) is considered an independent mortality and cardiovascular risk factor in chronic kidney disease (CKD) patients, and contributes to the development of renal fibrosis. Quercetin (QC), a natural component of foods, protects against renal injury. Here, we explored the possible mechanisms that are responsible for ADMA-induced renal fibrosis and the protective effect of QC. We found that ADMA treatment activated the endoplasmic reticulum (ER) stress sensor proteins phosphorylated protein kinase RNA-activated-like ER kinase (PERK) and inositol requiring-1α (IRE1), which correspondingly induced C/EBP homologous protein (CHOP) expression and phosphorylated c-Jun N-terminal kinase (JNK) phosphorylation in glomerular endothelial cells (GEnCs). Following this, ADMA promoted ER stress-induced apoptosis and resulted in transforming growth factor β (TGF-β) expression in GEnCs. SP600125, an inhibitor of JNK, and CHOP siRNA protected against ADMA-induced cell apoptosis and TGF-β expression. QC prevented ADMA-induced PERK and IRE1 apoptotic ER stress pathway activation. Also, ADMA-induced GEnCs apoptosis and TGF-β expression was reduced by QC. Overexpression of CHOP blocked QC-mediated protection from apoptosis in ER stressed cells. Overall, these observations indicate that ADMA may induce GEnCs apoptosis and TGF-β expression by targeting the PERK-CHOP and IRE1-JNK pathway. In addition, drugs such as QC targeting ER stress may hold great promise for the development of novel therapies against ADMA-induced renal fibrosis.

Lung cancer has become one of the leading causes of cancer mortality worldwide, and non-small-cell lung cancer (NSCLC) accounts for ~85% of all lung cancer cases. Currently, platinum-based chemotherapy drugs, including cisplatin and carboplatin, are the most effective treatment for NSCLC. However, the clinical efficacy of chemotherapy is markedly reduced later in the treatment because drug resistance develops during the treatment. Recently, a series of studies has suggested the involvement of FAT10 in the development and malignancy of multiple cancer types. In this study, we focused our research on the function of FAT10 in NSCLC, which has not been previously reported in the literature. We found that the expression levels of FAT10 were elevated in quick chemoresistance NSCLC tissues, and we demonstrated that FAT10 promotes NSCLC cell proliferation, migration, and invasion. Furthermore, the protein levels of FAT10 were elevated in cisplatin- and carboplatin-resistant NSCLC cells, and knockdown of FAT10 reduced the drug resistance of NSCLC cells. In addition, we gained evidence that FAT10 regulates NSCLC malignancy and drug resistance by modulating the activity of the nuclear factor kappa B signaling pathway.

Here, we investigated the impact of mulberry fruit (MBF) extracts on lipopolysaccharide (LPS)-induced inflammatory responses in RAW 264.7 macrophages, and the therapeutic efficacy of MBF diet in mice with dextran sulfate sodium (DSS)-induced acute colitis and MUC2(-/-) mice with colorectal cancer. In vitro, LPS-induced nitric oxide (NO) production was significantly inhibited by MBF extracts via suppressing the expression of proinflammatory molecules, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1 beta (IL-β) and IL-6. Particularly, a dose-dependent inhibition on LPS-induced inflammatory responses was observed following treatment with MBF dichloromethane extract (MBF-DE), in which linoleic acid and ethyl linolenate were identified as two active compounds. Moreover, we elucidated that MBF-DE attenuated LPS-induced inflammatory responses by blocking activation of both NF-κB/p65 and pERK/MAPK pathways. In vivo, DSS-induced acute colitis was significantly ameliorated in MBF-fed mice as gauged by weight loss, colon morphology and histological damage. In addition, MBF-fed MUC2(-/-) mice displayed significant decrease in intestinal tumor and inflammation incidence compared to control diet-fed group. Overall, our results demonstrated that MBF suppressed the development of intestinal inflammation and tumorgenesis both in vitro and in vivo, and supports the potential of MBF as a therapeutic functional food for testing in human clinical trials.

Paired box 8 (PAX8) has been documented to be downregulated in gastric cancer. However, its biological function in this malignancy is poorly understood.

MEG3 downregulated the expression in several tumors and inhibits human tumorigenesis. But so far, the mechanism of MEG3 in tumorigenesis is still unclear.

In this work, coumarin derivatives (C) are used to enhance the fluorescence of graphene quantum dots (GQDs) by covalently linking the carboxyl groups on the edge of the GQD sheet. The as-synthesized coumarin-modified graphene quantum dots (C-GQDs) have a uniform particle size with an average diameter of 3.6 nm. Simultaneously, the C-GQDs have strong fluorescence emission, excellent photostability, and high fluorescence quantum yield. C-GQDs and CN- can form a C-GQDs+CN- system due to deprotonation and/or intermolecular interactions. The introduced hydroquinone (HQ) is oxidized to benzoquinone (BQ), and the interaction between BQ and the C-GQDs+CN- system could lead to fluorescence enhancement of C-GQDs. Meanwhile, the redox reaction between BQ and ascorbic acid (AA) can be used for quantitative detection of AA with CN- and HQ being used as substrates. Based on the above mechanism, C-GQDs are developed as a multicomponent detection and sensing platform, and the detection limits for CN-, HQ, and AA were 4.7, 2.2, and 2.2 nM, respectively. More importantly, satisfactory results were obtained when the platform was used to detect CN-, HQ, and AA in living cells and fresh fruits.

Over the past years, the study about bone tissue engineering in the field of regenerative medicine has been a main research topic. Using three-dimensional (3D) porous degradable scaffold complexed with mesenchymal stem cells (MSCs) and growth factor gene to improve bone tissue repair and regeneration has raised much interest. This study mainly evaluated the osteogenesis of alveolar bone defects of animal in the following experimental groups: sham-operated (SO), 3D printed bioglass (3D-BG), 3D-BG with BMP-2 gene loaded CS (3D-BG + BMP/CS) and 3D-BG with rhesus marrow bone MSCs and BMP/CS (3D-BG + BMP/CS + rBMSCs). Simulated human bone defect with critical size of 10 × 10 × 5 mm were established in quadrumana - rhesus monkeys, and in vivo osteogenesis was characterized by X-ray, micro-Computed Tomography (mCT) and history. Our results revealed that 3D-BG + rBMSCs + BMP/CS scaffold could improve bone healing best by showing its promote osteogenic properties in vivo. Considering the great bone repair capacity of 3D-BG + BMP/CS + rBMSCs in humanoid primate rhesus monkeys, it could be a promising therapeutic strategy for surgery trauma or accidents, especially for alveolar bones defects.

The functions of HULC have been demonstrated in several cancers. However, its mechanism has not been elucidated in human liver cancer stem cells.

miR-155 is associated with the promotion of tumorigenesis. Herein, we indicate that abnormal miR-155 was negatively correlated with the expression of P21WAF1/Cip1. Our results suggest that miR-155 alters the transcriptome and inhibits the expression of H3F3A in liver cancer cells. Therefore, miR-155 inhibits the methylation modification of histone H3 on the 27th lysine. Notably, on the one hand, miR-155-dependent CTCF loops cause the CDK2 interacting with cyclin E in liver cancer cells; on the other hand, miR-155 promotes the phosphorylation modification of CDK2 by inhibiting H3F3A. Subsequently, miR-155 competitively blocks the binding of RNA polymerase II (RNA Pol II) to the P21WAF1/CIP1 promoter by increasing the phosphorylation of CDK2, inhibiting the transcription and translation of P21WAF1/CIP1. Strikingly, excessive P21WAF1/CIP1 abolishes the cancerous function of miR-155. In conclusion, miR-155 can play a positive role in the development of liver cancer and influence a series of gene expression through epigenetic regulation.

Circular RNAs (circRNAs) are essential participants in tumour progression. This study focused on investigating the mechanism of a novel functional circRNA in gastric cancer (GC).

Five undescribed harziane-type diterpene derivatives, namely harzianol K (1), harzianol L (4), harzianol M (5), harzianol N (6), harzianol O (7), along with two known compounds, hazianol J (2) and harzianol A (3) were isolated from the deep-sea sediment-derived fungus Trichoderma sp. SCSIOW21. The relative configurations were determined by meticulous spectroscopic methods including 1D, 2D NMR spectroscopy, and HR-ESI-MS. The absolute configurations were established by the ECD curve calculations and the X-ray crystallographic analysis. These compounds (1, and 4-7) contributed to increasing the diversity of the caged harziane type diterpenes with highly congested skeleton characteristics. Harzianol J (2) exhibited a weak anti-inflammatory effect with 81.8% NO inhibition at 100 µM.

Exosomes are cell-secreted nanoparticles (generally with a size of 30-150 nm) bearing numerous biological molecules including nucleic acids, proteins and lipids, which are thought to play important roles in intercellular communication. As carriers, exosomes hold promise as advanced platforms for targeted drug/gene delivery, owing to their unique properties, such as innate stability, low immunogenicity and excellent tissue/cell penetration capacity. However, their practical applications can be limited due to insufficient targeting ability or low efficacy in some cases. In order to overcome these existing challenges, various approaches have been applied to engineer cell-derived exosomes for a higher selectivity and effectiveness. This review presents the state-of-the-art designs and applications of advanced exosome-based systems for targeted cargo delivery. By discussing experts' opinions, we hope this review will inspire the researchers in this field to develop more practical exosomal delivery systems for clinical applications.