Intermittent theta burst stimulation to the left dorsolateral prefrontal cortex improves cognitive function in polydrug use disorder patients: a randomized controlled trial.

Background: Polydrug abuse is common among opioid users. Individuals who use both heroin and methamphetamine (MA) have been shown to experience a wide range of cognitive deficits. Previous research shows that repetitive transcranial magnetic stimulation (rTMS) can change cerebral cortical excitability and regulate neurotransmitter concentration, which could improve cognitive function in drug addiction.

The relationship between physical activity and depression among community-dwelling adults in Wuhan, China.

Background: While the association between physical activity (PA) and depression has been established, there is limited research on the effect of PA on the risk of depression among Chinese individuals. Thus, this study aimed to investigate the relationship between PA and depression among Chinese individuals.

Methods: We used a stratified random sampling approach to recruit participants from five urban districts in Wuhan, China.

Development of a novel multi-functional integrated bioconjugate effectively targeting K-Ras mutant pancreatic cancer.

Folate receptor (FR) overexpression occurs in a variety of cancers, including pancreatic cancer. In addition, enhanced macropinocytosis exists in K-Ras mutant pancreatic cancer. Furthermore, the occurrence of intensive desmoplasia causes a hypoxic microenvironment in pancreatic cancer.

The recombinant defensin/HSA fusion protein that inhibits NF-κb associated with intensive macropinocytosis shows potent efficacy against pancreatic cancer.

KRAS mutation and NF-κB both play crucial role in pancreatic cancer; in addition, defensin, the peptide mediator in innate immunity, can inhibit NF-κB. Assuming a strategy that targets both NF-κB and concomitantly the mutated KRAS indirectly via intensive macropinocytosis, we designed and generated a recombinant protein DF-HSA which consists of two molecules of human beta-defensin 2 (HBD2) and a moiety of human serum albumin (HSA). As shown, the recombinant protein DF-HSA markedly down-regulated NF-κB in both KRAS mutant MIA PaCa-2 cells and wild type BxPC-3 cells.

Metabolomics Tools Assisting Classic Screening Methods in Discovering New Antibiotics from Mangrove Actinomycetia in Leizhou Peninsula.

Mangrove actinomycetia are considered one of the promising sources for discovering novel biologically active compounds. Traditional bioactivity- and/or taxonomy-based methods are inefficient and usually result in the re-discovery of known metabolites. Thus, improving selection efficiency among strain candidates is of interest especially in the early stage of the antibiotic discovery program.

Pingyangmycin enhances the antitumor efficacy of anti-PD-1 therapy associated with tumor-infiltrating CD8 T cell augmentation.

Purpose: To investigate the antitumor efficacy of pingyangmycin (PYM) in combination with anti-PD-1 antibody and determine the capability of PYM to induce immunogenic cell death (ICD) in cancer cells.

Methods: The murine 4T1 breast cancer and B16 melanoma models were used for evaluation of therapeutic efficacy of the combination of PYM with anti-PD-1 antibody. The ELISA kits were used to quantify the ICD related ATP and HMGB1 levels.

DBDx-based drug combinations show highly potent therapeutic efficacy against human pancreatic cancer xenografts in athymic mice.

Previous studies have shown that DBDx, a combination consisting of dipyridamole, bestatin and dexamethasone is highly effective against several cancer xenografts in athymic mice. Here the therapeutic effects of DBDx and its combination with gemcitabine or capcitabine against human pancreatic cancer xenografts and the mechanism were studied. In vivo experiments performed in athymic mice showed that the antitumor efficacy of DBDx was much stronger than that of gemcitabine or capecitabine alone.

Attitude Toward Seeking Professional Psychological Help Among Community-Dwelling Population in China.

Objective: To explore the attitudes and factors in seeking professional psychological help among a Chinese community-dwelling population in order to promote positive help-seeking behaviors and better utilization of mental health services.

Methods: Using system and simple random sampling with Kish selection table methods, 912 community-dwelling residents were included in this study and asked about their attitudes toward seeking professional psychological help, depression symptoms, family function, depression literacy, help-seeking intention, and stigma.

Results: Scores on the Attitudes Toward Seeking Professional Psychological Help scale (ATSPPH-SF) indicated a neutral attitude toward openness to seeking treatment for psychological problems and a negative attitude toward the value and need to seek treatment with a negative total score.

The novel quinolizidine derivate IMB-HDC inhibits STAT5a phosphorylation at 694 and 780 and promotes DNA breakage and cell apoptosis via blocking STAT5a nuclear translocation.

Sophoridine is a quinolizidine natural product and the exploration of its derivatives has been carried out, and the potent anticancer compound IMB-HDC was acquired. Although previous studies have revealed that some sophoridine derivatives could induce DNA breakage, the underlying mechanisms of inhibition of DNA damage repair (ATR inactivation) and the apoptosis independent of p53, have not been elucidated. Our research reveals a novel DNA response mechanism different from general DNA-damaging agents, and that sophoridine derivate inhibits the phosphorylation of Tyr694 and Ser780 of STAT5a to induce the lessened shuttle from the cytoplasm to the nucleus, and leads to the decreased nuclear STAT5a and subsequently inhibits the expression of STAT5a target gene RAD51 that contributes to the checkpoint activation, thus inhibiting ATR activation.

Dexamethasone enhances the antitumor efficacy of Gemcitabine by glucocorticoid receptor signaling.

Gemcitabine (Gem) is currently used as the first-line therapy for liver and pancreatic cancer but has limited efficacy in most cases. Dexamethasone (Dex) have been applied as a chemoprotectant and chemosensitizer in cancer chemotherapy. This study further explored the potential of combination of Gem and Dex and tested the hypothesis that glucocorticoid receptor signaling is essential for the synergistic antitumor activity.

Survey of Chinese persons managing depressive symptoms: Help-seeking behaviours and their influencing factors.

Objectives: To explore help-seeking behaviours of Chinese persons managing depressive symptoms and factors that influence these behaviours.

Methods: A survey of residents living in communities in Wuhan, China was conducted using stratified random sampling. The Patient Health Questionnaire (PHQ-2), the Actual Help-Seeking Questionnaire (AHSQ) and a socio-demographic questionnaire were completed by participants.

Depressive Symptoms in Elderly Chinese Primary Care Patients: Prevalence and Sociodemographic and Clinical Correlates.

Objective: To estimate the prevalence of depressive symptoms (depression thereafter) and to identify the sociodemographic and clinical correlates of depression in a sample of elderly patients treated in the primary care setting in Wuhan, China.

Background: Primary care is an opportune setting for the management of late-life depression in China, but there have been no representative studies on the clinical epidemiology of depression in elderly Chinese primary care patients.

Methods: In total, 752 elderly patients (≥ 65 years) were consecutively recruited from 13 primary care centers in Wuhan, China, and interviewed with a standardized questionnaire.

The ionophore antibiotic gramicidin A inhibits pancreatic cancer stem cells associated with CD47 down-regulation.

Background: Pancreatic cancer stem cells (CSCs), a special population of cells, renew themselves infinitely and resist to various treatment. Gramicidin A (GrA), an ionophore antibiotic derived from microorganism, can form channels across the cell membrane and disrupt cellular ionic homeostasis, leading to cell dysfunction and death. As reported, the ionophore antibiotic salinomycin (Sal) has been proved to kill CSCs effectively.

Quality of life of older Chinese adults receiving primary care in Wuhan, China: a multi-center study.

Background: Quality of life (QOL) is an important primary care outcome, but the QOL of older adults treated in primary care is understudied in China. This study examined QOL and its associated factors in older adults treated in Chinese primary care.

Methods: A total of 752 older patients (65+ years) were consecutively recruited from 13 primary care centers in Wuhan, China, and interviewed with a standardized questionnaire, concerning socio-demographics, major medical conditions, loneliness, and depression.

An EGFR-targeting antibody-drug conjugate LR004-VC-MMAE: potential in esophageal squamous cell carcinoma and other malignancies.

Epidermal growth factor receptor (EGFR) is a rational target for cancer therapy, because its overexpression plays an important oncogenic role in a variety of solid tumors; however, EGFR-targeted antibody-drug conjugate (ADC) therapy for esophageal squamous cell carcinoma (ESCC) is exceedingly rare. LR004 is a novel anti-EGFR antibody with the advantages of improved safety and fewer hypersensitivity reactions. It may be of great value as a carrier in ADCs with high binding affinity and internalization ability.

EGFR-targeting, β-defensin-tailored fusion protein exhibits high therapeutic efficacy against EGFR-expressed human carcinoma via mitochondria-mediated apoptosis.

Defensins play an essential role in innate immunity. In this study, a novel recombinant β-defensin that targets the epidermal growth factor receptor (EGFR) was designed and prepared. The EGFR-targeting β-defensin consists of an EGF-derived oligopeptide (Ec), a β-defensin-1 peptide (hBD1) and a lidamycin-derived apoprotein (LDP), which serves as the "scaffold" for the fusion protein (Ec-LDP-hBD1).

Loneliness in Chinese older adults in primary care: prevalence and correlates.

Background: Loneliness is a significant public health concern among older adults (OA) given its association with a wide range of adverse health outcomes. Primary care is an opportune setting to manage loneliness. However, the epidemiology of loneliness in Chinese OA treated in primary care remains unclear.

Intensive fibrosarcoma-binding capability of the reconstituted analog and its antitumor activity.

Fibrosarcomas are highly aggressive malignant tumors. It is urgently needed to explore targeted drugs and modalities for more effective therapy. Matrix metalloproteinases (MMPs) play important roles in tumor progression and metastasis, while several MMPs are highly expressed in fibrosarcomas.

Mithramycin-loaded mPEG-PLGA nanoparticles exert potent antitumor efficacy against pancreatic carcinoma.

Previous studies have shown that mithramycin A (MIT) is a promising candidate for the treatment of pancreatic carcinoma through inhibiting transcription factor Sp1. However, systemic toxicities may limit its clinical application. Here, we report a rationally designed formulation of MIT-loaded nanoparticles (MIT-NPs) with a small size and sustained release for improved passive targeting and enhanced therapeutic efficacy.

Recombinant EGFR/MMP-2 bi-targeted fusion protein markedly binding to non-small-cell lung carcinoma and exerting potent therapeutic efficacy.

Overexpression of EGFR and MMP-2 plays an essential role in the initiation and progression of non-small-cell lung carcinoma (NSCLC). In this study, a novel format of EGFR/MMP-2 bi-targeted fusion protein Ec-LDP-TIMP2 and its enediyne-integrated analogue Ec-LDP(AE)-TIMP2 have been prepared by genetic engineering and molecular reconstitution. The Ec-LDP(AE)-TIMP2 comprises endogenous inhibitor of matrix metalloproteinase 2 (TIMP2), EGF-derived oligopeptide (Ec), lidamycin apoprotein (LDP), and the extremely potent cytotoxic enediyne (AE).

A CD13-targeting peptide integrated protein inhibits human liver cancer growth by killing cancer stem cells and suppressing angiogenesis.

CD13 is a marker of angiogenic endothelial cells, and recently it is proved to be a biomarker of human liver cancer stem cells (CSCs). Herein, the therapeutic effects of NGR-LDP-AE, a fusion protein composed of CD13-targeting peptide NGR and antitumor antibiotic lidamycin, on human liver cancer and its mechanism were studied. Western blot and immunofluorescence assay demonstrated that CD13 (WM15 epitope) was expressed in both human liver cancer cell lines and vascular endothelial cells, while absent in normal liver cells.

[Sexual satisfaction and its associated factors among individuals with hearing disability].

Objective: To investigate sexual satisfaction (SS) and the factors associated with decreased SS among individuals with hearing disability.

Methods: We conducted an investigation on SS among 439 individuals (268 males and 171 females, aged ≥18 yr) with hearing disability using a general information questionnaire, Center for Epidemiologic Studies Depression Scale, Social Support Rating Scale, and a self-report on SS. We identified the factors of decreased SS by multivariate ordinal logistic regression analysis.

A Novel Nitrobenzoate Microtubule Inhibitor that Overcomes Multidrug Resistance Exhibits Antitumor Activity.

Multidrug resistance is a major limitation for microtubule-binding agents in cancer treatment. Here we report a novel microtubule inhibitor (2-morpholin-4-yl-5-nitro-benzoic acid 4-methylsulfanyl-benzyl ester, IMB5046), its cytotoxicity against multidrug-resistant cell lines and its antitumor efficacy in animal models. IMB5046 disrupted microtubule structures in cells and inhibited purified tubulin polymerization in vitro.