The Association Between Rumination and Craving in Chinese Methamphetamine-Dependent Patients: The Masking Effect of Depression.

BACKGROUND: Craving is a core feature of addiction. Rumination and depression play a crucial role in the process of methamphetamine addiction. The aim of this study was to examine the relationship between rumination, depression and craving in methamphetamine patients, which has not been explored yet. METHODS: A total of 778 patients with methamphetamine user disorder (MUD) at the Xinhua Drug Rehabilitation Center, located in Mianyang City, Sichuan Province, China. We used a set of self-administered questionnaires that included socio-demographic, detailed drug use history, rumination, depression and craving information. The Rumination Response Scale (RRS) was used to measure rumination, the Beck Depression Inventory (BDI) to measure depression and the Visual Analogue Scale (VAS) to measure craving. RESULTS: There was a significant positive correlation between rumination and craving, or depression, and between depression and craving. Furthermore, depression mediated between rumination and craving, with a mediation effect of 160%. CONCLUSIONS: Our findings suggest that there is a close interrelationship between rumination, craving and depression in MUD patients, and that depression may play a mediating role between rumination and craving.

This is the first study to investigate the relationship between rumination and craving during withdrawal in methamphetamine dependent patients and the mediating role of depression.Among methamphetamine patients, it was found that reflection was positively correlated with rumination and depression, depression and craving, rumination and craving, and depression plays the mediating role between rumination and craving.These findings suggest that interventions to reduce depression and rumination may also be effective for withdrawal and relapse reduction in methamphetamine patients, providing further rationale for the treatment of methamphetamine patients.

A self-assembling peptide inhibits the growth and function of fungi via a wrapping strategy.

Fungal infections contribute substantially to human morbidity and mortality. A particular concern is the high rate of mortality associated with invasive fungal infections, which often exceeds 50.0% despite the availability of several antifungal drugs. Herein, we show a self-assembling antifungal peptide (AFP), which is able to bind to chitin on the fungal cell wall and in situ form AFP nanofibers, wrapping fungi. As a result, AFP limits the proliferation of fungi, slows down the morphological transformation of biphasic fungi, and inhibits the adhesion of fungi to host cells and the formation of biofilms. Compared to the broad-spectrum antifungal fluconazole, AFP achieved a comparable inhibitory effect (MIC50 = 3.5 µM) on fungal proliferation. In addition, AFP significantly inhibited the formation of fungal biofilms with the inhibition rate of 69.6% at 1 µM, better than fluconazole (17.2% at 1 µM). In a skin infection model of mice, it was demonstrated that AFP showed significantly superior efficacy to fluconazole. In the systemic candidiasis mouse model, AFP showed similar efficacy to first-line antifungal amphotericin B (AmpB) and anidulafungin (AFG). This study provides a promising wrapping strategy for anti-fungal infection.

Binding-induced fibrillogenesis peptide inhibits RANKL-mediated osteoclast activation against osteoporosis.

Osteoporosis is primarily driven by an imbalance between bone resorption and formation, stemming from enhanced osteoclast activity during bone remodeling. At the crux of this mechanism lies the pivotal RANK-RANKL-OPG axis. In our study, we designed two binding-induced fibrillogenesis (BIF) peptides, namely BIFP and BIFY, targeting RANK and RANKL, respectively. These BIF peptides, with distinct hydrophilic and hydrophobic characteristics, assemble into nanoparticles (NPs) in aqueous solution. Through specific ligand-receptor interactions, these NPs efficiently target and bind to specific proteins, resulting in the formation of fibrous networks that effectively inhibit the RANK-RANKL associations. Experiments have confirmed the potent inhibitory effects of peptides on both osteoclast differentiation and function. Compared with the +RANKL controls, BIFP and BIFY demonstrated a more remarkable reduction in tartrate resistant acid phosphatase (TRAP)-positive cells, achieving an impressive decline of 82.8% and 70.7%, respectively. Remarkably, the administration of BIFP led to a substantial reduction in bone resorption pit area by 17.4%, compared to a significant increase of 92.4% in the +RANKL groups. In vivo experiments on an ovariectomized mouse model demonstrated that the BIFP treated group exhibited an impressive 2.6-fold elevation in bone mineral density and an astounding 4.0-fold enhancement in bone volume/total volume as against those of the PBS-treated group. Overall, BIF peptides demonstrate remarkable abilities to impede osteoclast differentiation, presenting promising prospects for the treatment of osteoporosis.

Worm Generator: A System for High-Throughput in Vivo Screening.

Large-scale screening of molecules in organisms requires high-throughput and cost-effective evaluating tools during preclinical development. Here, a novel in vivo screening strategy combining hierarchically structured biohybrid triboelectric nanogenerators (HB-TENGs) arrays with computational bioinformatics analysis for high-throughput pharmacological evaluation using Caenorhabditis elegans is described. Unlike the traditional methods for behavioral monitoring of the animals, which are laborious and costly, HB-TENGs with micropillars are designed to efficiently convert animals' behaviors into friction deformation and result in a contact-separation motion between two triboelectric layers to generate electrical outputs. The triboelectric signals are recorded and extracted to various bioinformation for each screened compound. Moreover, the information-rich electrical readouts are successfully demonstrated to be sufficient to predict a drug's identity by multiple-Gaussian-kernels-based machine learning methods. This proposed strategy can be readily applied to various fields and is especially useful in in vivo explorations to accelerate the identification of novel therapeutics.

Obsessive-compulsive disorder in Chinese methamphetamine patients: Prevalence, demographics, and clinical characteristics.

BACKGROUND AND OBJECTIVES: Methamphetamine (MA) is one of the most common addictive substances and has become the second most commonly used drug worldwide. Obsessive-compulsive disorder (OCD) has been shown to influence the effectiveness of addiction treatment, and there may be overlapping neurobiological mechanisms between OCD and addiction. The aim of this study was to investigate the prevalence and clinical correlates of OCD among MA patients. METHODS: A total of 457 MA patients were recruited, and clinical and demographic data were collected. The Yale-Brown Obsessive-Compulsive Scale was utilized for OCD symptoms, and the Obsessive-Compulsive Drug Use Scale was used for MA craving. RESULTS: The prevalence of OCD among MA patients was 7.7%. Compared to those patients without OCD, patients with OCD had a longer length of abstinence and higher OCDUS frequency of craving subscale and total scores. Multiple regression showed that longer length of abstinence and higher MA carving were independently associated with OCD in MA patients. DISCUSSION AND CONCLUSIONS: Chinese Han MA patients have a high prevalence of OCD. Some clinical parameters may be associated with OCD in MA patients. SCIENTIFIC SIGNIFICANCE: This is the first study to examine the prevalence, sociodemographic and clinical correlates of OCD in MA patients in a Chinese Han population.

An intelligent peptide recognizes and traps Mycobacterium tuberculosis to inhibit macrophage phagocytosis.

Tuberculosis is a major public health concern worldwide, and it is a serious threat to human health for a long period. Macrophage phagocytosis of Mycobacterium tuberculosis (M. tuberculosis) is a crucial process for granuloma formation, which shelters the bacteria and gives them an opportunity for re-activation and spread. Herein, we report an intelligent anti-microbial peptide that can recognize and trap the M. tuberculosis, inhibiting the macrophage phagocytosis process. The peptide (Bis-Pyrene-KLVFF-WHSGTPH, in abbreviation as BFH) first self-assembles into nanoparticles, and then forms nanofibers upon recognizing and binding M. tuberculosis. Subsequently, BFH traps M. tuberculosis by the in situ formed nanofibrous networks and the trapped M. tuberculosis are unable to invade host cells (macrophages). The intelligent anti-microbial peptide can significantly inhibit the phagocytosis of M. tuberculosis by macrophages, thereby providing a favorable theoretical basis for inhibiting the formation of tuberculosis granulomas.

Smart Peptide Defense Web In Situ Connects for Continuous Interception of IgE against Allergic Rhinitis.

Allergic rhinitis (AR) is a chronic inflammatory reaction by immunoglobulin E (IgE) mediators after individual contact with allergens. It affects 10-40% of the world's population and reduces the quality of life. Long-term symptoms of rhinitis can cause inflammation to spread and trigger asthma, which can harm human health. Herein, we develop a Smart PeptIde defeNse (SPIN) web technique, which in situ constructs a peptide web, trapping IgE against AR. Two candidate SPINs, SPIN-1 and SPIN-2, are designed with different IgE-binding sequences. The SPIN-1 or SPIN-2 is able to bind to IgE and transform from nanoparticles into entangled nanofibers. In turn, the web of SPIN-1 or SPIN-2 acts as a long-term trap of IgE to prevent the IgE from binding to mast cells. SPIN-1 or SPIN-2 (10 mg/kg) is able to treat AR model Balb/c mice with high efficiency and reduced symptoms of rhinitis and inflammatory factors, even better than a first-line clinical drug, cetirizine (10 mg/kg). For example, the amount of IL-4 released in the AR group (185.5 ± 6.8 pg/mL) is significantly reduced after the treatment with SPIN-1 (70.4 ± 14.1 pg/mL), SPIN-2 (86.0 ± 9.3 pg/mL), or cetirizine (112.8 ± 19.3 pg/mL). More importantly, compared with the cetirizine group (1 day), the SPIN-1 or SPIN-2 group shows long-term therapeutic effects (1 week). The SPIN web technique shows the great potential for blocking IgE binding to mast cells in vivo, attenuating AR or other allergic reactions.

Biomimetic peptide nanoparticles participate in natural coagulation for hemostasis and wound healing.

Uncontrolled hemorrhage is a major problem both in surgical intervention and after trauma. Herein, we design an in situ constructable peptide network, mimicking and participating in the native coagulation process for enhanced hemostasis and wound healing. The network consists of two peptides including C6KL, mimicking platelets and C6KG, mimicking fibrin. The C6KL nanoparticles could bind to the collagen at the wound site and transform into C6KL nanofibers. The C6KG nanoparticles could bind to GPIIb/IIIa receptors on the surface of activated platelets and transform into C6KG nanofibers. The in situ formed peptide network could interwind platelets, fibrin and red blood cells, causing embolism at the wound site. In a lethal femoral artery, vein, and nerve cut model of rats, the amount of bleeding was reduced to 32.8% by C6KL and C6KG with chitosan/alginate. The biomimetic peptides show great clinical potential as trauma hemostatic agents.

Tardive dyskinesia in Chinese patients with schizophrenia: Prevalence, clinical correlates and relationship with cognitive impairment.

OBJECTIVE: Tardive dyskinesia (TD) has a high prevalence and is one of the distressing side effects of antipsychotic medications. Few studies have explored the relationship between TD, clinical correlates, and cognition. The aim of this study was to assess the prevalence, clinical correlates and cognitive impairment of co-occurring TD in Chinese patients with schizophrenia. METHODS: We recruited 655 patients with chronic schizophrenia who met the DSM-IV diagnostic criteria for schizophrenia and collected clinical and demographic data. All patients were assessed using the Abnormal Involuntary Movement Scale (AIMS) for the severity of TD, Positive and Negative Syndrome Scale (PANSS) for psychopathological symptoms, and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) for cognition. RESULTS: The overall TD prevalence was 41.1%, 42.9% (246/574) in men and 28.4% (23/81) in women (χ2 = 6.1 df = 1, p < 0.05). There were significant differences in age, sex, duration of illness, number of hospitalizations, drug type, smoking and PANSS negative symptom subscore between TD and non-TD groups (all p < 0.05). Moreover, patients with TD scored lower for immediate memory, attention, delayed memory, and RBANS total scores (all p < 0.05). Logistic regression showed a significant correlation between TD and age, sex, drug type and attention subscore. CONCLUSION: Our results suggest that multiple demographic and clinical variables may be associated with the development of TD. Moreover, TD patients may exhibit more cognitive impairment than non-TD patients.

TRAF3 promoted ROS-induced oxidative stress in model of cardiac infarction through the regulation of ULK1 ubiquitination.

OBEJECTIVES: Cardiac infarction is a dynamic, nonlinear and unpredictable course of disease, and who die of acute myocardial infarction, and coronary thrombosis. TRAF3 provide novel targets for the clinical prevention and treatment for tumors, viral infection, and so on.We investigated the mechanisms of TRAF3 gene, which plays a possible role in cardiac infarction and contributes to the pathogenesis of cardiac infarction-induced oxidative stress. METHODS: Serum samples of patients with cardiac infarction and normal healthy volunteers were obtained from the 920 Hospital of PLA joint service support force. C57BL/6 mice were ligated and H9C2 cells were induced with 1% O2,5%CO2 and 94% N2. RESULTS: The mRNA expression levels of TRAF3 in patients with cardiac infarction were increased, compared to healthy volunteers. Serum mRNA of TRAF3 was in positive correlation with serum CK levels in patients with cardiac infarction. Over-expression of TRAF3 heightened ROS-induced oxidative stress in vitro model of cardiac infarction. Then, TRAF3 recombinant protein could promote oxidative stress and aggravated cardiac infarction in mice model. Over-expression of TRAF3 induced ULK1 protein expression and reduced ULK1 ubiquitination in vitro model. The activation of ULK1 reduced the effects of TRAF3 on oxidative stress in vitro model of cardiac infarction. Meanwhile, the inhibition of ULK1 reversed the effects of si-TRAF3 on oxidative stress in vitro model of cardiac infarction. CONCLUSIONS: This study identified that TRAF3 promoted ROS-induced oxidative stress in model of cardiac infarction through the regulation of ULK1 ubiquitination, which could potentially give rise to a new strategy for the treatment of cardiac infarction.