Spatial configuration of Fe-Co dual-sites boosting catalytic intermediates coupling toward oxygen evolution reaction.

Oxygen evolution reaction (OER) is the pivotal obstacle of water splitting for hydrogen production. Dual-sites catalysts (DSCs) are considered exceeding single-site catalysts due to the preternatural synergetic effects of two metals in OER. However, appointing the specific spatial configuration of dual-sites toward more efficient catalysis still remains a challenge. Herein, we constructed two configurations of Fe-Co dual-sites: stereo Fe-Co sites (stereo-Fe-Co DSC) and planar Fe-Co sites (planar-Fe-Co DSC). Remarkably, the planar-Fe-Co DSC has excellent OER performance superior to stereo-Fe-Co DSC. DFT calculations and experiments including isotope differential electrochemical mass spectrometry, in situ infrared spectroscopy, and in situ Raman reveal the *O intermediates can be directly coupled to form *O-O* rather than *OOH by both the DSCs, which could overcome the limitation of four electron transfer steps in OER. Especially, the proper Fe-Co distance and steric direction of the planar-Fe-Co benefit the cooperation of dual sites to dehydrogenate intermediates into *O-O* than stereo-Fe-Co in the rate-determining step. This work provides valuable insights and support for further research and development of OER dual-site catalysts.

Cynipid wasps systematically reprogram host metabolism and restructure cell walls in developing galls.

Many insects have evolved the ability to manipulate plant growth to generate extraordinary structures called galls, in which insect larva can develop while being sheltered and feeding on the plant. In particular, cynipid (Hymenoptera: Cynipidae) wasps have evolved to form morphologically complex galls and generate an astonishing array of gall shapes, colors, and sizes. However, the biochemical basis underlying these remarkable cellular and developmental transformations remains poorly understood. A key determinant in plant cellular development is cell wall deposition that dictates the physical form and physiological function of newly developing cells, tissues, and organs. However, it is unclear to what degree cell walls are restructured to initiate and support the formation of new gall tissue. Here, we characterize the molecular alterations underlying gall development using a combination of metabolomic, histological, and biochemical techniques to elucidate how valley oak (Quercus lobata) leaf cells are reprogrammed to form galls. Strikingly, gall development involves an exceptionally coordinated spatial deposition of lignin and xylan to form de novo gall vasculature. Our results highlight how cynipid wasps can radically change the metabolite profile and restructure the cell wall to enable the formation of galls, providing insights into the mechanism of gall induction and the extent to which plants can be entirely reprogrammed to form unique structures and organs.

Chemoproteomic mapping of the glycolytic targetome in cancer cells.

Hyperactivated glycolysis is a metabolic hallmark of most cancer cells. Although sporadic information has revealed that glycolytic metabolites possess nonmetabolic functions as signaling molecules, how these metabolites interact with and functionally regulate their binding targets remains largely elusive. Here, we introduce a target-responsive accessibility profiling (TRAP) approach that measures changes in ligand binding-induced accessibility for target identification by globally labeling reactive proteinaceous lysines. With TRAP, we mapped 913 responsive target candidates and 2,487 interactions for 10 major glycolytic metabolites in a model cancer cell line. The wide targetome depicted by TRAP unveils diverse regulatory modalities of glycolytic metabolites, and these modalities involve direct perturbation of enzymes in carbohydrate metabolism, intervention of an orphan transcriptional protein's activity and modulation of targetome-level acetylation. These results further our knowledge of how glycolysis orchestrates signaling pathways in cancer cells to support their survival, and inspire exploitation of the glycolytic targetome for cancer therapy.

An Ultrasensitive and Efficient microRNA Nanosensor Empowered by the CRISPR/Cas Confined in a Nanopore.

This work presents a clustered regularly interspaced short palindromic repeat (CRISPR)/Cas-nanopipette nano-electrochemistry (Cas = CRISPR-associated proteins) capable of ultrasensitive microRNA detection. Nanoconfinement of the CRISPR/Cas13a within a nanopipette leads to a high catalytic efficacy of ca. 169 times higher than that in bulk electrolyte, contributing to the amplified electrochemical responses. CRISPR/Cas13a-enabled detection of representative microRNA-25 achieves a low limit of detection down to 10 aM. Practical application of this method is further demonstrated for single-cell and real human serum detection. Its general applicability is validated by addressing microRNA-141 and the SARS-CoV-2 RNA gene fragment. This work introduces a new CRISPR/Cas-empowered nanotechnology for ultrasensitive nano-electrochemistry and bioanalysis.

Characterization of Parallel-Stranded DNA Duplexes by Surface-Enhanced Raman Spectroscopy and Bromide-Modified Gold Nanoparticles.

The parallel double-stranded DNA (dsDNA) demonstrates potential utility in molecular biology, diagnosis, therapy, and molecular assembly. However, techniques for the characterization of parallel dsDNA are limited. Here, we demonstrate that a series of intensive characteristic Raman bands of three parallel dsDNAs, which are stabilized by reverse Hoogsteen A+·A+ base pairs or hemiprotonated C+·C, G·G minor groove edge, Hoogsteen A·A base pairs, or Hoogsteen T·A, C+·G base pairs, have been observed by surface-enhanced Raman spectroscopy (SERS) when the gold nanoparticles modified by bromine and magnesium ions (Au BMNPs) were used as substrates. The featured bands can not only accurately discriminate parallel dsDNA from antiparallel one but also identify the strand orientation within dsDNA. The proposed approach will have a significant impact on DNA analysis, especially in the detection and differentiation of various DNA conformations.

Diagnosis of Nonalcoholic Fatty Liver Disease via a H2S-Responsive Bioluminescent Probe Combined with Firefly Luciferase mRNA Delivery.

The early detection of nonalcoholic fatty liver disease (NAFLD) through bioluminescent probes is of great significance. However, there remains a challenge to apply them in nontransgenic natural animals due to the lack of exogenous luciferase. To address this issue, we herein report a new strategy for in situ monitoring of endogenous hydrogen sulfide (H2S) in the liver of NAFLD mice by leveraging a H2S-responsive bioluminescent probe (H-Luc) combined with firefly luciferase (fLuc) mRNA delivery. The probe H-Luc was created by installing a H2S recognition moiety, 2,4-dinitrophenol, onto the luciferase substrate (d-luciferin), which is allowed to release cage-free d-luciferin in the presence of H2S via a nucleophilic aromatic substitution reaction. In the meantime, the intracellular luciferase was introduced by lipid nanoparticle (LNP)-mediated fLuc mRNA delivery, rendering it suitable for bioluminescence (BL) imaging in vitro and in vivo. Based on this luciferase-luciferin system, the endogenous H2S could be sensitively and selectively detected in living cells, showing a low limit of detection (LOD) value of 0.72 µM. More importantly, after systematic administration of fLuc mRNA-loaded LNPs in vivo, H-Luc was able to successfully monitor the endogenous H2S levels in the NAFLD mouse model for the first time, displaying a 28-fold higher bioluminescence intensity than that in the liver of normal mice. We believe that this strategy may shed new light on the diagnosis of inflammatory liver disease, further elucidating the roles of H2S.

Fast-Responsive HClO-Activated Near-Infrared Fluorescent Probe for In Vivo Diagnosis of Inflammatory Bowel Disease and Ex Vivo Optical Fecal Analysis.

Inflammatory bowel disease (IBD) is an idiopathic intestinal inflammatory disease, whose etiology is intimately related to the overproduction of hypochlorous acid (HClO). Optical monitoring of HClO in the living body favors real-time diagnosis of inflammatory diseases. However, HClO-activated near-infrared (NIR) fluorescent probes with rapid response and high inflammatory cell uptake are still lacking. Herein, we report an activatable acceptor-π-acceptor (A-π-A)-type NIR fluorescent probe (Cy-DM) bearing two d-mannosamine groups for the sensitive detection of HClO in early IBD and stool testing. Once reacted with HClO, nonfluorescent Cy-DM could be turned on within 2 s by generating a donor-π-acceptor (D-π-A) structure due to the enhanced intramolecular charge transfer mechanism, showing intense NIR fluorescence emission at 700 nm and a large Stokes shift of 115 nm. Moreover, it was able to sensitively and selectively image exogenous and endogenous HClO in the lysosomes of living cells with a detection limit of 0.84 µM. More importantly, because of the d-mannosamine modification, Cy-DM was efficiently taken up by inflammatory cells in the intestine after intravenous administration, allowing noninvasive visualization of endogenous HClO in a lipopolysaccharide-induced IBD mouse model with a high fluorescence contrast of 6.8/1. In addition, water-soluble Cy-DM has also been successfully applied in ex vivo optical fecal analysis, exhibiting a 3.4-fold higher fluorescence intensity in the feces excreted by IBD mice. We believe that Cy-DM is promising as an invaluable tool for rapid diagnosis of HClO-related diseases as well as stool testing.

Single-Cell Caspase-3 Measurement Using a Biomimetic Nanochannel.

Direct single-cell caspase-3 (Casp-3) analysis has remained challenging. A study of single-cell Casp-3 could contribute to revealing the fundamental pathogenic mechanisms in Casp-3-associated diseases. Here, a biomimetic nanochannel capable of single-cell sampling and ionic detection of intracellular Casp-3 is devised, which is established upon the installment of target-specific organic molecules (luc-DEVD) within the orifice of a glass nanopipette. The specific cleavage of luc-DEVD by Casp-3 could induce changes of inner-surface chemical groups and charge properties, thus altering the ionic response of the biomimetic nanochannel for direct Casp-3 detection. The practical applicability of this biomimetic nanochannel is confirmed by probing intracellular Casp-3 fluctuation upon drug stimulation and quantifying the Casp-3 evolution during induced apoptosis. This work realizes ionic single-cell Casp-3 analysis and provides a different perspective for single-cell protein analysis.

Microfluidic Device-Based In Vivo Detection of PD-L1-Positive Small Extracellular Vesicles and Its Application for Tumor Monitoring.

Liquid biopsy is of great significance in tumor early diagnosis and treatment stratification. PD-L1-positive small extracellular vesicles (PD-L1+ sEVs) are closely related to tumor growth and immunotherapy response, which are considered valuable liquid biopsy biomarkers. In contrast to conventional in vitro detection, in vivo detection has the ability to improve the detection efficiency and enable continuous or real-time dynamic monitoring. However, in vivo detection of PD-L1+ sEVs has multiple difficulties, such as high cell background, complex blood environments, and lack of a specific and stable detection method. Herein, the in vivo detection of PD-L1+ sEVs method was constructed, which efficiently separated sEVs based on the microfluidic device and quantitatively analyzed PD-L1+ sEVs by aptamer recognition and hybridization chain reaction. The concentration of PD-L1+ sEVs was continuously monitored, and significant differences at different stages of tumor as well as a correlation with tumor volume were found. Diseased and healthy individuals could also be effectively distinguished based on the concentration of PD-L1+ sEVs. The method with good stability, biocompatibility, and detection performance provided a powerful means for in vivo detection of PD-L1+ sEVs, contributing to the clinical diagnosis and treatment of tumor.

Expression in poplar of dehydroshikimate dehydratase induces transcriptional and metabolic changes in the phenylpropanoid pathway.

Modification of lignin in feedstocks via genetic engineering aims to reduce biomass recalcitrance to facilitate efficient conversion processes. These improvements can be achieved by expressing exogenous enzymes that interfere with native biosynthetic pathways responsible for the production of the lignin precursors. In-planta expression of a 3-dehydroshikimate dehydratase (QsuB) in poplar trees reduced lignin content and altered their monomer composition, which enabled higher yields of sugars after cell wall polysaccharide hydrolysis. Understanding how plants respond to such genetic modifications at the transcriptional and metabolic levels is needed to facilitate further improvement and field deployment. In this work, we amassed fundamental knowledge on lignin-modified QsuB poplar using RNA-seq and metabolomics. The data clearly demonstrate that changes in gene expression and metabolite abundance can occur in a strict spatiotemporal fashion, revealing tissue-specific responses in the xylem, phloem, or periderm. In the poplar line that exhibits the strongest reduction in lignin, we found that 3% of the transcripts had altered expression levels and ~19% of the detected metabolites had differential abundance in the xylem from older stems. Changes affect predominantly the shikimate and phenylpropanoid pathways as wells as secondary cell wall metabolism, and result in significant accumulation of hydroxybenzoates derived from protocatechuate and salicylate.

Multi-ecosystem services differently affected by over-canopy and understory nitrogen additions in a typical subtropical forest.

Obtaining a holistic understanding of the impacts of atmospheric nitrogen deposition on multiple ecosystem services of forest is essential for developing comprehensive and sustainable strategies, particularly in heavy N deposition regions such as subtropical China. However, such impacts remain incompletely understood, with most previous studies focus on individual ecosystem function or service via understory N addition experiments. To address this knowledge gap, we quantified the effects of over-canopy and understory N additions on multiple ecosystem services based on a 7-year large-scale field experiment in a typical subtropical forest. Our results showed continued over-canopy N addition with 50 kg ha-1 year-1 over a period of 4-7 years significantly increased plant nutrient retention, but did not affect the services of soil nutrient accumulation, water yield, C sequestration (in plants and soil), or oxygen release. There were trade-offs between the soil and plant on providing the services of nutrient accumulation/retention and C sequestration under over-canopy N addition. However, without uptake and retention of tree canopy, the trade-off between soil and plant were more weaken under the understory N addition with 50 kg ha-1 year-1 , and their relationships were even synergetic under the understory N addition with 25 kg ha-1 year-1 . The results suggest that understory N addition cannot accurately simulate the effects of atmospheric N deposition on multiple services, along with mutual relationships. Interestingly, the services of plant N, P retention, and C sequestration exhibited a synergetic increase under the over-canopy N addition but a decrease under the understory N addition. Our results also found tree layer plays a primary role in providing plant nutrient retention service and is sensitive to atmospheric N deposition. Further studies are needed to investigate the generalized effects of forest canopy processes on alleviating the threaten of global change factors in different forest ecosystems.

Phosphodiesterase 8 (PDE8): Distribution and Cellular Expression and Association with Alzheimer's Disease.

Phosphodiesterase 8 (PDE8), as a member of PDE superfamily, specifically promotes the hydrolysis and degradation of intracellular cyclic adenosine monophosphate (cAMP), which may be associated with pathogenesis of Alzheimer's disease (AD). However, little is currently known about potential role in the central nervous system (CNS). Here we investigated the distribution and expression of PDE8 in brain of mouse, which we believe can provide evidence for studying the role of PDE8 in CNS and the relationship between PDE8 and AD. Here, C57BL/6J mice were used to observe the distribution patterns of two subtypes of PDE8, PDE8A and PDE8B, in different sexes in vivo by western blot (WB). Meanwhile, C57BL/6J mice were also used to demonstrate the distribution pattern of PDE8 in selected brain regions and localization in neural cells by WB and multiplex immunofluorescence staining. Furthermore, the triple transgenic (3×Tg-AD) mice and wild type (WT) mice of different ages were used to investigate the changes of PDE8 expression in the hippocampus and cerebral cortex during the progression of AD. PDE8 was found to be widely expressed in multiple tissues and organs including heart, kidney, stomach, brain, and liver, spleen, intestines, and uterus, with differences in expression levels between the two subtypes of PDE8A and PDE8B, as well as two sexes. Meanwhile, PDE8 was widely distributed in the brain, especially in areas closely related to cognitive function such as cerebellum, striatum, amygdala, cerebral cortex, and hippocampus, without differences between sexes. Furthermore, PDE8A was found to be expressed in neuronal cells, microglia and astrocytes, while PDE8B is only expressed in neuronal cells and microglia. PDE8A expression in the hippocampus of both female and male 3×Tg-AD mice was gradually increased with ages and PDE8B expression was upregulated only in cerebral cortex of female 3×Tg-AD mice with ages. However, the expression of PDE8A and PDE8B was apparently increased in both cerebral cortex and hippocampus in both female and male 10-month-old 3×Tg-AD mice compared WT mice. These results suggest that PDE8 may be associated with the progression of AD and is a potential target for its prevention and treatment in the future.

m 6 A reader IGF2BP1 reduces the sensitivity of nasopharyngeal carcinoma cells to Taxol by upregulation of AKT2.

Taxol is widely used in the treatment of nasopharyngeal carcinoma (NPC); nevertheless, the acquired resistance of NPC to Taxol remains one of the major obstacles in clinical treatment. In this study, we aimed to investigate the role and mechanism of insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in Taxol resistance of NPC. Taxol-resistant NPC cell lines were established by exposing to gradually increased concentration of Taxol. Relative mRNA and protein levels were tested using qRT-PCR and western blot, respectively. NPC cell viability and apoptosis were assessed by cell counting kit-8 and flow cytometry analysis, respectively. Cell migration and invasion capacities were measured using transwell assay. Interaction between IGF2BP1 and AKT2 was examined by RNA immunoprecipitation assay. The N6-methyladenosine level of AKT2 was tested using methylated RNA immunoprecipitation-qPCR. IGF2BP1 expression was enhanced in Taxol-resistant NPC cell lines. Knockdown of IGF2BP1 strikingly enhanced the sensitivity of NPC cells to Taxol and repressed the migration and invasion of NPC cells. Mechanistically, IGF2BP1 elevated the expression of AKT2 by increasing its mRNA stability. Furthermore, overexpression of AKT2 reversed the inhibitory roles of IGF2BP1 silence on Taxol resistance and metastasis. Our results indicated that IGF2BP1 knockdown enhanced the sensitivity of NPC cells to Taxol by decreasing the expression of AKT2, implying that IGF2BP1 might be promising candidate target for NPC treatment.

Equisetin protects from atherosclerosis in vivo by binding to STAT3 and inhibiting its activity.

Atherosclerosis is a chronic inflammatory vascular disease characterized by lipid metabolism disorder and lipid accumulation. Equisetin (EQST) is a hemiterpene compound isolated from fungus of marine sponge origin, which has antibacterial, anti-inflammatory, lipid-lowering, and weight loss effects. Whether EQST has anti-atherosclerotic activity has not been reported. In this study, we revealed that EQST displayed anti- atherosclerosis effects through inhibiting macrophage inflammatory response, lipid uptake and foam cell formation in vitro, and finally ameliorated high-fat diet (HFD)-induced atherosclerosis in AopE-/- mice in vivo. Mechanistically, EQST directly bound to STAT3 with high-affinity by forming hydrophobic bonds at GLN247 and GLN326 residues, as well as hydrogen bonds at ARG325 and THR346 residues. EQST interacted with STAT3 physically, and functionally inhibited the transcription activity of STAT3, thereby regulating atherosclerosis. Therefore, these results supports EQST as a candidate for developing anti-atherosclerosis therapeutic agent.

Dendrobium officinale Kinura et Migo glycoprotein promotes skin wound healing by regulating extracellular matrix secretion and fibroblast proliferation on the proliferation phase.

Dendrobium officinale Kinura et Migo (DOKM) has a variety of medicinal applications; however, its ability to promote wound healing has not been previously reported. The purpose of this study is to investigate the proliferative phase of the wound-healing effect of DOKM glycoprotein (DOKMG) in rats and to elucidate its mechanism of action in vitro. In the present study, the ointment mixture containing DOKMG was applied to the dorsal skin wounds of the full-thickness skin excision rat model, and the results showed that the wound healing speed was faster in the proliferative phase than vaseline. Histological analysis demonstrates that DOKMG promoted the re-epithelialization of wound skin. Immunofluorescence staining and quantitative polymerase chain reaction assays revealed that DOKMG promotes the secretion of Fibronectin and inhibits the secretion of Collagen IV during the granulation tissue formation period, indicating that DOKMG could accelerate the formation of granulation tissue by precisely regulating extracellular matrix (ECM) secretion. In addition, we demonstrated that DOKMG enhanced the migration and proliferation of fibroblast (3T6 cell) in two-dimensional trauma by regulating the secretion of ECM, via a mechanism that may implicate the AKT and JAK/STAT pathways under the control of epidermal growth factor receptor (EGFR) signalling. In summary, we have demonstrated that DOKMG promotes wound healing during the proliferative phase. Therefore, we suggest that DOKMG may have a potential therapeutic application for the treatment and management of cutaneous wounds.

Fast detection of hypobromous acid in cells and the water environment using a lysosome-targeted fluorescent probe.

A new fluorescent probe SWJT-23 with lysosomal targeting ability for detection of hypobromous acid (HBrO) was synthesised based on the naphthalimide skeleton. This probe exhibited a fast response (within 3s), a low detection limit (1.24 nM), excellent selectivity and a high fluorescence quantum yield (Φ = 0.490). Moreover, SWJT-23 not only realized the sensitive detection of HBrO in cells and water samples, but also was fabricated as a paper-based sensor. In consequence, SWJT-23 is expected to be an efficient and powerful tool for monitoring HBrO in organisms and the environment in realistic scenarios.

The association between the neutrophil-to-lymphocyte ratio and type 2 diabetes mellitus: a cross-sectional study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a prevalent chronic disease often accompanied by low-grade inflammation. Recently, the neutrophil-to-lymphocyte ratio (NLR) has garnered researchers' interest as an emerging inflammation biomarker. This study aimed to comprehensively explore the relationship between NLR and T2DM using the National Health and Nutrition Examination Survey (NHANES) database. METHOD: We employed a cross-sectional study design to analyze data from five NHANES cycles from 2007 to 2016, excluding individuals with incomplete data. This study utilized a weighted logistic regression model, subgroup analyses, and restricted cubic spline (RCS) analysis to assess the potential relationship between NLR and T2DM. RESULTS: A total of 9903 participants were eligible for the analysis, of which 1280 were diagnosed with T2DM. The T2DM group exhibited significantly higher NLR levels than the non-T2DM group. After adjusting for potential confounders, elevated NLR levels were associated with an increased risk of developing T2DM, indicated by an odds ratio (OR) of 1.14, 95% CI: (1.05,1.24), P = 0.003. The results of the subgroup analyses revealed a significant interaction effect between NLR and T2DM concerning race and hypertension (P for interaction < 0.05). In contrast, no significant interactions were found for age, sex, education level, body mass index (BMI), smoking status, recreational activities, and alcohol drinker (P for interaction > 0.05). RCS analysis showed a significant non-linear relationship between NLR and T2DM, with an inflection point at 2.27 (all P for non-linearity < 0.05). CONCLUSION: Our study indicates that an elevated neutrophil-to-lymphocyte ratio is associated with a higher risk of T2DM.

Association of empathy with clinical symptoms and cognitive function in chronic schizophrenia patients with and without suicide attempts.

Cognitive impairment is recognized as a risk factor for suicide in schizophrenia (SZ) patients. Despite empathy being an important aspect of social cognition, the association between suicidal behavior and empathy has received little attention. We aimed to compare empathy and neurocognition in SZ patients with and without suicide attempts (SAs), and to explore the relationship between empathy, neurocognition, and clinical symptoms in SZ patients with and without SAs. Data on SAs and socio-demographic characteristics were collected from 628 chronic SZ patients. The patients' symptomatology was measured by the Positive and Negative Syndrome Scale (PANSS). Empathy and neurocognition were assessed with the Interpersonal Reactivity Index (IRI) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), respectively. Patients with SAs performed better on all IRI domains (except for Perspective Taking) and total scores. Regression results showed that negative symptoms, positive symptoms, and duration of illness were independently associated with IRI total score in patients without SAs (adjusted R2 = 0.048). In patients without SAs, negative symptoms, general psychopathology, education, age, and sex were independently associated with RBANS total score (adjusted R2 = 0.265), while in patients with SAs, education, PANSS total score, and age at onset were independently associated with RBANS total score (adjusted R2 = 0.456). Our results show that SZ patients with SAs may have better empathic performance than patients without SAs. In chronic SZ patients, negative and positive symptoms may have different effects on cognition in the SAs and non-SAs groups.

Association between drug craving and aggression in Chinese male methamphetamine-dependent patients with and without depressive symptoms.

Depressive symptoms and aggression are common in patients with substance use disorder. Drug craving is one of the main drivers of drug-seeking behavior. This study aimed to explore the relationship between drug craving and aggression in methamphetamine use disorder (MAUD) patients with and without depressive symptoms. Totally, 613 male patients with MAUD were recruited in this study. Patients with depressive symptoms were identified by the 13-item Beck Depression Inventory (BDI-13). Drug craving and aggression were assessed by the Desires for Drug Questionnaire (DDQ) and the Buss & Perry Aggression Questionnaire (BPAQ), respectively. 374 patients (61.01%) were confirmed to meet the criteria of depressive symptoms. Patients with depressive symptoms had significantly higher DDQ and BPAQ total scores than those without depressive symptoms. DDQ desire and intention were positively correlated with verbal aggression and hostility in patients with depressive symptoms, whereas they were correlated with self-directed aggression in patients without depressive symptoms. In patients with depressive symptoms, DDQ negative reinforcement and a history of suicide attempts were independently associated with BPAQ total score. Our study suggests that male MAUD patients have a high incidence of depressive symptoms and that patients with depressive symptoms may have greater drug cravings and aggression. Depressive symptoms may play a role in the association between drug craving and aggression in patients with MAUD.

Childhood abuse and craving in methamphetamine-dependent individuals: the mediating role of alexithymia.

Individuals with a history of childhood abuse (CA, including neglect and abuse by caregivers before the age of 18 years) have more severe substance dependence problems than those without a history of childhood abuse. However, whether a history of CA exacerbates craving and the mechanism of this effect remain largely unknown. The aim of this study was to explore the role of alexithymia in the effects of CA on craving in a large sample of methamphetamine-dependent individuals based on latent vulnerability theory. A total of 324 methamphetamine-dependent individuals who met DSM-5 criteria for substance use disorder were recruited. CA, alexithymia, and craving data were collected from the Childhood Trauma Questionnaire, the Toronto Alexithymia Scale-20, and the Obsessive Compulsive Drug Use Scale, respectively. t tests and ANCOVA were conducted to compare variables between the CA and non-CA groups, while partial correlation and mediation analyses were conducted to examine the potential mediating role of alexithymia in the relationship between CA and craving. Abused methamphetamine-dependent individuals reported higher levels of craving and higher levels of alexithymia than those of non-abused methamphetamine-dependent individuals. Alexithymia partially mediated the link between CA and craving, especially the effect of CA on craving frequency was fully mediated by alexithymia. Our findings reveal that a history of childhood abuse has a lasting effect on craving in stimulant-dependent individuals, and alexithymia contributes to some extent to the severity of substance abuse problems in abused methamphetamine-dependent individuals.