Recombinant parainfluenza virus 5 expressing clade 2.3.4.4b H5 hemagglutinin protein confers broad protection against H5Ny influenza viruses.

The global circulation of clade 2.3.4.4b H5Ny highly pathogenic avian influenza viruses (HPAIVs) in poultry and wild birds, increasing mammal infections, continues to pose a public health threat and may even form a pandemic. An efficacious vaccine against H5Ny HPAIVs is crucial for emergency use and pandemic preparedness. In this study, we developed a parainfluenza virus 5 (PIV5)-based vaccine candidate expressing hemagglutinin (HA) protein of clade 2.3.4.4b H5 HPAIV, termed rPIV5-H5, and evaluated its safety and efficacy in mice and ferrets. Our results demonstrated that intranasal immunization with a single dose of rPIV5-H5 could stimulate H5-specific antibody responses, moreover, a prime-boost regimen using rPIV5-H5 stimulated robust humoral, cellular, and mucosal immune responses in mice. Challenge study showed that rPIV5-H5 prime-boost regimen provided sterile immunity against lethal clade 2.3.4.4b H5N1 virus infection in mice and ferrets. Notably, rPIV5-H5 prime-boost regimen provided protection in mice against challenge with lethal doses of heterologous clades 2.2, 2.3.2, and 2.3.4 H5N1, and clade 2.3.4.4h H5N6 viruses. These results revealed that rPIV5-H5 can elicit protective immunity against a diverse clade of highly pathogenic H5Ny virus infection in mammals, highlighting the potential of rPIV5-H5 as a pan-H5 influenza vaccine candidate for emergency use.IMPORTANCEClade 2.3.4.4b H5Ny highly pathogenic avian influenza viruses (HPAIVs) have been widely circulating in wild birds and domestic poultry all over the world, leading to infections in mammals, including humans. Here, we developed a recombinant PIV5-vectored vaccine candidate expressing the HA protein of clade 2.3.4.4b H5 virus. Intranasal immunization with rPIV5-H5 in mice induced airway mucosal IgA responses, high levels of antibodies, and robust T-cell responses. Importantly, rPIV5-H5 conferred complete protection in mice and ferrets against clade 2.3.4.4b H5N1 virus challenge, the protective immunity was extended against heterologous H5Ny viruses. Taken together, our data demonstrate that rPIV5-H5 is a promising vaccine candidate against diverse H5Ny influenza viruses in mammals.

Thermal multiferroics in all-inorganic quasi-two-dimensional halide perovskites.

Multiferroic materials, particularly those possessing simultaneous electric and magnetic orders, offer a platform for design technologies and to study modern physics. Despite the substantial progress and evolution of multiferroics, one priority in the field remains to be the discovery of unexplored materials, especially those offering different mechanisms for controlling electric and magnetic orders1. Here we demonstrate the simultaneous thermal control of electric and magnetic polarizations in quasi-two-dimensional halides (K,Rb)3Mn2Cl7, arising from a polar-antipolar transition, as evidenced using both X-ray and neutron powder diffraction data. Our density functional theory calculations indicate a possible polarization-switching path including a strong coupling between the electric and magnetic orders in our halide materials, suggesting a magnetoelectric coupling and a situation not realized in oxide analogues. We expect our findings to stimulate the exploration of non-oxide multiferroics and magnetoelectrics to open access to alternative mechanisms, beyond conventional electric and magnetic control, for coupling ferroic orders.

Specific Inhibition of Interpeduncular Nucleus GABAergic Neurons Alleviates Anxiety-Like Behaviors in Male Mice after Prolonged Abstinence from Methamphetamine.

Anxiety is one of the most common withdrawal symptoms of methamphetamine (METH) abuse, which further drives relapse to drugs. Interpeduncular nucleus (IPN) has been implicated in anxiety-like behaviors and addiction, yet its role in METH-abstinence-induced anxiety remains unknown. Here, we found that prolonged abstinence from METH enhanced anxiety-like behaviors in male mice, accompanied by more excited IPN GABAergic neurons, as indicated by the increased c-fos expression and the enhanced neuronal excitability by electrophysiological recording in the GABAergic neurons. Using the designer receptors exclusively activated by designer drugs method, specific inhibition of IPN GABAergic neurons rescued the aberrant neuronal excitation of IPN GABAergic neurons and efficiently reduced anxiety-like behaviors, whereas it did not induce depression-like behaviors in male mice after prolonged abstinence from METH. These findings reveal that IPN GABAergic neurons should be a promising brain target to alleviate late withdrawal symptoms from METH with few side effects.SIGNIFICANCE STATEMENT Prolonged abstinence from METH triggers IPN GABAergic neurons and ultimately increases anxiety in male mice. Suppressing IPN GABAergic neurons rescues METH abstinence-induced aberrant neuronal excitation of IPN GABAergic neurons and efficiently reduces anxiety in mice.

CRISPR-Cas13d screens identify KILR, a breast cancer risk-associated lncRNA that regulates DNA replication and repair.

BACKGROUND: Long noncoding RNAs (lncRNAs) have surpassed the number of protein-coding genes, yet the majority have no known function. We previously discovered 844 lncRNAs that were genetically linked to breast cancer through genome-wide association studies (GWAS). Here, we show that a subset of these lncRNAs alter breast cancer risk by modulating cell proliferation, and provide evidence that a reduced expression on one lncRNA increases breast cancer risk through aberrant DNA replication and repair. METHODS: We performed pooled CRISPR-Cas13d-based knockdown screens in breast cells to identify which of the 844 breast cancer-associated lncRNAs alter cell proliferation. We selected one of the lncRNAs that increased cell proliferation, KILR, for follow-up functional studies. KILR pull-down followed by mass spectrometry was used to identify binding proteins. Knockdown and overexpression studies were performed to assess the mechanism by which KILR regulates proliferation. RESULTS: We show that KILR functions as a tumor suppressor, safeguarding breast cells against uncontrolled proliferation. The half-life of KILR is significantly reduced by the risk haplotype, revealing an alternative mechanism by which variants alter cancer risk. Mechanistically, KILR sequesters RPA1, a subunit of the RPA complex required for DNA replication and repair. Reduced KILR expression promotes breast cancer cell proliferation by increasing the available pool of RPA1 and speed of DNA replication. Conversely, KILR overexpression promotes apoptosis in breast cancer cells, but not normal breast cells. CONCLUSIONS: Our results confirm lncRNAs as mediators of breast cancer risk, emphasize the need to annotate noncoding transcripts in relevant cell types when investigating GWAS variants and provide a scalable platform for mapping phenotypes associated with lncRNAs.

Ultrafine Pt Nanoparticles on Defective Tungsten Oxide for Photocatalytic Ethylene Synthesis.

The selective conversion of ethane (C2H6) to ethylene (C2H4) under mild conditions is highly wanted, yet very challenging. Herein, it is demonstrated that a Pt/WO3-x catalyst, constructed by supporting ultrafine Pt nanoparticles on the surface of oxygen-deficient tungsten oxide (WO3-x) nanoplates, is efficient and reusable for photocatalytic C2H6 dehydrogenation to produce C2H4 with high selectivity. Specifically, under pure light irradiation, the optimized Pt/WO3-x photocatalyst exhibits C2H4 and H2 yield rates of 291.8 and 373.4 µmol g-1 h-1, respectively, coupled with a small formation of CO (85.2 µmol g-1 h-1) and CH4 (19.0 µmol g-1 h-1), corresponding to a high C2H4 selectivity of 84.9%. Experimental and theoretical studies reveal that the vacancy-rich WO3-x catalyst enables broad optical harvesting to generate charge carriers by light for working the redox reactions. Meanwhile, the Pt cocatalyst reinforces adsorption of C2H6, desorption of key reaction species, and separation and migration of light-induced charges to promote the dehydrogenation reaction with high productivity and selectivity. In situ diffuse reflectance infrared Fourier transform spectroscopy and density functional theory calculation expose the key intermediates formed on the Pt/WO3-x catalyst during the reaction, which permits the construction of the possible C2H6 dehydrogenation mechanism.

ProSAP: a GUI software tool for statistical analysis and assessment of thermal stability data.

The Cellular Thermal Shift Assay (CETSA) plays an important role in drug-target identification, and statistical analysis is a crucial step significantly affecting conclusion. We put forward ProSAP (Protein Stability Analysis Pod), an open-source, cross-platform and user-friendly software tool, which provides multiple methods for thermal proteome profiling (TPP) analysis, nonparametric analysis (NPA), proteome integral solubility alteration and isothermal shift assay (iTSA). For testing the performance of ProSAP, we processed several datasets and compare the performance of different algorithms. Overall, TPP analysis is more accurate with fewer false positive targets, but NPA methods are flexible and free from parameters. For iTSA, edgeR and DESeq2 identify more true targets than t-test and Limma, but when it comes to ranking, the four methods show not much difference. ProSAP software is available at https://github.com/hcji/ProSAP and https://zenodo.org/record/5763315.

Combined thioredoxin reductase and glutaminase inhibition exerts synergistic anti-tumor activity in MYC-high high-grade serous ovarian carcinoma.

Approximately 50%-55% of high-grade serous ovarian carcinoma (HGSOC) patients have MYC oncogenic pathway activation. Because MYC is not directly targetable, we have analyzed molecular pathways enriched in MYC-high HGSOC tumors to identify potential therapeutic targets. Here, we report that MYC-high HGSOC tumors show enrichment in genes controlled by NRF2, an antioxidant signaling pathway, along with increased thioredoxin redox activity. Treatment of MYC-high HGSOC tumors cells with US Food and Drug Administration (FDA)-approved thioredoxin reductase 1 (TrxR1) inhibitor auranofin resulted in significant growth suppression and apoptosis in MYC-high HGSOC cells in vitro and also significantly reduced tumor growth in an MYC-high HGSOC patient-derived tumor xenograft. We found that auranofin treatment inhibited glycolysis in MYC-high cells via oxidation-induced GAPDH inhibition. Interestingly, in response to auranofin-induced glycolysis inhibition, MYC-high HGSOC cells switched to glutamine metabolism for survival. Depletion of glutamine with either glutamine starvation or glutaminase (GLS1) inhibitor CB-839 exerted synergistic anti-tumor activity with auranofin in HGSOC cells and OVCAR-8 cell line xenograft. These findings suggest that applying a combined therapy of GLS1 inhibitor and TrxR1 inhibitor could effectively treat MYC-high HGSOC patients.

Mode of inheritance for pesticide resistance, importance and prevalence: A review.

Pesticides remain a cornerstone in pest control, yet their extensive and irrational use also fuel the evolution of resistance. This review analyzes globally published experimental data spanning from the 1970s to 2023 to focus on how phenotypic and underlying genotypic variations are shaped during the selective response. The discussion commences with an examination of sex-linked/maternal resistance. Observations related to maternal inheritance have enriched our understanding of pesticide mode of action, notably exemplified by bifenazate. However, the predominant control of the resistant phenotype is attributed to autosomal traits, with a high prevalence of dominance and monogenic inheritance observed, also evident in field strains. This observation raises concerns regarding resistance management strategies due to their potential to accelerate the spread of resistance. The interplay between dominance levels and monogenic inheritance is further explored, with dominant traits being significantly more prevalent in polygenic inheritance. This observation may be attributed to the accumulation of enhanced metabolism. Notably, further analysis indicated that field strains exhibit a higher incidence of monogenic inheritance compared to other selected strains, aligning with established theoretical frameworks. In conclusion, the genetic architecture of resistance warrants increased research focus for its pivotal role in guiding resistance management strategies and advancing fundamental research.

A comprehensive review on the heterotrophic production of bioactive compounds by microalgae.

Bioactive compounds derived from microalgae have garnered considerable attention as valuable resources for drugs, functional foods, and cosmetics. Among these compounds, photosynthetic pigments and polyunsaturated fatty acids (PUFAs) have gained increasing interest due to their numerous beneficial properties, including anti-oxidant, anti-viral, anti-bacterial, anti-fungal, anti-inflammatory, and anti-tumor effects. Several microalgae species have been identified as rich sources of bioactive compounds, including the Chlorophyceae Dunaliella and Haematococcus, the Bacillariophyta Phaeodactylum and Nitzschia, and the dinoflagellate Crypthecodinium cohnii. However, most of the reported microalgae species primarily grow through autotrophic mechanisms, resulting in low yields and high production costs of bioactive compounds. Consequently, the utilization of heterotrophic microalgae, such as Chromochloris zofingiensis and Nitzschia laevis, has shown significant advantages in the production of astaxanthin and eicosapentaenoic acid (EPA), respectively. These heterotrophic microalgae exhibit superior capabilities in synthesizing target compounds. This comprehensive review provides a thorough examination of the heterotrophic production of bioactive compounds by microalgae. It covers key aspects, including the metabolic pathways involved, the impact of cultivation conditions, and the practical applications of these compounds. The review discusses how heterotrophic cultivation strategies can be optimized to enhance bioactive compound yields, shedding light on the potential of microalgae as a valuable resource for high-value product development.

Metal-Organic Frameworks Derived Carbon-Supported Metal Electrocatalysts for Energy-Related Reduction Reactions.

Electrochemical reduction reactions, as cathodic processes in many energy-related devices, significantly impact the overall efficiency determined mainly by the performance of electrocatalysts. Metal-organic frameworks (MOFs) derived carbon-supported metal materials have become one of star electrocatalysts due to their tunable structure and composition through ligand design and metal screening. However, for different electroreduction reactions, the required active metal species vary in phase component, electronic state, and catalytic center configuration, hence requiring effective customization. From this perspective, this review comprehensively analyzes the structural design principles, metal loading strategies, practical electroreduction performance, and complex catalytic mechanisms, thereby providing insights and guidance for the future rational design of such electroreduction catalysts.

Enhanced neural synchrony associated with long-term ballroom dance training.

Long-term dance training offers numerous benefits, including improvements in physical health, posture, body coordination, and mental health and well-being. Since dance is an art form of body-to-body communication, professional dancers may share feelings and thoughts on dance with their partners, owing to their shared training experiences. Considering this perspective, one may expect that professional dancers would demonstrate pronounced neural similarities when viewing dancing videos, which could be associated with their training duration. To test these hypotheses, we collected functional magnetic resonance imaging (fMRI) data while presenting ballroom dancing and neutral video clips with long durations (∼100 s each) to 41 professional ballroom dancers (19 pairs of dance partners) and 39 age- and sex-matched nondancers. Our findings revealed that dancers exhibited broader and stronger neural similarities across the whole brain when watching dancing video clips, as compared to the control group. These increased neural similarities could be interpreted in at least two distinct ways. First, neural similarities in certain brain regions within the motor control circuit (i.e., frontal cortical-basal ganglia-thalamic circuit) were significantly correlated with dance-related information (e.g., dance partners' cooperation duration), which reinforced the impact of long-term dance training on neural synchronization. Second, neural similarities in other brain regions (e.g., memory-related brain regions) were significantly correlated with subjects' impression of the viewed videos (i.e., whether they have watched before, familiarity, and liking), which may not necessarily be directly linked to long-term dance training. Altogether, our study provided solid evidence for synchronized neural mechanisms in professional dancers due to long-term dance training.

Scaled-Down Thermal Profiling and Coaggregation Analysis of the Proteome for Drug Target and Protein Interaction Analysis.

Thermal proteome profiling (TPP), an experimental technique combining the cellular thermal shift assay (CETSA) with quantitative protein mass spectrometry (MS), identifies interactions of drugs and chemicals with endogenous proteins. Thermal proximity coaggregation (TPCA) profiling extended TPP to study the intracellular dynamics of protein complexes. In TPP and TPCA, samples are subjected to multiple denaturing temperatures, each requiring over 100 µg of proteins, which restricts their applications for rare cells and precious clinical samples. We developed a workflow termed STASIS (scaled-down thermal profiling and coaggregation analysis with SISPROT) that scales down the required protein to as low as 1 µg per temperature. This is achieved by heating and centrifugation using the same PCR tube, processing samples with the SISPROT technology (simple and integrated spintip-based proteomics technology), and tip-based manual fractionation of TMT-labeled peptides. We evaluate the STASIS workflow with starting protein quantities of 10, 5, and 1 µg per temperature prior to heating, identifying between 4000 and 5000 proteins with 6 h of acquisition time. Importantly, we observed a high correlation in the Tm of proteins with minimal difference in TPCA performance for predicting protein complexes. Moreover, STASIS could identify the targets of methotrexate and panobinostat with high precision with 1 µg of proteins per temperature. In conclusion, STASIS is a robust cost-effective technique for target deconvolution and extended TPCA to rare primary cells and precious clinical samples for the analysis of protein complexes.

Serum globulin levels are associated with HIV reservoir size and immune restoration during long-term ART.

OBJECTIVES: The objectives of this study were to analyze the relationship between serum globulin levels and immune restoration and HIV reservoir size during long-term antiretroviral therapy (ART). METHODS: We enrolled 13 patients living with HIV who had been receiving ART for 5 years. We measured levels of serum globulin, cell-associated (CA) HIV DNA and RNA, and p24 antibody at 0, 1, 3, and 5 years of ART. CD38 and human leukocyte antigen - DR isotype (HLA-DR) were used as activation markers for T-cell activation. Serum concentrations of the inflammatory cytokines interferon gamma-inducible protein (IP)-10 and soluble CD163 (sCD163) were detected by enzyme-linked immunosorbent assay. We analyzed the relationship between serum globulin levels, HIV reservoir size, immune restoration, T-cell immune activation, and inflammatory levels during long-term ART. RESULTS: Our data showed that serum globulin levels in people living with HIV were higher than in healthy controls and significantly decreased during the first year of ART. Serum globulin levels during long-term ART were positively correlated with CA HIV DNA, CA HIV RNA, p24 antibody levels, and CD8+ T-cell counts and negatively correlated with CD4+ T-cell counts and CD4/CD8 ratios. Moreover, serum globulin levels were positively correlated with CD4+ and CD8+ T-cell activation and the concentrations of inflammatory biomarkers IP-10 and sCD163 during long-term ART. CONCLUSIONS: Our findings suggest that serum globulin levels may be associated with HIV reservoir size and immune restoration during long-term ART.

Self-Supported Ru-Incorporated NiSe2 for Ampere-Level Current Density Hydrogen Evolution.

To meet the requirements for industrial water splitting to generate hydrogen, it is urgent, but still quite challenging to develop highly active and stable electrocatalysts for large-current-density hydrogen evolution reaction (HER). Herein, Ru-incorporated NiSe2 (Ru-NiSe2 ) was designed and synthesized. The introduction of Ru results in the formation of hierarchically structured Ru-NiSe2 with large electrochemical active surface area, and well-modified electronic structure. As expected, the as-fabricated Ru-NiSe2 displays impressive HER activity in 1.0 M KOH, with a low overpotential of 180.8 mV to reach the current density of 1000 mA cm-2 . Ru-NiSe2 also presents outstanding long-term stability at high current densities, owing to its high intrinsic chemical stability, and strong catalyst-support interface. Notably, when performed at a certain current density of 1000 mA cm-2 , the overpotential increase after 90 h is only 13 mV. Such excellent HER performance of Ru-NiSe2 demonstrates its great potential for practical use in industrial water splitting.

Deep learning based on carotid transverse B-mode scan videos for the diagnosis of carotid plaque: a prospective multicenter study.

OBJECTIVES: Accurate detection of carotid plaque using ultrasound (US) is essential for preventing stroke. However, the diagnostic performance of junior radiologists (with approximately 1 year of experience in carotid US evaluation) is relatively poor. We thus aim to develop a deep learning (DL) model based on US videos to improve junior radiologists' performance in plaque detection. METHODS: This multicenter prospective study was conducted at five hospitals. CaroNet-Dynamic automatically detected carotid plaque from carotid transverse US videos allowing clinical detection. Model performance was evaluated using expert annotations (with more than 10 years of experience in carotid US evaluation) as the ground truth. Model robustness was investigated on different plaque characteristics and US scanning systems. Furthermore, its clinical applicability was evaluated by comparing the junior radiologists' diagnoses with and without DL-model assistance. RESULTS: A total of 1647 videos from 825 patients were evaluated. The DL model yielded high performance with sensitivities of 87.03% and 94.17%, specificities of 82.07% and 74.04%, and areas under the receiver operating characteristic curve of 0.845 and 0.841 on the internal and multicenter external test sets, respectively. Moreover, no significant difference in performance was noted among different plaque characteristics and scanning systems. Using the DL model, the performance of the junior radiologists improved significantly, especially in terms of sensitivity (largest increase from 46.3 to 94.44%). CONCLUSIONS: The DL model based on US videos corresponding to real examinations showed robust performance for plaque detection and significantly improved the diagnostic performance of junior radiologists. KEY POINTS: • The deep learning model based on US videos conforming to real examinations showed robust performance for plaque detection. • Computer-aided diagnosis can significantly improve the diagnostic performance of junior radiologists in clinical practice.

Ni-Doped MnO2 Nanosheet Arrays for Efficient Urea Oxidation.

Urea oxidation reaction (UOR), with a low thermodynamic potential, offers great promise for replacing anodic oxygen evolution reaction of electrolysis systems such as water splitting, carbon dioxide reduction, etc., thus reducing the overall energy consumption. To promote the sluggish kinetics of UOR, highly efficient electrocatalysts are required, and Ni-based materials have been widely investigated. However, most of these reported Ni-based catalysts suffer from large overpotentials, as they generally undergo self-oxidation to form NiOOH species at high potentials, which act as catalytically active sites for UOR. Herein, Ni-doped MnO2 (Ni-MnO2) nanosheet arrays were successfully prepared on nickel foam. The as-fabricated Ni-MnO2 shows distinct UOR behavior with most of the previously reported Ni-based catalysts, as urea oxidation on Ni-MnO2 proceeds before the formation of NiOOH. Notably, a low potential of 1.388 V vs reversible hydrogen electrode was required to achieve a high current density of 100 mA cm-2 on Ni-MnO2. It is suggested that both Ni doping and nanosheet array configuration are responsible for the high UOR activities on Ni-MnO2. The introduction of Ni modifies the electronic structure of Mn atoms, and more Mn3+ species are generated in Ni-MnO2, contributing to its outstanding UOR performance.

Optimal concentration of Lugol's solution for detecting early esophageal carcinoma: A randomized controlled trial.

BACKGROUND AND AIM: Lugol chromoendoscopy is the standard technique to detect an esophageal squamous cell carcinoma (ESCC). However, a high concentration of Lugol's solution can induce mucosal injury and adverse events. We aimed to investigate the optimal concentration of Lugol's solution to reduce mucosal injury and adverse events without degrading image quality. METHODS: This was a two-phase double-blind randomized controlled trial. In phase I, 200 eligible patients underwent esophagogastroduodenoscopy and then were randomly (1:1:1:1:1) sprayed with 1.2%, 1.0%, 0.8%, 0.6%, or 0.4% Lugol's solution. Image quality, gastric mucosal injury, adverse events, and operation satisfaction were compared to investigate the minimal effective concentration. In phase II, 42 cases of endoscopic mucosectomy for early ESCC were included. The patients were randomly assigned (1:1) to the minimal effective (0.6%) or conventional (1.2%) concentration of Lugol's solution for further comparison of the effectiveness. RESULTS: In phase I, the gastric mucosal injury was significantly reduced in 0.6% group (P < 0.05). Furthermore, there was no statistical significance in image quality between 0.6% and higher concentrations of Lugol's solution (P > 0.05, respectively). It also showed that the operation satisfaction decreased in 1.2% group compared with the lower concentration groups (P < 0.05). In phase II, the complete resection rate was 100% in both groups, while 0.6% Lugol's solution showed higher operation satisfaction (W = 554.500, P = 0.005). CONCLUSIONS: The study indicates that 0.6% might be the optimal concentration of Lugol's solution for early detection and delineation of ESCC, considering minimal mucosal injury and satisfied image. The registry of clinical trials: ClinicalTrials.gov (NCT03180944).

Gegen-Qinlian decoction-A traditional Chinese medicine formula-Alleviates methamphetamine withdrawal induced anxiety by targeting GABAergic interneuron-pyramidal neuron pathway in mPFC.

Methamphetamine (Meth) withdrawal elicits anxiety, which is a public health concern with limited therapeutic options. Previous studies implied a strong correlation between mPFC and Meth withdrawal. Here, we examined the role of Gegen-Qinlian decoction (GQD) in Meth withdrawal anxiety and explored potential therapeutic targets in mPFC. We found that intra-gastric administration of GQD during the withdrawal period efficiently alleviated anxiety-like behaviours in Meth-withdrawn mice. Further, GQD could restore Meth withdrawal-triggered pathway of GABAergic interneurons (GABA IN)-pyramidal neurons (PN) in the mPFC of Meth-withdrawn mice, especially the prelimbic cortex (PrL) sub-region and PV-positive GABA IN. While, GQD had no obvious effects on the glial cells in the mPFC of Meth-withdrawn mice. By transcriptomic analysis and validation of several gene candidates, we found that genes in the MAPK signalling pathway, especially those related to heat shock proteins, including Hspa1a, Hspa1b and Hspb1, might be GQD-targeting genes in mPFC to treat Meth withdrawal anxiety, as indicated that these genes were up-regulated by Meth withdrawal but rescued by GQD in mPFC. Collectively, our findings identified for the first time that GQD could efficiently alleviate Meth withdrawal anxiety, partially through regulating the local GABA IN-PN pathway and transcriptomic profile of mPFC. The present study confirms that TCM, such as GQD, will be a desirable therapeutic approach in the treatment of drug addiction and related emotional deficits.

Sex-specific metabolic signatures in methamphetamine addicts.

Methamphetamine (METH) is a commonly abused addictive psychostimulant, and METH-induced neurotoxic and behavioural deficits are in a sex-specific manner. However, there is lack of biomarkers to evaluate METH addiction in clinical practice, especially for gender differences. We utilized ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) to detect the serum metabolomics in METH addicts and controls, specially exploring the sex-specific metabolic alterations by METH abuse. We found that many differently expressed metabolites in METH addicts related to metabolisms of amino acid, energy, vitamin and neurological disorders. Further, METH abuse caused different patterns of metabolomics in a sex-specific manner. As to amino acid metabolism, L-phenylalanine, L-tryptophan and L-histidine in serum of male addicts and betaine in serum of female addicts were significantly changed by METH use. In addition, it seemed that purine and pyrimidine-related metabolites (e.g., xanthosine and adenosine 5'-monophosphate) in male and the metabolites of hormone (e.g., cortisol) and folate biosynthesis (e.g., 7,8-dihydrobiopterin and 4-hydroxybenzoic acid) in female were more sensitive to METH addiction. Our findings revealed that L-glutamic acid, L-aspartic acid, alpha-ketoglutarate acid and citric acid may be potential biomarkers for monitoring METH addiction in clinic. Considering sex-specific toxicity by METH, the metabolites of purine and pyrimidine metabolism in male and those of stress-related hormones in female may be used to facilitate the accurate diagnosis and treatment for METH addicts of different genders.

Diagnostic performance of radiomics model for preoperative risk categorization in thymic epithelial tumors: a systematic review and meta-analysis.

BACKGROUND: Incidental thymus region masses during thoracic examinations are not uncommon. The clinician's decision-making for treatment largely depends on imaging findings. Due to the lack of specific indicators, it may be of great value to explore the role of radiomics in risk categorization of the thymic epithelial tumors (TETs). METHODS: Four databases (PubMed, Web of Science, EMBASE and the Cochrane Library) were screened to identify eligible articles reporting radiomics models of diagnostic performance for risk categorization in TETs patients. The quality assessment of diagnostic accuracy studies 2 (QUADAS-2) and radiomics quality score (RQS) were used for methodological quality assessment. The pooled area under the receiver operating characteristic curve (AUC), sensitivity and specificity with their 95% confidence intervals were calculated. RESULTS: A total of 2134 patients in 13 studies were included in this meta-analysis. The pooled AUC of 11 studies reporting high/low-risk histologic subtypes was 0.855 (95% CI, 0.817-0.893), while the pooled AUC of 4 studies differentiating stage classification was 0.826 (95% CI, 0.817-0.893). Meta-regression revealed no source of significant heterogeneity. Subgroup analysis demonstrated that the best diagnostic imaging was contrast enhanced computer tomography (CECT) with largest pooled AUC (0.873, 95% CI 0.832-0.914). Publication bias was found to be no significance by Deeks' funnel plot. CONCLUSIONS: This present study shows promise for preoperative selection of high-risk TETs patients based on radiomics signatures with current available evidence. However, methodological quality in further studies still needs to be improved for feasibility confirmation and clinical application of radiomics-based models in predicting risk categorization of the thymic epithelial tumors.