Array-optimized artificial olfactory sensor enabling cost-effective and non-destructive detection of mycotoxin-contaminated maize.

The MobileNetV3-based improved sine-cosine algorithm (ISCA-MobileNetV3) was combined with an artificial olfactory sensor (AOS) to address the redundancy in olfactory arrays, thereby achieving low-cost and high-precision detection of mycotoxin-contaminated maize. Specifically, volatile organic compounds of maize interacted with unoptimized AOS containing eight porphyrins and eight dye-attached nanocomposites to obtain the scent fingerprints for constructing the initial data set. The optimal decision model was MobileNetV3, with more than 98.

Baseline symptom-related white matter tracts predict individualized treatment response to 12-week antipsychotic monotherapies in first-episode schizophrenia.

There is significant heterogeneity in individual responses to antipsychotic drugs, but there is no reliable predictor of antipsychotics response in first-episode psychosis. This study aimed to investigate whether psychotic symptom-related alterations in fractional anisotropy (FA) and mean diffusivity (MD) of white matter (WM) at the early stage of the disorder may aid in the individualized prediction of drug response. Sixty-eight first-episode patients underwent baseline structural MRI scans and were subsequently randomized to receive a single atypical antipsychotic throughout the first 12 weeks.

Identification of Brain-Penetrant ATP-Competitive mTOR Inhibitors for CNS Syndromes.

The allosteric inhibitor of the mechanistic target of rapamycin (mTOR) everolimus reduces seizures in tuberous sclerosis complex (TSC) patients through partial inhibition of mTOR functions. Due to its limited brain permeability, we sought to develop a catalytic mTOR inhibitor optimized for central nervous system (CNS) indications. We recently reported an mTOR inhibitor () that is able to block mTOR functions in the mouse brain and extend the survival of mice with neuronal-specific ablation of the 1 gene.

Brain Structure Measurements Predict Individualized Treatment Outcome of 12-Week Antipsychotic Monotherapies in First-episode Schizophrenia.

Background And Hypothesis: Early prediction of treatment response to antipsychotics in schizophrenia remains a challenge in clinical practice. This study aimed to investigate if brain morphometries including gray matter volume and cortical thickness could serve as potential predictive biomarkers in first-episode schizophrenia.

Study Design: Sixty-eight drug-naïve first-episode patients underwent baseline structural MRI scans and were subsequently randomized to receive a single antipsychotic throughout the first 12 weeks.

Discovery of a Brain-Penetrant ATP-Competitive Inhibitor of the Mechanistic Target of Rapamycin (mTOR) for CNS Disorders.

Recent clinical evaluation of everolimus for seizure reduction in patients with tuberous sclerosis complex (TSC), a disease with overactivated mechanistic target of rapamycin (mTOR) signaling, has demonstrated the therapeutic value of mTOR inhibitors for central nervous system (CNS) indications. Given that everolimus is an incomplete inhibitor of the mTOR function, we sought to develop a new mTOR inhibitor that has improved properties and is suitable for CNS disorders. Starting from an in-house purine-based compound, optimization of the physicochemical properties of a thiazolopyrimidine series led to the discovery of the small molecule , a potent and selective brain-penetrant ATP-competitive mTOR inhibitor.

Functional CRISPR screening identifies the ufmylation pathway as a regulator of SQSTM1/p62.

SQSTM1 is an adaptor protein that integrates multiple cellular signaling pathways and whose expression is tightly regulated at the transcriptional and post-translational level. Here, we describe a forward genetic screening paradigm exploiting CRISPR-mediated genome editing coupled to a cell selection step by FACS to identify regulators of SQSTM1. Through systematic comparison of pooled libraries, we show that CRISPR is superior to RNAi in identifying known SQSTM1 modulators.

Association of MTOR Mutations With Developmental Brain Disorders, Including Megalencephaly, Focal Cortical Dysplasia, and Pigmentary Mosaicism.

Importance: Focal cortical dysplasia (FCD), hemimegalencephaly, and megalencephaly constitute a spectrum of malformations of cortical development with shared neuropathologic features. These disorders are associated with significant childhood morbidity and mortality.

Objective: To identify the underlying molecular cause of FCD, hemimegalencephaly, and diffuse megalencephaly.

Macroautophagy is dispensable for growth of KRAS mutant tumors and chloroquine efficacy.

Macroautophagy is a key stress-response pathway that can suppress or promote tumorigenesis depending on the cellular context. Notably, Kirsten rat sarcoma (KRAS)-driven tumors have been reported to rely on macroautophagy for growth and survival, suggesting a potential therapeutic approach of using autophagy inhibitors based on genetic stratification. In this study, we evaluated whether KRAS mutation status can predict the efficacy to macroautophagy inhibition.

Anti-N-methyl-d-aspartate receptor encephalitis in a patient with a 7-year history of being diagnosed as schizophrenia: complexities in diagnosis and treatment.

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a form of autoimmune encephalitis associated with antibodies against the NR1 subunits of NMDARs. Although new-onset acute prominent psychotic syndromes in patients with NMDAR encephalitis have been well documented, there is a lack of case studies on differential diagnosis and treatment of anti-NMDAR encephalitis after a long-term diagnostic history of functional psychotic disorders. The present study reports an unusual case of anti-NMDAR encephalitis.

Selective VPS34 inhibitor blocks autophagy and uncovers a role for NCOA4 in ferritin degradation and iron homeostasis in vivo.

Cells rely on autophagy to clear misfolded proteins and damaged organelles to maintain cellular homeostasis. In this study we use the new autophagy inhibitor PIK-III to screen for autophagy substrates. PIK-III is a selective inhibitor of VPS34 that binds a unique hydrophobic pocket not present in related kinases such as PI(3)Kα.

Atg4b-dependent autophagic flux alleviates Huntington's disease progression.

The accumulation of aggregated mutant huntingtin (mHtt) inclusion bodies is involved in Huntigton's disease (HD) progression. Medium sized-spiny neurons (MSNs) in the corpus striatum are highly vulnerable to mHtt aggregate accumulation and degeneration, but the mechanisms and pathways involved remain elusive. Here we have developed a new model to study MSNs degeneration in the context of HD.

[Epidemiological survey on neuropsychiatric disorders in Tibet of China: neuroses, alcohol-related disorders, mental retardation and epilepsy].

Objective: To investigate the prevalence of four common neuropsychiatric disorders in Tibet, with an aim to providing information support to health planning.

Methods: The survey was carried out in four regions of Tibet. The sampling strategy was adapted from that of a national psychiatric epidemiological survey in China in 1982 and 1993.

Facial emotion processing in patients with schizophrenia and their non-psychotic siblings: a functional magnetic resonance imaging study.

Background: Previous studies have shown that patients with schizophrenia show abnormalities in brain activation when processing emotional faces. However, very few studies have examined if such abnormalities are also found in non-western patient samples and in at-risk individuals. The current study explored whether patients with schizophrenia and siblings of patients in China would show abnormal brain activation during processing of emotional faces.

RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulates axin degradation and Wnt signalling.

The Wnt/β-catenin signalling pathway plays essential roles in embryonic development and adult tissue homeostasis, and deregulation of this pathway has been linked to cancer. Axin is a concentration-limiting component of the β-catenin destruction complex, and its stability is regulated by tankyrase. However, the molecular mechanism by which tankyrase-dependent poly(ADP-ribosyl)ation (PARsylation) is coupled to ubiquitylation and degradation of axin remains undefined.

Inhibition of tumorigenesis driven by different Wnt proteins requires blockade of distinct ligand-binding regions by LRP6 antibodies.

Disregulated Wnt/beta-catenin signaling has been linked to various human diseases, including cancers. Inhibitors of oncogenic Wnt signaling are likely to have a therapeutic effect in cancers. LRP5 and LRP6 are closely related membrane coreceptors for Wnt proteins.

[Application of the Children's Impact of Event Scale (Chinese Version) on a rapid assessment of posttraumatic stress disorder among children from the Wenchuan earthquake area].

Objective: To explore the reliability and validity of the Children's Impact of Event Scale (Chinese version, CRIES-13) and to determine the value and the optimal cutoff point of the score of CRIES-13 in screening posttraumatic stress disorder (PTSD), so as to provide evidence for PTSD prevention and identify children at risk in Wenchuan earthquake areas.

Methods: A total of 253 children experienced the Wenchuan earthquake were tested through Stratified random cluster sampling. The authors examined CRIES-13's internal consistency, discriminative validity and predictive value of the cut-off.

Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling.

The stability of the Wnt pathway transcription factor beta-catenin is tightly regulated by the multi-subunit destruction complex. Deregulated Wnt pathway activity has been implicated in many cancers, making this pathway an attractive target for anticancer therapies. However, the development of targeted Wnt pathway inhibitors has been hampered by the limited number of pathway components that are amenable to small molecule inhibition.

A mutation in NFkB interacting protein 1 results in cardiomyopathy and abnormal skin development in wa3 mice.

We have identified waved 3 (wa3), a novel recessive mutation that causes abnormalities of the heart and skin. The cardiac defect results in a severe and rapidly progressive dilated cardiomyopathy. We identified the gene mutated in these mice, which we call NFkB interacting protein1 (Nkip1), using positional cloning.

A defect in a novel ADAMTS family member is the cause of the belted white-spotting mutation.

Several features of the pigment defect in belted (bt) mutant mice suggest that it occurs as a result of a defect in melanocyte development that is unique from those described for other classical white-spotting mutations. We report here that bt mice carry mutations in Adamts20, a novel member of the ADAMTS family of secreted metalloproteases. Adamts20 shows a highly dynamic pattern of expression in the developing embryo that generally precedes the appearance of melanoblasts in the same region, and is not expressed in the migrating cells themselves.

A defect in a novel Nek-family kinase causes cystic kidney disease in the mouse and in zebrafish.

The murine autosomal recessive juvenile cystic kidney (jck) mutation results in polycystic kidney disease. We have identified in jck mice a mutation in Nek8, a novel and highly conserved member of the Nek kinase family. In vitro expression of mutated Nek8 results in enlarged, multinucleated cells with an abnormal actin cytoskeleton.

Efficient generation and mapping of recessive developmental mutations using ENU mutagenesis.

Treatment with N-ethyl-N-nitrosourea (ENU) efficiently generates single-nucleotide mutations in mice. Along with the renewed interest in this approach, much attention has been given recently to large screens with broad aims; however, more finely focused studies have proven very productive as well. Here we show how mutagenesis together with genetic mapping can facilitate the rapid characterization of recessive loci required for normal embryonic development.