Trends in prevalence, mortality, and risk factors of dementia among the oldest-old adults in the United States: the role of the obesity epidemic.

The oldest-old population, those aged ≥ 80 years, is the fastest-growing group in the United States (US), grappling with an increasingly heavy burden of dementia. We aimed to dissect the trends in dementia prevalence, mortality, and risk factors, and predict future levels among this demographic. Leveraging data from the Global Burden of Disease Study 2019, we examined the trends in dementia prevalence, mortality, and risk factors (with a particular focus on body mass index, BMI) for US oldest-old adults. Through decomposition analysis, we identified key population-level contributors to these trends. Predictive modeling was employed to estimate future prevalence and mortality levels over the next decade. Between 1990 and 2019, the number of dementia cases and deaths among the oldest-old in the US increased by approximately 1.37 million and 60,000 respectively. The population growth and aging were highlighted as the primary drivers of this increase. High BMI emerged as a growing risk factor. Females showed a disproportionately higher dementia burden, characterized by a unique risk factor profile, including BMI. Predictions for 2030 anticipate nearly 4 million dementia cases and 160,000 related deaths, with a marked increase in prevalence and mortality anticipated among those aged 80-89. The past 30 years have witnessed a notable rise in both the prevalence and mortality of dementia among the oldest-old in the US, accompanied by a significant shift in risk factors, with obesity taking a forefront position. Targeted age and sex-specific public health strategies that address obesity control are needed to mitigate the dementia burden effectively.

Investigating metabolic dysregulation in serum of triple transgenic Alzheimer's disease male mice: implications for pathogenesis and potential biomarkers.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease that lacks convenient and accessible peripheral blood diagnostic markers and effective drugs. Metabolic dysfunction is one of AD risk factors, which leaded to alterations of various metabolites in the body. Pathological changes of the brain can be reflected in blood metabolites that are expected to explain the disease mechanisms or be candidate biomarkers. The aim of this study was to investigate the changes of targeted metabolites within peripheral blood of AD mouse model, with the purpose of exploring the disease mechanism and potential biomarkers. Targeted metabolomics was used to quantify 256 metabolites in serum of triple transgenic AD (3 × Tg-AD) male mice. Compared with controls, 49 differential metabolites represented dysregulation in purine, pyrimidine, tryptophan, cysteine and methionine and glycerophospholipid metabolism. Among them, adenosine, serotonin, N-acetyl-5-hydroxytryptamine, and acetylcholine play a key role in regulating neural transmitter network. The alteration of S-adenosine-L-homocysteine, S-adenosine-L-methionine, and trimethylamine-N-oxide in AD mice serum can served as indicator of AD risk. The results revealed the changes of metabolites in serum, suggesting that metabolic dysregulation in periphery in AD mice may be related to the disturbances in neuroinhibition, the serotonergic system, sleep function, the cholinergic system, and the gut microbiota. This study provides novel insights into the dysregulation of several key metabolites and metabolic pathways in AD, presenting potential avenues for future research and the development of peripheral biomarkers.

Study on the mechanism of arsenic-induced renal injury based on SWATH proteomics technology.

BACKGROUND: Arsenic (As) poisoning is a worldwide endemic disease affecting thousands of people. As is excreted mainly through the renal system, and arsenic has toxic effects on the kidneys, but the mechanism has not been elucidated. In this study, the molecular basis of arsenic's nephrotoxicity was studied by using a high-throughput proteomics technique. METHODS: Eight SD (Sprague-Dawley) rats, half male and half female, were fed an As diet containing 50 mg/kg NaAsO2. Age- and sex-matched rats fed with regular chow were used as controls. At the end of the experiment (90 days), kidney tissue samples were collected and assessed for pathological changes using hematoxylin-eosin staining. Proteomic methods were used to identify alterations in protein expression levels in kidney tissues, and bioinformatic analyses of differentially expressed proteins between arsenic-treated and control groups were performed. The expression of some representative proteins was validated by Western blot analysis. RESULTS: NaAsO2 could induce renal injury. Compared with the control group, 112 proteins were up-regulated, and 46 proteins were down-regulated in the arsenic-treated group. These proteins were associated with the electron transport chain, oxidative phosphorylation, mitochondrial membrane, apoptosis, and proximal tubules, suggesting that the mechanisms associated with them were related to arsenic-induced kidney injury and nephrotoxicity. The expressions of Atp6v1f, Cycs and Ndufs1 were verified, consistent with the results of omics. CONCLUSION: These results provide important evidence for arsenic-induced kidney injury and provide new insights into the molecular mechanism of arsenic-induced kidney injury.

A study of genetic heterogeneity in autism spectrum disorders based on plasma proteomic and metabolomic analysis: multiomics study of autism heterogeneity.

Genetic heterogeneity poses a challenge to research and clinical translation of autism spectrum disorder (ASD). In this study, we conducted a plasma proteomic and metabolomic study of children with ASD with and without risk genes (de novo mutation) and controls to explore the impact of genetic heterogeneity on the search for biomarkers for ASD. In terms of the proteomic and metabolomic profiles, the groups of children with ASD carrying and those not carrying de novo mutation tended to cluster and overlap, and integrating them yielded differentially expressed proteins and differential metabolites that effectively distinguished ASD from controls. The mechanisms associated with them focus on several common and previously reported mechanisms. Proteomics results highlight the role of complement, inflammation and immunity, and cell adhesion. The main pathways of metabolic perturbations include amino acid, vitamin, glycerophospholipid, tryptophan, and glutamates metabolic pathways and solute carriers-related pathways. Integrating the two omics analyses revealed that L-glutamic acid and malate dehydrogenase may play key roles in the pathogenesis of ASD. These results suggest that children with ASD may have important underlying common mechanisms. They are not only potential therapeutic targets for ASD but also important contributors to the study of biomarkers for the disease.

Effects of arsenic exposure on trace element levels in the hippocampus and cortex of rats and their gender differences.

BACKGROUND: Exposure to arsenic (As) is a major public health challenge worldwide. Chronic exposure to As can cause various human health effects, including skin diseases, cardiovascular disease, neurological disorders, and cancer. Studies have shown that As exposure can lead to disturbances in the balance of trace elements in the body. Moreover, As readily crosses the blood-brain barrier and can be enriched in the hippocampus and cortex, causing neurotoxic damage. At present, there are few reports on the effect of As on trace element levels in the central nervous system (CNS). Therefore, we sought to explore As-induced neurotoxicity and the effects of As on CNS trace element levels. METHODS: An As-induced neurological injury model in rats was established by feeding As chow for 90 days of continuous exposure, and 19 elements were detected in the hippocampus and cortex of As-exposed rats by inductively coupled plasma mass spectrometry. RESULTS: The results showed that the As levels in the hippocampus and cortex of As-exposed rats were significantly higher than those in the control group, The As levels in the cortex were significantly higher than in the hippocampus group. The levels of Cd, Ho, and Rb were increased in the hippocampus and decreased in Au, Ba, Ce, Cs, Pd, Se, Sr, and Tl in the As-exposed group, while the levels of Cd and Rb were increased and Se and Au were decreased in the cortex. Significant gender differences in the effects of As on hippocampal Cd, Ba, Rb, and Sr, and cortical Cd and Mo. CONCLUSION: It is suggested that elemental imbalance may be a risk factor for developing As toxicity plays a synergistic or antagonistic role in As-induced toxicity and is closely related to As-induced CNS damage.

Subcellular proteomics insights into Alzheimer's disease development.

Alzheimer's disease (AD), one of the most common dementias, is a neurodegenerative disease characterized by cognitive impairment and decreased judgment function. The expected number of AD patient is increasing in the context of the world's advancing medical care and increasing human life expectancy. Since current molecular mechanism studies on AD pathogenesis are incomplete, there is no specific and effective therapeutic agent. Mass spectrometry (MS)-based unbiased proteomics studies provide an effective and comprehensive approach. Many advances have been made in the study of the mechanism, diagnostic markers, and drug targets of AD using proteomics. This paper focus on subcellular level studies, reviews studies using proteomics to study AD-associated mitochondrial dysfunction, synaptic, and myelin damage, the protein composition of amyloid plaques (APs) and neurofibrillary tangles (NFTs), changes in tissue extracellular vehicles (EVs) and exosome proteome, and the protein changes in ribosomes and lysosomes. The methods of sample separation and preparation and proteomic analysis as well as the main findings of these studies are involved. The results of these proteomics studies provide insights into the pathogenesis of AD and provide theoretical resource and direction for future research in AD, helping to identify new biomarkers and drugs targets for AD.

Proteomic Study on the Mechanism of Arsenic Neurotoxicity in the Rat Cerebral Cortex and the Protective Mechanism of Dictyophora Polysaccharides against Arsenic Neurotoxicity.

Arsenic (As) is a toxic element, and long-term exposure to As can cause neurotoxicity. The bioactive natural compound Dictyophora polysaccharide (DIP) from edible plants has been reported to reduce the toxicity of As. In this study, As poisoning was simulated by feeding As-containing feed, followed by proteomic analysis after one month of DIP treatment. The proteomic analysis showed that 145, 276, and 97 proteins were differentially expressed between the As-treated rats and control rats (As/Ctrl group), DIP-treated + As-treated and As-treated rats (DIP + As/As group), and DIP + As and control rats (DIP + As/Ctrl group), respectively. The differentially expressed proteins (DEPs) in the As/Ctrl and DIP + As/Ctrl groups were mainly related to apoptosis, synapses, energy metabolism, nervous system development, and mitochondria. After DIP treatment, the expression of the dysregulated proteins in the As/Ctrl group was restored or reversed, and 12 of them were reversed proteins. These results suggest that energy metabolism disorder, apoptosis, mitochondrial dysfunction, nervous system development injury, synaptic dysfunction, and oxidative stress may be the key pathological mechanisms of As-induced nerve injury in rats. DIP can restore or reverse the expression of related proteins, which may be the main mechanism of its intervention in As poisoning.

Structural Analysis Implicates CASK-Liprin-α2 Interaction in Cerebellar Granular Cell Death in MICPCH Syndrome.

Microcephaly with pontine and cerebellar hypoplasia (MICPCH) syndrome is a neurodevelopmental disorder caused by the deficiency of the X-chromosomal gene CASK. However, the molecular mechanisms by which CASK deficiency causes cerebellar hypoplasia in this syndrome remain elusive. In this study, we used CASK knockout (KO) mice as models for MICPCH syndrome and investigated the effect of CASK mutants. Female CASK heterozygote KO mice replicate the progressive cerebellar hypoplasia observed in MICPCH syndrome. CASK KO cultured cerebellar granule (CG) cells show progressive cell death that can be rescued by co-infection with lentivirus expressing wild-type CASK. Rescue experiments with CASK deletion mutants identify that the CaMK, PDZ, and SH3, but not L27 and guanylate kinase domains of CASK are required for the survival of CG cells. We identify missense mutations in the CaMK domain of CASK derived from human patients that fail to rescue the cell death of cultured CASK KO CG cells. Machine learning-based structural analysis using AlphaFold 2.2 predicts that these mutations disrupt the structure of the binding interface with Liprin-α2. These results suggest that the interaction with Liprin-α2 via the CaMK domain of CASK may be involved in the pathophysiology of cerebellar hypoplasia in MICPCH syndrome.

SWATH proteomics analysis of placental tissue with intrahepatic cholestasis of pregnancy.

INTRODUCTION: Intrahepatic cholestasis of pregnancy (ICP) usually occurs in the second and third trimesters. The disease's etiology and diagnostic criteria are currently unknown. Based on a sequence window to obtain all theoretical fragment ions (SWATH) proteomic approach, this study sought to identify potential proteins in placental tissue that may be involved in the pathogenesis of ICP and adverse fetal pregnancy outcomes. METHODS: The postpartum placental tissue of pregnant women with ICP were chosen as the case group (ICP group) (subdivided into mild ICP group (MICP group) and severe ICP group (SICP group)), and healthy pregnant women were chosen as the control group (CTR). The hematoxylin-eosin (HE) staining was used to observe the histologic changes of placenta. The SWATH analysis combined with liquid chromatography-tandem mass spectrometry (LC-MS) was used to screen the differentially expressed proteins (DEPs) in ICP and CTR groups, and bioinformatics analysis was used to find out the biological process of these differential proteins. RESULTS: Proteomic studies showed there were 126 DEPs from pregnant women with ICP and healthy pregnant women. Most of the identified proteins were functionally related to humoral immune response, cell response to lipopolysaccharide, antioxidant activity and heme metabolism. A subsequent examination of placentas from patients with mild and severe ICP revealed 48 proteins that were differentially expressed. Through death domain receptors and fibrinogen complexes, these DEPs primarily regulate extrinsic apoptotic signaling pathways, blood coagulation, and fibrin clot formation. The differential expressions of HBD, HPX, PDE3A, and PRG4 were down-regulated by Western blot analysis, which was consistent with proteomics. DISCUSSION: This preliminary study helps us to understand the changes in the placental proteome of ICP patients, and provides new insights into the pathophysiology of ICP.

A Systematic Investigation of Complement and Coagulation-Related Protein in Autism Spectrum Disorder Using Multiple Reaction Monitoring Technology.

Autism spectrum disorder (ASD) is one of the common neurodevelopmental disorders in children. Its etiology and pathogenesis are poorly understood. Previous studies have suggested potential changes in the complement and coagulation pathways in individuals with ASD. In this study, using multiple reactions monitoring proteomic technology, 16 of the 33 proteins involved in this pathway were identified as differentially-expressed proteins in plasma between children with ASD and controls. Among them, CFHR3, C4BPB, C4BPA, CFH, C9, SERPIND1, C8A, F9, and F11 were found to be altered in the plasma of children with ASD for the first time. SERPIND1 expression was positively correlated with the CARS score. Using the machine learning method, we obtained a panel composed of 12 differentially-expressed proteins with diagnostic potential for ASD. We also reviewed the proteins changed in this pathway in the brain and blood of patients with ASD. The complement and coagulation pathways may be activated in the peripheral blood of children with ASD and play a key role in the pathogenesis of ASD.

Global incidence pattern and factors associated with common cutaneous reactions related to COVID-19 vaccination of 2.55 million participants in real-world settings: A systematic review and meta-analysis.

Background: Understanding the incidence pattern of cutaneous reactions is crucial for promoting COVID-19 vaccination. We aimed to report the global incidence pattern of, and factors associated with common cutaneous reactions related to COVID-19 vaccination in real-world settings. Methods: We searched five databases (PubMed, Web of Science, Embase, CNKI, and Wanfang) from inception to May 13, 2022, for studies reporting the incidence of common cutaneous reactions related to COVID-19 vaccines in real-world settings. The outcomes were the systematic skin reactions (rash and urticaria) and the local injection site reactions (pain, swelling, redness, and erythema). We conducted random-effects meta-analyses and explored associated factors using multi-step statistical analyses. Results: We included 35 studies and assessed 2 549 968 participants from 23 countries. The pooled incidence of overall systemic skin reactions was 3.8% (95% confidence interval (CI) = 2.4%-5.5%) with short duration (about one week). Specifically, the pooled incidence rates of rash and urticaria were 3.0% (95% CI = 2.1%-3.9%) and 1.1% (95% CI = 0.7%-1.5%), respectively. For overall local injection site reactions, the pooled incidence was 72.4% (95% CI = 65.7%-78.7%) with short duration (1 to 4.5 days). Except for local pain (72.2%, 95% CI = 65.3%-78.5%), other localized reactions had low incidence, including swelling (13.3%, 95% CI = 9.5%-17.7%), redness (11.5%, 95% CI = 5.7%-19.0%), and erythema (5.8%, 95% CI = 0.7%-15.4%). Geographically, different distribution patterns were observed for these reactions. Regarding associated factors, mRNA vaccines showed lower incidence of urticaria (P < 0.001). Asia population showed higher incidence of urticaria (P < 0.001). We observed lower incidence rates of overall local injection site reactions and pain among inactivated vaccines (P < 0.001). We found no significant difference among reactions between the first and the second dose of vaccines. Conclusions: We examined the global incidence pattern of common cutaneous reactions related to COVID-19 vaccination and found low incidence and short duration of systemic skin reactions and local injection site reactions (except for pain); discrepancies in these reactions were observed across different vaccine types. The cutaneous side effects related to COVID-19 vaccination do not seem to cause concern. Registration: PROSPERO: CRD42021258012.

Study on the Mechanism of Arsenic-Induced Lung Injury Based on SWATH Proteomics Technology.

Chronic arsenic poisoning is a global health problem that affects millions of people, and studies have found that long-term ingestion of arsenic-containing compounds can lead to lung damage, but the exact mechanism is unknown. In this study, Sprague-Dawley (SD) rats were used as the research object, and the proteomic analysis method based on sequential window acquisition of all theoretical fragment ions (SWATH) was used to detect the changes in the expression levels of related proteins in the lung tissue of arsenic-exposed rats, and to explore the mechanism of arsenic compound-induced lung injury. The results showed that arsenic exposure resulted in the abnormal expression of collagen type III and proteins involved in metabolic, immune, and cellular processes, leading to the dysfunction of important pathways associated with these proteins, resulting in lung injury. It suggested that the underlying mechanism of arsenic-induced lung injury may be related to oxidative stress, immune injury, cell junction, and collagen type III. This result provides a new research idea for revealing the mechanism of lung injury caused by arsenic exposure.

Effect of Helicobacter Pylori Eradication on Human Gastric Microbiota: A Systematic Review and Meta-Analysis.

Background: Helicobacter pylori (H. pylori) infection is a major risk factor for gastric cancer and eradication of H. pylori is recommended as an effective gastric cancer prevention strategy. The infected individuals show microbial dysbiosis of gastric microbiota. In recent years, agrowing number of studies have focused on gastric microbiota changes following H. pylori eradication. In the present study, we aim to evaluate the influence of successful H. pylori eradication on the short-term and long-term alterations of human gastric microbiota using a method of systematic review and meta-analysis. Methods: We did a systematic search based on three databases (PubMed, EMBASE, and Web of Science) in November 2021. Additional articles were also identified by reviewing references cited in the included papers. Human studies that reported changes in gastric microbiota following successful H. pylori eradication were enrolled. PROSPERO registration number: CRD42021293796. Results: In total, nine studies enrolling 546 participants were included. Regarding quadruple therapy, alpha diversity indexes increased within 1 month after eradication; significant differences in gastric microbial community structure between before and after eradication were also seen within 1 month. The trends of the above-mentioned diversity changes persisted with a follow-up of 6 months. The microbial composition altered significantly after eradication and the relative abundance of H. pylori-related taxa decreased. Accordingly, gastric commonly dominant commensals were enriched. Bioinformatic analyses of microbiota functions showed that bacteria reproduction-related pathways were down-regulated and pathways of gastric acid secretion, etc. were up-regulated. For triple therapy, similar trends of alpha diversity and beta diversity changes were observed in the short-term and long-term follow-up. Also, after eradication, H. pylori was not the gastric dominant bacteria and similar changes in gastric microbial composition were found. For gastric microbial interactions, a decrease in microbial interactions was seen after eradication. Additionally, regarding whether successful H. pylori eradication could restore gastric microbiota to uninfected status, the results remain controversial. Conclusion: In conclusion, successful H. pylori eradication could reverse the gastric microbiota dysbiosis and show beneficial effects on gastric microbiota. Our findings may provide new insight for exploring the role of H. pylori and the whole gastric microbiota in gastric carcinogenesis.

A Combined Proteomics and Metabolomics Profiling to Investigate the Genetic Heterogeneity of Autistic Children.

Autism spectrum disorder (ASD) has become one of the most common neurological developmental disorders in children. However, the study of ASD diagnostic markers faces significant challenges due to the existence of heterogeneity. In this study, genetic testing was performed on children who were clinically diagnosed with ASD. Children with ASD susceptibility genes and healthy controls were studied. The proteomics of plasma and peripheral blood mononuclear cells (PBMCs) as well as plasma metabolomics were carried out. The results showed that although there was genetic heterogeneity in children with ASD, the differentially expressed proteins (DEPs) in plasma, peripheral blood mononuclear cells, and differential metabolites in plasma could still effectively distinguish autistic children from controls. The mechanism associated with them focuses on several common and previously reported mechanisms of ASD. The biomarkers for ASD diagnosis could be found by taking differentially expressed proteins and differential metabolites into consideration. Integrating omics data, glycerophospholipid metabolism and N-glycan biosynthesis might play a critical role in the pathogenesis of ASD.

Oxidative Stress in Autism Spectrum Disorder-Current Progress of Mechanisms and Biomarkers.

Autism spectrum disorder (ASD) is a type of neurodevelopmental disorder that has been diagnosed in an increasing number of children around the world. Existing data suggest that early diagnosis and intervention can improve ASD outcomes. However, the causes of ASD remain complex and unclear, and there are currently no clinical biomarkers for autism spectrum disorder. More mechanisms and biomarkers of autism have been found with the development of advanced technology such as mass spectrometry. Many recent studies have found a link between ASD and elevated oxidative stress, which may play a role in its development. ASD is caused by oxidative stress in several ways, including protein post-translational changes (e.g., carbonylation), abnormal metabolism (e.g., lipid peroxidation), and toxic buildup [e.g., reactive oxygen species (ROS)]. To detect elevated oxidative stress in ASD, various biomarkers have been developed and employed. This article summarizes recent studies about the mechanisms and biomarkers of oxidative stress. Potential biomarkers identified in this study could be used for early diagnosis and evaluation of ASD intervention, as well as to inform and target ASD pharmacological or nutritional treatment interventions.

iTRAQ-Based Proteomics Analysis of Rat Cerebral Cortex Exposed to Valproic Acid before Delivery.

Autism spectrum disorder (ASD) is a neurological and developmental disorder characterized by social and communication difficulties. Valproic acid (VPA) injection during pregnancy elicits autism-like behavior in the offspring, making it a classic animal model of ASD. However, the mechanisms involved have not yet been determined. In this study, we used iTRAQ (isobaric tags for relative and absolute quantification) proteomics analysis of the cerebral cortex of a VPA rat model (VPA group) and controls (CON group). The results showed that 79 differentially expressed proteins (DEPs) were identified between the VPA group and the CON group. Based on bioinformatics analysis, the DEPs were mainly enriched at synapses, especially glutamatergic synapses and GABAergic synapses. Some DEPs were involved in energy metabolism, thyroid hormone synthesis pathway, and Na+-K+-ATPase. Cytoskeleton and endoplasmic reticulum (ER) stress-related proteins were also involved. Some DEPs matched either the ASD gene database or previous reports on cerebral cortical transcriptome studies in VPA rat models. Dysregulation of these DEPs in the cerebral cortex of VPA rats may be responsible for autism-like behavior in rats. We also found that some DEPs were associated with neuropsychiatric disorders, implying that these diseases share common signaling pathways and mechanisms. Moreover, increased expression of DEPs was associated with energy metabolism in the cerebral cortex of VPA rats, implying that ASD may be a distinct type of mitochondrial dysfunction that requires further investigation.

IQSEC3 Deletion Impairs Fear Memory Through Upregulation of Ribosomal S6K1 Signaling in the Hippocampus.

BACKGROUND: IQSEC3, a gephyrin-binding GABAergic (gamma-aminobutyric acidergic) synapse-specific guanine nucleotide exchange factor, was recently reported to regulate activity-dependent GABAergic synapse maturation, but the underlying signaling mechanisms remain incompletely understood. METHODS: We generated mice with conditional knockout (cKO) of Iqsec3 to examine whether altered synaptic inhibition influences hippocampus-dependent fear memory formation. In addition, electrophysiological recordings, immunohistochemistry, and behavioral assays were used to address our question. RESULTS: We found that Iqsec3-cKO induces a specific reduction in GABAergic synapse density, GABAergic synaptic transmission, and maintenance of long-term potentiation in the hippocampal CA1 region. In addition, Iqsec3-cKO mice exhibited impaired fear memory formation. Strikingly, Iqsec3-cKO caused abnormally enhanced activation of ribosomal P70-S6K1-mediated signaling in the hippocampus but not in the cortex. Furthermore, inhibiting upregulated S6K1 signaling by expressing dominant-negative S6K1 in the hippocampal CA1 of Iqsec3-cKO mice completely rescued impaired fear learning and inhibitory synapse density but not deficits in long-term potentiation maintenance. Finally, upregulated S6K1 signaling was rescued by IQSEC3 wild-type, but not by an ARF-GEF (adenosine diphosphate ribosylation factor-guanine nucleotide exchange factor) inactive IQSEC3 mutant. CONCLUSIONS: Our results suggest that IQSEC3-mediated balanced synaptic inhibition in hippocampal CA1 is critical for the proper formation of hippocampus-dependent fear memory.

Trace Element Changes in the Plasma of Autism Spectrum Disorder Children and the Positive Correlation Between Chromium and Vanadium.

Existing data demonstrate a significant correlation between autism spectrum disorder (ASD) and the status of biologically essential and toxic trace elements. However, there is still a lack of data on the steady state of trace elements in ASD. We performed a case-control study to explore the association between the risk of ASD and 23 trace elements in plasma. The results showed that children with ASD had considerably decreased lithium (Li), manganese (Mn), selenium (Se), barium (Ba), mercury (Hg), and tin (Sn) levels when compared to their age- and sex-matched controls. Meanwhile, children with ASD had considerably increased plasma chromium (Cr) and vanadium (V) concentrations. We also divided each group into subgroups based on age and gender and created element-related networks for each subgroup. We detected significant element correlations within or between subgroups, as well as changes in correlations that included all elements examined. Finally, more element correlations were observed among males, which may open a new avenue for understanding the complicated process behind the sex ratio of children with ASD. Overall, our data revealed a novel relationship between elements and ASD, which may extend current understanding about ASD.

Gastric microbiota in gastric cancer: Different roles of Helicobacter pylori and other microbes.

Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide. The gastric microbiota plays a critical role in the development of GC. First, Helicobacter pylori (H. pylori) infection is considered a major risk factor for GC. However, recent studies based on microbiota sequencing technology have found that non-H. pylori microbes also exert effects on gastric carcinogenesis. Following the infection of H. pylori, gastric microbiota dysbiosis could be observed; the stomach is dominated by H. pylori and the abundances of non-H. pylori microbes reduce substantially. Additionally, decreased microbial diversity, alterations in the microbial community structure, negative interactions between H. pylori and other microbes, etc. occur, as well. With the progression of gastric lesions, the number of H. pylori decreases and the number of non-H. pylori microbes increases correspondingly. Notably, H. pylori and non-H. pylori microbes show different roles in different stages of gastric carcinogenesis. In the present mini-review, we provide an overview of the recent findings regarding the role of the gastric microbiota, including the H. pylori and non-H. pylori microbes, in the development of GC.

Inhibition of DNA ligase IV enhances the CRISPR/Cas9-mediated knock-in efficiency in mouse brain neurons.

CRISPR/Cas9-mediated gene knock-in in in vivo neurons using in utero electroporation is a powerful technique, but the knock-in efficiency is generally low. We previously demonstrated that co-transfection with RAD51, a key molecule of the initial step of homology-directed repair (HDR), expression vector increased EGFP knock-in efficiency in the ß-actin site up to 2.5-fold in the pyramidal neurons in layer 2/3 of the somatosensory cortex of mouse brain. To further improve the efficiency, we examined the effect of inhibition of DNA ligase IV (LIG4) that is an essential molecule for non-homologous end joining (NHEJ). Co-transfection with small hairpin RNA for LIG4 (shlig4) expression vector increased the EGFP knock-in efficiency in the ß-actin site up to 3.6-fold compared to the condition without shlig4. RAD51 and shlig4 expression vector co-transfection further increased the knock-in efficiency up to 4.7-fold of the control condition. These results suggest that the inhibition of LIG4 is more effective than RAD51 overexpression, and it enhances the effect of RAD51 overexpression on HDR-mediated gene knock-in in vivo neurons.