Computational Study on Interlocked-Ferroelectricity-Contributed High-Performance Memristors Based on Two-Dimensional van der Waals Ferroelectric Semiconductors.

In order to realize the prevailing artificial intelligence technology, memristor-implemented in-memory or neuromorphic computing is highly expected to break the bottleneck of von Neumann computers. Although high-performance memristors have been vigorously developed in labs or in industry, systematic computational investigations on memristors are seldom. Hence, it is urgent to provide theoretical or computational support for the exploration of memristor operating mechanisms or the screening of memristor materials. Here, a computational method based on the main input parameters learned from the first-principles calculations was developed to measure resistance switching of two-terminal memristors with sandwiched metal/ferroelectric semiconductor/metal architectures, which strikingly agrees with the experimental measurements. Based on our developed method, the diverse multiterminal memristors were designed to fully exploit the application of interlocked ferroelectricity of a ferroelectric semiconductor and realize their heterosynaptic plasticity, and their heterosynaptic behaviors can still be well described. Our developed method can provide a paradigm for the emulation of ferroelectric memristors and inspire subsequent computational exploration. Furthermore, our study also supplies a device optimization strategy based on the interlocked ferroelectricity and easy processing of two-dimensional van der Waals ferroelectric semiconductors, and our proposed heterosynaptic memristors still await further experimental exploration.

VX-509 attenuates the stemness characteristics of colorectal cancer stem-like cells by regulating the epithelial-mesenchymal transition through Nodal/Smad2/3 signaling.

BACKGROUND: Colorectal cancer stem cells (CCSCs) are heterogeneous cells that can self-renew and undergo multidirectional differentiation in colorectal cancer (CRC) patients. CCSCs are generally accepted to be important sources of CRC and are responsible for the progression, metastasis, and therapeutic resistance of CRC. Therefore, targeting this specific subpopulation has been recognized as a promising strategy for overcoming CRC. AIM: To investigate the effect of VX-509 on CCSCs and elucidate the underlying mechanism. METHODS: CCSCs were enriched from CRC cell lines by in conditioned serum-free medium. Western blot, Aldefluor, transwell and tumorigenesis assays were performed to verify the phenotypic characteristics of the CCSCs. The anticancer efficacy of VX-509 was assessed in HCT116 CCSCs and HT29 CCSCs by performing cell viability analysis, colony formation, sphere formation, flow cytometry, and western blotting assessments in vitro and tumor growth, immunohistochemistry and immunofluorescence assessments in vivo. RESULTS: Compared with parental cells, sphere cells derived from HCT116 and HT29 cells presented increased expression of stem cell transcription factors and stem cell markers and were more potent at promoting migration and tumorigenesis, demonstrating that the CRC sphere cells displayed CSC features. VX-509 inhibited the tumor malignant biological behavior of CRC-stem-like cells, as indicated by their proliferation, migration and clonality in vitro, and suppressed the tumor of CCSC-derived xenograft tumors in vivo. Besides, VX-509 suppressed the CSC characteristics of CRC-stem-like cells and inhibited the progression of epithelial-mesenchymal transition (EMT) signaling in vitro. Nodal was identified as the regulatory factor of VX-509 on CRC stem-like cells through analyses of differentially expressed genes and CSC-related database information. VX-509 markedly downregulated the expression of Nodal and its downstream phosphorylated Smad2/3 to inhibit EMT progression. Moreover, VX-509 reversed the dedifferentiation of CCSCs and inhibited the progression of EMT induced by Nodal overexpression. CONCLUSION: VX-509 prevents the EMT process in CCSCs by inhibiting the transcription and protein expression of Nodal, and inhibits the dedifferentiated self-renewal of CCSCs.

Mouse Models of Orofacial Clefts: SHH and TGF-ß Pathways.

Birth defects have always been one of the most important diseases in medical research as they affect the quality of the birth population. Orofacial clefts (OFCs) are common birth defects that place a huge burden on families and society. Early screening and prevention of OFCs can promote better natal and prenatal care and help to solve the problem of birth defects. OFCs are the result of genetic and environmental interactions; many genes are involved, but the current research has not clarified the specific pathogenesis. The mouse animal model is commonly used for research into OFCs; common methods of constructing OFC mouse models include transgenic, chemical induction, gene knockout, gene knock-in and conditional gene knockout models. Several main signal pathways are involved in the pathogenesis of OFCs, including the Sonic hedgehog (SHH) and transforming growth factor (TGF)-ß pathways. The genes and proteins in each molecular pathway form a complex network to jointly regulate the formation and development of the lip and palate. When one or more genes, proteins or interactions is abnormal, OFCs will form. This paper summarises the mouse models of OFCs formed by different modelling methods, as well as the key pathogenic genes from the SHH and TGF-ß pathways, to help to clarify the pathogenesis of OFCs and develop targets for early screening and prevention.

Effects of urea solution concentration on soil hydraulic properties and water infiltration capacity.

Elucidating the effect of fertigation on soil hydraulic parameters and water-solute transportation is fundamental to the design of farmland irrigation systems and their sustainable utilization. Few studies have focused on soil hydraulic parameters or water infiltration characteristics or how they are influenced by urea solution concentration. In this study, the clay loam and sandy loam in Yangling District of Shaanxi Province, China, were used as test soil, and experiments involving seven urea solution concentrations (0.2, 0.4, 0.6, 0.8, 1, 3, and 5 g/L) and a control treatment (0 g/L) were conducted to explore the influence of the various urea solution concentrations on soil hydraulic parameters and water infiltration characteristics. The results indicated that the cumulative infiltration and wetting front migration depth increased with urea solution concentration, as accurately estimated using the Kostiakov model and a power function, respectively. In addition, the coefficients of the Kostiakov model and the power function increased with urea solution concentration. Treatment with multiple concentrations of urea solution resulted in an increase in the volume of macro pores in the soil but a reduction in the volume of mesopores and micro pores in the soil, leading to increases in the saturated water content, saturated hydraulic conductivity, soil water diffusivity, and infiltration capacity and a reduction in the water-holding capacity of the soil. The effect of urea solute potential on the inhibition of soil water movement is small, and this inhibitory effect is far weaker than the improvement effect of the urea solution on soil structure, and hence enhance the soil water infiltration capacity. Our results increase the understanding of soil hydrological mechanisms and may be usefully applied for improving the management of fertigation.

Decoding the mechanical conductance switching behaviors of dipyridyl molecular junctions.

Dipyridyl molecular junctions often show intriguing conductance switching behaviors with mechanical modulations, but the mechanisms are still not completely revealed. By applying the ab initio-based adiabatic simulation method, the configuration evolution and electron transport properties of dipyridyl molecular junctions in stretching and compressing processes are systematically investigated. The numerical results reveal that the dipyridyl molecular junctions tend to form specific contact configurations during formation processes. In small electrode gaps, the pyridyls almost vertically adsorb on the second Au layers of the tip electrodes by pushing the top Au atoms aside. These specific contact configurations result in stronger molecule-electrode couplings and larger electronic incident cross-sectional areas, which consequently lead to large breaking forces and high conductance. On further elongating the molecular junctions, the pyridyls shift to the top Au atoms of the tip electrodes. The additional scattering of the top Au atoms dramatically decreases the conductance and switches the molecular junctions to the lower conductive states. Perfect cyclical conductance switches are obtained as observed in the experiments by repeatedly stretching and compressing the molecular junctions. The O atom in the side-group tends to hinder the pyridyl from adsorbing on the second Au layer and further inhibits the conductance switch of the dipyridyl molecular junction.

[Thoughts of treatment of tumor diseases based on toxic pathogen theory].

The toxic pathogen theory, an important part of the theories of traditional Chinese medicine(TCM), began in the Qin and Han dynasties, formed in the Jin, Sui, Tang, and Song dynasties, developed rapidly in the Ming and Qing dynasties, and conti-nued to develop in contemporary times based on the achievements of its predecessors. The continuous exploration, practice, and inheri-tance of many medical practitioners over the generations have facilitated the enrichment of its connotation. The toxic pathogen is violent, fierce, dangerous, prolonged, rapid in transmission, easy to hurt the internal organs, hidden, and latent, with many changes, and it is closely related to the development of tumor diseases. TCM has a history of thousands of years in the prevention and treatment of tumor diseases. It is gradually realized that the etiology of tumor is mainly attributed to the deficiency of healthy Qi and excess of to-xic pathogen, and the struggle between healthy Qi and toxic pathogen runs through the whole course of tumor, with the deficiency of healthy Qi as the prerequisite and the invasion of toxic pathogen as the root of the occurrence. The toxic pathogen has a strong carcinogenic effect and is involved in the whole process of tumor development, which is closely related to the malignant behaviors of tumors, including proliferation, invasion, and metastasis. This study discussed the historical origin and modern interpretation of the toxic pathogen theory in the prevention and treatment of tumors, with aims of sorting out the theoretical system based on the toxic pathogen theory in the treatment of tumor diseases, and illustrating the importance of the toxic pathogen theory in the treatment of tumors in the context of modern research on pharmacological mechanisms and the development and marketing of relevant anti-tumor Chinese medicinal preparations.

[Spatial Distribution Characteristics and Influencing Factors of Soil Organic Carbon Density in Yellow River Basin Based on MGWR Model].

As the largest terrestrial carbon pool, the spatial distribution characteristics and influencing factors of soil organic carbon have important implications for global carbon cycle processes. Soil organic carbon density (SOCD) and influencing factors were predicted in the Yellow River basin using a mixed geographically weighted regression (MGWR) model based on soil organic carbon density data and environmental factors. The results showed that:① the SOCD ranged from 0-14.82 kg·m-2 and 0-32.39 kg·m-2 for the soil depths of 0-20 cm and 0-100 cm, with mean values of 3.48 kg·m-2 and 8.07 kg·m-2 and reserves of 2.76 Pg and 6.48 Pg, respectively. The high SOCD value areas were mainly located in the southern part of the Qinghai-Tibet Plateau and Loess Plateau, and the low value areas were located in the eastern part of the upper Yellow River and the inland flow area. ②Among the ecosystem types, the SOCD of soil depth in 0-20 cm was in the descending order of:forest>water body and wetland>other>grassland>farmland>settlement>desert, with mean values of 4.52, 4.31, 3.84, 3.73, 2.89, 2.78, and 2.22 kg·m-2, respectively, and the SOCD of the 0-100 cm soil depth was in the descending order of:water bodies and wetlands>forest>other>grassland>farmland>settlement>desert, with mean values of 9.58, 9.58, 8.85, 8.66, 7.07, 6.81, and 5.29 kg·m-2, respectively. The SOCR in descending order was:grassland>farmland>forest>desert>water bodies and wetlands>settlement>others, with 1.40, 0.60, 0.47, 0.11, 0.07, 0.06, and 0.05 Pg at a soil depth of 0-20 cm and 3.31, 1.49, 0.99, 0.26, 0.17, 0.14, and 0.12 Pg at a soil depth of 0-100 cm, respectively. ③ The main factors affecting the SOCD distribution were intercept, profile curvature, NDVI, and precipitation; in addition, curvature and silt also had important effects on the deep SOCD distribution in the Yellow River basin. Among the ecosystem types, precipitation and NDVI were the main factors affecting the SOCD distribution. The intercept also had important effects on the SOCD distribution in the all ecosystems except forests, whereas curvature and silt only had important effects on deserts and other ecosystems. These results revealed the spatial distribution of SOCD, influencing factors, and SOCR in the Yellow River basin and can provide a scientific basis for carbon balance, soil quality evaluation, and ecological management restoration and consolidation in the region.

Mapping network connectivity between internet addiction and residual depressive symptoms in patients with depression.

Background and aims: Depression often triggers addictive behaviors such as Internet addiction. In this network analysis study, we assessed the association between Internet addiction and residual depressive symptoms in patients suffering from clinically stable recurrent depressive disorder (depression hereafter). Materials and methods: In total, 1,267 depressed patients were included. Internet addiction and residual depressive symptoms were measured using the Internet Addiction Test (IAT) and the two-item Patient Health Questionnaire (PHQ-2), respectively. Central symptoms and bridge symptoms were identified via centrality indices. Network stability was examined using the case-dropping procedure. Results: The prevalence of IA within this sample was 27.2% (95% CI: 24.7-29.6%) based on the IAT cutoff of 50. IAT15 ("Preoccupation with the Internet"), IAT13 ("Snap or act annoyed if bothered without being online") and IAT2 ("Neglect chores to spend more time online") were the most central nodes in the network model. Additionally, bridge symptoms included the node PHQ1 ("Anhedonia"), followed by PHQ2 ("Sad mood") and IAT3 ("Prefer the excitement online to the time with others"). There was no gender difference in the network structure. Conclusion: Both key central and bridge symptoms found in the network analysis could be potentially targeted in prevention and treatment for depressed patients with comorbid Internet addiction and residual depressive symptoms.

COVID-19 vaccine acceptance and perceived stigma in patients with depression: a network perspective.

The association between coronavirus disease (COVID-19) vaccine acceptance and perceived stigma of having a mental illness is not clear. This study examined the association between COVID-19 vaccine acceptance and perceived stigma among patients with recurrent depressive disorder (depression hereafter) using network analysis. Participants were 1149 depressed patients (842 men, 307 women) who completed survey measures of perceived stigma and COVID-19 vaccine attitudes. T-tests, chi-square tests, and Kruskal-Wallis tests were used to compare differences in demographic and clinical characteristics between depressed patients who indented to accepted vaccines and those who were hesitant. Hierarchical multiple regression analyses assessed the unique association between COVID-19 vaccine acceptance and perceived stigma, independent of depression severity. Network analysis examined item-level relations between COVID-19 vaccine acceptance and perceived stigma after controlling for depressive symptoms. Altogether, 617 depressed patients (53.7%, 95 confidence intervals (CI) %: 50.82-56.58%) reported they would accept future COVID-19 vaccination. Hierarchical multiple regression analyses indicated higher perceived stigma scores predicted lower levels of COVID-19 vaccination acceptance (ß = -0.125, P < 0.001), even after controlling for depression severity. In the network model of COVID-19 vaccination acceptance and perceived stigma nodes, "Feel others avoid me because of my illness", "Feel useless", and "Feel less competent than I did before" were the most influential symptoms. Furthermore, "COVID-19 vaccination acceptance" had the strongest connections with illness stigma items reflecting social rejection or social isolation concerns ("Employers/co-workers have discriminated", "Treated with less respect than usual", "Sense of being unequal in my relationships with others"). Given that a substantial proportion of depressed patients reported hesitancy with accepting COVID-19 vaccines and experiences of mental illness stigma related to social rejection and social isolation, providers working with this group should provide interventions to reduce stigma concerns toward addressing reluctance in receiving COVID-19 vaccines.

Brainstem abscesses caused by Listeria monocytogenes: A case report.

BACKGROUND: Intracranial Listeria infections are common in newborns and immunocompromised individuals, but brainstem abscesses are rare. CASE SUMMARY: We report a rare case of brainstem abscesses caused by Listeria monocytogenes in a previously healthy adult patient. The patient's magnetic resonance imaging examination showed multiple brain abscesses, and his second cerebrospinal fluid culture test indicated the presence of Listeria monocytogenes. Despite early empirical therapy, the patient's condition progressively deteriorated. Because the patient's abscesses were located in the brainstem and multiple lobes, surgery was not possible. The patient died 40 d after admission. CONCLUSION: This case highlights the importance of rational clinical use of drugs to avoid potentially serious infectious complications.

Integrated systematic pharmacology analysis and experimental validation to reveal the mechanism of action of Semen aesculi on inflammatory bowel diseases.

BACKGROUND AND ETHNOPHARMACOLOGICAL RELEVANCE: Semen aesculi (SA), a traditional Chinese herb, has been used in the treatment of gastrointestinal disease for thousands of years. The escin was the main components of SA. A growing number of research showed that escin has a wide range of pharmacological activities in intestinal barrier dysfunction. AIM OF THE STUDY: Inflammatory bowel diseases (IBD) are an idiopathic disease of the intestinal tract with the hallmark features of mucosal inflammation and loss of barrier function. The theory of traditional Chinese medicine (TCM) suggests that SA plays a potential role in protecting the gastrointestinal diseases. The present study aimed to explore the effects of SA on the intestinal barrier under existing inflammatory conditions and elucidate underlying mechanisms. MATERIALS AND METHODS: The bioactive components of SA and their predicted biological targets were combined to develop a compound target pathway network. It is used to predict the bioactive components, molecular targets, and molecular pathways of SA in improving IBD. The ingredients of SA were extracted by decoction either in water and ethanol and separated into four fractions (AE, EE, PEE and PCE). The effects of extractions were evaluated in the lipopolysaccharide (LPS)-induced RAW264.7 macrophages cell model, LPS-induced intestinal barrier injury model and imodium-induced constipation model. The high-performance liquid chromatography (HPLC) analysis was performed to identify the bioactive components. RESULTS: The compound-target pathway network was identified with 10 bioactive compounds, 166 IBD-related targets, and 52 IBD-related pathways. In LPS-induced RAW264.7 cells, PEE and PCE significantly decreased nitric oxide (NO) production and TNF-α level. In mice, PEE and PCE administration improved intestinal barrier damage, increased intestinal motility, reduced levels of TNF-α and diamine oxidase (DAO). Furthermore, PEE and PCE administration not only decreased expression of p-Akt, p-IκBα, nuclear p-p65, and TNF-α level, but also increased expression of the zonula occludin-1 (ZO-1) in LPS-induced intestinal barrier injury model. The escin content of AE, EE, PEE and PCE gradually increased with an increase of the bioactivity. CONCLUSIONS: Escin was the main bioactive components of SA. The effects of SA on IBD were mediated by repairing the intestinal barrier and promoting intestinal motility. The mechanism of action of SA is related to inhibiting the Akt/NF-κB signaling pathway in intestinal tissue, at least, in part. Our results provide a scientific basis for further exploring the mechanisms involved in the beneficial effects of SA in IBD.

Muscone and (+)-Borneol Cooperatively Strengthen CREB Induction of Claudin 5 in IL-1ß-Induced Endothelium Injury.

Claudin 5 is one of the major proteins of tight junctions and is responsible for cerebrovascular integrity and BBB function. Muscone and (+)-borneol is the major ingredient of moschus and borneolum, respectively, with antioxidative and anti-inflammatory activities. This study investigated whether muscone and (+)-borneol combination protected claudin 5 by targeting ROS-mediated IL-1ß accumulation. Muscone and (+)-borneol reduced cerebral infarct volume and cerebrovascular leakage with claudin 5 protection in mice after stroke, largely due to inhibiting ROS accumulation and inflammatory infiltrate of microglia. Muscone reduced ROS and then blocked the CaN/Erk1/2 pathway to decrease IL-1ß release, while (+)-borneol removed mitochondrial ROS and attenuated the SDH/Hif-1α pathway to inhibit IL-1ß transcription, thereby jointly reducing IL-1ß production. Accumulated IL-1ß disrupted cAMP/CREB activation and attenuated transcriptional regulation of claudin 5. Muscone and (+)-borneol combination cooperatively protected BBB function by blocking IL-1ß-mediated cAMP/CREB/claudin 5 cascades. Mutation of Ser133 site of CREB or knockdown of claudin 5 weakened the effects of muscone and (+)-borneol on upregulation of TEER value and downregulation of FITC-dextran permeability, suggesting that targeting CREB/claudin 5 was an important strategy to protect vascular integrity. This study provided ideas for the studies of synergistic protection against ischemic brain injury about the active ingredients of traditional Chinese medicines (TCMs).

Suicidality in clinically stable bipolar disorder and schizophrenia patients during the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has a disproportionate impact on vulnerable subpopulations, including those with severe mental illness (SMI). This study examined the one-year prevalence of suicidal ideation (SI), suicide plans (SP), and suicide attempts (SA) in bipolar disorder (BD) and schizophrenia (SCZ) patients during the pandemic. Prevalence rates were compared between the two disorders and associated factors were examined. A survey was conducted in six tertiary psychiatric hospitals and psychiatric units. People with a diagnosis of BD or SCZ were invited to participate. SI, SP, and SA (suicidality for short) were assessed and associated factors were examined using binary logistical regression. The 1-year prevalence of SI, SP and SA in BD patients were 58.3%, (95% CI: 54.1-62.6%), 38.4% (95% CI: 34.3-42.6%) and 38.6% (95% CI: 34.5-42.8%), respectively, which were higher than the corresponding figures in SCZ patients (SI: 33.2%, 95% CI: 28.6-37.8%; SP: 16.8%, 95% CI: 13.2-20.5%; SA: 19.4%, 95% CI: 15.5-23.3%). Patients with younger age, experience of cyberbullying, a history of SA among family or friends, a higher fatigue and physical pain score, inpatient status, and severe depressive symptoms were more likely to have suicidality. The COVID-19 pandemic was associated with increased risk of suicidality, particularly in BD patients. It is of importance to regularly screen suicidality in BD and SCZ patients during the pandemic even if they are clinically stable.

The prevalence of internet addiction and its association with quality of life among clinically stable patients with major depressive disorder.

BACKGROUND: Internet addiction (IA) is associated with mental health problems but its impact on quality of life (QOL) is understudied. We examined the prevalence of IA and its association with QOL in clinically stable patients with major depressive disorder (MDD). METHODS: In a cross-sectional survey between September 2020 and July 2021, the Young's Internet Addiction Test (IAT), the Patient Health Questionnaire-2 (PHQ-2) and the World Health Organization Quality of Life Brief version scale (WHOQOL-BREF) were administered to 1267 patients with MDD. Logistic regression was used to examine the correlates of IA, while analysis of covariance (ANCOVA) was used to examine the association between IA and QOL." RESULTS: The prevalence of IA (IAT total scores ≥50) was 27.2 % (95 % CI: 24.7 %-29.6 %) in MDD patients. Compared to patients without IA, those with IA had lower QOL (F(1, 1267) = 19.1, P < 0.001). Logistic regression revealed that higher education (senior high school and above; OR = 1.85, 95 % CI: 1.13-3.03), family history of psychiatric disorders (OR = 1.72, 95 % CI: 1.08-2.73), and higher PHQ-2 total score (OR = 1.23, 95 % CI: 1.14-1.32) were positively associated with IA while older age (OR = 0.93, 95 % CI: 0.91-0.96) was inversely related to IA. CONCLUSION: IA is much more common in clinically stable patients with MDD compared to the reported figures in the general population. It would be prudent to screen and monitor internet use in MDD patients and treat those with IA.

Hydroxysafflor Yellow A Blocks HIF-1α Induction of NOX2 and Protects ZO-1 Protein in Cerebral Microvascular Endothelium.

Zonula occludens-1 (ZO-1) is a tight junction protein in the cerebrovascular endothelium, responsible for blood-brain barrier function. Hydroxysafflor yellow A (HSYA) is a major ingredient of safflower (Carthamus tinctorius L.) with antioxidative activity. This study investigated whether HSYA protected ZO-1 by targeting ROS-generating NADPH oxidases (NOXs). HSYA administration reduced cerebral vascular leakage with ZO-1 protection in mice after photothrombotic stroke, largely due to suppression of ROS-associated inflammation. In LPS-stimulated brain microvascular endothelial cells, HSYA increased the ratio of NAD+/NADH to restore Sirt1 induction, which bound to Von Hippel-Lindau to promote HIF-1αdegradation. NOX2 was the predominant isoform of NOXs in endothelial cells and HIF-1α transcriptionally upregulated p47phox and Nox2 subunits for the assembly of the NOX2 complex, but the signaling cascades were blocked by HSYA via HIF-1α inactivation. When oxidate stress impaired ZO-1 protein, HSYA attenuated carbonyl modification and prevented ZO-1 protein from 20S proteasomal degradation, eventually protecting endothelial integrity. In microvascular ZO-1 deficient mice, we further confirmed that HSYA protected cerebrovascular integrity and attenuated ischemic injury in a manner that was dependent on ZO-1 protection. HSYA blocked HIF-1α/NOX2 signaling cascades to protect ZO-1 stability, suggestive of a potential therapeutic strategy against ischemic brain injury.

Internet addiction and its association with quality of life in patients with major depressive disorder: a network perspective.

Depressive disorders and internet addiction (IA) are often comorbid. The aims of this study were to examine the network structure of IA in patients with major depressive disorders (MDD) and explore the association between IA and quality of life (QoL) in this population. This was a multicenter, cross-sectional survey. IA and QoL were assessed with the Internet Addiction Test (IAT) and the World Health Organization Quality of Life-brief version, respectively. Node expected influence (EI) was used to identify central symptoms in the network model, while the flow network of QoL was generated to examine its association with IA. A total of 1,657 patients with MDD was included. "Preoccupation with the Internet," "Job performance or productivity suffer because of the Internet," and "Neglect chores to spend more time online" were central symptoms. The symptom "Form new relationships with online users" had the strongest direct positive relation with QoL, while "Spend more time online over going out with others" and "Job performance or productivity suffer because of the Internet" had the strongest direct negative relations with QoL. Neglecting work caused by IA correlated with QoL, while making friends online appropriately was related to better QoL among MDD patients. Appropriate interventions targeting the central symptoms may potentially prevent or reduce the risk of IA in MDD patients.

Plasma Extracellular Vesicle Long RNAs Have Potential as Biomarkers in Early Detection of Colorectal Cancer.

Background: Early detection of colorectal cancer (CRC) is crucial to the treatment and prognosis of patients. Traditional screening methods have disadvantages. Methods: 231 blood samples were collected from 86 CRC, 56 colorectal adenoma (CRA), and 89 healthy individuals, from which extracellular vesicle long RNAs (exLRs) were isolated and sequenced. An CRC diagnostic signature (d-signature) was established, and prognosis-associated cell components were evaluated. Results: The exLR d-signature for CRC was established based on 17 of the differentially expressed exLRs. The d-signature showed high diagnostic efficiency of CRC and control (CRA and healthy) samples with an area under the curve (AUC) of 0.938 in the training cohort, 0.943 in the validation cohort, and 0.947 in an independent cohort. The d-signature could effectively differentiate early-stage (stage I-II) CRC from healthy individuals (AUC 0.990), as well as differentiating CEA-negative CRC from healthy individuals (AUC 0.988). A CRA d-signature was also generated and could differentiate CRA from healthy individuals both in the training (AUC 0.993) and validation (AUC 0.978) cohorts. The enrichment of class-switched memory B-cells, B-cells, naive B-cells, and mast cells showed increasing trends between CRC, CRA, and healthy cohorts. Class-switched memory B-cells, mast cells, and basophils were positively associated with CRC prognosis while natural killer T-cells, naive B-cells, immature dendritic cells, and lymphatic endothelial cells were negatively associated with prognosis. Conclusions: Our study identified that the exLR d-signature could differentiate CRC from CRA and healthy individuals with high efficiency and exLR profiling also has potential in CRA screening and CRC prognosis prediction.

[Relationship between Oral Microbiota and Alzheimer's Disease].

Alzheimer's disease (AD) is a common neurodegenerative disease. In an aging society, the high prevalence of AD and the low quality of life of AD patients create serious problems for individuals, families and the society. However, the etiology and pathogenesis of AD are still not fully understood. Age, genetics, environment and other factors are all relevant to AD, and treatment has not achieved satisfactory results. Recent studies have found that oral dysbiosis is closely related to the pathogenesis of AD, and that oral bacterial infection may be one of the causes of AD. Oral cavity is the largest microbial ecosystem of human body, and its homeostasis is critical to health. Bacterial infections caused by oral dysbiosis can directly and indirectly induce the metabolic imbalance of amyloid ß-protein (Aß) in the brain and the hyperphosphorylation of Tau protein. Then, the precipitation forms senile plaques and neurofibrillary tangles (NFTs) that damage neurons. Based on the latest research findings, we herein discussed the correlation between oral microbiota and the pathogenesis of AD and the mechanisms involved, as well as the pathogenic mechanism of main oral bacteria. In addition, we explored the potential application prospects of oral microbiota-targeted therapy.

Prevalence of suicidality in clinically stable patients with major depressive disorder during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic is associated with an increased risk of mental health problems including suicide in many subpopulations, but its influence on stable patients with major depressive disorder (MDD) has been studied fleetingly. This study examined the one-year prevalence of suicidality including suicidal ideation (SI), suicide plans (SP), and suicide attempts (SA) as well as their correlates in clinically stable MDD patients during the COVID-19 pandemic. METHODS: A cross-sectional, observational study was conducted between October 1, 2020, and October 15, 2021, in six tertiary psychiatric hospitals. Socio-demographic information, clinical data and one-year prevalence of suicidality were recorded. RESULTS: Altogether, 1718 participants who met the eligibility criteria were included. The overall one-year prevalence of suicidality during the COVID-19 pandemic was 68.04% (95% confidence intervals (CI) =65.84-70.25%), with one-year SI prevalence of 66.4% (95%CI = 64.18-68.65%), SP prevalence of 36.26% (95%CI = 33.99-38.54%), and SA prevalence of 39.35% (95%CI = 37.04-41.66%). Binary logistic regression analyses revealed male gender, married marital status, college education level and above and age were negatively associated with risk of suicidality. Urban residence, unemployed work status, experiences of cyberbullying, a history of suicide among family members or friends, and more severe fatigue, physical pain, and residual depressive symptoms were positively associated with risk of suicidality. CONCLUSIONS: Suicidality is common among clinically stable MDD patients during the COVID-19 pandemic. Regular suicide screening and preventive measures should be provided to clinically stable MDD patients during the pandemic.

Blockage of citrate export prevents TCA cycle fragmentation via Irg1 inactivation.

The metabolism of activated macrophages relies on aerobic glycolysis, while mitochondrial oxidation is disrupted. In lipopolysaccharide-activated macrophages, the citrate carrier (CIC) exports citrate from mitochondria to enhance glycolytic genes through histone acetylation. CIC inhibition or Slc25a1 knockdown reduces the occupancy of H3K9ac to hypoxia-inducible factor-1α (HIF-1α) binding sites in promoters of glycolytic genes to restrain glycolysis. HIF-1α also transcriptionally upregulates immune-responsive gene 1 for itaconate production, which is inhibited by CIC blocking. Isotopic tracing of [U-13C6] glucose shows that CIC blockage prevents citrate accumulation and itaconate production by reducing glycolytic flux and facilitating metabolic flux in the TCA cycle. Isotopic tracing of [U-13C5] glutamine reveals that CIC inhibition reduces succinate accumulation from glutaminolysis and the gamma-aminobutyric acid shunt by enhancing mitochondrial oxidation. By restraining glycolysis, CIC inhibition increases NAD+ content to ensure mitochondrial biogenesis for oxidative phosphorylation. Furthermore, blockage of citrate export reduces cerebral thrombosis by inactivation of peripheral macrophages.