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Integrase strand transfer inhibitors (INSTIs) have emerged as the first-line choice for treating human immunodeficiency virus (HIV) infection due to their superior efficacy and safety. However, the impact of INSTIs on the development of neuropsychiatric conditions in people living with HIV (PLWH) is not fully understood due to limited data. In this study, we conducted a cross-sectional examination of PLWH receiving antiretroviral therapy, with a specific focus on HIV-positive men who have sex with men (MSM) on INSTI-based regimens (n = 61) and efavirenz (EFV)-based regimens (n = 28). Participants underwent comprehensive neuropsychiatric evaluations and multimodal magnetic resonance imaging (MRI) scans, including T1-weighted images and resting-state functional MRI. Compared to the EFV group, the INSTI group exhibited primarily reduced gray matter volume (GMV) in the right superior parietal gyrus, higher regional homogeneity (ReHo) in the left postcentral gyrus, lower ReHo in the right orbital part of the inferior frontal gyrus, and increased voxel-wise functional connectivity for the seed region in the left inferior temporal gyrus with clusters in the right cuneus. Furthermore, the analysis revealed a main effect of antiretroviral drugs on GMV changes, but no main effect of neuropsychiatric disorders or their interaction. The repeated analysis of participants who did not switch regimens confirmed the GMV changes in the INSTI group, validating the initial findings. Our study demonstrated gray matter atrophy and functional brain changes in PLWH on INSTI-based regimens compared to those on EFV-based regimens. These neuroimaging results provide valuable insights into the characteristics of brain network modifications in PLWH receiving INSTI-based regimens.

BackgroundMultiple sclerosis (MS), a chronic autoimmune disorder marked by demyelination in the central nervous system, is exceptionally uncommon in China, and remains poorly understood in terms of its peripheral blood manifestations.MethodsWe conducted a cohort study comprising 39 MS patients and 40 normal controls (NC). High-dimensional mass cytometry, protein arrays, and targeted metabolomics were utilized to profile immune subsets, proteins, and metabolites in blood. Differences in multi-omics signatures were scrutinized across varying MS subtypes.ResultsImmune profiling demonstrated an elevation in various B cell subsets and monocytes, alongside a reduction in dendritic cells among MS patients. Proteomic data revealed a downregulation in neurotrophic and tissue repair proteins. Metabolomic assessment showed a noted decrease in anti-inflammatory molecules and sphingolipids. Integrated analysis identified distinct molecular patterns distinguishing MS from controls. Additionally, multi-omics differences among different MS subtypes were uncovered. Notably, hippuric acid levels was consistently lower in MS subgroups with greater disease severity.ConclusionThis study represents the pioneering exploration of multi-omics in Chinese MS patients, presenting a comprehensive view of the peripheral blood changes in MS. Our study underscores the robust capability of multi-omics assessments in identifying peripheral blood biomarkers that delineate the varied clinical presentation, and facilitates future development of biomarkers and targeted therapeutic interventions in MS.

BackgroundPeople living with HIV (PLWH) exhibits an increased susceptibility to anxiety disorders, concomitant with heightened vulnerability to aberrant immune activation and inflammatory responses, and endocrine dysfunction. There exists a dearth of scholarly investigations pertaining to the neurological, immune, and endocrine dimensions of HIV-associated anxiety disorders.MethodThis study aimed to compare a group of 16 individuals diagnosed with HIV-associated anxiety disorders (HIV ANXs) according to the Diagnostic and statistical manual of mental disorders (5th ed.), with a HIV individual control group (HIV control) of 49 PLWH without mental disorders. Muti-modal magnetic resonance was employed to assess the brain function and structure of both groups. Seed-based functional connectivity (FC) was used to assess the regional intrinsic brain activity and the influence of regional disturbances on FC with other brain regions. Peripheral blood cytokines and chemokines concentrations were measured using liquid chip and ELISA.ResultsAmplitude of low-frequency fluctuations in the right inferior temporal gyrus (ITG) was increased. There is a significant decreased regional homogeneity in HIV ANXs in the right superior occipital gyrus (SOG). The right ITG and the right SOG were separately set as the seed brain region of interest (ROI 1 and ROI 2) to be analyzed the FC. FC decreased in HIV ANXs between ROI1 and the right middle occipital gyrus, the right SOG, FC between ROI2 and left ITG increased in HIV ANXs. No significant structural difference was found between two groups. Pro-inflammatory chemokines showed higher levels in the HIV ANXs. Pro-inflammatory cytokines, neurotrophic factors, and endocrine factors were significantly correlated with alterations in brain function.ConclusionThis study suggests that patients with HIV-associated anxiety disorders may exhibit abnormalities in neurologic, immune, and endocrine functioning. Consequently, it is imperative to implement additional screening and intervention measures for anxiety disorders among PLWH.

Abstract Objective To determine whether adverse childhood experiences (ACEs) of children of alcoholics (COA) in male were associated with their current “risky drinking”. Methods This case–control study used the Alcohol Use Disorder Identification Test (AUDIT, cutoff is 7) to divide the participants into two groups, a “risky drinking” group (N = 53) and a "non-risky drinking” group (N = 97). Demographic data, Adverse Childhood Experiences-International Questionnaire (ACE-IQ), the Hamilton Anxiety Rating Scale (HAMA), the Hamilton Depression Rating Scale (HAMD) and the Mini-International Neuropsychiatric Interview (MINI) were used for assessment. The specific relationships between ACEs and “risky drinking” were explored. Results Respondents ranged in age from 29.70 ± 6.72 years; 74.5% were females; 94.7% were of Han nationality; 56.7% had a level of education above high school; 12% had no formal or stable job. There was difference in attitude to self-drinking between two groups (P

AimAppraise the clinical features and influencing factors of the hospitalization times and length of stay in bipolar disorder (BD) patients.MethodsThis is a multicenter, observational, cohort study of patients diagnosed of type I or type II bipolar disorder. Five hundred twenty outpatients in seven hospitals from six cities in China were recruited from February 2013 to June 2014 and followed up using a continuous sampling pattern. The research included a retrospective period of 12 months and the prospective period of 9 months. The demographic and clinical features of the patients were collected. The influencing factors that could affect the length of stay (number of days spent in the hospital in the prospective period) were analyzed by poisson's regression and the hospitalization times (times of hospitalization in the prospective and retrospective period) was analyzed by general linear model. The selected variables included gender, age, years of education, occupational status, residence status, family history of mental disease, comorbid substance abuse, comorbid anxiety disorder, times of suicide (total suicide times that occurred in the retrospective and prospective period), polarity of the first mood episode, and BD type(I/II).ResultsPoisson's regression analysis showed that suicide times [Incidence Rate Ratio (IRR) = 1.20, p < 0.001], use of antipsychotic (IRR = 0.62, p = 0.011), and use of antidepressant (IRR = 0.56, p < 0.001) were correlated to more hospitalization times. Linear regression analysis showed that BD type II (β = 0.28, p = 0.005) and unemployment (β = 0.16, p = 0.039) which might mean longer duration of depression and poor function were correlated to longer length of stay. However, patients who experienced more suicide times (β = −0.21, p = 0.007) tended to have a shorter length of stay.ConclusionOverall, better management of the depressive episode and functional rehabilitation may help to reduce the length of stay. BD patients with more hospitalization times were characterized by higher risk of suicide and complex polypharmacy. Patients at high risk of suicide tended to have inadequate therapy and poor compliance, which should be assessed and treated adequately during hospitalization.Clinical trial registrationwww.ClinicalTrials.gov, Identifier: NCT01770704.

Introduction Major depressive disorder (MDD) represents a worldwide burden on healthcare and the response to antidepressants remains limited. Systems biology approaches have been used to explore the precision therapy. However, no reliable biomarker clinically exists for prognostic prediction at present. The objectives of the Integrated Module of Multidimensional Omics for Peripheral Biomarkers (iMORE) study are to predict the efficacy of antidepressants by integrating multidimensional omics and performing validation in a real-world setting. As secondary aims, a series of potential biomarkers are explored for biological subtypes.Methods and analysis iMore is an observational cohort study in patients with MDD with a multistage design in China. The study is performed by three mental health centres comprising an observation phase and a validation phase. A total of 200 patients with MDD and 100 healthy controls were enrolled. The protocol-specified antidepressants are selective serotonin reuptake inhibitors and serotonin–norepinephrine reuptake inhibitors. Clinical visits (baseline, 4 and 8 weeks) include psychiatric rating scales for symptom assessment and biospecimen collection for multiomics analysis. Participants are divided into responders and non-responders based on treatment response (>50% reduction in Montgomery-Asberg Depression Rating Scale). Antidepressants’ responses are predicted and biomarkers are explored using supervised learning approach by integration of metabolites, cytokines, gut microbiomes and immunophenotypic cells. The accuracy of the prediction models constructed is verified in an independent validation phase.Ethics and dissemination The study was approved by the ethics committee of Shanghai Mental Health Center (approval number 2020-87). All participants need to sign a written consent for the study entry. Study findings will be published in peer-reviewed journals.Trial registration number NCT04518592.

This study optimized the slope and slope length factor (LS) and crop management factor (P) of the RUSLE model and then introduced the gravity centre model to analyze the spatial–temporal variation patterns of soil erosion in Yellow River Basin from a new perspective. Results showed that: (1) The improved model of RUSLE with optimized factors of LS and P had better applicability in Yellow River Basin; (2) The average erosion intensity was 2777.5 t/a, which belonged to moderate erosion. The soil erosion intensity of the Yellow River Basin showed an overall trend of increasing firstly (1990–2005) and then decreasing (2005–2015). (3) During 1990–2015, the gravity centre of soil erosion moved to the southwest, indicating that the increment and increasing rate of soil erosion in the southwest parts of the Yellow River Basin were greater than that in the northeast parts. (4) The intensity of soil erosion aggravated with the increasing slope. The sandy soil, chestnut soil, light-grey calcium soil and fluvo aquic soil had severe erosion intensity due to the regional climate and their own physical–chemical structure. The woodland and shrubbery land were more susceptible to soil erosion.

Based on the datasets of MODIS NDVI and SPOT VETGETATION NDVI from 1999 to 2018, this study has introduced the gravity centre model and time-lag analysis model to explore the spatial–temporal change patterns of the NDVI in China in different sub-regions and its response to climate factors. Results showed that: (1) In 1999–2018, there was an increasing trend in vegetation coverage in China on the whole, with a larger increase occurring in central south and northeast China. (2) The NDVIs of six land use types showed a similar change trend with temperature and precipitation with different time lags. (3) The maximum correlation coefficients between the NDVIs of different land types and climate factors appeared at Lag 0–1 (current month and previous one month) and Lag 0–2 (current month, previous one and two month), while the correlation coefficients were the lowest at Lag 3 (previous three month). (4) During the past twenty years, the gravity centres of the NDVI, temperature and precipitation moved northward as a whole with similar migration trajectories. These results could provide important decision supports for vegetation restorations and ecological protections in different sub-regions of China.

The COVID-19 pandemic threatens physical and mental health of adolescents worldwide and has caused increased risks of dependence and addiction on Internet use during home quarantine. Internet addiction has become an important issue in mental healthcare and its prevention and treatment is of great significance for the development of adolescents. We have gathered leading experts in China and developed this guideline to provide references and suggestions to prevent and treat Internet addiction in adolescents during home quarantine and help them get through the pandemic.

The rainfall erosivity in China have shown different change characteristics and patterns at different spatial–temporal scales. In this article, we introduced a gravity centre model for use in studying and analyzing the spatial–temporal distribution patterns of rainfall erosivity in China in the past 58 years combined with traditional geostatistical analysis methods at different spatial–temporal scales. During 1961–2018, rainfall erosivity in China showed a decreasing trend from southeast to northwest in spatial distribution. Moreover, the spatial distribution patterns of the annual average rainfall erosivity had been negatively affected by altitude. In terms of interannual variability, rainfall erosivity had shown a fluctuating upward trend in the past 58 years, with a steep upward slope in 1982 and a steep downward slope in 1990. In the past 58 years, the gravity centre of rainfall erosivity in China had moved southeastward, which indicated that the increment and increasing rate of rainfall erosivity in eastern and southern China were greater than those in western and northern China. These results could provide important data to support decisions regarding the prevention and control of soil erosion at regional and national scales.

c-Met has emerged as an attractive target for targeted cancer therapy because of its abnormal activation in many cancer cells. To identify high potent and selective c-Met inhibitors, we started with profiling the potency and in vitro metabolic stability of a reported hit 7. By rational design, a novel sulfonylpyrazolo[4,3-b]pyridine 9 with improved DMPK properties was discovered. Further elaboration of p-p stacking interactions and solvent accessible polar moieties led to a series of highly potent and selective type I c-Met inhibitors. On the basis of in vitro and in vivo pharmacological and pharmacokinetics studies, compound 46 was selected as a preclinical candidate for further anticancer drug development. [ABSTRACT FROM AUTHOR]

We have developed a chromogenic and fluorescent chemodosimeter 3, based on a novel anion-catalyzed intramolecular hydrogen transfer, which displayed drastic changes in UV-Vis absorption as well as fluorescence emission intensities showing selectively for F− over other anions. [ABSTRACT FROM AUTHOR]