The association between problematic short video use and suicidal ideation and self-injurious behaviors: the mediating roles of sleep disturbance and depression.

BACKGROUND: Prior work suggests that problematic short video use was associated with adverse psychological, physiological, and educational outcomes. With the prevailing of short video platforms, the potential relationships between this problematic behavior and suicidal ideation and self-injurious behaviors have yet to be thoroughly examined. Besides, considering the potential dual nature of problematic short video use, particularly its positive aspects, a potential mechanism may exist linking such problematic behavior to SI and SIBs, ultimately driving individuals towards extreme outcomes. Nevertheless, such mediation paths have not been rigorously examined. Thus, the current study aimed to investigate their relationships and delve into the underlying mechanism, specifically identifying potential mediators between sleep disturbance and depression. METHODS: A quantitative cross-sectional study design was employed to model data derived from a large sample of first- and second-year university students residing in mainland China (N = 1,099; Mage = 19.80 years; 51.7% male). RESULTS: Results showed that problematic short video use has a dual impact on SI and SIBs. On the one hand, problematic short video use was directly related to the decreased risk of suicidal ideation, attempts, and NSSI. On the other hand, such problematic behavior was indirectly associated with the increased risk of NSSI through sleep disturbance, and it indirectly related to the elevated risk of suicidal ideation, attempts, and NSSI through depression. Besides, on the whole, problematic short video use was positively associated with NSSI but not suicidal ideation and attempts. CONCLUSIONS: These findings indicated that problematic short video use had a dual impact on SI and SIBs. Consequently, it is paramount to comprehend the genuine magnitude of the influence that such problematic behavior holds over these intricate psychological conditions.

Sensitivity to Control Signals in Triphasic Rhythmic Neural Systems: A Comparative Mechanistic Analysis via Infinitesimal Local Timing Response Curves.

Similar activity patterns may arise from model neural networks with distinct coupling properties and individual unit dynamics. These similar patterns may, however, respond differently to parameter variations and specifically to tuning of inputs that represent control signals. In this work, we analyze the responses resulting from modulation of a localized input in each of three classes of model neural networks that have been recognized in the literature for their capacity to produce robust three-phase rhythms: coupled fast-slow oscillators, near-heteroclinic oscillators, and threshold-linear networks. Triphasic rhythms, in which each phase consists of a prolonged activation of a corresponding subgroup of neurons followed by a fast transition to another phase, represent a fundamental activity pattern observed across a range of central pattern generators underlying behaviors critical to survival, including respiration, locomotion, and feeding. To perform our analysis, we extend the recently developed local timing response curve (lTRC), which allows us to characterize the timing effects due to perturbations, and we complement our lTRC approach with model-specific dynamical systems analysis. Interestingly, we observe disparate effects of similar perturbations across distinct model classes. Thus, this work provides an analytical framework for studying control of oscillations in nonlinear dynamical systems and may help guide model selection in future efforts to study systems exhibiting triphasic rhythmic activity.

The association between victimization experiences and suicidality: The mediating roles of sleep and depression.

BACKGROUND: Prior work suggests that multiple forms of victimization were associated with higher suicide risk among adolescents. However, the mechanisms underlying this association remain unclear. The present study aimed to understand the relationships between the multiple forms of victimization and suicidality by examining the potential mediators of sleep duration and depression. METHODS: Data for this study came from the 2019 Youth Risk Behavior Survey (YRBS). The hypothesized mediation model included 13,677 American adolescents in 9th through 12th-grade students (48.6 % female) were analyzed using Mplus 7.4, and suicidality (including suicidal ideation, plan, and attempts) as the outcome variables and the multiple forms of victimization (including bullying at school, being threatened at school, electronic bullying, sexual victimization, sexual dating victimization, and physical dating victimization) as the main explanatory variable. RESULTS: The relationships between the multiple forms of victimization and suicide risk were mediated by sleep duration, depression, and also serially mediated by sleep duration and depression. LIMITATIONS: This is a cross-sectional study, and the results cannot inform the causality between these variables. This investigation only included adolescent sleep duration, and other specific sleep problem indicators should be included. CONCLUSIONS: Longer sleep duration is an important protective factor, pointing the way forward for developing suicide prevention strategies and targeted interventions for adolescents.

Comprehensive analysis of endoplasmic reticulum-related and secretome gene expression profiles in the progression of non-alcoholic fatty liver disease.

Endoplasmic reticulum (ER) is the principal organelle for protein synthesis, such as hepatokines and transmembrane proteins, and is critical for maintaining physiological function. Dysfunction of ER is associated with metabolic disorders. However, the role of ER homeostasis as well as hepatokines in the progression of non-alcoholic fatty liver disease (NAFLD) remains to be elucidated. Here we comprehensively analyzed the RNA-seq profiles of liver biopsies from 206 NAFLD patients and 10 controls from dataset GSE135251. The co-expression modules were constructed based on weighted gene co-expression network analysis and six co-expression modules were identified, of which brown module stood out to be significantly associated with fibrosis stage and NAFLD activity score (NAS). Subsequently, cytoscape with cytoHubba plugin was applied to identify hub genes in the brown module. GO and KEGG enrichment analysis of the top 20 hub genes were performed and showed the involvement of extracellular matrix formation, collagen synthesis and decomposition, etc. Further, the expression of the top 20 hub genes were found to be a consistent increasing trend as the fibrosis stages and NAS increased, which have been validated both in HFD fed and HFHC fed mice. Among these genes, THY1, PTGDS, TMPRSS3, SPON1, COL1A2, RHBDF1, COL3A1, COL5A1, COL1A1 and IGFBP7 performed well in distinguishing fibrosis stage, while COL1A2, COL3A1, THY1, RHBDF1 and COL1A2 exhibited good capacity to discriminate NAS. Besides, RHBDF1, COL3A1, QSOX1, STING1, COL5A1, IGFBP7, COL4A2, COL1A1, FKBP10 and COL1A2 also showed a strong power in the diagnosis of NAFLD. In addition, COL1A1, COL1A2, COL3A1, COL8A2, IGFBP7, PGF, PTGDS, SPON1, THY1 and TIMP1 were identified as secretome genes from the top 20 hub genes. Of them, circulated THY1 and collagen III level were validated to be significantly elevated in the MCD diet-induced mice. Thus, we provided a systemic view on understanding the pathological roles and mechanisms of ER as well as secretome in NAFLD progression. THY1, COL1A1, COL1A2, COL3A1 and RHBDF1 could be served as candidate biomarkers to evaluate the progression of NAFLD.

A homeostasis criterion for limit cycle systems based on infinitesimal shape response curves.

Homeostasis occurs in a control system when a quantity remains approximately constant as a parameter, representing an external perturbation, varies over some range. Golubitsky and Stewart (J Math Biol 74(1-2):387-407, 2017) developed a notion of infinitesimal homeostasis for equilibrium systems using singularity theory. Rhythmic physiological systems (breathing, locomotion, feeding) maintain homeostasis through control of large-amplitude limit cycles rather than equilibrium points. Here we take an initial step to study (infinitesimal) homeostasis for limit-cycle systems in terms of the average of a quantity taken around the limit cycle. We apply the "infinitesimal shape response curve" (iSRC) introduced by Wang et al. (SIAM J Appl Dyn Syst 82(7):1-43, 2021) to study infinitesimal homeostasis for limit-cycle systems in terms of the mean value of a quantity of interest, averaged around the limit cycle. Using the iSRC, which captures the linearized shape displacement of an oscillator upon a static perturbation, we provide a formula for the derivative of the averaged quantity with respect to the control parameter. Our expression allows one to identify homeostasis points for limit cycle systems in the averaging sense. We demonstrate in the Hodgkin-Huxley model and in a metabolic regulatory network model that the iSRC-based method provides an accurate representation of the sensitivity of averaged quantities.

High efficacy and safety of CD38 and BCMA bispecific CAR-T in relapsed or refractory multiple myeloma.

BACKGROUND: B-cell maturation antigen (BCMA) chimeric antigen receptor T (CAR-T) cell therapy has obtained promising results in relapsed or refractory multiple myeloma (R/R MM), while some patients do not response, or relapse in short term after treatment. Combining with anti-CD38 might solve the problem of targeting BCMA alone. We aimed to assess the efficacy and safety of BCMA and CD38 (BCMA-CD38) bispecific CAR-T cells in R/R MM patients. METHODS: We did a single-center, single-arm clinical study at the Second Affiliated Hospital of Yangtze University in China. Patients meeting with the inclusion criteria were administered with fludarabine and cyclophosphamide before CAR-T cells infusion. Response and adverse events were assessed after infusion. This study was registered with the Chinese Clinical Trial Registration Center (ChiCTR1900026286). RESULTS: First, we found BCMA-CD38 CAR-T cells exhibited enhanced killing effect on BCMA+CD38+ cells in vitro, compared to BCMA CAR-T and CD38 CAR-T cells. We further demonstrated its anti-tumor activity in vivo. Then, we enrolled 16 R/R MM patients for safety and efficacy analyses. Of the 16 evaluable patients, 14 (87.5%) respond to the treatment, including 13 stringent complete response (sCR) and one partial response (PR), while two patients did not respond. At a median follow-up of 11.5 months, of the 13 patients who achieved sCR, 76.9% (10/13) did not relapse or progress during follow-up. Relapse occurred in 3 patients (Patient 2, 3 and 4) after achieving sCR. In sum, four patients died, of which one died of hemophagocytic lymphohistiocytosis syndrome secondary to severe cytokine release syndrome (CRS) and three died of disease progression or relapse. The 1-year progression-free survival rates was 68.8%. The 1-year overall survival rate was 75.0%. Extramedullary lesions were eliminated in 62.5% (5/8) patients. The most common symptoms after CAR-T infusion were cytopenia (16, 100%), fever (10, 62.5%), fatigue (8, 50.0%) and myalgias (8, 50.0%). Twelve patients (75.0%) were observed with various grades of CRS, of which five patients (31.3%) got serious CRS (Grade ≥ 3). The CAR+ cell expansion levels were associated with the severity of CRS. Transient clonal isotype switch was observed after CAR-T infusion. CONCLUSION: Our results confirm that BCMA-CD38 CAR-T cells therapy is feasible in treating R/R MM patients, with high response rate, low recurrence rate and manageable CRS, which will be a promising treatment option for R/R MM. TRIAL REGISTRATION: ChiCTR1900026286, registered on September 29, 2019, retrospectively registered, URL: https://www.chictr.org.cn/showproj.aspx?proj=43805.

hsa­miR­429 targets CBX8 to promote cell apoptosis in diffuse large B­cell lymphoma.

Diffuse large B­cell lymphoma (DLBCL) is the most common type of non­Hodgkin lymphoma worldwide. Several studies have indicated that Homo sapiens (hsa)­microRNA (miR)­429 exerts a tumor­suppressive effect on a variety of malignant tumors. To the best of our knowledge, the molecular function and mechanism of action of hsa­miR­429 in DLBCL have not been evaluated to date. The present study demonstrated that the expression of hsa­miR­429 in DLBCL cells was significantly reduced. hsa­miR­429 inhibited the proliferation of the DLBCL cell lines, SUDHL­4 and DB, and promoted apoptosis. A dual luciferase reporter assay was used to demonstrate that chromobox 8 (CBX8) was the target gene of hsa­miR­429. Overexpression of CBX8 promoted the proliferation of SUDHL­4 and DB cells and inhibited apoptosis, thereby playing a cancer­promoting role. Transfection of hsa­miR­429 mimic into DB cells overexpressing CBX8 antagonized the effect of CBX8 on the proliferation of DB cells. Moreover, the apoptotic rate was increased in DB cells overexpressing CBX8 and transfected with hsa­miR­429 mimic, while the proportion of cells in the G2/M phase was significantly reduced. These results demonstrated the antagonistic effect of hsa­miR­429 on the oncogenic function of CBX8. Therefore, in DLBCL, the tumor suppressor effect of hsa­miR­429 may be achieved by targeted downregulation of CBX8, suggesting that hsa­miR­429 may be used as a diagnostic marker and a potential nucleic acid drug for DLBCL. CBX8 may also represent an effective therapeutic target for DLBCL.

Responses in PM2.5 and its chemical components to typical unfavorable meteorological events in the suburban area of Tianjin, China.

Air pollution is the result of enormous emissions and unfavorable meteorological conditions. The role of meteorology, particularly extremely unfavorable meteorological events (EUMEs), in processing atmospheric PM2.5 pollution has not been fully addressed. This work examined the variations of PM2.5 mass and its chemical components associated with various meteorological parameters and three EUMEs based on meteorological observations and analysis combined with one-year long in situ measurement in 2018 in the suburban area of Tianjin, China. Analysis shows that the polluted days in 2018 were mostly related to the increase in sulfate, nitrate, and ammonium (SNA). Temperature between -2 to 13 °C is more favorable for the formation of SNA, while high temperature exceeding 28 °C is favorable for the formation of organic carbon and sulfate. Most of the ions and carbon components showed significant increase in concentrations when relative humidity exceeded 80%. The maximum decreasing rate of PM2.5 concentrations due to increase in wind speed and planetary boundary height could be 15.35 µg m-3 (m s-1)-1, and 34.37 µg m-3 (100 m)-1, respectively. EUMEs showed significant impacts on PM2.5 components, in which PM2.5 concentrations showed the most significant increase under temperature inversion (TI) events, and surface-based TI (SBTI) events usually have much stronger impacts on PM2.5 concentrations than elevated TI (ELTI). Nitrate was found to be the most sensitive component to EUMEs, especially under multiple EUMEs. The synthetic effects of multiple EUMEs could result in an increase of nitrate by 35.53 µg m-3 (523.3%). In addition, OC and sulfate are more sensitive to heat wave events. Our analysis provides improved understanding of the formation of PM2.5 pollution with respect to meteorology, particularly EUMEs. Based on such information, more attention may be needed on the collaborative prediction of EUMEs and air pollution episodes.

Dynamical consequences of sensory feedback in a half-center oscillator coupled to a simple motor system.

We investigate a simple model for motor pattern generation that combines central pattern generator (CPG) dynamics with a sensory feedback (FB) mechanism. Our CPG comprises a half-center oscillator with conductance-based Morris-Lecar model neurons. Output from the CPG drives a push-pull motor system with biomechanics based on experimental data. A sensory feedback conductance from the muscles allows modulation of the CPG activity. We consider parameters under which the isolated CPG system has either "escape" or "release" dynamics, and we study both inhibitory and excitatory feedback conductances. We find that increasing the FB conductance relative to the CPG conductance makes the system more robust against external perturbations, but more susceptible to internal noise. Conversely, increasing the CPG conductance relative to the FB conductance has the opposite effects. We find that the "closed-loop" system, with sensory feedback in place, exhibits a richer repertoire of behaviors than the "open-loop" system, with motion determined entirely by the CPG dynamics. Moreover, we find that purely feedback-driven motor patterns, analogous to a chain reflex, occur only in the inhibition-mediated system. Finally, for pattern generation systems with inhibition-mediated sensory feedback, we find that the distinction between escape- and release-mediated CPG mechanisms is diminished in the presence of internal noise. Our observations support an anti-reductionist view of neuromotor physiology: Understanding mechanisms of robust motor control requires studying not only the central pattern generator circuit in isolation, but the intact closed-loop system as a whole.

[Size Distribution of Aerosol Hygroscopic Growth Factors in Winter in Tianjin].

Aerosol hygroscopic growth factors[g(RH)] are key for evaluating aerosol light extinction and direct radiative forcing. The hygroscopic tandem differential mobility analyzer (HTDMA) was utilized to measure the size-resolved gm(RH) under different polluted conditions in winter in Tianjin. Furthermore, based on the size distribution of aerosol water-soluble ions, the gκ(RH) across a wide size range (60 nm to 9.8 µm) was estimated using the κ-Köhler theory, which provides a basis for the estimation of aerosol optical parameters and direct radiative forcing under ambient conditions. Under clean conditions, ultrafine particles (<100 nm) were more hygroscopic and gm(RH=80%) was higher than 1.30 due to the active photolysis reaction. However, under severely polluted conditions, the proportion of water-soluble ions in aerosols increased with the increasing size; gm(RH) increased with particle size, where gm(RH=80%) and gm(RH=85%) for 300 nm particles was 1.39 and 1.46, respectively. For a wide size range (60 nm to 9.8 µm), the aerosols in the accumulation mode were more hygroscopic and aerosols in the Aitken mode were less hygroscopic, with coarse mode aerosols being the least hygroscopic. During the polluted period, the particulate size notably increased, and the mass fraction of NO3- and SO42- in the accumulation mode aerosols was significantly higher than during the clean period. Accordingly, the hygroscopicity of accumulation mode aerosols was strongly enhanced during the polluted period[gκ(RH)=1.3-1.4] and aerosols in the 0.18-3.1 µm size range all had a strong hygroscopicity. On polluted days, the synergistic effect of the increase in particle size, water-soluble ions, and aerosol hygroscopicity results in the considerable deterioration of visibility.

miR­140­5p inhibits the proliferation of multiple myeloma cells by targeting VEGFA.

MicroRNA (miR)­140­5p is associated with the growth and metastasis of various tumor cell types, yet its role in multiple myeloma (MM) remains unclear. Therefore, the present study aimed to investigate the regulatory effect of miR­140­5p on MM. Reverse transcription­quantitative PCR analysis demonstrated that miR­140­5p was downregulated in MM cell lines, particularly in U266 and RPMI 8226 cells. A Cell Counting Kit­8, wound healing and Transwell assays, as well as flow cytometry indicated that a miR­140­5p mimic could suppress cell viability, migration and invasion. In addition, the mimic promoted apoptosis of U266 and RPMI 8226 cells. Western blot data demonstrated that transfection with miR­140­5p mimic significantly reduced the expression levels of Ki­67, cyclin D1, vimentin, Snail, matrix metalloproteinase (MMP)­2 and MMP­3. Moreover, as predicted by TargetScan7.2 and verified by luciferase activity assay, it was demonstrated that vascular endothelial growth factor A (VEGFA) was targeted by miR­140­5p. Further experiments indicated that VEGFA overexpression promoted cell viability, migration and invasion and suppressed apoptosis of MM cells, and that the miR­140­5p mimic partially reversed the effects of VEGFA overexpression. Therefore, miR­140­5p suppressed MM progression by targeting VEGFA. The present findings provide insight into potential therapeutic strategies for the treatment of MM.

Nomograms for Prediction of Molecular Phenotypes in Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) patients with different molecular phenotypes, including microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and somatic mutations in BRAF and KRAS gene, vary in treatment response and prognosis. However, molecular phenotyping under adequate quality control in a community-based setting may be difficult. We aimed to build the nomograms based on easily accessible clinicopathological characteristics to predict molecular phenotypes. METHODS: Three hundred and six patients with pathologically confirmed stage I-IV CRC were included in the cohort. The assays for MSI, CIMP, and mutations in BRAF and KRAS gene were performed using resected tumor samples. The candidate predictors were identified from clinicopathological variables using multivariate Logistic regression analyses to construct the nomograms that could predict each molecular phenotype. RESULTS: The incidences of MSI, CIMP, BRAF mutation and KRAS mutation were 25.3% (72/285), 2.5% (7/270), 3.4% (10/293), and 34.8% (96/276) respectively. In the multivariate Logistic analysis, poor differentiation and high neutrophil/lymphocyte ratio (NLR) were independently associated with MSI; poor differentiation, high NLR and high carcinoembryonic antigen/tumor size ratio (CSR) were independently associated with CIMP; poor differentiation, lymphovascular invasion and high CSR were independently associated with BRAF mutation; poor differentiation, proximal tumor, mucinous tumor and high NLR were independently associated with KRAS mutation. Four nomograms for MSI, CIMP, BRAF mutation and KRAS mutation were developed based on these independent predictors, the C-indexes of which were 61.22% (95% CI: 60.28-62.16%), 95.57% (95% CI: 95.20-95.94%), 83.56% (95% CI: 81.54-85.58%), and 69.12% (95% CI: 68.30-69.94%) respectively. CONCLUSION: We established four nomograms using easily accessible variables that could well predict the presence of MSI, CIMP, BRAF mutation and KRAS mutation in CRC patients.

[Characteristics of Component Particle Size Distributions of Particulate Matter Emitted from a Waste Incineration Plant].

There are few analyses on the components of particulate matter emitted from waste incineration plants. In past studies, analyses of particle size distribution characteristics of the components were mainly targeted at particles with larger particle sizes. An electrical low pressure impactor (ELPI) was used in this study to collect the particulate matter emitted from a waste incineration plant, and the elements and carbonaceous components of these samples were analyzed. The particle size characteristics of organic carbon (OC), elemental carbon (EC), and heavy metal elements in 14 particle size segments were analyzed and composition profiles of elements and carbonaceous components of PM1, PM2.5, and PM10 from the waste incineration plant were established to provide a reference for refined source apportionment research. The results showed that the main components of the waste incineration plant included Al, Si, S, Ca, Cr, Fe, OC, EC, etc. OC and Ca were dominating components, and mass fractions of these components in the PM2.5 profile were 10.15% and 12.37%, respectively. The contents of heavy metals were ranked as Cr > Pb > Zn > Mn > Cu > Cd > Ni, and the mass fractions of Cr and Pb in PM2.5 amounted to 1.83% and 0.74%, respectively. OC in the range of 2.39-3.99 and 6.68-9.91 µm accounted for 15.02% and 20.45% of the total OC content, respectively, and the content of OC in fine particles was higher than that in coarse particles. The content of EC in fine particles was much higher than that in coarse particles, and it accounted for 14.8% in the 0.382-0.613 µm particle size. Heavy metal elements such as Cr, Mn, Ni, Cu, Zn, Cd, and Pb were mainly concentrated in the fine particles.