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The harm caused by rumors is immeasurable. Studying the dynamic characteristics of rumors can help control their spread. In this paper, we propose a nonsmooth rumor model with a nonlinear propagation rate. First, we utilize the positive invariant regions to prove the boundedness of solutions. Second, we analyze the conditions for the existence of equilibrium points in both the left and right systems. Additionally, we confirm the occurrence of saddle-node bifurcation in the left system. Next, by considering the influence of spatial diffusion, we establish the conditions for Turing instability. Then we discuss the conditions for spatial homogeneous and inhomogeneous Hopf bifurcations in the left and right systems, respectively. We differentiate between supercritical and subcritical bifurcations using the Lyapunov coefficient. Furthermore, we examine the conditions for the existence of discontinuous Hopf bifurcation at the demarcation point. Finally, in the numerical simulation section, we validate our theorems on Turing patterns. We also investigate the impact of parameter changes on rumor propagation and conclude that an increase in the psychological inhibitory factor significantly reduces the rate of rumor propagation, providing an effective strategy for curbing rumors. To that end, we fit actual data to our system and the results are excellent, confirming the validity of the system. [ABSTRACT FROM AUTHOR]

Background: Congenital heart defects (CHDs) are the most common birth defects. Assessment of the incidence, distribution, disease spectrum, and genetic deficits of fetal CHDs in China is urgently needed. Methods: A national echocardiography screening program for fetal CHDs was implemented in 92 prenatal screening–diagnostic centers in China. Findings: A total of 18,171 fetal CHD cases were identified from 2,452,249 pregnancies, resulting in 7·4/1,000 as the national incidence rate of fetal CHD. The incidences of fetal CHD in the six geographical regions, the southern, central, eastern, southwestern, northern, and northwestern, were 7·647 (CI: 7·383–7·915), 7·839 (CI: 7·680–8·000), 7·647 (CI: 7·383–7·915), 7·562 (CI: 7·225–7·907), 5·618 (CI: 5·337–5·906), and 4·716 (CI: 4·341–5·108), respectively, per 1,000 pregnancies. Overall, ventricular septal defect was the most common fetal CHD, accounting for 17.04% of screened pregnancies nationwide, and tetralogy of Fallot, the most common anomaly in the major defect of fetal CHD, was the second most common, accounting for 9.72%. A total of 76.24% cases of fetal CHD were found to be an isolated intracardiac single defect. The remaining 23.76% of cases of fetal CHD had multiple heart defects. Among all extracardiac malformations, the central nervous system (CNS) was the most common tissue with extracardiac anomalies associated with CHD, accounting for 22.89% of fetal CHD cases. Chromosomal karyotyping identified trisomy 18 as the most common chromosomal abnormality in fetal CHD. We also documented that CHD-containing syndromes could be identified with a comprehensive approach integrating prenatal ultrasound, MRI, pathological autopsy, and cytogenetics and molecular genetics. Conclusion: Implementation of prenatal echocardiography as a practically feasible platform to screen fetal CHD will reduce the financial and emotional burden of CHD, which may facilitate intrauterine and neonatal intervention of CHD. [ABSTRACT FROM AUTHOR]

The skin is heterogeneous and exerts strong scattering and aberration onto excitation light in multiphoton microscopy (MPM). Shifting to longer excitation wavelengths may help reduce skin scattering and aberration, potentially enabling larger imaging depths. However, previous demonstrations of skin MPM employ excitation wavelengths only up to the 1700 nm window, leaving an open question as to whether longer excitation wavelengths are suitable for deep-skin MPM. Here, in order to explore the longer-wavelength territory, first, we demonstrate characterization of the broadband transmittance of excised mouse skin, revealing a high transmittance window at 2200 nm. Then, we demonstrate third-harmonic generation (THG) imaging in mouse skin in vivo excited at this window. With 9 mW optical power on the skin surface operating at 1 MHz repetition rate, we can get THG signals of 250 μ m below the skin surface. Comparative THG imaging excited at the 1700 nm window shows that as imaging depth increases, THG signals decay even faster than those excited at 2200 nm. Our results thus uncover the 2200 nm window as a new, promising excitation window potential for deep-skin MPM. [ABSTRACT FROM AUTHOR]

The aging of sewer networks in old residential neighborhoods in China causes frequent problems with their integrity and functionality, such as sanitary sewer overflows and hydraulic overloading of wastewater treatment plants. In order to assess the performance of the sewer system in an old residential area in Ningbo, China, and to evaluate the effectiveness of the sewer system upgrade, the sewer system was continuously monitored for about 8 months. The quantity and quality of wastewater were comprehensively analyzed. The rainfall-derived inflow and infiltration (RDII) characterization was identified in the sewershed by using the R-value method and the triangle method. The R-values before and after the sewer upgrade were about 28% and 7%, respectively. The effects of the sewer upgrade were also quantified through comparing the concentration of pollutants before and after the program. The findings of this study will help to understand the performance of small-scale urban drainage systems, especially in old residential areas and/or in developing countries, and to provide guidance for future system upgrades. [ABSTRACT FROM AUTHOR]

Sirtuin1 (SIRT1), an NAD+-dependent histone deacetylase, plays a crucial role in regulating molecular signaling pathways. Recently, inhibition of SIRT1 rather than its activation shows the therapeutic potential for central nervous system disorder, however, the discovered SIRT1 inhibitors remains limited. In this work, a dual recognition-based strategy was developed to screen SIRT1 inhibitors from natural resources in situ. This approach utilized a Ni-modified metal-organic framework (Ni@Tyr@UiO-66-NH 2) along with cell lysate containing an engineered His-tagged SIRT1 protein, eliminating the need for purified proteins, pure compounds, and protein immobilization. The high-performance Ni@Tyr@UiO-66-NH 2 was synthesized by modifying the surface of UiO-66-NH 2 with Ni2+ ions to specifically capture His-tagged SIRT1 while persevering its enzyme activity. By employing dual recognition, in which Ni@Tyr@UiO-66-NH 2 recognized SIRT1 and SIRT1 recognized its ligands, the process of identifying SIRT1 inhibitors from complex matrix was vastly streamlined. The developed method allowed the efficient discovery of 16 natural SIRT1 inhibitors from Chinese herbs. Among them, 6 compounds were fully characterized, and suffruticosol A was found to have an excellent IC 50 value of 0.95 ± 0.12 μM. Overall, an innovative dual recognition-based strategy was proposed to efficiently identify SIRT1 inhibitors in this study, offering scientific clues for the development of drugs targeting CNS disorders. [Display omitted] • A new Ni-modified MOF (Ni@Tyr@UiO-66-NH 2) was synthesized. • The MOF adsorbed His-tagged SIRT1 efficiently while maintaining the enzyme activity. • A dual recognition-based strategy was established based on the new MOF and His-tag. • 16 new natural SIRT1 inhibitors were identified in situ by applying the strategy. [ABSTRACT FROM AUTHOR]

Identifying medicinally relevant compounds from natural resources generally involves the tedious work of screening plants for the desired activity before capturing the bioactive molecules from them. In this work, we created a paper-based ligand fishing platform to vastly simplify the discovery process. This paper-based method exploits the enzymatic cascade reaction between α -glucosidase (GAA), glucose oxidase (GOx), and horseradish peroxidase (HRP), to simultaneously screen the plants and capture the GAA inhibitors from them. The designed test strip could capture ligands in tandem with screening the plants, and it features a very simply operation based on direct visual assessment. Multiple acylated flavonol glycosides from the leaves of Quercus variabilis Blume were newly found to possess GAA inhibitory activities, and they may be potential leads for new antidiabetic medications. Our study demonstrates the prospect of the newly discovered GAA ligands as potential bioactive ingredients as well as the utility of the paper-based ligand fishing method. [Display omitted] • Test strip (GDTS) built on enzyme cascade reaction and dopamine-paper was newly set. • GDTS can screen bioactive plants and concurrently capture α -glucosidase inhibitors. • Four plants were screened by GDTS as targets from fourteen plants. • Twenty-two inhibitors were acquired from target plants via GDTS. • Acylated flavonol glucosides in Quercus variabilis were new GAA inhibitors. [ABSTRACT FROM AUTHOR]

• 2M-118, as a superantigen SEC2 (H118A/T20L/G22E) mutant, increase cytokines production and splenocyte proliferation in vitro results. • 2M-118 can effectively inhibit tumor development, increase lymphocytes and cytokines, and not induce side effects in a tumor-bearing BALB/c mouse model. • 2M-118 has immunoregulatory effects on the tumor microenvironment by reducing the number of myeloid-derived suppressor cells, increasing the number of CD4+ and CD8+ TILs, and inducing tumor cell apoptosis. • We explore the antitumor effects of 2M-118, focusing on the changes in immune responses and tumor immune microenvironment, to illustrate the role of 2M-118 in inhibiting tumor proliferation through cell-mediated immunity. Staphylococcal enterotoxin C2 (SEC2) is used as an immunotherapeutic drug in China. However, SEC2 are limited due to its immunosuppressive and toxic effects. A SEC2 2M-118 (H118A/T20L/G22E) mutant generated by site-directed mutagenesis was studied to elucidate the underlying antitumor mechanism. The effects of 2M-118 on mouse fibrosarcoma (Meth-A) cells and cytokine responses were tested in vitro using a transwell assay and ELISA, respectively. 2M-118 effect on immune function in tumor-bearing mice was tested. Cytokine levels and antitumor responses were measured using ELISA and flow cytometry, respectively. TUNEL staining and immunohistochemistry were employed to detect the tumor apoptosis and CD4+ and CD8+ tumor infiltrating lymphocytes (TILs) in tumor tissue. 2M-118 demonstrated the growth inhibition on tumor cells, increase of cytokines production (IL-2, IFN-γ, and TNF-α) and splenocyte proliferation in vitro. 2M-118 effectively inhibited tumor development and increased lymphocytes and cytokines in a tumor-bearing mouse model. Additionally, 2M-118 regulated the tumor microenvironment by reducing the number of myeloid-derived suppressor cells (MDSCs), increasing the number of TILs, and inducing tumor cell apoptosis. 2M-118 promotes immune function and enhances antitumor response. This indicates that 2M-118 could potentially be developed as a novel anti-tumor drug with-high efficiency and low toxicity. [ABSTRACT FROM AUTHOR]

In this paper, a reaction-diffusion model is established to study the dynamic behavior of rumor propagation. Firstly, we consider the existence of the positive equilibrium points. Then, we perform a stability analysis to study the conditions for the occurrence of Turing instability. Secondly, we use multiscale analysis to derive the expression of the amplitude equation. In the process of numerical simulation, the reality is considered. It shows that controlling the spread rate of rumor and the number of new Internet users have a great effect on curbing the spread of online rumor. Furthermore, it is proved that the analysis of amplitude equation plays a decisive role in the formation of Turing patterns. We also discuss the phenomenon of Turing patterns when the network structure changes and verify the rationality of the model by Monte Carlo method. Finally, we consider two methods based on statistical principle and convolutional neural network severally to identify the parameters of the reaction-diffusion system with Turing instability by using stable patterns. The statistical principle-based method offers superior accuracy, whereas the convolutional neural network-based approach significantly reduces recognition time and cuts down time costs. • This paper investigates a rumor propagation system with reaction-diffusion behavior. • The properties of Turing pattern with or without network background are studied. • We compare different methods to select the optimal parameter identification for system. [ABSTRACT FROM AUTHOR]

Background: Birth defects are responsible for approximately 7% of neonatal deaths worldwide by World Health Organization in 2004. Many methods have been utilized for examining the congenital anomalies in fetuses. This study aims to investigate the efficiency of simultaneous CNV-seq and whole-exome sequencing (WES) in the diagnosis of fetal anomaly based on a large Chinese cohort.Methods: In this cohort study, 1800 pregnant women with singleton fetus in Hubei Province were recruited from 2018 to 2020 for prenatal ultrasonic screening. Those with fetal structural anomalies were transferred to the Maternal and Child Health Hospital of Hubei Province through a referral network in Hubei, China. After multidisciplinary consultation and decision on fetal outcome, products of conception (POC) samples were obtained. Simultaneous CNV-seq and WES was conducted to identify the fetal anomalies that can compress initial DNA and turnaround time of reports.Results: In total, 959 couples were finally eligible for the enrollment. A total of 227 trios were identified with a causative alteration (CNV or variant), among which 191 (84.14%) were de novo. Double diagnosis of pathogenic CNVs and variants have been identified in 10 fetuses. The diagnostic yield of multisystem anomalies was significantly higher than single system anomalies (32.28% vs. 22.36%, P  = 0.0183). The diagnostic rate of fetuses with consistent intra- and extra-uterine phenotypes (172/684) was significantly higher than the rate of these with inconsistent phenotypes (17/116, P  = 0.0130).Conclusions: Simultaneous CNV-seq and WES analysis contributed to fetal anomaly diagnosis and played a vital role in elucidating complex anomalies with compound causes. [ABSTRACT FROM AUTHOR]

Objective: LVADs are surgically implanted mechanical pumps that improve survival rates of individuals with advanced heart failure. LVAD therapy is associated with high morbidity, which can be partially attributed to challenges with detecting LVAD complications before adverse events occur. Current methods used to monitor for complications with LVAD support require frequent clinical assessments at specialized LVAD centers. Analysis of recorded precordial sounds may enable real-time, remote monitoring of device and cardiac function for early detection of LVAD complications. The dominance of LVAD sounds in the precordium limits the utility of routine cardiac auscultation of LVAD recipients. In this work, we develop a signal processing pipeline to mitigate sounds generated by the LVAD. Methods: We collected in vivo precordial sounds from 17 LVAD recipients, and contemporaneous echocardiograms from 12 of these individuals, to validate heart valve closure timings. Results: We characterized various acoustic signatures of heart sounds extracted from in vivo recordings, and report preliminary findings linking fundamental heart sound characteristics and level of LVAD support. Conclusion: Mitigation of LVAD sounds from precordial sound recordings of LVAD recipients enables analysis of intrinsic heart sounds. Significance: These findings provide proof-of-concept evidence of the clinical utility of heart sound analysis for bedside and remote monitoring of LVAD recipients. [ABSTRACT FROM AUTHOR]

Background: The strategy of successful ageing is an important means to deal with the challenges of the current ageing society. This paper aims to explore the effects of different intensities of physical activity on the successful ageing of the elderly.Methods: Our data were from wave 4 of the China Health and Retirement Longitudinal Survey (CHARLS), involving 9026 residents aged 60 years and older. The intensity of physical activity was divided into three levels: vigorous, moderate and mild. The concept of successful ageing adopted a four-dimensional model of life satisfaction added to the theoretical model of Rowe and Kahn's. Propensity score matching (PSM) with controlling nine confounding factors were used to analyse the effects of different intensities of physical activity.Results: The percentage of successful ageing was 1.88% among all subjects. Among them, 30.26, 29.57 and 29.40% of the elderly often participated in vigorous, moderate and mild physical activity, respectively. The results of PSM showed that participation in moderate activity increased the probability of successful ageing of the elderly by 0.76-0.78% (P < 0.001), while participation in vigorous and mild physical activity had no significant effect on successful ageing (P > 0.05). Moderate physical activity had statistically significant effects on four components of successful aging, including major disease, physical function, life satisfaction, and social participation (P < 0.05).Conclusion: Moderate-intensity physical activity was most beneficial to the successful ageing of the elderly and should be promoted in the elderly population. [ABSTRACT FROM AUTHOR]

Background: Online ride-hailing is a fast-developing new travel mode. However, tobacco control policies on its drivers remain underdeveloped. This study aims to reveal the status and determine the influencing factors of ride-hailing drivers' smoking behaviour to provide a basis for the formulation of tobacco control policies.Methods: We derived our cross-sectional data from an online survey of full-time ride-hailing drivers in China. We used a survey questionnaire to collect variables, including sociodemographic and work-related characteristics, health status, health behaviour, health literacy and smoking status. Finally, we analysed the influencing factors of current smoking by conducting chi-square test and multivariate logistic regression.Results: A total of 8990 ride-hailing drivers have participated in the survey, in which 5024 were current smokers, accounting to 55.9%. Nearly one-third of smokers smoked in their cars (32.2%). The logistic regression analysis results were as follows: male drivers (OR = 0.519, 95% CI [0.416, 0.647]), central regions (OR = 1.172, 95% CI [1.049, 1.309]) and eastern regions (OR = 1.330, 95% CI [1.194, 1.480]), working at both daytime and night (OR = 1.287, 95% CI [1.164, 1.424]) and non-fixed time (OR = 0.847, 95% CI [0.718, 0.999]), ages of 35-54 years (OR = 0.585, 95% CI [0.408, 0.829]), current drinker (OR = 1.663, 95% CI [1.526, 1.813]), irregular eating habits (OR = 1.370, 95% CI [1.233, 1.523]), the number of days in a week of engaging in at least 10 min of moderate or vigorous exercise ≥3 (OR = 0.752, 95% CI [0.646, 0.875]), taking the initiative to acquire health knowledge occasionally (OR = 0.882, 95% CI [0.783, 0.992]) or frequently (OR = 0.675, 95% CI [0.591, 0.770]) and underweight (OR = 1.249, 95% CI [1.001, 1.559]) and overweight (OR = 0.846, 95% CI [0.775, 0.924]) have association with the prevalence of current smoking amongst online ride-hailing drivers.Conclusion: The smoking rate of ride-hailing drivers was high. Sociodemographic and work-related characteristics and health-related factors affected their smoking behaviour. Psychological and behavioural interventions can promote smoking control management and encourage drivers to quit or limit smoking. Online car-hailing companies can also establish a complaint mechanism combined with personal credit. [ABSTRACT FROM AUTHOR]

In terms of ligand fishing, the amount and the relative activity recovery of enzymes immobilized on magnetic particles and nanoparticles are not preeminent. Therefore, the metal-organic framework (MOF) UiO-66-NH 2 was synthesized to immobilize the porcine pancreatic lipase (PPL) via precipitation-cross-linking, and the resulting novel biological matrices named PPL@MOF manifested high PPL loading capacity (98.31 mg/g) and relative activity recovery (104.4%). Moreover, the novel enzyme-MOF composite was applied to screen lipase inhibitors from Prunella vulgaris L. to enrich and improve the techniques of ligand fishing. As a result, 13 lipase ligands were obtained, and 12 compounds were determined by HPLC-Q-TOF-MS/MS. All of these ligands were further confirmed to be potential inhibitors through the verification of the activity assay and molecular docking. The proposed approach based on PPL@MOF was superior in terms of abundant protein loading capacity, high enzyme catalytic activity and easy preparation process. Taken together, our newly developed method provided a new platform for efficient discovering bioactive molecules from natural herbs. Image 1 • Pancreatic lipase was successful immobilized onto the metal-organic framework via the precipitation-cross-linking method. • PPL@MOF manifested high PPL loading capacity (98.31 mg) and relative activity recovery (104.4%). • 13 compounds were harvested from Prunella vulgaris efficiently and conveniently by the method of ligand fishing based PPL@MOF. • MOF-enzyme composite was first used for obtaining bioactive compounds directly from natural herbs. [ABSTRACT FROM AUTHOR]

Background: Evidence-based studies are increasingly being focused on evaluating the efficacy and safety of adalimumab (ADA) for moderately to severely active ulcerative colitis (UC). However, the dosage pattern of ADA for UC management is still not clear. Objective: A meta-analysis was conducted to evaluate the efficacy and safety of different ADA dosage regimens for moderately to severely active UC. Methods: The Medline, EMBASE, ISI Web of Knowledge, and Cochrane databases were searched from their inception to January 2015. Randomized controlled trials (RCTs) comparing ADA with placebo were eligible for initial inclusion. The efficacy and side effects were evaluated for ADA 160/80 (ADA 160/80 mg at weeks 0/2 and then 40 mg at weeks 4 and 6), and ADA 80/40 (ADA 80/40 mg at weeks 0/2 and then 40 mg at weeks 4 and 6) induction therapy, with ADA 40 mg every other week (EOW) for maintenance therapy of 52 weeks. The pooled risk ratio (RR) and its 95 % confidence interval (CI) were calculated. Results: Three RCTs were included. All of the studies were considered to have a low risk of bias. ADA 160/80 was more effective than placebo for induction of clinical remission (RR 1.62, 95 % CI 1.15-2.29), clinical response (RR 1.37, 95 % CI 1.19-1.59), mucosal healing (RR 1.27, 95 % CI 1.08-1.50), and inflammatory bowel disease questionnaire (IBDQ) response (RR 1.22, 95 % CI 1.05-1.43) and did not increase adverse events (RR 1.10, 95 % CI 0.95-1.27). Compared with placebo, ADA 80/40 did not show significant differences for induction of clinical remission and clinical response and did not increase adverse events. ADA 40 mg EOW was superior to placebo in maintaining clinical remission (RR 2.38, 95 % CI 1.57-3.59), clinical response (RR 1.69, 95 % CI 1.29-2.21), mucosal healing (RR 1.69, 95 % CI 1.26-2.28), and IBDQ response (RR 1.73, 95 % CI 1.28-2.34). Compared with placebo, ADA 40 mg EOW increased adverse events (RR 1.28, 95 % CI 1.06-1.54). Conclusion: ADA 160/80 was a safe and effective treatment for induction management of moderately to severely active UC, but the benefits of ADA 80/40 application were limited. ADA 40 mg EOW was effective for maintenance management of UC. Additional well designed RCTs are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Aneurysm of the mitral-aortic intervalvular fibrosa (A-MAIVF) is a rare but potentially fatal condition. The aneurysm is located between the mitral and aortic valves and communicates with the left ventricular outflow tract, and the differential diagnoses include dilated coronary sinuses and coronary arteriovenous fistula. We describe the first reported case of an A-MAIVF diagnosed in the fetus. [ABSTRACT FROM AUTHOR]

Objective: To provide a practical guidance for the analysis of N-of-1 trials by comparing four commonly used models. Methods: The four models, paired t-test, mixed effects model of difference, mixed effects model and meta-analysis of summary data were compared using a simulation study. The assumed 3-cycles and 4-cycles N-of-1 trials were set with sample sizes of 1, 3, 5, 10, 20 and 30 respectively under normally distributed assumption. The data were generated based on variance-covariance matrix under the assumption of (i) compound symmetry structure or first-order autoregressive structure, and (ii) no carryover effect or 20% carryover effect. Type I error, power, bias (mean error), and mean square error (MSE) of effect differences between two groups were used to evaluate the performance of the four models. Results: The results from the 3-cycles and 4-cycles N-of-1 trials were comparable with respect to type I error, power, bias and MSE. Paired t-test yielded type I error near to the nominal level, higher power, comparable bias and small MSE, whether there was carryover effect or not. Compared with paired t-test, mixed effects model produced similar size of type I error, smaller bias, but lower power and bigger MSE. Mixed effects model of difference and meta-analysis of summary data yielded type I error far from the nominal level, low power, and large bias and MSE irrespective of the presence or absence of carryover effect. Conclusion: We recommended paired t-test to be used for normally distributed data of N-of-1 trials because of its optimal statistical performance. In the presence of carryover effects, mixed effects model could be used as an alternative. [ABSTRACT FROM AUTHOR]

For an ellipsoid suspended in a dual-fiber optic trap with transverse offset, the optical force, torque and posture are theoretically analyzed. When importing a transverse offset between two fibers, in the water environment, the azimuthal angle between the long axis and the optical axis increases with the offset distance. In the vacuum environment, the ellipsoid will spin in the trap center. When the offset is great than the threshold, the ellipsoid will move around the trap center along an elliptic trajectory, accompanied with the spin motion. The results will contribute to better understanding of the spin motion in the transversely misaligned dual-beam fiber-optic trap. [ABSTRACT FROM AUTHOR]

Latent autoimmune diabetes in adult (LADA), classified as between type 1 and type 2 diabetes mellitus, has received widespread attention. A number of studies have investigated the association between HLA DQA-DQB, DRB-DQB haplotypes and the onset of LADA. However, the conclusions remained inconsistent. Therefore, this study aims to clarify the impact of these HLA haplotypes on the pathogenesis of LADA. Systematic searches were carried out on the Medline, PubMed, Embase and Wan Fang respectively to investigate the association of LADA with HLA DQA-DQB, DRB-DQB up to June 05, 2020. We performed this retrospective research using meta-analysis. The pooled results demonstrated that in Chinese, DQA1*05-DQB1*0201, DQA1*03-DQB1*0401, and DQA1*03-DQB1*0303 were statistically significantly associated with increasing the risk of LADA (P < 0.001), while DQA1*0102-DQB1*0602 was statistically significantly correlated with decreasing the susceptibility to the disease (P = 0.003). However, there was no obvious association found between DQA1*0201-DQB1*0201 (P = 0.984), DQA1*03-DQB1*0302 (P = 0.110), DQA1*0601-DQB1*0301 (P = 0.398) and LADA. In Japanese, DRB1*0802-DQB1*0302 (P = 0.003) and DRB1*0901-DQB1*0303 (P = 0.001), but not DRB1*0405-DQB1*0401 (P = 0.136), were found to be a risk factor for LADA. As for Caucasian, both DRB1*03-DQB1*0201 and DRB1*04-DQB1*0302 were predisposed to the development of LADA with a statistical significance (P < 0.001). In all, HLA DQA-DQB, HLA DRB-DQB haplotypes might play a role in the risk of LADA, which could provide an improved understanding of LADA pathogenesis and the detection of susceptible HLA haplotypes in the diagnosis and therapy of this disease. [ABSTRACT FROM AUTHOR]

Objectives: Asian Americans have poor HIV-related outcomes, yet culturally salient barriers to care remain unclear, limiting development of targeted interventions for this group. We applied the 'what matters most' theory of stigma to identify structural and cultural factors that shape the nature of stigma before and after immigration from China to the US. Design: Semi-structured interviews were conducted with 16 immigrants to New York from China, recruited from an HIV clinic and community centers. Deductive followed by focal inductive qualitative analyses examined how Chinese cultural values (lian, guanxi, renqing) and structural factors influenced stigma before and after immigration. Results: In China, HIV stigma was felt through the loss of lian (moral status) and limited guanxi (social network) opportunities. A social structure characterized by limited HIV knowledge, discriminatory treatment from healthcare systems, and human rights violations impinged on the ability of people living with HIV to fulfill culturally valued goals. Upon moving to the US, positions of structural vulnerability shifted to enable maintenance of lian and formation of new guanxi, thus ameliorating aspects of stigma. Conclusions: HIV prevention and stigma reduction interventions among Chinese immigrants may be most effective by both addressing structural constraints and facilitating achievement of cultural values through clinical, peer, and group interventions. [ABSTRACT FROM AUTHOR]

Background: Receiving informal care from family members is the mainstream way of care for the elderly in China because of the influence of the culture of filial piety. However, the relationship between informal care and health care use in urban and rural areas needs to be further explored. This study aimed to understand the association between informal care and health care utilisation for the elderly and explore how this effect may differ between urban and rural China.Method: A total of 5704 residents aged 65 years and above were selected from wave 3 (2015) and wave 4 (2018) of the China Health and Retirement Longitudinal Study, which is a nationally representative survey. A negative binomial regression model for the panel data was used to explore the relationship between informal care and health care utilisation. A fixed-effect binary choice model for panel data was used for the sensitivity test.Result: The elderly who received informal care had increased in outpatient and inpatient visits compared with those who did not receive informal care. The inpatient visits of the elderly who received 15-29 days of informal care was higher than the elderly who did not receive informal care (incidence rate ratio [IRR] = 2.082, P < 0.05). Moreover, the elderly who received informal care for more than 30 days had 39.6% more inpatient visits (IRR = 1.396, P < 0.01) and 37.4% more outpatient visits than the elderly who did not receive informal care (IRR = 1.374, P < 0.05). For urban respondents, receiving informal care can facilitate outpatient use of the elderly, but for rural respondents, receiving informal care can predict an increase in outpatient and inpatient visits.Conclusion: Informal care was associated with higher use of health services. The association between informal care and health care utilisation varies between rural and urban residents. These findings indicate the role of informal care and remind that relevant departments should pay attention to the differences in medical service utilisation levels amongst different elderly groups. [ABSTRACT FROM AUTHOR]

Myelin sheaths wrapping axons are key structures that help maintain the propagation speed of action potentials in both central and peripheral nervous systems (CNS and PNS). However, noninvasive, deep imaging technologies visualizing myelin sheaths in the digital skin in vivo are lacking in animal models. 3-photon fluorescence (3PF) imaging excited at the 1700-nm window enables deep imaging of myelin sheaths, but necessitates labeling by exogenous fluorescent dyes. Since myelin sheaths are lipid-rich structures which generate strong third-harmonic signals, in this paper, we perform a detailed comparative experimental study of both third-harmonic generation (THG) and 3PF imaging in the mouse digital skin in vivo. Our results show that THG imaging also enables visualization of myelin sheaths deep in the mouse digital skin, which shows colocalization with 3PF signals from labeled myelin sheaths. Besides its superior label-free advantage, THG does not suffer from photobleaching due to its 3PF property. [ABSTRACT FROM AUTHOR]

Glioblastoma stem cells (GSCs) exert a crucial influence on glioblastoma (GBM) development, progression, resistance to therapy, and recurrence, making them an attractive target for drug discovery. UTX, a histone H3K27 demethylase, participates in regulating multiple cancer types. However, its functional role in GSCs remains insufficiently explored. This study aims to investigate the role and regulatory mechanism of UTX on GSCs. Analysis of TCGA data revealed heightened UTX expression in glioma, inversely correlating with overall survival. Inhibiting UTX suppressed GBM cell growth and induced apoptosis. Subsequently, we cultured primary GSCs from three patients, observing that UTX inhibition suppressed cell proliferation and induced apoptosis. RNA‐seq was performed to analyze the gene expression changes after silencing UTX in GSCs. The results indicated that UTX‐mediated genes were strongly correlated with GBM progression and regulatory tumor microenvironment. The transwell co‐cultured experiment showed that silencing UTX in the transwell chamber GSCs inhibited the well plate cell proliferation. Protein–protein interaction analysis revealed that periostin (POSTN) played a role in the UTX‐mediated transcriptional regulatory network. Replenishing POSTN reversed the effects of UTX inhibition on GSC proliferation and apoptosis. Our study demonstrated that UTX inhibition hindered POSTN expression by enhancing the H3K27me2/3 level, eventually resulting in inhibiting proliferation and promoting apoptosis of patient‐derived GSCs. Our findings may provide a novel and effective strategy for the treatment of GBM. [ABSTRACT FROM AUTHOR]

Background: About 31 individuals with CLTC variants have been reported worldwide, and all reported individuals have motor and mental retardation. CLTC is known to lead to intellectual developmental disorder, autosomal dominant 56. Few studies are focusing on the prenatal stage of the disease. Method: An ultrasound examination was performed to obtain the prenatal phenotype. Whole-exome sequencing was used to find the pathogenic variant. Multiple computational tools predicted the conservation and deleteriousness. Minigene assay and western blot were utilized to investigate the effect on splicing of mRNA and protein expression. Result: Here we found a novel de novo variant of CLTC in a fetus. The fetus manifested bilateral choroid plexus cysts of the brain, hyperechogenic kidneys, and ventricular septal defect. A heterozygous variant c.3249 + 1G > C was identified in the fetus. This position was conserved and the variant was predicted to be deleterious. Minigene assay revealed the presence of a truncating transcript with the retention of intron 20. Western blot result showed the c.3249 + 1G > C variant elicited degradation of the protein. Conclusion: To the best of our knowledge, our study identified a novel de novo variant of CLTC and provided the earliest clinical characteristic of the CLTC variant at the prenatal stage. The functional experiment suggested the variant caused the altering of the RNA splicing and the protein expression. We extended the mutational spectrum of CLTC and provided guidance on genetic counseling. [ABSTRACT FROM AUTHOR]

Three‐photon fluorescence (3PF) imaging excited at 1700 nm window is an enabling technology for visualizing deep brain structures and dynamics. Recently, the 2200 nm window has emerged as the longest excitation window suitable for deep‐brain 3PF imaging. Bright fluorescent probes lay the material basis for deep‐brain 3PF imaging. Among various fluorescent probes, aggregation‐induced emission luminogens (AIEgens) have great potential in 3PF imaging excited at the 1700 nm window in vivo. However, to the best of knowledge, there is no AIEgens applicable to 3PF imaging excited at both the 1700 and 2200 nm windows. To readily fill this gap, here this study designs and synthesizes a novel AIEgen, namely TPE‐DPTT‐ICP, which generates bright 3PF signals excited at both 1700 and 2200 nm. The accordingly fabricated TPE‐DPTT‐ICP nanoparticles (NPs) possess excellent water dispersibility, colloidal stability, biocompatibility, photostability and large 3P action cross section, key to in vivo imaging. In mouse brain in vivo, TPE‐DPTT‐ICP NPs enable deep‐brain 3PF imaging of subcortical structures excited at both the two windows, reaching depths of 1640 and 880 µm below the brain surface, respectively. TPE‐DPTT‐ICP NPs are thus a versatile material simultaneously catering to the need at two infrared optical windows with deep tissue penetration. [ABSTRACT FROM AUTHOR]

Coronary artery disease (CAD) is a leading cause of death worldwide. Recent genome-wide association studies have identified more than one hundred susceptibility loci associated with CAD. However, the underlying mechanism of these genetic loci to CAD susceptibility is still largely unknown. We performed a tissue-specific network analysis of CAD using the summary statistics from one of the largest genome-wide association studies. Variant-level associations were summarized into gene-level associations, and a CAD-related interaction network was built using experimentally validated gene interactions and gene coexpression in coronary artery. The network contained 102 genes, of which 53 were significantly associated with CAD. Pathway enrichment analysis revealed that many genes in the network were involved in the regulation of peripheral arteries. In summary, we performed a tissue-specific network analysis and found abnormalities in the peripheral arteries might be an important pathway underlying the pathogenesis of CAD. Future functional characterization might further validate our findings and identify potential therapeutic targets for CAD. [ABSTRACT FROM AUTHOR]

The potential of neural stem cells (NSCs) for neurological disorders the treatment has relied in large part upon identifying the NSCs fate decision. The hormone leptin has been reported to be a crucial regulator of brain development, able to influence the glial and neural development, yet, the underlying mechanism of leptin acting on NSCs' biological characteristics is still poorly understood. This study aims to investigate the role of leptin in the biological properties of NSCs. In this study, we investigate the possibility that leptin may regulate the NSCs' fate decision, which may promote the proliferation and neuronal differentiation of NSCs and thus act positively in neurological disorders. NSCs from the embryonic cerebral cortex were used in this study. We used CCK-8 assay, ki67 immunostaining, and FACS analysis to confirm that 25–100 ng/mL leptin promotes the proliferation of NSCs in a concentration-dependent pattern. This change was accompanied by the upregulation of p-AKT and p-ERK1/2, which are the classical downstream signaling pathways of leptin receptors b (LepRb). Inhibition of PI3K/AKT or MAPK/ERK signaling pathways both abolished the effect of leptin-induced proliferation. Moreover, leptin also enhanced the directed neuronal differentiation of NSCs. A blockade of the PI3K/AKT pathway reversed leptin-stimulated neurogenesis, while a blockade of JAK2/STAT3 had no effect on it. Taken together, our results support a role for leptin in regulating the fate of NSCs differentiation and promoting NSCs proliferation, which could be a promising approach for brain repair via regulating the biological characteristics of NSCs. [ABSTRACT FROM AUTHOR]

Anesthetics such as sevoflurane are commonly administered to infants and children. However, the possible neurotoxicity caused by prolonged or repetitive exposure to it should be a concern. The neuroprotective effects of metformin are observed in many models of neurological disorders. In this study, we investigated whether metformin could reduce the developmental neurotoxicity induced by sevoflurane exposure in neonatal rats and the potential mechanism. Postnatal day 7 (PND 7) Sprague-Dawley rats and neural stem cells (NSCs) were treated with normal saline or metformin before sevoflurane exposure. The Morris water maze (MWM) was used to observe spatial memory and learning at PND 35–42. Immunofluorescence staining was used to detect neurogenesis in the subventricular zone (SVZ) of the lateral ventricle and the subgranular zone (SGZ) of the dentate gyrus at PND 14. MTT assays, immunofluorescence staining, and TUNEL staining were used to assess the viability, proliferation, differentiation, and apoptosis of NSCs. Western blotting and ELISA were used to assess the protein expression of cleaved caspase-3, nuclear factor erythroid 2-related factor 2 (Nrf2), and glucose-6-phosphate dehydrogenase (G6PD) pathway-related molecules. Exposure to sevoflurane resulted in late cognitive defects, impaired neurogenesis in both the SVZ and SGZ, reduced NSC viability and proliferation, increased NSC apoptosis, and decreased protein expression of G6PD in vitro. Metformin pretreatment attenuated sevoflurane-induced cognitive functional decline and neurogenesis inhibition. Metformin pretreatment also increased the protein expression of Nrf2 and G6PD. However, treatment with the Nrf2 inhibitor, ML385 or the G6PD inhibitor, dehydroepiandrosterone (DHEA) reversed the protective effect of metformin on sevoflurane-induced NSC damage in vitro. Our findings suggested that metformin could reduce sevoflurane-induced neurogenesis damage and neurocognitive defects in the developing rat brain by influencing the Nrf2/G6PD signaling pathways. [ABSTRACT FROM AUTHOR]

Neural stem cells (NSCs) persist in the subgranular zone (SGZ) throughout the lifespan and hold immense potential for the repair and regeneration of the central nervous system, including hippocampal-related diseases. Several studies have demonstrated that cellular communication network protein 3 (CCN3) regulates multiple types of stem cells. However, the role of CCN3 in NSCs remains unknown. In this study, we identified CCN3 expression in mouse hippocampal NSCs and observed that supplementing CCN3 improved cell viability in a concentration-dependent manner. Additionally, in vivo results showed that the injection of CCN3 in the dentate gyrus (DG) increased Ki-67- and SOX2-positive cells while decreasing neuron-specific class III beta-tubulin (Tuj1) and doublecortin (DCX)-positive cells. Consistently with the in vivo results, supplementing CCN3 in the medium increased the number of BrdU and Ki-67 cells and the proliferation index but decreased the number of Tuj1 and DCX cells. Conversely, both the in vivo and in vitro knockdown of the Ccn3 gene in NSCs had opposite effects. Further investigations revealed that CCN3 promoted cleaved Notch1 (NICD) expression, leading to the suppression of PTEN expression and eventual promotion of AKT activation. In contrast, Ccn3 knockdown inhibited the activation of the Notch/PTEN/AKT pathway. Finally, the effects of changes in CCN3 protein expression on NSC proliferation and differentiation were eliminated by FLI-06 (a Notch inhibitor) and VO-OH (a PTEN inhibitor). Our findings imply that while promoting proliferation, CCN3 inhibits the neuronal differentiation of mouse hippocampal NSCs and that the Notch/PTEN/AKT pathway may be a potential intracellular target of CCN3. Our findings may help develop strategies to enhance the intrinsic potential for brain regeneration after injuries, particularly stem cell treatment for hippocampal-related diseases. [ABSTRACT FROM AUTHOR]

We have fully investigated the integrated lensing effect that the beam suffers in a dual-fiber optical trap. A modified model for coupling of a beam to the opposing fiber has been built in consideration of the integrated lensing effect. We discussed the effect of z-axial position, radius and refractive index of the trapped sphere on the coupling efficiency using the modified coupling coefficient model. The measured and calculated coupling efficiency as a function of z-axial position have the same tendency in the allowable error. Comparison among above simulation and experiment has made clear that the magnitude relation between the smallest spot size and the mode field radius decide whether the spot size matching or wavefront phase matching dominate the coupling coefficient. What’s more, we point out that the dependence of relative coupling coefficient on the refractive index has knee point. That is an obstacle to the application of single live cell refractive index measurement method based on lensing effect. Nevertheless, this method is absorbing and promising because there is a linear range for the known experimental parameters in an optical trap, and it needs no additional accessory. [ABSTRACT FROM AUTHOR]

Metabolic adaption drives microglial inflammatory responses, and lactate shapes immunological and inflammatory states. However, whether lactate was involved in the regulation of microglial inflammatory responses after cerebral ischemia remains unclear. In this study, the expression of iNOS, arginase-1, phosphorylated NF-κB p65 and IκB-α, and HIF-1α in BV2 cells after oxygen-glucose deprivation (OGD) were detected by western blotting and immunofluorescence. The mRNA levels of microglial responsive markers and inflammatory factors were assessed by real-time-qPCR. The effect of lactate-treated BV2 cells on the survival of primary neurons was observed using transwell co-culture. The results showed that the protein levels of iNOS and arginase-1, the ratio of mRNA levels of iNOS/CD206, CD86/Ym1, IL-6/IL-10, TNF-α/IL-10 and the mRNA levels of IL-6 and TNF-α, as well as the protein levels of phosphorylated NF-κB p65 and IκB-α, were increased after OGD. Lactate treatment inhibited the OGD-induced increase in the protein levels of iNOS, phosphorylated NF-κB p65 and IκB-α, as well as iNOS/CD206, CD86/Ym1, IL-6/IL-10, TNF-α/IL-10, IL-6 and TNF-α mRNA levels in BV2 cells, while promoted arginase-1 protein expression as well as IL-10 and TGF-β mRNA level. Interestingly, lactate activated HIF-1α and the HIF-1α inhibitor YC-1 reversed the effect of lactate on levels of microglial responsive markers and phosphorylated NF-κB p65 and IκB-α in BV2 cells. Moreover, knockdown of HIF-1α by lentivirus-delivered shRNA also reversed the effect of lactate on phosphorylated NF-κB p65 and IκB-α in BV2 cells after OGD. Finally, and importantly, lactate-treated BV2 microglia increased the viability and decreased the apoptosis of neurons after OGD. These findings revealed that lactate inhibited NF-κB pathway and skewed BV2 microglia toward the protective response through activation of HIF-1α after OGD, thereby improving neuronal survival. • Lactate skewed BV2 microglia toward the protective response after oxygen-glucose deprivation (OGD). • Lactate inhibited NF-κB pathway in BV2 cells after OGD. • Lactate activated HIF-1α to modulate microglial inflammatory responses after OGD. • Lactate-treated BV2 microglia improved neuronal survival after OGD. [ABSTRACT FROM AUTHOR]

Therapeutic strategies based on neural stem cells (NSCs) transplantation bring new hope for neural degenerative disorders, while the biological behaviors of NSCs after being grafted that were affected by the host tissue are still largely unknown. In this study, we engrafted NSCs that were isolated from a rat embryonic cerebral cortex onto organotypic brain slices to examine the interaction between grafts and the host tissue both in normal and pathological conditions, including oxygen–glucose deprivation (OGD) and traumatic injury. Our data showed that the survival and differentiation of NSCs were strongly influenced by the microenvironment of the host tissue. Enhanced neuronal differentiation was observed in normal conditions, while significantly more glial differentiation was observed in injured brain slices. The process growth of grafted NSCs was guided by the cytoarchitecture of host brain slices and showed the distinct difference between the cerebral cortex, corpus callosum and striatum. These findings provided a powerful resource for unraveling how the host environment determines the fate of grafted NSCs, and raise the prospect of NSCs transplantation therapy for neurological diseases. [ABSTRACT FROM AUTHOR]

With the gradual shift of coal mining to deeper levels in recent years, rock burst has become one of the primary dynamic hazards faced in deep mining. It has been shown that the pore structure in rocks affects the mechanical properties, but the relationship with the rock burst phenomenon still needs to be clarified. In this paper, we investigated the causes and effects of pore structure on impact mechanical properties using RFPA2D numerical simulation software, established several numerical models with different porosities and pore diameters, and analyzed the stress-strain curves, the relationships between porosity and pore diameter and each the bursting liability indices of the coal rock body were elaborated, and the fitting equations in the range of porosity (0%~10%) and pore diameter (0.25~2.0 mm) were obtained. The results showed that the increase in porosity and pore diameter effectively attenuated the bursting ability of coal rocks, which has some reference significance for the study of early warning and prevention of rock burst phenomenon. [ABSTRACT FROM AUTHOR]

• NCOA3 was overexpressed in the joint tissues of type II collagen-induced arthritis. • The administration of two NCOA3 inhibitors significantly alleviated inflammation and improved the outcomes of CIA mice. • NCOA3 assembled a transcriptional complex with p300 and NF-κB subunits and this complex specifically controlled the expression of proinflammatory cytokine genes by binding to their promoters. Rheumatoid arthritis (RA) is an autoimmune disorder in which the immune system mistakenly attacks joints. The molecular mechanisms underlying RA pathology are still under investigation. In this study, we discovered overexpression of nuclear receptor coactivator 3 (NCOA3) in the joint tissues of type II collagen-induced arthritis (CIA) mice, an important autoimmune model of human RA. Administration of two NCOA3 inhibitors, gossypol (GSP) and SI-2 hydrochloride (SHC), significantly alleviated inflammation and improved the outcomes of CIA mice. In vivo and in vitro experiments revealed that NCOA3 assembled a transcriptional complex with a histone acetyltransferase p300 and two subunits of nuclear factor kappa B (NF-κB). This complex specifically controlled the expression of proinflammatory cytokine genes by binding to their promoters. Knockdown of NCOA3 or in vitro treatments with GSP and SHC impaired the assembly of NCOA3-p300-NF-κB complex and decreased the expression of proinflammatory cytokine genes. Taken together, our results demonstrated that NCOA3 acts as a mediator of proinflammatory cytokine genes in CIA mice and that inhibition of the NCOA3-p300-NF-κB complex may represent a new avenue for improving RA outcomes. [ABSTRACT FROM AUTHOR]

Fluorophores lay the material basis for tissue labeling and fluorescence imaging, especially for deep‐brain multiphoton microscopy (MPM) in animal models. Among various fluorescent materials, those with aggregation‐induced emission (AIE) characteristics, i.e., AIEgens, have excellent optical properties and biocompatibility and thus have found widespread applications in biomedical imaging. However, their application to deep‐brain MPM has so far been limited in imaging depth, which undoubtedly poses a hindrance to neurological research aiming to probe the deeper brain. In order to address the issue, here a novel bright AIEgen, namely MTTCM, is designed and synthesized via facile reactions routes. The self‐assembled MTTCM nanoparticles (NPs) with their water‐dispersible feature, have good biocompatibility and good photostability. Furthermore, they are spectrally advantageous for deep‐brain MPM: their emission lies in the NIR‐I region, they generate 3‐photon fluorescence with NIR‐III excitation and show only a slight blue‐shift in the emitted 3‐photon fluorescence in vivo. From a fundamental photochemical perspective, it is also confrimed that MTTCM NPs obey Kasha's rule since the measured 3‐photon and 1‐photon fluorescence spectra overlap. All these merits make MTTCM NPs the enabling fluorophores for record depth in brain imaging in vivo: 1905 µm after craniotomy and 1100 µm through an intact skull, excited at 1660 nm. Furthermore, a record 752 µm hemodynamic imaging depth before craniotomy is demonstrated, from which the blood flow speed can be measured. MTTCM NPs are thus promising fluorophores for deep‐brain 3‐photon imaging in vivo. [ABSTRACT FROM AUTHOR]

Context: Shuangbai San is a Chinese herb preparation used externally to treat pain. There have been few randomized controlled trials addressing the safety and usefulness of Shuangbai San, such as its effect on pain relief and quality of life (QOL) improvement.Objectives: This study was conducted to evaluate the effect of Shuangbai San on relieving pain and improving QOL in primary liver cancer patients with cancer pain.Methods: A total of 134 primary liver cancer patients with mild pain (numerical rating scale [NRS] ≤ 3), either locally in the liver or in the upper abdomen, were enrolled and randomly allocated to the group receiving Shuangbai San or the control group (receiving placebo). The primary outcome measures were the NRS score and QOL scales, including the QOL scale for patients with liver cancer, version 2.0 and the European Organization for Research and Treatment of Cancer QOL Questionnaire-C30. The secondary outcome measures included the Karnofsky Performance Status score, blood indicators, and liver and kidney function before and after treatment.Results: The NRS scores decreased more significantly in the Shuangbai San group than in the placebo group (P < 0.05) at the corresponding time points. The changes in the scores for the physical function, psychological function, and symptoms/adverse effects domains of the QOL scale for patients with liver cancer, version 2.0 and the physical, emotional, and cognitive domains of the European Organization for Research and Treatment of Cancer QOL Questionnaire-C30 were significantly greater in the Shuangbai San group than in the placebo group (P < 0.05). The changes in the scores for the other domains were not significantly different (P > 0.05).Conclusion: The use of Shuangbai San can relieve mild pain in liver cancer patients and improve their QOL. [ABSTRACT FROM AUTHOR]

Previous studies showed that the electromagnetic stimulation could effectively activate damaged neurons. However, electrical stimulation effects would be greatly decayed after penetrating into biological tissues. In this paper, based on the magnetic stimulation system, the principle of magnetic stimulation devices for sciatic nerves recovery is analyzed. The simulation based on Schwarz model and biological experiments are conducted. The selected 20 Sprague Dawley rats were divided into experimental group (Group A) and control group (Group B). Group A was given 30 min magnetic stimulation every day while none was given for Group B. The sciatic functional index and the maximum evoked potential of gastrocnemius muscle were obtained. The recovery rate of gastrocnemius muscle wet weight was obtained. The experimental results showed that Group A was superior to Group B, and the results were statistically significant. It is shown that the magnetic stimulation with appropriate frequency and amplitude is in favor of the recovery of injured sciatic nerve. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM), the most aggressive primary heterogeneous primary brain tumor, is a glioma subtype that originates from the glial cells of the central nervous system. Glioblastoma stem cells (GSCs), situated at the top of the hierarchy, initiate and maintain the tumor and are largely accountable for GBM resistance to the mainstay treatment and recurrence. The LIM homeobox transcription factor islet 1 (ISL1) induces tumorigenicity in various tumors; however, its function in GSCs has been less reported. We aimed to generate GSCs from surgical specimens of human GBM and investigate the effect of ISL1 knockdown on GSCs. We established patient-derived GSCs, determined cancer stem cell marker expression, and immunostained GSCs to assess cell viability and apoptosis. We demonstrated that ISL1 deletion decreased the GSC viability and proliferation, and upregulated apoptosis. Moreover, we performed enzyme-linked immunosorbent assay and western blotting and found that ISL1 knockdown affected the expression of sonic hedgehog (SHH) and its downstream regulator GLI1, and further validated these results by supplementing the cells with recombinant SHH. Our results suggested that ISL1 played a critical role in regulating GBM growth and that an ISL1/SHH/GLI1 pathway was required for the maintenance of GBM progression and malignancy. The regulation of GSC growth through ISL1 might be a mechanism of interest for future therapeutic studies. [ABSTRACT FROM AUTHOR]

Background: Previous studies have demonstrated the effect of socioeconomic status on the health status of the elderly. Nevertheless, the specific dimensions of the effect and the mechanism await further investigation. In this study, socioeconomic status was divided into three dimensions and we used social participation as the mediation variable to investigate the specific path of effect.Methods: Using the 2018 Waves of Chinese Longitudinal Healthy Longevity Survey (CLHLS) dataset, a total of 10,197 effective samples of the elderly over 65 years old were screened out. Socioeconomic status included income, education level, and main occupation before retirement. The physical health and mental health of the elderly was measured by the Instrumental Activities of Daily Living Scale and the Minimum Mental State Examination, respectively. The social participation of the elderly was the mediation variable, including group exercise, organized social activities and interacting with friends. Omnibus mediation effect analysis was adopted to examine the mediation effect and mediation analysis was completed using the SPSS PROCESS program.Results: First, the results showed that when the income gap between the elderly reached a certain level, there was a significant difference in health status. Significant differences existed in health status amongst with different education levels. There was no sufficient evidence to show that occupation has a significant effect on the physical health. But when the dependent variable was mental health, the effect was significant. Second, group exercise mediated 64.11% (aib = 0.24, 95% CI [0.17,0.3]) and up to 20.44% (aib = 0.12, 95% CI [0.07,0.17]) of the disparity in physical and mental health due to income gap, respectively. And it could mediate the effect up to 56.30% (aib = 0.62, 95% CI [0.52,0.73]) and 17.87% (aib = 0.50, 95% CI [0.4,0.61]) of education on physical and mental health status, respectively. The proportion of relative mediation effect of occupation was up to 28.74% (aib = 0.19, 95% CI [0.13,0.25]) on mental health. Interacting with friends mediated only on the path that the education affected the health status of the elderly. The proportion was up to 33.72% (aib = 0.29, 95% CI [0.16,0.44]). The relative mediation effect of organized social activities on the health gap caused by income or education level gap was significant at some levels. The proportion was up to 21.20% (aib = 0.33, 95% CI [0.26,0.4]).Conclusion: The SES of the elderly including relatively large income gap, different education levels and occupational categories could indeed have a significant effect on health status of the elderly, and the reason why this effect existed could be partly explained by the mediation effect of social participation. Policymakers should pay more attention to the social participation of the elderly. [ABSTRACT FROM AUTHOR]

Background: Short-rib thoracic dysplasia 3 with or without polydactyly (SRTD3, OMIM: 613091) is an autosomal recessive disorder. SRTD3 presents clinically with a narrow thorax, short ribs, shortened tubular bones, and acetabular roof abnormalities. Clinical signs of SRTD3 vary among individuals. Pathogenic variants of DYNC2H1 (OMIM: 603297) have been reported to cause SRTD3. Methods: We performed a detailed clinical prenatal sonographic characterization of a foetus with SRTD3. Trio whole-exome sequencing was used to identify causative variants in the family. The identified variants in the families were validated by Sanger sequencing and mass spectrometry. Multiple computational tools were used to predict the harmfulness of the two variants. A minigene splicing assay was carried out to evaluate the impact of the splice-site variant. Results: We evaluated prenatal sonographic images of the foetus with SRTD3, including abnormal rib curvature, narrow thorax, bilateral hypoplastic lungs, bilateral polydactyly, syndactyly, and foetal visceral situs inversus with mirror-image dextrocardia. We revealed novel compound variants of DYNC2H1 (NM_001377.3:c.11483T > G (p.Ile3828Arg) and c.2106 + 3A > T). Various statistical methods predicted that the variants would cause harmful effects on genes or gene products. The minigene assay findings suggested that c.2106 + 3A > T caused the skipping over exon 14, producing an exon 14 loss in the protein. Conclusion: This study identified a foetus with SRTD3 with situs inversus totalis with mirror-image dextrocardia in a Chinese family, revealing two novel compound heterozygous dynein cytoplasmic 2 heavy chain 1 (DYNC2H1) variants, expanding the phenotypic spectrum of SRTD3. The minigene study of c.2106 + 3A > T was predicted to cause an inframe exclusion of exon 14, which was predicted to have important molecular functions. Our findings strongly supported the use of WES in prenatal diagnosis and helped to understand the correlation of genotype and phenotypes of DYNC2H1. The specific sonographic findings and the molecular diagnosis helped add experience to further our expertise in prenatal counselling for SRTD3. [ABSTRACT FROM AUTHOR]

Background We recently showed that miR-494 was downregulated in gastric carcinoma ( GC). The objectives of this study were to determine the role of miR-494 in GC malignancy and to identify its target genes. Methods Real-time polymerase chain reaction was employed to quantify the expression level of miR-494 and c-myc in gastric cancer tissues. Bioinformatics was used to predict the downstream target genes of miR-494, which were confirmed by luciferase and RNA immunoprecipitation assays. Cell functional analyses and a xenograft mouse model were used to evaluate the role of miR-494 in malignancy. Results miR-494 was downregulated in human GC tissues and in GC cells and was negatively correlated with c-myc expression. High level of c-myc or low level of mi R-494 correlated with poor prognosis. The miR-494-binding site in the c-myc 3′ untranslated region was predicted using TargetScan and was confirmed by the luciferase assay. Additionally, c-myc and miR-494 were enriched in coimmunoprecipitates with tagged Argonaute2 proteins in cells overexpressing miR-494. Furthermore, a miR-494 mimic significantly downregulated endogenous c-myc expression, which may contribute to the delayed G1/ S transition, decreased synthesis phase bromodeoxyuridine incorporation, and impaired cell growth and colony formation; on the other hand, treatment with a miR-494 inhibitor displayed the opposite effects. Reduced tumor burden and decreased cell proliferation were observed following the delivery of miR-494 into xenograft mice. Conclusion miR-494 is downregulated in human GC and acts as an anti-oncogene by targeting c-myc. miR-494 plays a role in the pathogenesis of gastric cancer in a recessive fashion. [ABSTRACT FROM AUTHOR]

Purpose. The purpose of this study is to study the effects of heat-clearing Traditional Chinese Medicine (TCM) in the stable stage of bronchiectasis via N-of-1 trials. Methods. The N-of-1 trials in this study were randomized and double-blinded with crossover comparisons consisting of three pairs. Each pair was of two 4-week periods. Each patient took the individualized decoction in the experimental period and the individualized decoction was removed of heat-clearing drugs, mainly including heat-clearing and detoxifying drugs, in the control period for three weeks. After three weeks, the patients stopped taking the decoction for one week. The primary outcome was from patients' self-reporting symptoms scores on a 1–7-point Likert scale. Mixed-effects models were used to conduct statistical analysis on these N-of-1 trials. Results. Of the 21 patients enrolled, 15 completed three pairs of N-of-1 trials (71.43%). (1) Seen from the individual level, no statistical difference between the experimental decoction and the control (P > 0.05) was observed. However, 5 patients found better decoctions according to the clinical criteria. (2) As revealed by the group data of all the N-of-1 trials, the control was better than the individualized decoction in terms of symptom scores on the Likert scale (1.94 ± 0.69 versus 2.08 ± 0.68, P = 0.04, mean difference, and 95% CI: 0.19 (0.01, 0.37)) and on CAT scores (13.66 ± 6.57 versus 13.95 ± 6.97, P = 0.04, mean difference, and 95% CI: 0.86 (0.042, 1.67)), but such differences were not clinically significant. The other outcomes, such as Likert scale score of respiratory symptoms and 24-hour sputum volume, showed no statistical difference. Conclusion. The experimental design of this study can make the TCM individualized treatment fully play its role and can detect the individualized tendencies according to the severity of phlegm and heat in some subjects. With the intermittent use or reduced use of heat-clearing drugs, most of the subjects, at the group level, enrolled in the series of N-of-1 trials may improve the symptoms and quality of life while saving the cost of TCM and reducing the potential side effects of heat-clearing TCM. This trial is registered with clinicaltrials.goc (NCT03147443). [ABSTRACT FROM AUTHOR]

Purpose. The purpose of this study is to study the effects of heat-clearing Traditional Chinese Medicine (TCM) in the stable stage of bronchiectasis via N-of-1 trials. Methods. The N-of-1 trials in this study were randomized and double-blinded with crossover comparisons consisting of three pairs. Each pair was of two 4-week periods. Each patient took the individualized decoction in the experimental period and the individualized decoction was removed of heat-clearing drugs, mainly including heat-clearing and detoxifying drugs, in the control period for three weeks. After three weeks, the patients stopped taking the decoction for one week. The primary outcome was from patients' self-reporting symptoms scores on a 1–7-point Likert scale. Mixed-effects models were used to conduct statistical analysis on these N-of-1 trials. Results. Of the 21 patients enrolled, 15 completed three pairs of N-of-1 trials (71.43%). (1) Seen from the individual level, no statistical difference between the experimental decoction and the control (P > 0.05) was observed. However, 5 patients found better decoctions according to the clinical criteria. (2) As revealed by the group data of all the N-of-1 trials, the control was better than the individualized decoction in terms of symptom scores on the Likert scale (1.94 ± 0.69 versus 2.08 ± 0.68, P = 0.04, mean difference, and 95% CI: 0.19 (0.01, 0.37)) and on CAT scores (13.66 ± 6.57 versus 13.95 ± 6.97, P = 0.04, mean difference, and 95% CI: 0.86 (0.042, 1.67)), but such differences were not clinically significant. The other outcomes, such as Likert scale score of respiratory symptoms and 24-hour sputum volume, showed no statistical difference. Conclusion. The experimental design of this study can make the TCM individualized treatment fully play its role and can detect the individualized tendencies according to the severity of phlegm and heat in some subjects. With the intermittent use or reduced use of heat-clearing drugs, most of the subjects, at the group level, enrolled in the series of N-of-1 trials may improve the symptoms and quality of life while saving the cost of TCM and reducing the potential side effects of heat-clearing TCM. This trial is registered with clinicaltrials.goc (NCT03147443). [ABSTRACT FROM AUTHOR]

The trapping stiffness and width are two important parameters to characterize a counter-propagating dual-beam optical trap. We present two types of asymmetric counter-propagating dual-beam optical trap with the different numerical aperture (NA) and trapping power to eliminate the multi-equilibrium positions when two foci of the optical trap are not coincided. Meanwhile, the asymmetric dual-beam trap with the different NA enhances the axial trapping width and stiffness over five and three times, respectively, higher than the standard dual-beam trap with the higher and same average NA. Besides, it increases the transverse trapping stiffness when two foci are not coincided. The asymmetric dual-beam optical trap will benefit the future applications for the study of precision measurement, basic physics and biomaterials. [ABSTRACT FROM AUTHOR]