Inactivation of Mst/Nrf2/Keap1 signaling flexibly mitigates MAPK/NQO-HO1 activation in the reproductive axis of experimental fluorosis.

Fluoride induced reprotoxicity through oxidative stress-mediated reproductive cell death. Hence, the current study evaluated the importance of the MST/Nrf2/MAPK/NQO-HO1 signaling pathway in fluorosis-induced reproductive toxicity. For this purpose, the reproductive toxicity of sodium fluoride (NaF) at physiological, biochemical, and intracellular levels was evaluated. In-vivo, NaF at 100 mg/L instigated physiological dysfunction, morphological, stereological, and structural injuries in the gut-gonadal axis of fluorosis mice through weakening the antioxidant signaling, Nrf2/HO-1/NQO1signaling pathway, causing the gut-gonadal barrier disintegrated via oxidative stress-induced inflammation, mitochondrial damage, apoptosis, and autophagy. Similar trends were also observed in-vitro in the isolated Leydig cells (LCs) challenging with 20 mg/L NaF. Henceforth, activating the cellular antioxidant signaling pathway, Nrf2/HO-1/NQO1, inactivating autophagy and apoptosis, or attenuating lipopolysaccharide (LPS) can be the theoretical basis and valuable therapeutic targets for coping with NaF-induced reproductive toxicity.

JMJD2A participates in cytoskeletal remodeling to regulate castration-resistant prostate cancer docetaxel resistance.

BACKGROUND: To investigate underlying mechanism of JMJD2A in regulating cytoskeleton remodeling in castration-resistant prostate cancer (CRPC) resistant to docetaxel. METHODS: Tissue samples from CRPC patients were collected, and the expression of JMJD2A, miR-34a and cytoskeleton remodeling-related proteins were evaluated by qPCR, western blot and immunohistochemistry, and pathological changes were observed by H&E staining. Further, JMJD2A, STMN1 and TUBB3 were knocked down using shRNA in CRPC cell lines, and cell viability, apoptosis and western blot assays were performed. The interaction between miR-34a/STMN1/ß3-Tubulin was analyzed with dual-luciferase reporter and co-immunoprecipitation assays. RESULTS: In clinical experiment, the CRPC-resistant group showed higher expression of JMJD2A, STMN1, α-Tubulin, ß-Tubulin and F-actin, and lower expression of miR-34a and ß3-Tubulin compared to the sensitive group. In vitro experiments showed that JMJD2A could regulate cytoskeletal remodeling through the miR-34a/STMN1/ß3-Tubulin axis. The expression of miR-34a was elevated after knocking down JMJD2A, and miR-34a targeted STMN1. The overexpression of miR-34a was associated with a decreased expression of STMN1 and elevated expression of ß3-Tubulin, which led to the disruption of the microtubule network, decreased cancer cell proliferation, cell cycle arrest in the G0/G1 phase, and increased apoptosis. CONCLUSION: JMJD2A promoted docetaxel resistance in prostate cancer cells by regulating cytoskeleton remodeling through the miR-34a/STMN1/ß3-Tubulin axis.

Intestinal aberrant sphingolipid metabolism shaped-gut microbiome and bile acids metabolome in the development of hepatic steatosis.

Conjugated bile acids (CBAs) play major roles in hepatic gene regulation via nuclear S1P-inhibited histone deacetylase (HDACs). Gut microbiota modifies bile acid pool to generate CBAs and then CBAs returned to liver to regulate hepatic genes, fatty liver, and non-alcoholic fatty liver disease (NAFLD). However, it is not yet known how the gut microbiota was modified under the environment of inflammatory bowel disease (IBD). Here, we revealed that aberrant intestinal sphingosine kinases (SphKs), a major risk factor of IBD, modified gut microbiota by increasing the proportions of Firmicutes and Verrucomicrobia, which were associated with the increase in CBAs. When exposed to a high-fat diet (HFD), sphingosine kinases 2 knockout (SphK2KO) mice developed more severity of intestinal inflammation and hepatic steatosis than their wild-type (WT) littermates. Due to knockdown of nuclear SphK2, Sphk2KO mice exhibited an increase in sphingosine kinases 1 (SphK1) and sphingosine-1-phosphate (S1P) in intestinal epithelial cells. Therefore, the microbiota was modified in the environment of the SphK1/S1P-induced IBD. 16S rDNA amplicon sequencing of cecal contents indicated an increase of Firmicutes and Verrucomicrobia. Ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) measured an increase in CBAs, including taurocholic acid (TCA), taurodeoxycholic acid (TDCA), and glycocholic acid (GCA), in cecal contents and liver tissues of Sphk2KO mice. These CBAs accumulated in the liver promoted hepatic steatosis through downregulating the acetylation of H3K9, H3K14, H3K18 and H3K27 due to the CBAs-S1PR2-nuclear SphK2-S1P signaling pathway was blocked in HFD-SphK2KO mice. In summary, intestinal aberrant sphingolipid metabolism developed hepatic steatosis through the increase in CBAs associated with an increase in Firmicutes and Verrucomicrobia.

Rheology of graphene oxide stabilized Pickering emulsions.

Pickering emulgels stabilized by graphene oxide (GO) with didodecyldimethylammonium bromide (DDAB) as an auxiliary surfactant and liquid paraffin as the oil phase have proved to be an excellent 3D printable ink. This paper elucidates the structure of such emulgels by a combination of microscopy before and after intensive shear as well as broadband dielectric spectroscopy and rheology in the linear and nonlinear regime. An increase of the DDAB surfactant and GO-contents leads to a systematic increase of modulus and viscosity, a reduction of the limits of the nonlinear regime and a more complicated variation of the normal forces, with negative normal forces at high shear rate  for low GO-contents and positive normal forces at high GO-contents. The interfacial jamming behavior studied by morphology, rheology and dielectric spectroscopy is explained based on droplet deformation, jamming and recovery phenomena.

Construction of Functionalized α-Imino Ketones via Pd-Catalyzed C-H Addition to Nitriles/Aerobic Oxidation Sequences.

Pd(II)-catalyzed addition of sp2 C-H to nitrile/aerobic oxidation sequences for the preparation of functionalized α-imino ketones is described in which readily available heteroarenes and O-acyl cyanohydrins were employed. Various functionalized targeted molecules can be prepared in good yields with high atom and step economy. Moreover, a broad substrate scope and the ready manipulation and availability of the reaction partners enable this protocol to be appealing to explore the chemical space of the construction of functionalized α-imino ketones with high efficiency.

Smartphone video games improve cognitive function in patients with chronic schizophrenia: a randomized controlled trial.

This study aimed to examine the efficacy of video games in improving cognitive function in chronic patients with schizophrenia and to evaluate the biomarker of video games for cognitive function. The patients in the game group were requested to play single-player video games on their smartphones for 1 h per day, five times a week for 6 weeks. Those in the control group watched television for 1 h per day, five times a week for 6 weeks. Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Stroop Color and Word Test (SCWT). Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning (GAF), General Self-Efficacy Scale (GSE), Problematic Mobile Gaming Questionnaire (PMGQ), and Patient Health Questionnaire-9 (PHQ-9). The game group demonstrated improved RBANS total score during the trial. There were no significant group effects among all SCWT scores. The game group demonstrated greater improvement on the PANSS Negative Scale, and global function (GAF score). The PMGQ scores were lower than the cutoff score at all time points in both groups. There were no significant group differences in the PHQ-9 and GSE scores. The serum BDNF levels were significantly higher in the game group following 6 weeks of video game intervention. The BDNF serum levels of all participants were positively associated with the RBANS total scores. This preliminary study suggested that video games can improve cognitive function in schizophrenia patients. Serum BDNF levels may be a suitable biomarker for predicting an improvement in cognitive function in schizophrenia patients.Trial registration: This study was registered on March 11, 2021 (ChiCTR2100044113).Clinical trials: Smartphone video games improve cognitive function in patients with chronic schizophrenia; https://www.chictr.org.cn/hvshowproject.aspx?id=95623 ; ChiCTR2100044113.

Quantitative Relaxometry Assessment of Brain Microstructural Abnormality of Preschool Children With Autism Spectrum Disorder With Synthetic Magnetic Resonance Imaging.

OBJECTIVE: This study aimed to perform an assessment of brain microstructure in children with autism aged 2 to 5 years using relaxation times acquired by synthetic magnetic resonance imaging. MATERIALS AND METHODS: Thirty-four children with autism spectrum disorder (ASD) (ASD group) and 17 children with global developmental delay (GDD) (GDD group) were enrolled, and synthetic magnetic resonance imaging was performed to obtain T1 and T2 relaxation times. The differences in brain relaxation times between the 2 groups of children were compared, and the correlation between significantly changed T1/T2 and clinical neuropsychological scores in the ASD group was analyzed. RESULTS: Compared with the GDD group, shortened T1 relaxation times in the ASD group were distributed in the genu of corpus callosum (GCC) ( P = 0.003), splenium of corpus callosum ( P = 0.002), and right thalamus (TH) ( P = 0.014), whereas shortened T2 relaxation times in the ASD group were distributed in GCC ( P = 0.011), left parietal white matter ( P = 0.035), and bilateral TH (right, P = 0.014; left, P = 0.016). In the ASD group, the T2 of the left parietal white matter is positively correlated with gross motor (developmental quotient [DQ] 2) and personal-social behavior (DQ5), respectively ( r = 0.377, P = 0.028; r = 0.392, P = 0.022); the T2 of the GCC was positively correlated with DQ5 ( r = 0.404, P = 0.018); and the T2 of the left TH is positively correlated with DQ2 and DQ5, respectively ( r = 0.433, P = 0.009; r = 0.377, P = 0.028). All significantly changed relaxation values were not significantly correlated with Childhood Autism Rating Scale scores. CONCLUSIONS: The shortened relaxometry times in the brain of children with ASD may be associated with the increased myelin content and decreased water content in the brain of children with ASD in comparison with GDD, contributing the understanding of the pathophysiology of ASD. Therefore, the T1 and T2 relaxometry may be used as promising imaging markers for ASD diagnosis.

Understanding Gel-Powers: Exploring Rheological Marvels of Acrylamide/Sodium Alginate Double-Network Hydrogels.

This study investigates the rheological properties of dual-network hydrogels based on acrylamide and sodium alginate under large deformations. The concentration of calcium ions affects the nonlinear behavior, and all gel samples exhibit strain hardening, shear thickening, and shear densification. The paper focuses on systematic variation of the alginate concentration-which serves as second network building blocks-and the Ca2+-concentration-which shows how strongly they are connected. The precursor solutions show a typical viscoelastic solution behavior depending on alginate content and pH. The gels are highly elastic solids with only relatively small viscoelastic components, i.e., their creep and creep recovery behavior are indicative of the solid state after only a very short time while the linear viscoelastic phase angles are very small. The onset of the nonlinear regime decreases significantly when closing the second network (alginate) upon adding Ca2+, while at the same time the nonlinearity parameters (Q0, I3/I1, S, T, e3/e1, and v3/v1) increase significantly. Further, the tensile properties are significantly improved by closing the alginate network by Ca2+ at intermediate concentrations.

Atypical chemokine receptor 3 induces colorectal tumorigenesis in mice by promoting ß-arrestin-NOLC1-fibrillarin-dependent rRNA biogenesis.

Atypical chemokine receptor 3 (ACKR3) has emerged as a key player in various biological processes. Its atypical "intercepting receptor" properties have established ACKR3 as the major regulator in the pathophysiological processes in many diseases. In this study, we investigated the role of ACKR3 activation in promoting colorectal tumorigenesis. We showed that ACKR3 expression levels were significantly increased in human colon cancer tissues, and high levels of ACKR3 predicted the increased severity of cancer. In Villin-ACKR3 transgenic mice with a high expression level of CKR3 in their intestinal epithelial cells, administration of AOM/DSS induced more severe colorectal tumorigenesis than their WT littermates. Cancer cells of Villin-ACKR3 transgenic mice were characterised by the nuclear ß-arrestin-1 (ß-arr1)-activated perturbation of rRNA biogenesis. In HCT116 cells, cotreatment with CXCL12 and AMD3100 selectively activated ACKR3 and induced nuclear translocation of ß-arr1, leading to an interaction of ß-arr1 with nucleolar and coiled-body phosphoprotein 1 (NOLC1). NOLC1, as the phosphorylated protein, further interacted with fibrillarin, a conserved nucleolar methyltransferase responsible for ribosomal RNA methylation in the nucleolus, thereby increasing the methylation in histone H2A and promoting rRNA transcription in ribosome biogenesis. In conclusion, ACKR3 promotes colorectal tumorigenesis through the perturbation of rRNA biogenesis by the ß-arr1-induced interaction of NOLC1 with fibrillarin.

Childhood trauma and psychological sub-health among Chinese adolescents: the mediating effect of Internet addiction.

BACKGROUND: The factors related to psychological sub-health (PSH) have been widely described, but the research on the mechanism behind the complex relationship between childhood trauma and PSH is limited. This study investigated the current situation and risk factors of PSH among Chinese adolescents. And further, explore whether Internet addiction (IA) plays a potential mediating effect in childhood trauma and PSH. METHODS: The study was conducted in October 2020 in Anhui Province, China. The PSH state of 866 adolescents was investigated, including demographic information such as gender, age, and grade. Childhood trauma, IA, and PSH were measured by the Childhood Trauma Questionnaire Short Form (CTQ-SF), Young's Internet Addiction Test (IAT), and the Multidimensional Sub-health Questionnaire of Adolescents (MSQA). The mediating effect is further verified by the structural equation model (SEM). RESULTS: In this study, 866 adolescents were selected as subjects, and the proportion of male and female is roughly equal. The prevalence of PSH in adolescents was 25.8%, and left-behind children, boarding, or adolescents who have had non-suicidal self-injury (NSSI) are more likely to have PSH. Through the mediation test, the direct effect of childhood trauma on PSH was 0.23 (95% CI [4.91,9.00],p <0.001), and the mediating effect of IA on childhood trauma and PSH was 0.07 (95% CI [1.42, 3.32],p <0.001). and the proportion of them is 75.14% and 24.86% respectively. CONCLUSIONS: Childhood trauma has direct and indirect effects on PSH, and IA plays a mediating effect in the indirect effect. Therefore, clarifying these relationships helps formulate and implement effective interventions to improve psychological health (PH) in Chinese adolescents.

Increasing rates of long-term nitrogen deposition consistently increased litter decomposition in a semi-arid grassland.

The continuing nitrogen (N) deposition observed worldwide alters ecosystem nutrient cycling and ecosystem functioning. Litter decomposition is a key process contributing to these changes, but the numerous mechanisms for altered decomposition remain poorly identified. We assessed these different mechanisms with a decomposition experiment using litter from four abundant species (Achnatherum sibiricum, Agropyron cristatum, Leymus chinensis and Stipa grandis) and litter mixtures representing treatment-specific community composition in a semi-arid grassland under long-term simulation of six different rates of N deposition. Decomposition increased consistently with increasing rates of N addition in all litter types. Higher soil manganese (Mn) availability, which apparently was a consequence of N addition-induced lower soil pH, was the most important factor for faster decomposition. Soil C : N ratios were lower with N addition that subsequently led to markedly higher bacterial to fungal ratios, which also stimulated litter decomposition. Several factors contributed jointly to higher rates of litter decomposition in response to N deposition. Shifts in plant species composition and litter quality played a minor role compared to N-driven reductions in soil pH and C : N, which increased soil Mn availability and altered microbial community structure. The soil-driven effect on decomposition reported here may have long-lasting impacts on nutrient cycling, soil organic matter dynamics and ecosystem functioning.

Interaction of magnolia bark extracts with Staphylococcus aureus DNA and evaluation of the stability of their antibacterial activities.

Magnolia bark is an edible traditional Chinese medicine that has antibacterial activity against Staphylococcus aureus. In the present study, interactions between S. aureus DNA and raw magnolia bark (RMB) and ginger mix-fried magnolia bark (GMB) aqueous extracts were determined via spectroscopic methods. Fluorescence spectroscopy and Stern-Volmer constants showed that S. aureus DNA quenched the fluorescence of the extracts by static quenching. UV-Vis spectroscopy and iodide quenching experiments indicated that the interactions between S. aureus DNA and the fluorescent substances might involve groove binding or electrostatic interactions. In 4', 6-diamidino-2-phenylindole competitive assays, the fluorescence intensity at decreased as the extract amount was increased. This indicates that groove binding is responsible for the fluorescence quenching. The antibacterial activity of GMB aqueous extract treated under light, cold, heat and cycling hot-cold conditions decreased by 13.99, 9.31, 10.89 and 14.40%, respectively, whereas that of RMB aqueous extract treated under the same conditions decreased by 8.91, 14.99, 14.99 and 13.70%, respectively. The results indicate that S. aureus DNA quenches the fluorescence of GMB and RMB aqueous extracts by grooving interactions. Additionally, the antibacterial activities of GMB and RMB extracts are sensitive to light and temperature, respectively.

The quality of life in Chinese juvenile idiopathic arthritis patients: psychometric properties of the pediatric quality of life inventor generic core scales and rheumatology module.

BACKGROUND: Juvenile idiopathic arthritis (JIA) may seriously affects patients' quality of life (QoL), but it was rarely focused and studied in China, so we explore JIA children's QoL using Chinese version of the PedsQL4.0 Generic Core and PedsQL3.0 Rheumatology Module scale, and analyzed the psychometric properties of these two Scales among Chinese JIA children. METHODS: We recruited 180 JIA patients from Children's Hospital Affiliated to Capital Institute of Pediatrics and Hebei Yanda Hospital from July 2018 to August 2019. The questionnaires include information related on JIA, PedsQL4.0 generic core and PedsQL3.0 Rheumatology Module scales. According to the disease type, onset age of and course of JIA, we divided them into different groups, then compared the QoL status among different groups. Moreover, we analyzed the reliability and validity of these two scales in these 180 JIA children. RESULTS: The mean score of PedsQL4.0 generic core scale on these 180 patients was 82.85 ± 14.82, for these in active period was 72.05 ± 15.29, in remission period was 89.77 ± 9.23; the QoL score of systemic, polyarticular and oligoarticular JIA patients were 77.05 ± 19.11, 84.33 ± 12.46 and 87.12 ± 10.23. The mean score of PedsQL3.0 Rheumatology Module scale on 180 patients was 91.22 ± 9.45, for these in active period was 84.70 ± 11.37, in remission period was 95.43 ± 4.48; the QoL score of systemic, polyarticular and oligoarticular JIA patients were 89.41 ± 11.54, 89.38 ± 10.08 and 93.71 ± 6.92. In the PedsQL 4.0 Generic Core scale, the α coefficients of total scale and almost every dimension are all greater than 0.8 except for the school activity dimension of 0.589; the correlation coefficients of 22 items' scores (total 23 items) with the scores of dimensions they belong to are greater than 0.5 (maximum value is 0.864), and the other one is 0.406. In PedsQL3.0 Rheumatology Module scale, except for the treatment and worry dimensions of 0.652 and 0.635, the α coefficients of other dimensions and the total scale are all greater than 0.7; the correlation coefficients of all items' score were greater than 0.5 (the maximum is 0.933, the minimum is 0.515). CONCLUSIONS: The QoL of Chinese JIA children is worse than their healthy peers, these in active period and diagnosed as systemic type were undergoing worst quality of life. The reliability and validity of PedsQL 4.0 Generic Core and PedsQL3.0 Rheumatology Module scale in Chinese JIA children are satisfactory, and can be used in clinical and scientific researches.

Increased S1P induces S1PR2 internalization to blunt the sensitivity of colorectal cancer to 5-fluorouracil via promoting intracellular uracil generation.

Sphingosine-1-phosphate (S1P), the backbone of most sphingolipids, activating S1P receptors (S1PRs) and the downstream G protein signaling has been implicated in chemoresistance. In this study we investigated the role of S1PR2 internalization in 5-fluorouracil (5-FU) resistance in human colorectal cancer (CRC). Clinical data of randomly selected 60 CRC specimens showed the correlation between S1PR2 internalization and increased intracellular uracil (P < 0.001). Then we explored the regulatory mechanisms in CRC model of villin-S1PR2-/- mice and CRC cell lines. We showed that co-administration of S1P promoted S1PR2 internalization from plasma membrane (PM) to endoplasmic reticulum (ER), thus blunted 5-FU efficacy against colorectal tumors in WT mice, compared to that in S1PR2-/- mice. In HCT116 and HT-29 cells, application of S1P (10 µM) empowered S1PR2 to internalize from PM to ER, thus inducing 5-FU resistance, whereas the specific S1PR2 inhibitor JTE-013 (10 µM) effectively inhibited S1P-induced S1PR2 internalization. Using Mag-Fluo-AM-labeling [Ca2+]ER and LC-ESI-MS/MS, we revealed that internalized S1PR2 triggered elevating [Ca2+]ER levels to activate PERK-eLF2α-ATF4 signaling in HCT116 cells. The activated ATF4 upregulated RNASET2-mediated uracil generation, which impaired exogenous 5-FU uptake to blunt 5-FU therapy. Overall, this study reveals a previously unrecognized mechanism of 5-FU resistance resulted from S1PR2 internalization-upregulated uracil generation in colorectal cancer, and provides the novel insight into the significance of S1PR2 localization in predicting the benefit of CRC patients from 5-FU-based chemotherapy.

Self-esteem, social support and coping strategies of left-behind children in rural China, and the intermediary role of subjective support:a cross-sectional survey.

BACKGROUND: Negative coping strategies and behavioral problems are common among Chinese left-behind children, which are relate to a variety of negative consequences. At this stage of development, the relevant factors of coping strategies need to be further studied, in which social support and self-esteem are worthy of our attention. The aim of this study is to detect the current situation of self-esteem, social support, and coping styles of left-behind children (LBC) in rural China. METHODS: 322 children from 3 schools in China enrolled in this study, including 236 LBC and 86 non-left-behind children (NLBC) to assess self-esteem, social support and coping strategies. RESULTS: The LBC group had lower self-esteem score and lower total social support (subjective support, objective support and support-seeking behavior) than the NLBC group. In terms of coping strategies, the LBC group was lower than the NLBC group in problem-solving and rationalization. The self-esteem score in LBC was significant positive associated with the subjective support score, objective support score, problem-solving and help-seeking score. In addition, self-esteem has significant mediating effect between subjective support and problem-solving, subjective support and help-seeking, respectively. CONCLUSIONS: The finding indicate that Chinese LBC's self-esteem and social support need to be improved. Given the significant correlativity between self-esteem, subjective support and coping strategy, it is necessary to promote Chinese LBC's self-esteem and social support, especially subjective support.

The mediating role of prenatal depression in adult attachment and maternal-fetal attachment in primigravida in the third trimester.

BACKGROUND: Prenatal depression and adult attachment are factors that affect the establishment of an intimate relationship between a mother and fetus. The study explored differences in prenatal depression and maternal-fetal attachment (MFA) scores between different types of adult attachment and the effects of maternal depression scores and attachment dimensions on maternal intimacy with the fetus. METHODS: The Edinburgh Postnatal Depression Scale (EPDS), Experience of Close Relationship (ECR) scale, Maternal Antenatal Attachment Scale (MAAS) and a general data scale were used to investigate 260 primigravida. An exploratory analysis was performed to analyze the effects of the depression score and adult attachment on MFA. RESULTS: The results showed that pregnant women with insecure attachment exhibited an increased prevalence of prenatal depression, lower total MFA scores, and lower MFA quality compared with those women with secure adult attachment. The explorative analysis showed that the depression scores mediated the relationship between adult attachment avoidance and MFA quality. CONCLUSIONS: Primigravida who had insecure adult attachment exhibited an increased prevalence of prenatal depression and lower MFA. Maternal depression and adult attachment may affect the emotional bond between a mother and fetus. This finding should be seriously considered, and timely intervention needs to take personality traits into consideration.

Experiences and Attitudes of Elementary School Students and Their Parents Toward Online Learning in China During the COVID-19 Pandemic: Questionnaire Study.

BACKGROUND: Due to widespread SARS-CoV-2 infection, an emergency homeschooling plan was rigorously implemented throughout China. OBJECTIVE: This study aimed to investigate the experiences and attitudes of elementary school students and their parents (two generations from the same family) toward online learning in China during the pandemic. METHODS: A 16-item questionnaire was distributed at the 10-day and 40-day marks after the start of the first online course to 867 parent-child pairs and 141 parent-child pairs, respectively. The questionnaire was comprised of questions pertaining to course and homework completeness, effectiveness, reliability, and abundance as well as the students' enthusiasm for taking part in online classes and their satisfaction with the courses. RESULTS: Our findings indicate that 90.7% (786/867) of students exhibited high or moderate enthusiasm for participating in online classes. However, most students performed poorly in online learning classes and after-school homework. With regard to satisfaction, parents' and students' average scores were 7.35 and 7.25, respectively (10-point scoring system). During the second stage of this study, parents' positive evaluations for online learning declined, including those for the effectiveness and reliability of the courses. Furthermore, the proportion of students who completed the courses and homework on time decreased; this difference proved statistically significant (P=.047). The parents' and students' overall satisfaction with online learning also declined during the second stage (parents: 7.21; students: 7.23); however, the difference in overall satisfaction between the two stages was not statistically significant (parents: P=.53; students: P=.60). Several of the parents (315/867, 36.2%) indicated that assisting with and supervising the students' online learning resulted in increased stress. Further, 36% of parents expressed dissatisfaction with or provided suggestions for online learning; most parents and students hoped to return to face-to-face classes (parents: 823/867, 94.9%; students: 811/867, 93.5%). Finally, our results presented the following six main issues that parents were the most concerned about: (1) disappointment regarding timely interaction in courses; (2) apprehensiveness about students' understanding of the course; (3) the increased burden of annoying adult responsibilities; (4) concern about children's eyesight; (5) the idea that teachers' explanations were not detailed enough; and (6) concerns about the decline of students' interest in and attention toward online courses. CONCLUSIONS: Online learning can prevent the spread of infectious diseases while still allowing elementary school students to attain knowledge. However, in our study, children's completion of the courses and homework were not satisfactory. Furthermore, their parents often experienced stress and had many concerns and complaints. Measures such as increasing the interactivity of the courses and prohibiting teachers from assigning tasks to parents could improve the effectiveness of these courses and the mental health of parents and students.

Zinc finger protein A20 regulates the development and progression of osteoarthritis by affecting the activity of NF-κB p65.

OBJECTIVE: To investigate the role of Zinc finger protein A20 in osteoarthritis (OA) by regulating NF-κB p65. METHODS: A20, MMP1, MMP13 and IL-1ß expressions in human OA cartilage samples were detected by qRT-PCR. IL-1ß-induced chondrocyte was treated with A20 lentivirus activation particle, pyrrolidine dithiocarbamate (PDTC, a NF-κB inhibitor) with/without A20 siRNA. IL-6, TNF-α, and PGE2 levels were measured by ELISA, and NO production by Greiss reaction. Destabilization of the medial meniscus (DMM) surgery was used to construct the OA models, followed by injection of A20 adenovirus. MMP1 and MMP13 expression was measured by immunohistochemistry. The mRNA and protein expression were performed by qRT-PCR and western blotting, respectively. RESULTS: A20 was down-regulated in human OA cartilage samples, and negatively correlated with the expressions of MMP1, MMP13 and IL-1ß. The IL-1ß-induced chondrocyte manifested decreased A20 with increased NF-κB p65 activity. A20 overexpression suppressed the NF-κB p65 activity in IL-1ß-induced chondrocyte. Furthermore, PDTC decreased IL-1ß-induced chondrocyte apoptosis with the upregulated COL1A1, COL2A1, COL10A1 and ACAN, as well as the down-regulated MMP1, MMP13, COX2, iNOS, IL-6, TNF-α, NO and PGE2, which was reversed by A20 siRNA. In vivo, OA mice gained higher OARSI score and Mankin's score, exhibited up-regulations of MMP1 and MMP13, and decreased NF-κB p65 activity, which was improved after injection of A20 adenovirus. CONCLUSION: A20 was reduced in OA cartilage samples, and its overexpression, by suppressing the activity of NF-κB p65, could improve IL-1ß-induced chondrocyte degradation and apoptosis in vitro, as well as mitigate the inflammation in OA mice.

[Mitochondrial DNA and cGAS-STING Innate Immune Signaling Pathway: Latest Research Progress].

Mitochondria are important organelles that present extensively in cells, serving diverse functions. In addition to controlling cell energy production and metabolism, mitochondria are also involved in various biological processes, including anti-infection, apoptosis, and autophagy. Harmful stimuli from external environment or those generated by the cells themselves can damage mitochondria and cause mitochondrial stress response, during which the mitochondrial matrix containing mitochondrial DNA (mtDNA) can leak into the cytoplasm. Cytoplasmic mtDNA, acting as a damage-associated molecular pattern (DAMP), can activate a panel of DNA sensors and elicit innate immune response in organisms. Cyclic GMP-AMP synthase (cGAS), a key intracellular DNA sensor, can catalyze the conversion of GTP and ATP to cyclic GMP-AMP (2'3'-cGAMP), which serves as second messenger to bind and activate stimulator of interferon gene (STING), an endoplasmic adaptor protein. Beyond its critical roles in anti-microbial immunity, cGAS-STING pathway also serves important functions in many pathological and physiological processes such as autoimmunity, tumor and senescence. In this review, we focus on how the mtDNA released during mitochonrial stress response activates the cGAS-STING innate immune signaling pathway and the associated diseases, in order to help promote basic research about the role of mitochondria in innate immunity and provide new strategies for developing mitochondria-targeting drugs.

Targeting USP1-dependent KDM4A protein stability as a potential prostate cancer therapy.

The histone demethylase lysine-specific demethylase 4A (KDM4A) is reported to be overexpressed and plays a vital in multiple cancers through controlling gene expression by epigenetic regulation of H3K9 or H3K36 methylation marks. However, the biological role and mechanism of KDM4A in prostate cancer (PC) remain unclear. Herein, we reported KDM4A expression was upregulation in phosphatase and tensin homolog knockout mouse prostate tissue. Depletion of KDM4A in PC cells inhibited their proliferation and survival in vivo and vitro. Further studies reveal that USP1 is a deubiquitinase that regulates KDM4A K48-linked deubiquitin and stability. Interestingly, we found c-Myc was a key downstream effector of the USP1-KDM4A/androgen receptor axis in driving PC cell proliferation. Notably, upregulation of KDM4A expression with high USP1 expression was observed in most prostate tumors and inhibition of USP1 promotes PC cells response to therapeutic agent enzalutamide. Our studies propose USP1 could be an anticancer therapeutic target in PC.