Resveratrol prevents cognitive deficits induced by sleep deprivation via modulating sirtuin 1 associated pathways in the hippocampus.

Accumulating evidence confirms that sleep insufficiency is a high risk factor for cognitive impairment, which involves inflammation and synaptic dysfunction. Resveratrol, an agonist of the Sirt1, has demonstrated anti-inflammation and neuroprotective effects in models of Alzheimer's disease, Parkinson's disease, and schizophrenia. However, the beneficial effects of resveratrol on sleep deprivation-induced cognitive deficits and its underlying molecular mechanisms are unclear. In the present study, thirty-two male C57BL/6 J mice were randomly divided into a Control+DMSO group, Control+Resveratrol group, SD+DMSO group, and SD+Resveratrol group. The mice in the SD+Resveratrol group underwent 5 days of sleep deprivation after pretreatment with resveratrol (50 mg/kg) for 2 weeks, while the mice in the SD+DMSO group only underwent sleep deprivation. After sleep deprivation, we evaluated spatial learning and memory function using the Morris water maze test. We used general molecular biology techniques to detect changes in levels of pro-inflammatory cytokines and Sirt1/miR-134 pathway-related synaptic plasticity proteins. We found that resveratrol significantly reversed sleep deprivation-induced learning and memory impairment, elevated interleukin-1ß, interleukin-6, and tumor necrosis factor-α levels, and decreased brain-derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density protein-95, and synaptophysin levels by activating the Sirt1/miR-134 pathway. In conclusion, resveratrol is a promising agent for preventing sleep deprivation-induced cognitive dysfunction by reducing pro-inflammatory cytokines and improving synaptic function via the Sirt1/miR-134 pathway.

Preoperative pain sensitivity and its correlation with postoperative acute and chronic pain: a systematic review and meta-analysis.

BACKGROUND: Preoperative pain sensitivity (PPS) can be associated with postsurgical pain. However, estimates of this association are scarce. Confirming this correlation is essential to identifying patients at high risk for severe postoperative pain and for developing analgesic strategy. This systematic review and meta-analysis summarises PPS and assessed its correlation with postoperative pain. METHODS: PubMed, Scopus, Cochrane Library, and PsycINFO were searched up to October 1, 2023, for studies reporting the association between PPS and postsurgical pain. Two authors abstracted estimates of the effect of each method independently. A random-effects model was used to combine data. Subgroup analyses were performed to investigate the effect of pain types and surgical procedures on outcomes. RESULTS: A total of 70 prospective observational studies were included. A meta-analysis of 50 studies was performed. Postoperative pain was negatively associated with pressure pain threshold (PPT; r=-0.15, 95% confidence interval [CI] -0.23 to -0.07]) and electrical pain threshold (EPT; r=-0.28, 95% CI -0.42 to -0.14), but positively correlated with temporal summation of pain (TSP; r=0.21, 95% CI 0.12-0.30) and Pain Sensitivity Questionnaire (PSQ; r=0.25, 95% CI 0.13-0.37). Subgroup analysis showed that only TSP was associated with acute and chronic postoperative pain, whereas PPT, EPT, and PSQ were only associated with acute pain. A multilevel (three-level) meta-analysis showed that PSQ was not associated with postoperative pain. CONCLUSIONS: Lower PPT and EPT, and higher TSP are associated with acute postoperative pain while only TSP is associated with chronic postoperative pain. Patients with abnormal preoperative pain sensitivity should be identified by clinicians to adopt early interventions for effective analgesia. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42023465727).

Association between maternal health service utilization and under-five mortality rate in China and its provinces, 1990-2017.

BACKGROUND: The United Nations (UN) Sustainable Development Goal - 3.2 aims to eliminate all preventable under-five mortality rate (U5MR). In China, government have made efforts to provide maternal health services and reduce U5MR. Hence, we aimed to explore maternal health service utilization in relation to U5MR in China and its provinces in 1990-2017. METHODS: We obtained data from Global Burden of Disease 2017, China Health Statistics Yearbook, China Statistical Yearbook, and Human Development Report China Special Edition. The trend of U5MR in each province of China from 1990 to 2017 was analyzed using Joinpoint Regression model. We measured the inequities in maternal health services using HEAT Plus, a health inequity measurement tool developed by the UN. The generalized estimating equation model was used to explore the association between maternal health service utilization (including prenatal screening, hospital delivery and postpartum visits) and U5MR. RESULTS: First, in China, the U5MR per 1000 live births decreased from 50 in 1990 to 12 in 2017 and the average annual percentage change (AAPC) was - 5.2 (p < 0.05). Secondly, China had a high maternal health service utilization in 2017, with 96.5% for prenatal visits, 99.9% for hospital delivery, and 94% for postnatal visits. Inequity in maternal health services between provinces is declining, with hospital delivery rate showing the greatest decrease (SII, 14.01 to 1.87, 2010 to 2017). Third, an increase in the rate of hospital delivery rate can significantly reduce U5MR (OR 0.991, 95%CI 0.987 to 0.995). Postpartum visits rate with a one-year lag can reduce U5MR (OR 0.993, 95%CI 0.987 to 0.999). However, prenatal screening rate did not have a significant effect on U5MR. CONCLUSION: The decline in U5MR in China was associated with hospital delivery and postpartum visits. The design and implementation of maternal health services may provide references to other low-income and middle-income countries.

External validation and updating of the Rossi nomogram for predicting cesarean delivery following induction: is the Bishop score valuable?

OBJECTIVE: This study sought to validate the Rossi nomogram in a Chinese population and then to include the Bishop score to see if it has an effect on the accuracy of the nomogram. MATERIALS AND METHODS: The Rossi predictive model was applied and externally validated in a retrospective cohort from August 2017 and July 2023 in a Chinese tertiary-level medical center. For the revision and updating of the models, the regression coefficients of all the predictors (except race) were re-estimated and then the cervical Bishop score at the time of induction was added. Each model's performance was measured using the receiver-operating characteristic and calibration plots. Decision curve analysis determined the range of the probability threshold for each prediction model that would be of clinical value. RESULTS: A total of 721 women met the inclusion criteria, of whom 183 (25.4%) underwent a cesarean delivery. The calibration demonstrated the underestimation of the original model, with an area under the curve (AUC) of 0.789 (95% confidence interval [CI] 0.753-0.825, p < 0.001). After recalibrating the original model, the discriminative performance was improved from 0.789 to 0.803. Moreover, the discriminatory power of the updated model was further improved when the Bishop score at the time of induction was added to the recalibrated multivariable model. Indeed, the updated model demonstrated good calibration and discriminatory power, with an AUC of 0.811. The decision curve analysis indicated that all the models (original, recalibrated, and updated) provided higher net benefits of between 0 and 60% of the probability threshold, which indicates the benefits of using the models to make decisions concerning patients who fall within the identified range of the probability threshold. The net benefits of the updated model were higher than those of the original model and the recalibrated model. CONCLUSION: The nomogram used to predict cesarean delivery following induction developed by Rossi et al. has been validated in a Chinese population in this study. More specifically, adaptation to a Chinese population by excluding ethnicity and including the Bishop score prior to induction gave rise to better performance. The three models (original, recalibrated, and updated) offer higher net benefits when the probability threshold is between 0 and 60%.

ABA-responsive AREB1/ABI3-1/ABI5 cascade regulates IAA oxidase gene SlDAO2 to inhibit hypocotyl elongation in tomato.

Hypocotyl elongation is dramatically influenced by environmental factors and phytohormones. Indole-3-acetic acid (IAA) plays a prominent role in hypocotyl elongation, whereas abscisic acid (ABA) is regarded as an inhibitor through repressing IAA synthesis and signalling. However, the regulatory role of ABA in local IAA deactivation remains largely uncharacterized. In this study, we confirmed the antagonistic interplay of ABA and IAA during the hypocotyl elongation of tomato (Solanum lycopersicum) seedlings. We identified an IAA oxidase enzyme DIOXYGENASE FOR AUXIN OXIDATION2 (SlDAO2), and its expression was induced by both external and internal ABA signals in tomato hypocotyls. Moreover, the overexpression of SlDAO2 led to a reduced sensitivity to IAA, and the knockout of SlDAO2 alleviated the inhibitory effect of ABA on hypocotyl elongation. Furthermore, an ABA-responsive regulatory SlAREB1/SlABI3-1/SlABI5 cascade was identified to act upstream of SlDAO2 and to precisely control its expression. SlAREB1 directly bound to the ABRE present in the SlDAO2 promoter to activate SlDAO2 expression, and SlABI3-1 enhanced while SlABI5 inhibited the activation ability of SlAREB1 by directly interacting with SlAREB1. Our findings revealed that ABA might induce local IAA oxidation and deactivation via SlDAO2 to modulate IAA homoeostasis and thereby repress hypocotyl elongation in tomato.

Hyper-inflammation of astrocytes in patients of major depressive disorder: Evidence from serum astrocyte-derived extracellular vesicles.

Astrocyte-derived extracellular vesicles (ADEs) allow the in vivo probing of the inflammatory status of astrocytes practical. Serum sample and ADEs were used to test the inflammatory hypothesis in 70 patients with major depressive disorder (MDD) and 70 matched healthy controls (HCs). In serum, tumor necrosis factor α (TNF-α) and interleukin (IL)-17A were significantly increased, where as IL-12p70 was significantly reduced in the MDD patients compared with HCs. In ADEs, all inflammatory markers (Interferon-γ, IL-12p70, IL-1ß, IL-2, IL-4, IL-6, TNF-α, and IL-17A) except IL-10 were significantly increased in the MDD patients, the Hedge's g values of elevated inflammatory markers varied from 0.48 to 1.07. However, there were no differences of all inflammatory markers whether in serum or ADEs between MDD-drug free and medicated subgroups. The association of inflammatory biomarkers between ADEs and serum did not reach statistically significance after multi-comparison correction neither in the HCs nor MDD patients. The spearman coefficients between inflammatory factors and clinical characteristics in the MDD patients, such as onset age, disease course, current episode duration, and severity of depression, were nonsignificant after multi-comparison correction. In the receiver operating characteristic curves analysis, the corrected partial area under the curve (pAUC) of each inflammatory markers in ADEs ranged from 0.522 to 0.696, and the combination of these inflammatory factors achieved a high pAUC (>0.9). Our findings support the inflammatory glial hypothesis of depression, and suggests that in human ADEs could be a useful tool to probe the in vivo astrocyte status.

Optimization of hydrogen production in Enterobacter aerogenes by Complex I peripheral fragments destruction and maeA overexpression.

As a concentrated energy source with high added value, hydrogen has great development prospects, with special emphasis on sustainable microbial production as a replacement for traditional fossil fuels. In this study, λ-Red recombination was used to alter the activity of Complex I by single and combined knockout of nuoE, nuoF and nuoG. In addition, the conversion of malic to pyruvic acid was promoted by overexpressing the maeA gene, which could increase the content of NADH and formic acid in the bacterial cells. Compared to the original strain, hydrogen production was 65% higher in the optimized strain IAM1183-EFG/M, in which the flux of the formic acid pathway was increased by 257%, the flux of the NADH pathway was increased by 13%, and the content of metabolites also changed significantly. In further bioreactor, the total hydrogen production of the scale-up IAM1183-EFG/M after 44 h of fermentation was 4.76 L, which increased by 18% compared with the starting strain. This study provides a new direction for future exploration of microbial hydrogen production by combinatorial modification of multiple genes.

The role of military service in preventing depression in China: evidence from a nationally representative longitudinal survey.

BACKGROUND: Despite recognition in the West that military veterans experience more mental health issues than the general population, little research has focused on this subject in China. This study examined the associations between male veterans' military experience and depression in China. METHODS: A sample of 12,914 men including 669 veterans was included in the final analysis and propensity score matching, multivariable regressions and fixed effect model were used. RESULTS: The military experience was associated with a lower likelihood of depression in male veterans. In the subgroup analysis, military experience was associated with a lower likelihood of depression among married and urban male veterans. Military experience was also associated with a lower likelihood of depression in both "junior college and above" and "below junior college" groups. In contrast, evidence was lacking regarding the associations between military experience and depression for unmarried and rural veterans. CONCLUSIONS: Individual characteristics could influence the relationship between military experience and depression in male veterans, and the mental health of veterans should be paid more attention and guaranteed.

Does music intervention relieve depression or anxiety in people living with dementia? A systematic review and meta-analysis.

BACKGROUND: This study aimed to summarize the available evidence on music intervention alleviating depression or anxiety in dementia. METHODS: A comprehensive literature search was performed to analyze the effects of music intervention on depression or anxiety. Subgroups were created to explore the effect of intervention period, duration, and frequency on efficacy. The effect size was reported as a mean standardized difference (SMD) with 95% confidence interval (CI). RESULTS: The analysis included 19 articles involving 614 samples. Thirteen studies for relieving depression revealed that, with an increase in intervention period, the efficacy decreased and then increased, whereas with an increase of intervention duration, the effect became better. A weekly intervention is ideal. Seven studies verifying the impact on anxiety relief revealed that the effect of intervention within 12 wk is significant; with an increase of intervention duration, the effect became better. A weekly intervention is ideal. Collaborative analysis showed that long low-frequency interventions are more efficient than short high-frequency interventions. CONCLUSIONS: Music intervention can relieve depression or anxiety in people living with dementia. Weekly short interventions of more than 45 min are effective for emotional regulation. Future research should concentrate on severe dementia and follow-up impact.

CXCL10 serves as a potential serum biomarker complementing SCC-Ag for diagnosing cervical squamous cell carcinoma.

BACKGROUND: Cervical squamous cell carcinoma (CESC) is the most common histological type of cervical cancer which is the major cause of death in women worldwide. Although squamous cell carcinoma antigen (SCC-Ag) is widely used to detect CESC, it is not sensitive and specific enough to predict the disease. METHODS: We investigated serum CXC motif chemokine 10 (CXCL10) as potential diagnostic biomarker in detecting CESC in this study. Serum levels of CXCL10 and SCC-Ag were measured by ELISA or automated immunoassay in 345 participants, including 189 patients with different stages of CESC, 75 patients with cervical intraepithelial neoplasia, and 81 healthy individuals. Performances of CXCL10 and SCC-Ag as single biomarkers were analyzed by the ROC curves. The changes of serum levels of CXCL10 and SCC-Ag in 10 longitudinal followed-up CESC patients with partial response (PR) during chemoradiotherapy or chemotherapy were evaluated. RESULTS: The two markers showed similar diagnostic capacity in distinguishing both CESC early stage from healthy controls (AUCCXCL10 = 0.740, AUCSCC-Ag = 0.710) and all CESC from healthy controls (AUCCXCL10 = 0.775, AUCSCC-Ag =0.793). Moreover, CXCL10 showed ability in distinguishing cervical intraepithelial neoplasia from healthy control (AUCCXCL10 = 0.727) and cervical cancer SCC-Ag-negative from healthy control. (AUCCXCL10 = 0.739). The combination of CXCL10 and SCC-Ag displayed significant improvement of AUCs than individual SCC-Ag or CXCL10 in the analysis groups (healthy vs all cervical cancer, healthy vs cervical cancer early stage). The AUCs were improved to 0.877 (AUCSCC-Ag = 0.793, P < 0.05) to distinguish healthy controls from all CESC and 0.828(AUCSCC-Ag = 0.710, P < 0.05) to distinguish healthy controls from CESC early stage by the combination of the two markers, respectively. Significant differences of serum CXCL10 levels were found between CESC patients at late tumor stage and CESC patients at early tumor stage (P < 0.01). Serum CXCL10 levels of the CESC patients who had partial response after treatment significantly decreased during treatment (P = 0.013), whose consistent and inconsistent frequency with the response were the same as serum SCC-Ag levels. CONCLUSIONS: The results indicated that CXCL10 is a potential serum biomarker complementing SCC-Ag in prediction of CESC. CXCL10 showed ability in the diagnosis of SCC-Ag negative CESC and the combination of CXCL10 and SCC-Ag inhibited improved performance compared with SCC-Ag alone.

Ball-Milled Silicon with Amorphous Al2O3/C Hybrid Coating Embedded in Graphene/Graphite Nanosheets with a Boosted Lithium Storage Capability.

Electrochemical active silicon has attracted great attention as anodes for lithium-ion batteries owing to a high theoretical capacity of 4200 mA h g-1. In this work, ball-milled silicon particles with submicron size were strategically modified with a hybrid coating of amorphous alumina and carbon, which simultaneously embedded in a porous framework of in situ exfoliated graphene/graphite nanosheets (GGN). The composite exhibits an enhanced electrochemical performance, including high cycling stability and superior rate capability. An initial discharge capacity of 1294 mA h g-1 and a reversible charge capacity of 1044 mA h g-1 at 0.2 A g-1 can be achieved with a high initial Coulombic efficiency of up to ca. 81%. Additionally, the composite can remain 902 mA h g-1 after 100 discharge/charge cycles, accounting for a high retention of about 86%. This silicon composite is a promising anode material for high performance lithium-ion batteries with a high energy density, and the facile one-pot fabrication route is low cost and scalable, with a great prospect for practical application.

Effects of salt stress on the freeze-drying survival rate of Lactiplantibacillus plantarum LIP-1.

In this study, we examined the effects of different salt stress application methods on the Lactiplantibacillus plantarum LIP-1 freeze-drying survival rate. The application of salt stress during the stationary phase significantly improved Lactiplantibacillus plantarum LIP-1 freeze-drying survival rates (P < 0.05). The indirect application of salt stress via phosphate-buffered saline containing 0.4 mol/L NaCl (NB group) led to significantly higher freeze-drying survival rates compared to when salt stress was directly applied (NA group: the concentration of NaCl is 0.4 mol/L) (P < 0.05). Following exposure to salt stress, Lactiplantibacillus plantarum LIP-1 cells exuded excessive Na+ out of the cell and transported extracellular K+ into the cell, resulting in upregulation of the trkA gene, which is related to K+ transport, thereby significantly upregulating the expression of a lysR-type transcription factor, which increased the cell membrane unsaturated fatty acid content, reducing the degree of cell membrane damage and improving the freeze-drying survival rate. When the concentration of NaCl is 0.4 mol/L, compared with direct salt stress application, indirect application led to higher intracellular pH and ATP content, which effectively reduced DNA and cell membrane damage, respectively. Together, these results demonstrate that appropriate indirect salt stress application can improve Lactiplantibacillus plantarum LIP-1 freeze-drying resistance.

[Effects and correlation of ligustrazine hydrochloride-Salviae Miltiorrhizae Radix et Rhizoma compatibility on pharmacokinetics and CYP450 enzyme].

The present study investigated the effects of ligustrazine hydrochloride(LH)-Salviae Miltiorrhizae Radix et Rhizoma(SM) before and after compatibility on the pharmacokinetics of acute myocardial ischemia(AMI) rats and revealed the mechanism of pharmacokinetic changes from the perspective of metabolic enzymes. AMI rats underwent single injection of SM Glucose Injection, LH Glucose Injection, and LH-SM Glucose Injection in the caudal vein, respectively(3.78 mg·kg~(-1) salvianic acid, 0.049 mg·kg~(-1) rosmarinic acid, and 13.68 mg·kg~(-1) ligustrazine). Blood samples were collected from the orbital venous plexus at different time points, and the liver of the rats was removed after the last blood sampling. The plasma concentrations of salvianic acid, rosmarinic acid, and ligustrazine were detected by UPLC-MS/MS. Western blot was used to detect the protein expression of CYP1 A2, CYP2 C11, CYP2 C19, CYP2 D4, CYP2 E1, and CYP3 A2 in the liver of rats in each group. As revealed by the pharmacokinetic results, compared with the LH Glucose Injection group, the LH-SM Glucose Injection group showed a downward trend of T_(1/2) of ligustrazine in AMI rats and decreased AUC(P<0.05). Compared with the SM Glucose Injection, there were no significant differences in the pharmacokinetic parameters of salvianic acid and rosmarinic acid in the LH-SM Glucose Injection group. Protein expression results showed that the expression levels of CYP1 A2, CYP2 C11, CYP2 D4, CYP2 E1, and CYP3 A2 in the LH-SM Glucose Injection group increased(P<0.05) and the expression level of CYP2 C19 decreased(P<0.05) compared with those in the LH Glucose Injection group. CYP1 A2, CYP2 C11, and CYP3 A2 are isoenzymes involved in ligustrazine Ⅰ metabolism. When LH and SM were used in combination, the expression of these three enzymes increased, which changed the pharmacokinetic process in rats and accelerated the metabolism of ligustrazine.

[Intestinal absorption characteristics of root tuber of Cynanchum auriculatum extract in normal and functional dyspepsia model rats via everted intestine sac model].

The study investigated the difference of intestinal absorption characteristics of root tuber of Cynanchum auriculatum extract between normal and functional dyspepsia(FD) model rats with everted intestine sac model.The content of syringic acid, scopoletin, caudatin, baishouwu benzophenone, qingyangshengenin and deacyhmetaplexigenin in the C.auriculatum extract in different intestinal segments was detected by UPLC-MS/MS.The cumulative absorption amount(Q) and absorption rate constant(K_a) of the six chemical constituents were calculated.The results showed that the six components could be absorbed into the intestinal sac and were unsaturated, which indicated that the absorption mechanism of scopoletin was active transport in the intestine, while that of the other five components were passive diffusion.For normal group, the syringic acid and baishouwu benzophenone in ileum, qingyangshengenin and deacyhmetaplexigenin in ileum and duodenum, and caudatin in colon were well absorbed and scopoletin at low, medium and high concentrations was found excellent absorption in jejunum, ileum, and colon, respectively.Whereas the best absorption site of each component was ileum in model group.The absorption characteristics of each component between normal group and model group were complex at different concentrations, showing inconsistent tendency of absorption, which suggested that the components of root tuber of C.auriculatum extract were selectively absorbed in small intestine, and the absorption characteristics of the six components could be changed under FD status.This study provided theoretical basis for the clinical drug application and development of root tuber of C.auriculatum.

RNA methyltransferase METTL3 induces intrinsic resistance to gefitinib by combining with MET to regulate PI3K/AKT pathway in lung adenocarcinoma.

Clinical research data show that gefitinib greatly improves the progression-free survival of patients, so it is used in advanced non-small cell lung cancer patients with EGFR mutation. However, some patients with EGFR sensitive mutations do not have good effects on initial gefitinib treatment, and this mechanism is rarely studied. METTL3, a part of N6-adenosine-methyltransferase, has been reported to play an important role in a variety of tumours. In this study, we found that METTL3 is up-regulated in gefitinib-resistant tissues compared to gefitinib-sensitive tissues. Cell function experiments have proved that under the treatment of gefitinib, METTL3 knockdown promotes apoptosis and inhibits proliferation of lung cancer cells. Mechanistic studies have shown that METTL3 combines with MET and causes the PI3K/AKT signalling pathway to be manipulated, which affects the sensitivity of lung cancer cells to gefitinib. Therefore, our research shows that METTL3 can be used as a molecular marker to predict the efficacy of EGFR-TKI therapy in patients, and METTL3 may be a potential therapeutic target.

Efficacy and acquired resistance of EGFR-TKI combined with chemotherapy as first-line treatment for Chinese patients with advanced non-small cell lung cancer in a real-world setting.

BACKGROUND: To compare the benefits and explore the cause of acquired resistance of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and its combination with chemotherapy in advanced non-small-cell lung cancer (NSCLC) patients harboring EGFR mutation in a real-life setting. METHODS: This retrospective analysis included 117 advanced NSCLC patients with EGFR mutation who underwent next-generation sequencing (NGS) prior to treatment. The combination group included 50 patients who received the regimen of EGFR-TKI combined with chemotherapy, while the EGFR-TKI monotherapy group included 67 patients treated with TKI only. The primary endpoint of this study was progression-free survival (PFS); the secondary endpoints were overall survival (OS), response rate, and toxicity. RESULTS: The median PFS was significantly longer in the combination group than in the EGFR-TKI monotherapy group (19.00 months [95% CI, 14.67-23.33] vs. 11.70 months [95% CI, 10.81-12.59], p < 0.001). Subgroup analysis showed a similar trend of results. The median OS was not reached in the combination group and was 38.50 (95% CI, 35.30-41.70) months in the EGFR-TKI monotherapy group (p = 0.586). Patients in the combination group were more likely to experience adverse events, most of which showed the severity of grade 1 or 2. T790M mutation remains the main reason for acquired resistance, and the frequency of T790M mutation was similar between the two groups (p = 0.898). CONCLUSIONS: Compared with EGFR-TKI monotherapy, EGFR-TKI combined with chemotherapy significantly improved PFS in advanced NSCLC patients with EGFR mutation, with acceptable toxicity.

Caregivers' perceptions, challenges and service needs related to tackling childhood overweight and obesity: a qualitative study in three districts of Shanghai, China.

BACKGROUND: Childhood overweight and obesity (OWO) has become a major public concern worldwide including in Shanghai, one of the most developed areas of China. Understanding perceptions and challenges of tackling childhood OWO among caregivers of children is critical to provide services in need. METHODS: A qualitative descriptive study including in-depth interviews with seven parents and six focus group discussions with a total of 32 parents or grandparents of children zero to 6 years of age. Participants lived in three districts of Shanghai and indexed children included both those with OWO or non-OWO children. Data were analyzed using qualitative thematic analysis. RESULTS: Caregivers tended to underestimate children's weight status, and to regard chubby children as a sign of good parental care. Some caregivers even suggested that there were positive effects of childhood overweight. Caregivers identified a number of challenges to prevention of OWO in children, including difficulties in controlling dietary intake or increasing children's physical activities; discordant views between parents and grandparents, and barriers to accessing professional guidance. Caregivers desired more detailed advice regarding children's nutrition intake and physical activity, and preferred online approaches. CONCLUSIONS: Misconceptions regarding childhood overweight were found in caregivers of children in Shanghai. Professional guidance on childhood weight control for caregivers is desired via digital applications such as mobile phone applications and social media.

Zwitterionic Nanohydrogels-Decorated Microporous Membrane with Ultrasensitive Salt Responsiveness for Controlled Water Transport.

Highly sensitive responsiveness is vital for stimuli-responsive membranes. However, it is a great challenge to fabricate stimuli-responsive membranes with ultrahigh gating ratio (the ratio of the salt solution permeating flux to the pure water permeating flux) and high response speed simultaneously. In this work, a salt-responsive membrane with an ultrahigh gating ratio is fabricated via a facile strategy by grafting zwitterionic nanohydrogels onto a poly(acrylic acid)-grafting-poly(vinylidene fluoride) (PAA-g-PVDF) microporous membrane. Due to the synergistic effect of two functional materials, PAA chains and zwitterionic nanohydrogels tethered on PAA chains, this stimuli-responsive membrane exhibits an ultrasensitive salt responsiveness with a gating ratio of up to 8.76 times for Na+ ions, 89.6 times for Mg2+ ions, and 89.3 times for Ca2+ ions. In addition, such zwitterionic nanohydrogels-grafted PAA-g-PVDF (ZNG-g-PVDF) membranes exhibit very rapid responses to stimuli. The permeating flux changes swiftly while altering the feed solution in a continuous filtration process. The excellent salt-responsive characteristics endow such a ZNG-g-PVDF membrane with great potential for applications like drug delivery, water treatment, and sensors.

The selective ROCK2 inhibitor KD025 reduces IL-17 secretion in human peripheral blood mononuclear cells independent of IL-1 and IL-6.

Reducing the activities of the pro-inflammatory cytokine IL-17 is an effective treatment strategy for several chronic autoimmune disorders. Rho-associated coiled-coil containing kinase 2 (ROCK2) is a member of the serine-threonine protein kinase family that regulates IL-17 secretion in T cells via signal transducer and activator of transcription 3 (STAT3)-dependent mechanism. We reported here that the selective ROCK2 inhibitor KD025 significantly reduced in vitro production of IL-17 in unfractionated human peripheral blood mononuclear cells (PBMCs) stimulated with the dectin-1 agonist Candida albicans. C. albicans induced IL-17 was reduced by 70% (p < 0.0001); a similar reduction (80%) was observed in PBMC stimulated with the Toll-like receptor 2 agonist Staphylococcus epidermidis (p < 0.0001). Treatment of PBMC with KD025 was not associated with a reduction in IL-1ß, IL-6 or IL-1α levels; in contrast, a 1.5 fold increase in the level of IL-1 receptor antagonist (IL-1Ra) was observed (p < 0.001). KD025 down-regulated C. albicans-induced Myosin Light Chain and STAT3, whereas STAT5 phosphorylation increased. Using anti-CD3/CD28 activation of the TCR, KD025 similarly suppressed IL-17 independent of a reduction in IL-1ß. Thus, ROCK2 directly regulates IL-17 secretion independent of endogenous IL-1 and IL-6 supporting development of selective ROCK2 inhibitors for treatment of IL-17-driven inflammatory diseases.

The Transcriptional Activator Krüppel-like Factor-6 Is Required for CNS Myelination.

Growth factors of the gp130 family promote oligodendrocyte differentiation, and viability, and myelination, but their mechanisms of action are incompletely understood. Here, we show that these effects are coordinated, in part, by the transcriptional activator Krüppel-like factor-6 (Klf6). Klf6 is rapidly induced in oligodendrocyte progenitors (OLP) by gp130 factors, and promotes differentiation. Conversely, in mice with lineage-selective Klf6 inactivation, OLP undergo maturation arrest followed by apoptosis, and CNS myelination fails. Overlapping transcriptional and chromatin occupancy analyses place Klf6 at the nexus of a novel gp130-Klf-importin axis, which promotes differentiation and viability in part via control of nuclear trafficking. Klf6 acts as a gp130-sensitive transactivator of the nuclear import factor importin-α5 (Impα5), and interfering with this mechanism interrupts step-wise differentiation. Underscoring the significance of this axis in vivo, mice with conditional inactivation of gp130 signaling display defective Klf6 and Impα5 expression, OLP maturation arrest and apoptosis, and failure of CNS myelination.