Overexpression of FERONIA receptor kinase MdMRLK2 regulates lignin accumulation and enhances water use efficiency in apple under long-term water deficit condition.

Water use efficiency (WUE) is crucial for apple tree fitness and survival, especially in response to climatic changes. The receptor-like kinase FERONIA is reportedly an essential regulator of plant stress responses, but its role in regulating WUE under water deficit conditions is unclear. Here, we found that overexpressing the apple FERONIA receptor kinase gene, MdMRLK2, enhanced apple WUE under long-term water deficit conditions. Under drought treatment, 35S::MdMRLK2 apple plants exhibited higher photosynthetic capacity and antioxidant enzyme activities than wild-type (WT) plants. 35S::MdMRLK2 apple plants also showed increased biomass accumulation, root activity, and water potential compared to WT plants. Moreover, MdMRLK2 physically interacts with and phosphorylates cinnamoyl-CoA reductase 1, MdCCR1, an enzyme essential for lignin synthesis, at position Ser260. This interaction likely contributed to increased vessel density, vascular cylinder area, and lignin content in 35S::MdMRLK2 apple plants under drought conditions. Therefore, our findings reveal a novel function of MdMRLK2 in regulating apple WUE under water deficit conditions.

Overexpression of the FERONIA receptor kinase MdMRLK2 enhances apple cold tolerance.

Cold is one of the main abiotic stresses in temperate fruit crops, affecting the yield and fruit quality of apple in China and European countries. The plant receptor-like kinase FERONIA is widely reported to be involved in abiotic stresses. However, its function in apple cold resistance remains unknown. Modification of cell wall components and accumulation of soluble sugars and amino acids are important strategies by which plants cope with cold. In this study, expression of the apple FERONIA receptor-like kinase gene MdMRLK2 was rapidly induced by cold. Apple plants overexpressing MdMRLK2 (35S:MdMRLK2) showed enhanced cold resistance relative to the wild type. Under cold conditions, 35S:MdMRLK2 apple plants had higher amounts of water insoluble pectin, lignin, cellulose, and hemicellulose, which may have resulted from reduced activities of polygalacturonase, pectinate lyase, pectinesterase, and cellulase. More soluble sugars and free amino acids and less photosystem damage were also observed in 35S:MdMRLK2 apple plants. Intriguingly, MdMRLK2 interacted with the transcription factor MdMYBPA1 and promoted its binding to MdANS and MdUFGT promoters, leading to more anthocyanin biosynthesis, particularly under cold conditions. These findings complemented the function of apple FERONIA MdMRLK2 responding to cold resistance.

Hourly Air Pollution Exposure and Emergency Hospital Admissions for Stroke: A Multicenter Case-Crossover Study.

BACKGROUND: Daily exposure to ambient air pollution is associated with stroke morbidity and mortality; however, the association between hourly exposure to air pollutants and risk of emergency hospital admissions for stroke and its subtypes remains relatively unexplored. METHODS: We obtained hourly concentrations of fine particulate matter (PM2.5), respirable particulate matter (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and carbon monoxide (CO) from the China National Environmental Monitoring Center. We conducted a time-stratified case-crossover study among 86 635 emergency hospital admissions for stroke across 10 hospitals in 3 cities (Jinhua, Hangzhou, and Zhoushan) in Zhejiang province, China, between January 1, 2016 and December 31, 2021. Using a conditional logistic regression combined with a distributed lag linear model, we estimated the association between hourly exposure to multiple air pollutants and risk of emergency hospital admissions for total stroke, ischemic stroke, hemorrhagic stroke, and undetermined type. RESULTS: Hourly exposure to PM2.5, PM10, NO2, and SO2 was associated with an increased risk of hospital admissions for total stroke and ischemic stroke. The associations were most pronounced during the concurrent hour of exposure and lasted for ≈2 hours. We found that the risk was more pronounced among male patients or those aged <65 years old. CONCLUSIONS: Our findings suggest that exposure to PM2.5, PM10, NO2, and SO2, but not CO and O3, is associated with emergency hospital admissions for total stroke or ischemic stroke shortly after exposure. Implementing targeted pollution emission reduction measures may have significant public health implications in controlling and reducing the burden of stroke.

Endogenous Enzyme-Powered DNA Nanomotor Operating in Living Cells for microRNA Imaging.

Accurate and specific imaging of low-abundance microRNA (miRNA) in living cells is extremely important for disease diagnosis and monitoring of disease progression. DNA nanomotors have shown great potential for imaging molecules of interest in living cells. However, inappropriate driving forces and complex design and operation procedures have hindered their further application. Here, we proposed an endogenous enzyme-powered DNA nanomotor (EEPDN), which employs an endogenous APE1 enzyme as fuel to execute repetitive cycles of motion for miRNA imaging in living cells. The whole motor system is constructed based on gold nanoparticles without other auxiliary additives. Due to the high efficiency of APE1, this EEPDN system has achieved highly sensitive miRNA imaging in living cells within 1.5 h. This strategy was also successfully used to differentiate the expression of specific miRNA between tumor cells and normal cells, demonstrating a high tumor cell selectivity. This strategy can promote the development of novel nanomotors and is expected to be a perfect intracellular molecular imaging tool for biological and medical applications.

The effects of high plasma levels of Aß1-42 on mononuclear macrophage in mouse models of Alzheimer's disease.

More and more evidences are proving that microglia play a crucial role in the pathogenesis of Alzheimer's disease (AD) and the plasma Aß1-42 levels significantly increased 15 years before the onset of dominantly inherited AD. However, the effects of high plasma levels of Aß1-42 on mononuclear macrophage, the peripheral counterparts of microglia, remain unclear. In the present study, we used APP/PS1 transgenic (Tg) mice and a parabiotic model of wild type (Wt) mice and Tg mice (Parabiotic Wt-Tg, Pa (Wt-Tg)) to investigate the effects of high plasma levels of Aß1-42 on peripheral mononuclear macrophage. Our results showed that in the early stage of Tg mice (7 months) and Pa (Wt-Tg) mice (4 months), the proportions of pro-inflammatory macrophages in peritoneal cavity, myeloid derived suppressor cells (MDSCs) in spleen, granulocyte-monocyte progenitors (GMPs) in bone marrow, and the plasma levels of interleukin-6 (IL-6) were significantly decreased. While the proportions of pro-inflammatory macrophages, MDSCs, GMPs, and the plasma levels of IL-6 and tumor necrosis factor (TNF)-α, as well as the numbers of bone marrow-derived macrophages (BMDMs) in mice brain were increased in the late stage of Tg mice (11 months) and Pa (Wt-Tg) mice (8 months). In addition, the proportions of monocytes in spleen and the proliferation of bone marrow cells (BMCs) were enhanced consistently, and the phagocytic function of macrophages kept stably after high plasma levels of Aß1-42 sustaining stimulation. These results demonstrated that high plasma levels of Aß1-42 play a biphasic regulating role at different stages of the disease, namely inhibiting effects on peripheral pro-inflammatory macrophages in the early stage of AD model, while promoting effects in the late stage of AD model. The mechanism behind this may be associated with their effects on MDSCs in spleen and myeloid progenitor cells in bone marrow. Therefore, intervening the effects of plasma Aß1-42 on pro-inflammatory macrophages might offer a new therapeutic approach to AD.

The effectiveness of pay-it-forward in addressing HPV vaccine delay and increasing uptake among 15-18-year-old adolescent girls compared to user-paid vaccination: a study protocol for a two-arm randomized controlled trial in China.

BACKGROUND: Human papillomavirus (HPV) vaccination could prevent cervical and other HPV-associated cancers attributable to vaccine-associated HPV types. However, HPV vaccination coverage among women aged 9-18 years old is low in China. Common barriers include poor financial affordability, minimal public engagement, and low confidence in domestically produced HPV vaccines. Pay-it-forward offers an individual a free or subsidized service then an opportunity to voluntarily donate and/or create a postcard message to support future people. This study aims to assess the effectiveness of pay-it-forward as compared to standard-of-care self-paid vaccination to improve HPV vaccine uptake among adolescent girls aged 15-18 years, who are left out in the current pilot free HPV vaccination task force in some parts of China. METHODS: This is a two-arm randomized controlled trial in Chengdu, China. Eligible adolescent girls (via caregivers) will be randomly selected and recruited through four community health centers (one in the most developed urban areas, one in higher middle-income and one in lower middle-income suburban areas, and one in the least developed rural areas) using the resident registration list. A total of 320 participants will be randomized into two study arms (user-paid versus pay-it-forward vaccination) in a 1:1 ratio. The intervention assignment will be blinded to recruiters and participants using envelop concealment until the research assistants open the envelop to determine which treatment to deliver to each individual. The primary outcome of the study will be HPV vaccine uptake by administrative data. Secondary outcomes include costs, vaccine hesitancy, and the completion rates of the 3-dose HPV vaccination series. DISCUSSION: This study will investigate an innovative pay-it-forward strategy's effectiveness and economic costs to improve HPV vaccination among 15-18-year-old adolescent girls. Study findings will have implications for increasing HPV vaccine uptake in places where HPV vaccines are provided for a fee. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), ChiCTR2200055542. Registered on 11 January 2022.

The conservative management for improving Visual Analog Scale (VAS) pain scoring in greater trochanteric pain syndrome: a Bayesian analysis.

BACKGROUND: Greater trochanteric pain syndrome (GTPS) possesses a harmful influence on quality of life. Numerous conservative management modalities with varying success have been proposed for patients with GTPS. However, it is not clear which treatment is more effective for reducing pain. The purpose of this Bayesian analysis was to assess the current evidence for the effectiveness of conservative treatments on improving Visual Analog Scale (VAS) pain scoring of GTPS and to determine the most effective treatment protocol. METHODS: A comprehensive study search was performed from inception until July 18, 2022, via the electronic databases PubMed, the Cochrane Library, and Web of Science for potential research. The risk of bias assessment for the included studies was independently performed based on the Cochrane Collaboration Risk of Bias Tool. Bayesian analysis was conducted by using ADDIS software (v1.16.5). The DerSimonian-Laird random effects model was used to perform the traditional pairwise meta-analysis. RESULTS: Eight full-text articles with a total of 596 patients with GTPS were included in the analysis. In comparing ultrasound-guided platelet-rich plasma application (PRP-U) to ultrasound-guided corticosteroid injection (CSI-U), patients who received PRP therapy experienced reduced pain as the VAS decreased significantly (MD, -5.21; 95% CI, -6.24 to -3.64). VAS score in group of extracorporeal shockwave treatment (ESWT) was significant improved than that in exercise (EX) group (MD, -3.17; 95% CI, -4.13 to -2.15). There were no statistically significantly different VAS scores between the CSI-U group and the CSI under landmark (CSI-B) group. The treatment efficacy rankings of the different treatments on improving VAS scores showed that the most likely efficacious treatment was PRP-U (99%) followed by ESWT (81%), CIS-U (58%), usual care (48%), CIS-B (54%), and EX (84%). CONCLUSION: Bayesian analysis revealed that PRP injection and ESWT are relatively safe and effective in the treatment of GTPS. More multicenter high-quality randomized clinical trials with large sample sizes are still needed in the future to provide further evidence.

Light-Controlled Recruitable Hybridization Chain Reaction on Exosome Vehicles for Highly Sensitive MicroRNA Imaging in Living Cells.

Sensitive imaging of intracellular microRNA (miRNA) in living cells is of great significance. Isothermal hybridization chain reaction (HCR)-based methods, although have been widely used to monitor intracellular low-abundance miRNA, are still subjected to the challenges of limited signal amplification efficiency and compromised imaging resolution. In this work, we design a light-controlled recruitable HCR (LCR-HCR) strategy that enables us to well overcome these limitations. Exosomes as delivery and recruitment vehicles are modified with three cholesterol-modified hairpins (H1, H2, and H3), in which H1 is for anchoring target miRNA and H2 and H3 with photocleavable linkers (PC-linkers) are designed for spatiotemporal HCR. By controllably releasing probes with high local concentrations to efficiently trigger HCR and further recruiting the generated double-stranded DNA (dsDNA) polymers instead of dispersion in the cytoplasm, the LCR-HCR method can significantly improve the imaging contrast by confining all of the reactants on exosome vehicles. For a proof-of-concept demonstration, the miR-21 was analyzed by LCR-HCR with a limit of detection (LOD) down to 3.3 pM (corresponding to 165 amol per 50 µL) in vitro and four times higher response than traditional HCR in vivo. In general, the LCR-HCR method provides a powerful tool for sensitive miRNA imaging in living cells and cancer diagnosis.

Potential role of BAY11-7082, a NF-κB blocker inhibiting experimental autoimmune encephalomyelitis in C57BL/6J mice via declining NLRP3 inflammasomes.

Multiple sclerosis (MS) is an inflammatory autoimmune demyelinating disease of the central nervous system. NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome is implicated in the pathogenesis of MS and its animal model, experimental autoimmune encephalomyelitis (EAE). However, the exact mechanism by which NLRP3 inflammasome is involved in the development of MS and EAE is not clear. NF-kappaB (NF-κB) is associated with the activity of NLRP3 inflammasomes, but the role of NF-κB is controversial. We sought to demonstrate that both NF-κB and NLRP3 contribute to development of MS and EAE, and NF-κB pathway is positively correlated with NLRP3 activation in EAE. The inhibitor of NF-κB and NLRP3, BAY11-7082, can prevent and treat EAE. BAY11-7082 (5 and 20 mg/kg/i.p.) was intraperitoneally administered to EAE mice at the time of second injection of pertussis toxin (BAY11-7082 prevention group) or at the onset of symptoms (BAY11-7082 treatment group). mRNA expressions of NLRP3 were determined by qPCR. Protein expressions of NLRP3, NF-κB p65, and phosphorylated p65 were determined by western blotting. Serum levels of inflammatory cytokines were measured by cytometric bead array. Mice treated with BAY11-7082 (both prevention and treatment groups) showed lower clinical scores and attenuated pathological changes. NLRP3 inflammasome and activity of NF-κB in spinal cord of EAE mice was higher than that in control group. However, the level of NLRP3 inflammasome decreased in BAY11-7082 prevention and treatment groups. BAY11-7082 is a promising therapeutic agent for MS. NLRP3 activation in EAE maybe related with NF-κB pathway.

EBNA2-deleted Epstein-Barr virus (EBV) isolate, P3HR1, causes Hodgkin-like lymphomas and diffuse large B cell lymphomas with type II and Wp-restricted latency types in humanized mice.

EBV transforms B cells in vitro and causes human B-cell lymphomas including classical Hodgkin lymphoma (CHL), Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). The EBV latency protein, EBNA2, transcriptionally activates the promoters of all latent viral protein-coding genes expressed in type III EBV latency and is essential for EBV's ability to transform B cells in vitro. However, EBNA2 is not expressed in EBV-infected CHLs and BLs in humans. EBV-positive CHLs have type II latency and are largely driven by the EBV LMP1/LMP2A proteins, while EBV-positive BLs, which usually have type I latency are largely driven by c-Myc translocations, and only express the EBNA1 protein and viral non-coding RNAs. Approximately 15% of human BLs contain naturally occurring EBNA2-deleted viruses that support a form of viral latency known as Wp-restricted (expressing the EBNA-LP, EBNA3A/3B/3C, EBNA1 and BHRF1 proteins), but whether Wp-restricted latency and/or EBNA2-deleted EBV can induce lymphomas in humanized mice, or in the absence of c-Myc translocations, is unknown. Here we show that a naturally occurring EBNA2-deleted EBV strain (P3HR1) isolated from a human BL induces EBV-positive B-cell lymphomas in a subset of infected cord blood-humanized (CBH) mice. Furthermore, we find that P3HR1-infected lymphoma cells support two different viral latency types and phenotypes that are mutually exclusive: 1) Large (often multinucleated), CD30-positive, CD45-negative cells reminiscent of the Reed-Sternberg (RS) cells in CHL that express high levels of LMP1 but not EBNA-LP (consistent with type II viral latency); and 2) smaller monomorphic CD30-negative DLBCL-like cells that express EBNA-LP and EBNA3A but not LMP1 (consistent with Wp-restricted latency). These results reveal that EBNA2 is not absolutely required for EBV to form tumors in CBH mice and suggest that P3HR1 virus can be used to model EBV positive lymphomas with both Wp-restricted and type II latency in vivo.

The prediction effects of thyroid function in the severity of Guillain-Barré syndrome.

BACKGROUND: Guillain-Barré syndrome (GBS), an acquired immune-mediated inflammatory disorder affecting the peripheral nervous system (PNS), is usually complicated with autoimmune diseases including thyroid diseases. Herein, we explored roles of thyroid function and thyroid autoantibodies in the disease severity and its short-term prognosis of GBS. In addition, we further investigated the predictive value of thyroid function for GBS respiratory insufficiency. MATERIALS AND METHODS: We retrospectively analyzed the clinical data of 219 GBS patients. According to the thyroid function, the enrolled subjects were divided into 2 groups, that is, patients with abnormal thyroid function (case group) and those with normal thyroid function (control group). The clinical characteristics, disease severity, and short-term prognosis of the patients in 2 groups were compared. In addition, we also divided the 219 GBS patients into mechanical ventilation (MV) group and non-MV group according to whether MV was performed within 1 week after admission. The clinical characteristics, disease severity, short-term prognosis, Erasmus GBS respiratory insufficiency score (EGRIS), and the thyroid function were compared in the two groups. RESULTS: We found that GBS patients with abnormal thyroid function had longer duration of hospitalization, higher frequency of cranial nerve damage, and higher incidence of weakened tendon reflexes. Medical Research Council (MRC) scores on admission, at nadir, and at discharge were lower, and Hughes Functional Grading Scale (HFGS) scores on admission and at discharge were higher in GBS patients with abnormal thyroid function group. More patients in the abnormal thyroid function group had myelin, axonal, and myelin-axonal injuries. In the MV group, the time from onset to admission, MRC scores on admission, and the levels of free triiodothyronine (FT3) were lower; the levels of thyroglobulin antibody (TgAb) and EGRIS were significantly higher than those in the non-MV group. The combination of EGRIS and FT3 serum levels to predict GBS patients with MV, the area under the curve (AUC) was 0.905 (95% CI: 0.861 to 0.948, P < 0.05), sensitivity was 88.9%, and specificity was 84.7%. CONCLUSION: Our results suggest that the serum FT3 levels are negatively correlated with disease severity; the serum FT3 might be a biomarker for the incidence and severity of GBS. Both EGRIS and serum FT3 have a predictive value for the occurrence of acute respiratory insufficiency in GBS patients, and the combination of these two indicators can more accurately predict the risk of acute respiratory insufficiency in GBS patients.

Associations of excessive screen time and early screen exposure with health-related quality of life and behavioral problems among children attending preschools.

BACKGROUND: Both excessive screen time and early screen exposure have been linked to children's health outcomes, but few studies considered these two exposures simultaneously. The aim of this study was to explore the independent and interactive associations of excessive screen time and early screen exposure with health-related quality of life (HRQOL) and behavioral problems among Chinese children attending preschools. METHODS: A cross-sectional study of 4985 children aged between 3 and 6 years was conducted in Chengdu, China. Each parent has finished an online questionnaire regarding their children's screen use, HRQOL, and behavioral problems. Children with screen time over 1 h/day were considered as having excessive screen time. Early screen exposure was defined if the children had started using screen-based media before the age of 2 years. HRQOL was assessed by the Pediatric Quality of Life Inventory version 4.0 (PedsQL 4.0), while behavioral problems were confirmed with the 48-item Conners' Parent Rating Scale (CPRS-48). RESULTS: Of the 4985 children (2593 boys and 2392 girls) included, the mean age was 4.6 (SD: 1.0) years. After adjustment for confounders and early screen exposure, excessive screen time was significantly associated with worse HRQOL scores in all dimensions and summary scales, as well as each type of behavioral problems (all p values < 0.05). We also found that compared to children with later initiation of screen exposure, those with screen use before the age of 2 years had significantly lower emotional functioning score (ß: - 2.13, 95%CI: - 3.17, - 1.09) and psychosocial health summary score (ß: - 0.82, 95%CI: - 1.54, - 0.10) of HRQOL, as well as higher risks of conduct problems, learning problems, psychosomatic problems, impulsive-hyperactive, and hyperactivity index, which were independent of excessive screen use. Furthermore, there were significant interactive effects of excessive screen time and early screen exposure on emotional functioning domain of HRQOL scores and conduct problems. CONCLUSION: Excessive screen time and early screen exposure are two independent and interactive factors to children's HRQOL and behavioral problems. Our findings support current guidelines to limit screen exposure in children. Appropriate screen use may represent an important intervention target to improve children's HRQOL and reduce their behavioral problems.

Risk Factors for Mechanical Ventilation in Patients with Guillain-Barré Syndrome.

BACKGROUND: Respiratory support is required in 20-30% of patients with Guillain-Barré syndrome (GBS). We investigated clinical and biological risk factors for mechanical ventilation (MV) in northeast China through a retrospective GBS study. The Erasmus GBS Respiratory Insufficiency Score (EGRIS) is a prognostic model for MV in patients with GBS, and its usefulness has been validated in several countries but not in China. Therefore, we intended to validate the EGRIS model in our GBS cohort. METHODS: A total of 252 patients with GBS were included in this study from January 2013 to October 2017. Risk factors for MV were identified via multivariate logistic regression analysis. The prognostic value of the EGRIS was validated via receiver operating characteristic curve analysis. RESULTS: Thirty-one patients (12.3%) required MV (mean age 54.19 years), with a majority being male (77.4%). The risk factors for MV were male sex [odds ratio (OR) 3.720, 95% confidence interval (CI) 1.155-11.985, p < 0.05], shorter interval from onset to admission (OR 0.830, 95% CI 0.711-0.970, p < 0.05), lower Medical Research Council sum score at admission (OR 0.942, 95% CI 0.911-0.973, p < 0.001), neutrophil-to-lymphocyte ratio at admission (OR 1.174, 95% CI 1.049-1.315, p < 0.01), and cranial nerve deficit (OR 3.805, 95% CI 1.373-10.541, p < 0.05). The EGRIS had a good predictive ability for MV (area under the receiver operating curve 0.861) in patients with GBS, and a high EGRIS was a predictor for MV (OR 8.778, 95% CI 3.432-22.448, p < 0.001). However, there was no significant difference in ganglioside administration between ventilated and nonventilated patients. CONCLUSIONS: An elevated neutrophil-to-lymphocyte ratio at admission and a high EGRIS could serve as predictors for MV in our GBS cohort.

Expression profiles and potential roles of transfer RNA-derived small RNAs in atherosclerosis.

Knowledge regarding the relationship between the molecular mechanisms underlying atherosclerosis (AS) and transfer RNA-derived small RNAs (tsRNAs) is limited. This study illustrated the expression profile of tsRNAs, thus exploring its roles in AS pathogenesis. Small RNA sequencing was performed with four atherosclerotic arterial and four healthy subject samples. Using bioinformatics, the protein-protein interaction network and cellular experiments were constructed to predict the enriched signalling pathways and regulatory roles of tsRNAs in AS. Of the total 315 tsRNAs identified to be dysregulated in the AS group, 131 and 184 were up-regulated and down-regulated, respectively. Interestingly, the pathway of the differentiated expression of tsRNAs in cell adhesion molecules (CAMs) was implicated to be closely associated with AS. Particularly, tRF-Gly-GCC might participate in AS pathogenesis via regulating cell adhesion, proliferation, migration and phenotypic transformation in HUVECs and VSMCs. In conclusion, tsRNAs might help understand the molecular mechanisms of AS better. tRF-Gly-GCC may be a promising target for suppressing abnormal vessels functions, suggesting a novel strategy for preventing the progression of atherosclerosis.

Nuclear factor kappa B inhibitor suppresses experimental autoimmune neuritis in mice via declining macrophages polarization to M1 type.

Guillain-Barré syndrome (GBS) is an acute inflammatory and immune-mediated demyelinating disease of the peripheral nervous system (PNS). Macrophages play a central role in its animal model, experimental autoimmune neuritis (EAN), which has been well accepted. Additionally, nuclear factor (NF)-κB inhibitors have been used to treat cancers and have shown beneficial effects. Here, we investigated the therapeutic effect of M2 macrophage and the NF-κB pathway's correlation with macrophage activation in EAN in C57BL/6 mice. We demonstrate that M2 macrophage transfusion could alleviate the clinical symptoms of EAN by reducing the proportion of M1 macrophage in the peak period, inhibiting the phosphorylation of NF-κB p65. The NF-κB inhibitor (BAY-11-7082) could alleviate the clinical symptoms of EAN and shorten the duration of symptoms by reducing the proportion of M1 macrophages and the expression of proinflammatory cytokines. Consequently, BAY-11-7082 exhibits strong potential as a therapeutic strategy for ameliorating EAN by influencing the balance of M1/M2 macrophages and inflammatory cytokines.

Parity and the risks of adverse birth outcomes: a retrospective study among Chinese.

BACKGROUND: Nulliparity is considered to be a risk factor of preterm birth (PTB), low birth weight (LBW) and small for gestational age (SGA). With the new two-child policy launched in 2016, more Chinese women have delivered their 2nd baby. Yet few studies have assessed the impact of parity on adverse birth outcomes in China. This study aimed to examine the association between parity and risks of PTB, LBW and SGA in a Chinese population. The combined effects of maternal age and parity on adverse birth outcomes were also assessed. METHODS: This retrospective study included all non-malformed live births born during January 1, 2014 and December 31, 2018 in Chengdu, China. A total of 746,410 eligible live singletons with complete information were included in the analysis. Parity was classified into nulliparity (i.e. has never delivered a newborn before) and multiparity (i.e. has delivered at least one newborn before). Log-binomial regression analyses were applied to evaluate the association between parity and PTB, LBW and SGA. We further divided maternal age into different groups (< 25 years, 25-29 years, 30-34 years and ≥ 35 years) to assess the combined effects of maternal age and parity on adverse birth outcomes. RESULTS: Multiparity was associated with reduced risks of PTB (aRR = 0.91, 95% CI: 0.89-0.93), LBW (aRR = 0.74, 95% CI: 0.72-0.77) and SGA (aRR = 0.67, 95% CI: 0.66-0.69) compared with nulliparity. In each age group, we observed that multiparity was associated with lower risks of adverse birth outcomes. Compared to nulliparous women aged between 25 and 29 years, women aged ≥35 years had greater risks of PTB and LBW, regardless of their parity status. In contrast, multiparous women aged ≥35 years (aRR = 0.73, 95% CI: 0.70-0.77) and those aged < 25 years (aRR = 0.88, 95% CI: 0.84-0.93) were at lower risk of SGA compared with nulliparous women aged between 25 and 29 years. CONCLUSION: Multiparity was associated with lower risks of all adverse birth outcomes. Special attention should be paid to nulliparous mothers and those with advanced age during antenatal care, in order to reduce the risks of adverse birth outcomes.

Inducible Enrichment of Osa-miR1432 Confers Rice Bacterial Blight Resistance through Suppressing OsCaML2.

MicroRNAs (miRNAs) handle immune response to pathogens by adjusting the function of target genes in plants. However, the experimentally documented miRNA/target modules implicated in the interplay between rice and Xanthomonas oryzae pv. oryzae (Xoo) are still in the early stages. Herein, the expression of osa-miR1432 was induced in resistant genotype IRBB5, but not susceptible genotype IR24, under Xoo strain PXO86 attack. Overexpressed osa-miR1432 heightened rice disease resistance to Xoo, indicated by enhancive enrichment of defense marker genes, raised reactive oxygen species (ROS) levels, repressed bacterial growth and shortened leaf lesion length, whilst the disruptive accumulation of osa-miR1432 accelerated rice susceptibility to Xoo infection. Noticeably, OsCaML2 (LOC_Os03g59770) was experimentally confirmed as a target gene of osa-miR1432, and the overexpressing OsCaML2 transgenic plants exhibited compromised resistance to Xoo infestation. Our results indicate that osa-miR1432 and OsCaML2 were differently responsive to Xoo invasion at the transcriptional level and fine-tune rice resistance to Xoo infection, which may be referable in resistance gene discovery and valuable in the pursuit of improving Xoo resistance in rice breeding.

Periostin regulates osteogenesis of mesenchymal stem cells from ovariectomized rats through actions on the ILK/Akt/GSK-3ß Axis.

Osteoporosis is a condition of the skeleton that mainly results from estrogen deficiency. Periostin is a matricellular component in bone that is involved in osteoblast differentiation. However, how Periostin promotes osteogenesis remains largely unknown. Here, we isolated bone marrow skeletal stem cells (BMSCs) derived from an ovariectomy (OVX)-induced osteoporosis rat model and the effects of periostin on BMSCs derived from OVX rats (OVX-BMSCs) were assessed. Overexpression of periostin enhanced alkaline phosphatase (ALP) and alizarin red staining in OVX-BMSCs as well as the osteogenic genes OCN, BSP and Runx2. ILK is a downstream effector of signals from the extracellular matrix and participates in bone homeostasis. Overexpression of periostin also increased expression of protein levels for ILK, as well as the downstream targets pAkt and pGSK3ß. Suppression of ILK or Akt partially suppressed the enhancement of osteogenic ability induced by periostin overexpression in OVX-BMSCs. Thus, periostin may promote the osteogenic ability of OVX-BMSCs through actions on the ILK/Akt/GSK3ß axis.

[Screening results and genetic features of glucose-6-phosphate dehydrogenase deficiency in 54 025 preterm infants in Chengdu, China].

OBJECTIVE: To analyze the screening results of glucose-6-phosphate dehydrogenase (G6PD) deficiency and gene mutation distribution of G6PD deficiency in preterm infants in Chengdu, China, in order to provide a basis for the improvement of G6PD screening process in preterm infants. METHODS: Fluorescent spot test for G6PD deficiency using dried blood spots was used for G6PD screening of 54 025 preterm infants born from January 1, 2015 to December 31, 2019 in Chengdu, and G6PD enzymology and gene detection were used for the diagnosis of 213 infants with positive screening results. RESULTS: Among the 54 025 preterm infants, 192 were diagnosed with G6PD deficiency, with an incidence rate of 3.55‰. The incidence rate of G6PD deficiency in preterm infants was higher than that in full-term infants in the same period of time and tended to increase year by year. Birth in summer, gestational age <32 weeks, and birth weight <2 500 g were influencing factors for the increase in false positive rate of screening (P < 0.05). The diagnostic accordance rate of genetic tests was significantly higher than that of enzyme activity assay in female infants (P < 0.05). Nine gene mutations were detected in Chengdu, without compound heterozygous mutation. Homozygous mutation was not detected in female infants. In the 80 infants with gene mutations, the top three gene mutations were c.1388G>A in 26 infants (32%), c.1376G>T in 21 infants (26%), and c.1024C>T in 13 infants (16%), accounting for 75%. There was a significant difference in pathogenicity grading among the three gene mutations (P < 0.001). The pairwise comparison showed that c.1024C>T had a significantly lower pathogenicity grade than c.1376G>T and c.1388G>A (P < 0.0167), suggesting that c.1376G>T and c.1388G>A had greater influence on enzyme activity than c.1024C>T. CONCLUSIONS: Screening for G6PD deficiency in preterm infants should be taken seriously. It is recommended to apply cold-chain transportation of samples in summer to reduce the false positive rate of primary screening for G6PD deficiency. Genetic tests should be promoted in girls with positive screening results to improve the detection rate of G6PD deficiency in preterm female infants. There are various types of gene mutations in preterm infants with G6PD deficiency in Chengdu, and infants with c.1024C>T mutation tend to have mild conditions.

Dietary Inflammatory Index and Epithelial Ovarian Cancer in Southern Chinese Women: A Case-Control Study.

The association between inflammatory properties of diet and ovarian cancer risk has been investigated in some Western populations. However, little evidence is available from Asian women whose ovarian cancer incidence rates are low and dietary and lifestyle patterns are very different from their Western counterparts. We aimed to examine whether more pro-inflammatory diets, as indicated by higher dietary inflammatory index (DII®) scores, are associated with increased odds of epithelial ovarian cancer in southern China. A case-control study was conducted during 2006-2008 in Guangzhou, Guangdong Province. Energy-adjusted DII (E-DII) scores were calculated based on dietary intake assessed by a validated food frequency questionnaire administered to 500 incident epithelial ovarian cancer patients and 500 hospital-based controls. Logistic regression models were used to assess the relationship between E-DII scores and odds of ovarian cancer. Positive associations were observed between higher E-DII scores and ovarian cancer odds, using both continuous DII scores (odds ratio (OR) 1.87; 95% confidence interval (CI) 1.65, 2.13) and by DII tertiles (ORtertile3vs1 7.04, 95% CI: 4.70, 10.54, p for trend < 0.001). Likewise, a more pro-inflammatory diet was associated with a higher chance of serous and mucinous ovarian tumors. Our results suggest that a pro-inflammatory diet was associated with increased odds of developing epithelial ovarian cancer in southern Chinese women. The findings add to epidemiological evidence for the role of dietary inflammatory potential in ovarian cancer development.