Search

Microglia are the resident immune cells of the center nervous system and participate in various neurological diseases. Here we determined the function of microglia in epileptogenesis using microglial ablation approaches. Three different microglia-specific genetic tools were used, CX3CR1 CreER/+ :R26 iDTA/+ , CX3CR1 CreER/+ :R26 iDTR/+ , and CX3CR1 CreER/+ :Csf1r Flox/Flox mice. We found that microglial depletion led to worse kainic acid (KA)-induced status epilepticus, higher mortality rate, and increased neuronal degeneration in the hippocampus. In KA-induced chronic spontaneous recurrent seizures, microglial depletion increased seizure frequency, interictal spiking, and seizure duration. Therefore, microglial depletion aggravates the severity of KA-induced acute and chronic seizures. Interestingly, microglial repopulation reversed the effects of depletion upon KA-induced status epilepticus. Our results demonstrate a beneficial role of microglia in suppressing both acute and chronic seizures, suggesting that microglia are a potential therapeutic target for the management of epilepsy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

During sporulation of Bacillus subtilis , the cell cycle is reorganized to generate separated prespore and mother cell compartments, each containing a single fully replicated chromosome. The process begins with reorganization of the nucleoid to form an elongated structure, the axial filament, in which the two chromosome origins are attached to opposite cell poles, with the remainder of the DNA stretched between these sites. When the cell then divides asymmetrically, the division septum closes around the chromosome destined for the smaller prespore, trapping the origin-proximal third of the chromosome in the prespore. A translocation pore is assembled through which a DNA transporter, SpoIIIE/FtsK, transfers the bulk of the chromosome to complete the segregation process. Although the mechanisms involved in attaching origin regions to the cell poles are quite well understood, little is known about other aspects of axial filament morphology. We have studied the behavior of the terminus region of the chromosome during sporulation using time-lapse imaging of wild-type and mutant cells. The results suggest that the elongated structure involves cohesion of the terminus regions of the sister chromosomes and that this cohesion is resolved when the termini reach the asymmetric septum or translocation pore. Possible mechanisms and roles of cohesion and resolution are discussed. IMPORTANCE Endospore formation in Firmicutes bacteria provides one of the most highly resistant life forms on earth. During the early stages of endospore formation, the cell cycle is reorganized so that exactly two fully replicated chromosomes are generated, before the cell divides asymmetrically to generate the prespore and mother cell compartments that are critical for the developmental process. Decades ago, it was discovered that just prior to asymmetrical division the two chromosomes enter an unusual elongated configuration called the axial filament. This paper provides new insights into the nature of the axial filament structure and suggests that cohesion of the normally separated sister chromosome termini plays an important role in axial filament formation., (Copyright © 2020 Willis et al.)

In the course of screening for compounds with differential growth inhibition activity on a mutant of Bacillus subtilis lacking all four class A penicillin-binding proteins ( Δ4 ), we came across an isoquinoline derivative, IQ-1 carboxylic acid (IQC) with relatively high activity on the mutant compared to the wild type strain. Treated cells were slightly elongated and had altered chromosome morphology. Mutants of Δ4 resistant to IQC were isolated and subjected to whole genome sequencing. Most of the mutants were affected in the gene, pyrG , encoding CTP synthetase (CTPS). Purified wild type CTPS was inhibited in vitro by IQC. Two of the three mutant proteins purified showed decreased sensitivity to IQC in vitro . Finally, inhibition by IQC was rescued by addition of cytidine but not uridine to the growth medium, consistent with the notion that IQC acts by reducing the synthesis of CTP or a related compound. IQC provides a promising new starting point for antibiotic inhibitors of CTPS., (Copyright © 2020 Emami, Wu and Errington.)

Many bacteria can form wall-deficient variants, or L-forms, that divide by a simple mechanism that does not require the FtsZ-based cell division machinery. Here, we use microfluidic systems to probe the growth, chromosome cycle and division mechanism of Bacillus subtilis L-forms. We find that forcing cells into a narrow linear configuration greatly improves the efficiency of cell growth and chromosome segregation. This reinforces the view that L-form division is driven by an excess accumulation of surface area over volume. Cell geometry also plays a dominant role in controlling the relative positions and movement of segregating chromosomes. Furthermore, the presence of the nucleoid appears to influence division both via a cell volume effect and by nucleoid occlusion, even in the absence of FtsZ. Our results emphasise the importance of geometric effects for a range of crucial cell functions, and are of relevance for efforts to develop artificial or minimal cell systems.

Neuromyelitis optica (NMO) is a severe inflammatory autoimmune CNS disorder triggered by binding of an IgG autoantibody to the aquaporin 4 (AQP4) water channel on astrocytes. Activation of cytolytic complement has been implicated as the major effector of tissue destruction that secondarily involves myelin. We investigated early precytolytic events in the evolving pathophysiology of NMO in mice by continuously infusing IgG (NMO patient serum-derived or AQP4-specific mouse monoclonal), without exogenous complement, into the spinal subarachnoid space. Motor impairment and sublytic NMO-compatible immunopathology were IgG dose dependent, AQP4 dependent, and, unexpectedly, microglia dependent. In vivo spinal cord imaging revealed a striking physical interaction between microglia and astrocytes that required signaling from astrocytes by the C3a fragment of their upregulated complement C3 protein. Astrocytes remained viable but lost AQP4. Previously unappreciated crosstalk between astrocytes and microglia involving early-activated CNS-intrinsic complement components and microglial C3a receptor signaling appears to be a critical driver of the precytolytic phase in the evolving NMO lesion, including initial motor impairment. Our results indicate that microglia merit consideration as a potential target for NMO therapeutic intervention.

Objective: To investigate Changweishu's clinical effect on gastrointestinal dysfunction in patients with sepsis., Methods: Fifty patients with gastrointestinal dysfunction and sepsis were randomly divided into treatment and control groups. The control group patients received routine Western medicine treatments (meropenem, noradrenaline, glutamine glue, Bifidobacterium lactis triple-strain tablet), and the treatment group patients received routine Western medicine treatment combined with Changweishu. Treatments in both groups lasted 7 days. Changes in APACHE II score, gastrointestinal dysfunction score, serum levels of diamine oxidase (DAO), D-lactic acid, inflammatory factors (tumor necrosis factor (TNF)-α, interleukin (IL)-6, and high-mobility group box 1 (HMGB-1)), and the incidence of multiple organ dysfunction syndrome (MODS) and mortality were observed., Results: After treatment, APACHE II score, gastrointestinal dysfunction score, and DAO, D-lactic acid, TNF-α, IL-6, and HMGB-1 levels decreased significantly in both groups, but the decrease was more significant in the treatment group than in the control group. The incidence of MODS and mortality were significantly lower in the treatment group than in the control group., Conclusion: The addition of Changweishu to routine Western treatments can improve gastrointestinal function in patients with sepsis and gastrointestinal dysfunction, as well as decreasing the incidence of MODS and mortality and improving patient prognosis.

From 1310.6×10^{6}  J/ψ and 448.1×10^{6}  ψ(3686) events collected with the BESIII experiment, we report the first observation of Σ^{+} and Σ[over ¯]^{-} spin polarization in e^{+}e^{-}→J/ψ[ψ(3686)]→Σ^{+}Σ[over ¯]^{-} decays. The relative phases of the form factors ΔΦ have been measured to be (-15.5±0.7±0.5)° and (21.7±4.0±0.8)° with J/ψ and ψ(3686) data, respectively. The nonzero value of ΔΦ allows for a direct and simultaneous measurement of the decay asymmetry parameters of Σ^{+}→pπ^{0}(α_{0}=-0.998±0.037±0.009) and Σ[over ¯]^{-}→p[over ¯]π^{0}(α[over ¯]_{0}=0.990±0.037±0.011), the latter value being determined for the first time. The average decay asymmetry, (α_{0}-α[over ¯]_{0})/2, is calculated to be -0.994±0.004±0.002. The CP asymmetry A_{CP,Σ}=(α_{0}+α[over ¯]_{0})/(α_{0}-α[over ¯]_{0})=-0.004±0.037±0.010 is extracted for the first time, and is found to be consistent with CP conservation.

Microglial calcium signaling underlies a number of key physiological and pathological processes in situ, but has not been studied in vivo in awake mice. Using multiple GCaMP6 variants targeted to microglia, we assessed how microglial calcium signaling responds to alterations in neuronal activity across a wide range. We find that only a small subset of microglial somata and processes exhibited spontaneous calcium transients in a chronic window preparation. However, hyperactive shifts in neuronal activity (kainate status epilepticus and CaMKIIa Gq DREADD activation) triggered increased microglial process calcium signaling, often concomitant with process extension. Additionally, hypoactive shifts in neuronal activity (isoflurane anesthesia and CaMKIIa Gi DREADD activation) also increased microglial process calcium signaling. Under hypoactive neuronal conditions, microglia also exhibited process extension and outgrowth with greater calcium signaling. Our work reveals that microglia have highly distinct microdomain signaling, and that processes specifically respond to bi-directional shifts in neuronal activity through increased calcium signaling., Competing Interests: AU, LB, YY, YL, GW, LW No competing interests declared, (© 2020, Umpierre et al.)

Background: Humanitarian crises can lead to the rapid change in the health needs of women and newborns, which may give rise to a complex situation that would require various interventions as solutions. This study aimed to examine the health education and promotion patterns, health-seeking behaviour of mothers, and barriers to the use of maternal health services from public health facilities in two rural areas of Yemen., Methods: We used a qualitative approach. We conducted in-depth interviews and focus group discussions with frontline health professionals and mothers respectively. Nine in-depth interviews were conducted with the health professionals, including 4 health leaders and 5 midwives, and 2 focus group discussions with mothers aged 18-45 years in Abyan and Lahj. Thematic analysis approach was used to analyze the data in Atlas.ti (version 8) Software., Results: Our data showed that health education and promotion activities on maternal health were ad hoc and coverage was poor. Maternal health services were underutilized by women. According to the data from the focus group discussions, the poor quality of services, as indicated by inadequate numbers of female doctors, lack of medical equipment and medicines, and costs of services were barriers to use maternal health services. Moreover, the use of prenatal and postnatal care services was associated with women's' perceived need. However, according to the health professionals, the inadequate human resource, workload, and inadequate funding from government have contributed significantly to the perceived quality of maternal health services provided by public health facilities. Despite the identified barriers, we found that a safe motherhood voucher scheme was instituted in Lahj which facilitated the use of maternal health services by disadvantaged women by removing financial barriers associated with the use of maternal health services., Conclusion: This study identified several obstacles, which worked independently or jointly to minimize the delivery and use of health services by rural women. These included, inadequate funding, inadequate human resources, poor quality of health services, and high cost of services. These barriers need to be addressed to improve the use of reproductive health services in Yemen.

[This corrects the article DOI: 10.7150/thno.27882.]., (© The author(s).)

Objective: The aim of the study was to analyze the characteristics of renal function in patients diagnosed with COVID-19. Methods: In this retrospective, single-center study, we included all confirmed cases of COVID-19 in a tertiary hospital in Guangdong, China from January 20, 2020 to March 20, 2020. Blood and urine laboratory findings related to renal function were summarized, and the estimated glomerular filtration rate (eGFR) and endogenous creatinine clearance (Ccr) were also calculated to assess the renal function. Results: A total of 12 admitted hospital patients were diagnosed with COVID-19, included 3 severe cases, and 9 common cases. Serum creatinine (Scr) was not abnormally elevated in all of the patients, and blood urea nitrogen (BUN) was abnormally elevated in only 25.0% of the patients. However, compared with the recovery period, the patient's Scr and BUN increased significantly in peak of disease (p-scr = 0.002 & p-bun < 0.001). By observing the fluctuations in Scr and BUN from admission to recovery, it was found that the peak of Scr and BUN appeared within the first 14 day of the course of the disease. Urinary microprotein detection indicated that the abnormally elevated rates of urine microalbumin (UMA), α1-microglobulin (A1M), urine immunoglobulin-G (IGU), and urine transferring (TRU) standardized by urinary creatinine in peak of disease were 41.7, 41.7, 50.0, and 16.7%, respectively. The abnormal rates of the calculated eGFR and Ccr were 66.7 and 41.7%. Conclusion: Scr and BUN were generally increased during the course of COVID-19. Detection of urinary microproteins and application of multiple indicators assessment could be helpful for discovering abnormal renal function in patients with COVID-19. However, the evidence is limited due to the small sample size and observational nature. Additional studies, especially large prospective cohort studies, are required to confirm these findings., (Copyright © 2020 Hong, Chi, Liu, Huang, Guo, Fan, Lin, Qu, Chen, Wu, Wang, Zhang, Wu, Pan, Lin, Zhou and Zhang.)

Hyperuricemia/gout is a common metabolic disease in China, which is a serious threat to people's health. In clinical practice, the standardization of prevention and diagnosis and the rate of treat-to-target need to be improved. There is still a lack of education for the patients about the understanding of clinical guidelines, the disease knowledge and the importance of cooperating with doctors to carry out diagnosis and treatment. From the most concerned issues of the patients, we established the hyperuricemia/gout patient practice guideline working group with multidisciplinary physicians and patients. Seventeen opinions, as the hyperuricemia/gout patient practice guidelines, are proposed in accordance with the relevant principles of the "WHO guidelines development manual" , and with the international normative process, aiming to improve the patients compliance, improve the level of health management of the disease.

Background: Detection of hepatitis B virus (HBV) is vital for the diagnosis of hepatitis B infection. A novel test loop-mediated isothermal amplification (LAMP) has been successfully applied to detect various pathogens. However, the accuracy of LAMP in diagnosing HBV remains unclear. Therefore, in the present study, the accuracy of LAMP for HBV detection was evaluated systematically., Methods: Embase, Cochrane Library, and PubMed databases were searched for studies using LAMP to detect HBV. Then, two researchers extracted data and assessed the quality of literature using the QUADAS-2 tool independently. I 2 statistic and chi-square test were analyzed to investigate the heterogeneity, and Deek's funnel plot assessed the publication bias. The pooled sensitivity (SEN), specificity (SPE), positive LR (PLR), negative LR (NLR), diagnostic odds ratio (DOR), and 95% confidence intervals were displayed in forest plots. We calculated the area under the curve (AUC) to assess the overall efficiency of LAMP for HBV detection., Results: A total of nine studies with 1298 samples were finally included in this evaluation. The pooled sensitivity and specificity of HBV detection were 0.91 (95% CI: 0.89 ~ 0.92) and 0.97 (95% CI: 0.94 ~ 0.99), respectively. The PLR, NLR, and DOR were 16.93 (95% CI: 6.15 ~ 46.55), 0.08 (95% CI: 0.05 ~ 0.14), and 397.57 (95% CI: 145.41 ~ 1087.07). Besides, the AUC was 0.9872, and Deek's plot suggested that there existed publication bias in the studies., Conclusion: Compared with PCR, LAMP is a simple, rapid, and effective assay to diagnose HBV. However, additional evidence is essential to confirm that LAMP can replace other methods in diagnosing HBV infection., (© 2020 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals, Inc.)

We report the most precise measurements to date of the strong-phase parameters between D^{0} and D[over ¯]^{0} decays to K&#95;{S,L}^{0}π^{+}π^{-} using a sample of 2.93  fb^{-1} of e^{+}e^{-} annihilation data collected at a center-of-mass energy of 3.773 GeV with the BESIII detector at the BEPCII collider. Our results provide the key inputs for a binned model-independent determination of the Cabibbo-Kobayashi-Maskawa angle γ/ϕ&#95;{3} with B decays. Using our results, the decay model sensitivity to the γ/ϕ&#95;{3} measurement is expected to be between 0.7° and 1.2°, approximately a factor of three smaller than that achievable with previous measurements, based on the studies of the simulated data. The improved precision of this work ensures that measurements of γ/ϕ&#95;{3} will not be limited by knowledge of strong phases for the next decade. Furthermore, our results provide critical input for other flavor-physics investigations, including charm mixing, other measurements of CP violation, and the measurement of strong-phase parameters for other D-decay modes.

Using 2.93  fb^{-1} of e^{+}e^{-} collision data taken at a center-of-mass energy of 3.773 GeV with the BESIII detector, we report the first measurements of the absolute branching fractions of 14 hadronic D^{0(+)} decays to exclusive final states with an η, e.g., D^{0}→K^{-}π^{+}η, K&#95;{S}^{0}π^{0}η, K^{+}K^{-}η, K&#95;{S}^{0}K&#95;{S}^{0}η, K^{-}π^{+}π^{0}η, K&#95;{S}^{0}π^{+}π^{-}η, K&#95;{S}^{0}π^{0}π^{0}η, and π^{+}π^{-}π^{0}η; D^{+}→K&#95;{S}^{0}π^{+}η, K&#95;{S}^{0}K^{+}η, K^{-}π^{+}π^{+}η, K&#95;{S}^{0}π^{+}π^{0}η, π^{+}π^{+}π^{-}η, and π^{+}π^{0}π^{0}η. Among these decays, the D^{0}→K^{-}π^{+}η and D^{+}→K&#95;{S}^{0}π^{+}η decays have the largest branching fractions, which are B(D^{0}→K^{-}π^{+}η)=(1.853±0.025&#95;{stat}±0.031&#95;{syst})% and B(D^{+}→K&#95;{S}^{0}π^{+}η)=(1.309±0.037&#95;{stat}±0.031&#95;{syst})%, respectively. The charge-parity asymmetries for the six decays with highest event yields are determined, and no statistically significant charge-parity violation is found.

The processes X(3872)→D^{*0}D[over ¯]^{0}+c.c.,γJ/ψ,γψ(2S), and γD^{+}D^{-} are searched for in a 9.0  fb^{-1} data sample collected at center-of-mass energies between 4.178 and 4.278 GeV with the BESIII detector. We observe X(3872)→D^{*0}D^{0}[over ¯]+c.c. and find evidence for X(3872)→γJ/ψ with statistical significances of 7.4σ and 3.5σ, respectively. No evident signals for X(3872)→γψ(2S) and γD^{+}D^{-} are found, and the upper limit on the relative branching ratio R&#95;{γψ}≡{B[X(3872)→γψ(2S)]}/{B[X(3872)→γJ/ψ]}<0.59 is set at 90% confidence level. Measurements of branching ratios relative to decay X(3872)→π^{+}π^{-}J/ψ are also reported for decays X(3872)→D^{*0}D^{0}[over ¯]+c.c.,γψ(2S),γJ/ψ, and γD^{+}D^{-}, as well as the non-D^{*0}D^{0}[over ¯] three-body decays π^{0}D^{0}D^{0}[over ¯] and γD^{0}D^{0}[over ¯].

By analyzing a data sample corresponding to an integrated luminosity of 2.93  fb^{-1} collected at a center-of-mass energy of 3.773 GeV with the BESIII detector, we measure for the first time the absolute branching fraction of the D^{+}→ημ^{+}ν&#95;{μ} decay to be B&#95;{D^{+}→ημ^{+}ν&#95;{μ}}=(10.4±1.0&#95;{stat}±0.5&#95;{syst})×10^{-4}. Using the world averaged value of B&#95;{D^{+}→ηe^{+}ν&#95;{e}}, the ratio of the two branching fractions is determined to be B&#95;{D^{+}→ημ^{+}ν&#95;{μ}}/B&#95;{D^{+}→ηe^{+}ν&#95;{e}}=0.91±0.13&#95;{(stat+syst)}, which agrees with the theoretical expectation of lepton flavor universality within uncertainty. By studying the differential decay rates in five four-momentum transfer intervals, we obtain the product of the hadronic form factor f&#95;{+}^{η}(0) and the c→d Cabibbo-Kobayashi-Maskawa matrix element |V&#95;{cd}| to be f&#95;{+}^{η}(0)|V&#95;{cd}|=0.087±0.008&#95;{stat}±0.002&#95;{syst}. Taking the input of |V&#95;{cd}| from the global fit in the standard model, we determine f&#95;{+}^{η}(0)=0.39±0.04&#95;{stat}±0.01&#95;{syst}. On the other hand, using the value of f&#95;{+}^{η}(0) calculated in theory, we find |V&#95;{cd}|=0.242±0.022&#95;{stat}±0.006&#95;{syst}±0.033&#95;{theory}.

With the continuous development of Chinese medicine, traditional Chinese medicine(TCM) has been widely used in the treatment of diseases and health care. At the same time, the toxic and side effects of TCM have been gradually concerned. The liver, as an important place for drug metabolism, is a major target organ for drug toxicity. Clinical reports on liver injury caused by TCM are common, and the problem of liver toxicity of TCM has become an important reason to limit the internationalization of TCM. Metabono-mics is a newly booming subject to study the metabolic pathway of biological system. It shows integrity and systematicness in the study of hepatotoxicity of TCM, which provides a new technical method for finding the early biomarkers of liver injury of TCM and exploring the mechanism of hepatotoxicity of TCM. In this paper, the methods of metabonomics in the study of hepatotoxicity of TCM, as well as the research progress of hepatotoxicity monomer, extract and attenuation of hepatotoxic TCM based on metabonomics were reviewed in order to provide reference for the further study of hepatotoxicity of TCM.

Ethnopharmacological Relevance: Amygdalin is commonly distributed in plants of the Rosaceae, such as peach, plum, loquat, apple and bayberry, but most notably in the seeds (kernels) of apricot almonds. As a naturally aromatic cyanogenic compound, it has long been used in Asia, Europe and other regions for the treatment of various diseases including cough, asthma, nausea, leprosy and leukoderma. Importantly, in recent years, an increasing attention has been paid to its antitumor effect., Aim of the Study: The paper aims to review the pharmacological activities and toxicological effects of amygdalin and provide a reference and perspective for its further investigation., Methods: Electronic databases including the Web of Science, Cochrane Library, PubMed, EMBASE, the Chinese Biological Medicine Database, China National Knowledge Infrastructure, Wanfang database and VIP information database were searched up to November 2019 to identify eligible studies. A meticulous review was performed, an in-depth analysis on the pharmacological activity and toxicology of amygdalin was conducted, and perspectives for future research were also discussed., Results: A total of 110 papers about in vitro/in vivo studies on amygdalin have been reviewed. Analysis on the data suggested that this compound presented pharmacological activities of anti-tumor, anti-fibrotic, anti-inflammatory, analgesic, immunomodulatory, anti-atherosclerosis, ameliorating digestive system and reproductive system, improving neurodegeneration and myocardial hypertrophy, as well as reducing blood glucose. In addition, studies revealed that amygdalin's toxicity was caused by its poisonous decomposite product of benzaldehyde and hydrogen cyanide after oral ingestion, toxicity of intravenous administration route was far less than the oral route, and it can be avoidable with an oral dose ranging from 0.6 to 1 g per day., Conclusion: This paper has systematically reviewed the pharmacology and toxicology of amygdalin and provided comprehensive information on this compound. We hope this review highlights some perspectives for the future research and development of amygdalin., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Oviposition is an important reproductive behavior that is triggered by mating in insects, and biogenic amines might be involved in its regulation. The effects of biogenic amines on oviposition have only been studied in a few insect species, and the findings to date have not been conclusive. In addition, there are few studies on the effects of biogenic amines on oviposition of the diamondback moth, Plutella xylostella L. Here, we tested how mating and biogenic amines regulate oviposition of P. xylostella by injecting amines and amine receptor antagonists into virgin and mated females and counting the number of eggs laid afterward. Biogenic amines of octopamine and tyramine could induce virgin adults of P. xylostella to lay eggs, while dopamine and serotonin had no such effect on oviposition. Furthermore, the octopamine antagonists mianserin, epinastine, and phentolamine inhibited oviposition by mated females. The tyramine antagonist yohimbine, dopamine antagonist SCH23390, and serotonin antagonist ketanserin did not block oviposition by mated females, and octopamine and tyramine-inducing oviposition by virgin females could be inhibited by the octopamine antagonists mianserin and epinastine instead of the tyramine antagonist yohimbine. We conclude that octopamine and its receptors are involved in mating-triggered oviposition in P. xylostella , while tyramine acts as a subsidiary. Further, the inducing effect of tyramine on oviposition is achieved via octopamine receptors instead of tyramine receptors. This experiment is helpful to further understand the role of biogenic amines in mating regulation and to provide a new strategy for controlling P. xylostella ., (Copyright © 2020 Li, Li, Wu, Fan and Liu.)

Background: Despite the recent advances in treatments for rheumatoid arthritis (RA), there are still unmet needs in disease outcomes. This study aimed to analyze the satisfaction with drug therapies for RA according to the levels of disease severity (patient-assessed) and proportions of treatment cost to household income., Methods: This was a subgroup study of a cross-sectional study in patients with RA and their physicians. The patients were subdivided into different subgroups based on their self-assessed severity of RA and on the proportions of treatment cost to household income (<10%, 10-30%, 31-50%, and >50%). The Treatment Satisfaction Questionnaire for Medication version II was used to assess patients' treatment satisfaction., Results: When considering all medications, effectiveness, convenience, and global satisfaction scores were lower in the severe and moderate RA subgroups than those in the mild and extremely mild RA subgroups (all P < 0.001). Effectiveness, side effects, and convenience scores were higher in the <10% subgroup compared to those in the >50% subgroup (all P < 0.05). Global satisfaction score was higher in the <10% subgroup than that in the 31% to 50% subgroup (F = 13.183, P = 0.004). For biological disease-modifying anti-rheumatic drugs, effectiveness and convenience scores were lower in the severe RA subgroup than those in the extremely mild RA subgroup (both P < 0.05). Convenience score was higher in the <10% subgroup compared to that in the 31% to 50% and >50% subgroups (F = 12.646, P = 0.005). Global satisfaction score was higher in the <10% subgroup than that in the 31% to 50% subgroup (F = 8.794, P = 0.032)., Conclusion: Higher disease severity and higher financial burden were associated with lower patient satisfaction.

CO pretreatment was found to effectively improve the SCR performance of CeO 2 , with over 90% at about 300 °C. The larger specific area and the decrease of CeO 2 crystallization indicated the modification of the surface structure after CO pretreatment. Abundant Ce 3+ species and active oxygen, better reducibility, and the higher surface adsorption capacity were mainly responsible for its enhanced SCR performance. DRIFT analysis revealed the presumed coexistence of two reaction routes that the L-H mechanism was related to the reaction temperature, while the reaction rate of E-R route was almost directly proportional to the NO concentration at a certain temperature, based on the kinetic calculation. In addition, the CO-pretreated CeO 2 also exhibited a better poisoning tolerance for SO 2 and H 2 O and excellent thermal stability and circularity. Graphical abstract The process of NH 3 -SCR reaction over CeO 2 -CO catalyst.

Xanthatin, a natural sesquiterpene lactone, occurs as one of the major constituents of Xanthium plants (Compositae) and exhibits many important biological properties. To discover natural products-based pesticides, forty-nine Michael-type thiol/amino adducts of xanthatin were synthesized and characterized, while their pesticidal activities were investigated. Among them, compounds 2c, 2h, 2i, and 2t exhibited more potent antifungal activity against Botrytis cinerea (IC 50  = 0.96, 0.38, 6.33, and 7.21 µg/mL, respectively) than xanthatin and the two commercial fungicides. Compounds 2t and 2u displayed broad-spectrum and excellent antifungal effects against all tested phytopathogenic fungi, while their IC 50 values ranged from 7.21 to 75.88 µg/mL. Compounds 2a, 2f, 2l, 2m, 2v, 7c, 7e, 7h, 7i, and 7j showed moderate larvicidal activity against Plutella xylostella Linnaeus. Furthermore, compounds 2b, 7g, and 7h demonstrated significant ovicidal activity against P. xylostella with the LC 50 values of 14.04, 10.00, and 11.95 mg/L, respectively. These findings suggest that thiol/amino appended in the C-13 position of xanthatin may improve antifungal and ovicidal activities for the derivatives. It was also noticed that the exocyclic double bond of xanthatin is crucial for its larvicidal activity. This work also provides some important hints for further design, synthesis, and structural modification of the xanthanolides sesquiterpene lactones toward development of the new environmentally friendly pesticides for sustainable agricultural production., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In vivo two-photon imaging of microglia in the intact brain has revealed that microglia constantly survey neuronal soma. Research over the past decade and a recent paper by Cserép et al. published in Science are now uncovering the nature, mechanisms, and consequences of these interactions in health and injury., (Published by Elsevier Ltd.)

A partial-wave analysis is performed for the process e^{+}e^{-}→K^{+}K^{-}π^{0}π^{0} at the center-of-mass energies ranging from 2.000 to 2.644 GeV. The data samples of e^{+}e^{-} collisions, collected by the BESIII detector at the BEPCII collider with a total integrated luminosity of 300  pb^{-1}, are analyzed. The total Born cross sections for the process e^{+}e^{-}→K^{+}K^{-}π^{0}π^{0}, as well as the Born cross sections for the subprocesses e^{+}e^{-}→ϕπ^{0}π^{0}, K^{+}(1460)K^{-}, K&#95;{1}^{+}(1400)K^{-}, K&#95;{1}^{+}(1270)K^{-}, and K^{*+}(892)K^{*-}(892), are measured versus the center-of-mass energy. The corresponding results for e^{+}e^{-}→K^{+}K^{-}π^{0}π^{0} and ϕπ^{0}π^{0} are consistent with those of BABAR with better precision. By analyzing the cross sections for the four subprocesses, K^{+}(1460)K^{-}, K&#95;{1}^{+}(1400)K^{-}, K&#95;{1}^{+}(1270)K^{-}, and K^{*+}(892)K^{*-}(892), a structure with mass M=(2126.5±16.8±12.4)  MeV/c^{2} and width Γ=(106.9±32.1±28.1)  MeV is observed with an overall statistical significance of 6.3σ, although with very limited significance in the subprocesses e^{+}e^{-}→K&#95;{1}^{+}(1270)K^{-} and K^{*+}(892)K^{*-}(892). The resonant parameters of the observed structure suggest it can be identified with the ϕ(2170), thus the results provide valuable input to the internal nature of the ϕ(2170).

The chromatin modifier enhancer of zeste homolog 2 (EZH2) methylates lysine 27 of histone H3 (H3K27) and regulates T cell differentiation. However, the potential role of EZH2 in the pathogenesis of rheumatoid arthritis (RA) remains elusive. We analyzed EZH2 expression in PBMC, CD4 + T cells, CD19 + B cell, and CD14 + monocytes from active treatment-naïve RA patients and healthy controls (HC). We also suppressed EZH2 expression using EZH2 inhibitor GSK126 and measured CD4 + T cell differentiation, proliferation and apoptosis. We further examined TGFβ-SMAD and RUNX1 signaling pathways in EZH2-suppressed CD4 + T cells. Finally, we explored the regulation mechanism of EZH2 by RA synovial fluid and fibroblast-like synoviocyte (FLS) by neutralizing key proinflammatory cytokines. EZH2 expression is lower in PBMC and CD4 + T cells from RA patients than those from HC. EZH2 inhibition suppressed regulatory T cells (Tregs) differentiation and FOXP3 transcription, and downregulated RUNX1 and upregulated SMAD7 expression in CD4 + T cells. RA synovial fluid and fibroblast-like synoviocytes suppressed EZH2 expression in CD4 + T cells, which was partially neutralized by anti-IL17 antibody. Taken together, EZH2 in CD4 + T cells from RA patients was attenuated, which suppressed FOXP3 transcription through downregulating RUNX1 and upregulating SMAD7 in CD4 + T cells, and ultimately suppressed Tregs differentiation. IL17 in RA synovial fluid might promote downregulation of EZH2 in CD4 + T cells. Defective EZH2 in CD4 + T cells might contribute to Treg deficiency in RA., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To explore the clinical value of serum autoantibodies and human leukocyte antigen (HLA-B(27)) molecular testing in Uygur patients with human immunodeficiency virus (HIV) infection. Method: A total of 727 HIV-infected Uygur patients who visited Kuche infectious diseases hospital during May 2016 to March 2017 were include in this study. The other 390 healthy people were enrolled as controls. Serum antinuclear antibodies (ANA), anti-cyclic citrullinated peptide (CCP) antibody, anti-extractable nuclear antigen (ENAs) antibody and HLA-B(27) molecule were tested. Result: Among 727 HIV-infected Uygur patients, 317 were males and 410 were females with mean age (35.52±13.44) years old. The mean duration of disease was (6.34±3.05) years. There were 697 (95.87%) patients receiving highly active antiretroviral therapy (HAART) with mean duration of treatment (5.52±3.47) years. The mean CD4(+)T cell count was (520±271) cells/μl in 202 HIV-infected patients, and mean virus load was (108 139±20 498) copies/ml in 20 HIV-infected patients. Rheumatic manifestations were recorded in 238 (32.74%) HIV-infected Uygur patients, mainly with dry mouth and dry eye (15.41%) , alopecia (9.90%) , arthralgia (8.94%) , ect. Compared with the health controls, positive ANA was more common in HIV infected Uygur patients (33.43% vs. 17.43%, P< 0.001) with low titers (ANA titer:1∶100) . HIV-infected Uygur patients had higher positive anti-u1-RNP antibodies positive rate (1.10%), but lower anti-SSA antibodies positive rate (0.14%) and anti-CCP antibodies positive rate (0.28%). Patients with positive ANA in HAART group were significantly less than that in non-treatment group (32.71% vs. 50.00%, P= 0.049). There were no correlations between ANA and duration of HAART, CD4(+)T cell counts and virus load ( r values 0.061, 0.047, 0.121, respectively. P >0.05). Only one female patient was HLA-B(27) positive (0.14%), which was significantly lower than that in healthy controls (3.08%) ( P< 0.001). Also, only one patient was diagnosed with rheumatoid arthritis (RA). Conclusion: Autoimmune manifestations are common in HIV-infected Uygur patients. Several autoantibodies are positive, but the coincidence of rheumatic diseases is rare. It's noted that patients with autoimmune manifestations should be considered as a differential diagnosis of HIV infection.

Postnatal mammalian cochlear hair cells (HCs) can be regenerated by direct transdifferentiation or by mitotic regeneration from supporting cells through many pathways, including Atoh1, Wnt, Hedgehog and Notch signaling. However, most new HCs are immature HCs. In this study we used RNA-Seq analysis to compare the differences between the transcriptomes of Atoh1 overexpression-induced new HCs and the native HCs, and to define the factors that might help to promote the maturation of new HCs. As expected, we found Atoh1 -induced new HCs had obvious HC characteristics as demonstrated by the expression of HC markers such as Pou4f3 and Myosin VIIA (Myo7a). However, Atoh1 -induced new HCs had significantly lower expression of genes that are related to HC function such as Slc26a5 ( Prestin ), Slc17a8 and Otof . We found that genes related to HC cell differentiation and maturation ( Kcnma1 , Myo6 , Myo7a , Grxcr1 , Gfi1 , Wnt5a , Fgfr1 , Gfi1 , Fgf8 etc.) had significantly lower expression levels in new HCs compared to native HCs. In conclusion, we found a set of genes that might regulate the differentiation and maturation of new HCs, and these genes might serve as potential new therapeutic targets for functional HC regeneration and hearing recovery., Competing Interests: None., (AJSC Copyright © 2020.)

A new, general Pd/Cu-cocatalysed dicarbonylative benzannulation of 3-acetoxy-1,4-enynes with CO and silylboranes is described. The method utilizes CO as both a one-carbon (C1) unit and an external addition functional reagent to achieve an unprecedented dicarbonylative benzannulation process, and represents a facile, efficient route to 3-hydroxyarylacylsilanes. Mechanistically, the silyl-Cu intermediate formed from CuF2 and silylboranes, and silyl-Pd intermediate generated by transmetallation are two key factors for successfully targeting the reaction and selectivity.

Background: The disruption of the blood-brain barrier (BBB) is common in patients with neuromyelitis optica spectrum disorder (NMOSD), causing pro-inflammatory immune cells to migrate into the central nervous system (CNS) and active demyelinating lesions. Albumin quotient is commonly used as an indicator for BBB permeability or dysfunction, but its potential clinical value in NMOSD treatment has never been explored. The present study investigated the differences in the albumin quotient level among NMOSD patients with different antibodies (AQP4-IgG and MOG-IgG) and the relationship between the albumin quotient and neurological dysfunction., Methods: We retrospectively collected data from 141 patients with NMOSD (104 with AQP4-IgG and 37 with MOG-IgG) and reviewed their clinical features and albumin quotient levels., Results: The percentage of patients with an abnormal albumin quotient was significantly higher in the MOG-IgG group than in the AQP4-IgG group (48.6% vs 27.9%, P = 0.026); albumin quotient levels in the AQP4-IgG-positive group were similar to those in the MOG-IgG groups (5.65 vs 5.8, P = 0.23). Among those with an abnormal quotient, no differences in the proportions of severe neurological disability across treatment were found between patients with AQP4-IgG and those with MOG-IgG (pre-treatment: AQP4-IgG group vs MOG-IgG group: 58.6% vs 38.9%, P = 0.24; post-treatment: AQP4-IgG group vs MOG-IgG group: 31.0% vs 22.2%, P = 0.74)., Conclusions: The BBB breakdown in NMOSD patients with MOG-IgG may be more common than in those with AQP4-IgG. AQP4-IgG-positive patients and MOG-IgG-positive patients with severe neurological disability tend to exhibit similar disruptions to the BBB., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The immune system has long been recognised important in pain regulation through inflammatory cytokine modulation of peripheral nociceptive fibres. Recently, cytokine interactions in brain and spinal cord glia as well as dorsal root ganglia satellite glia have been identified important- in pain modulation. The result of these interactions is central and peripheral sensitisation of nociceptive processing. Additionally, new insights and the term 'autoimmune pain' have emerged through discovery of specific IgGs targeting the extracellular domains of antigens at nodal and synaptic structures, causing pain directly without inflammation by enhancing neuronal excitability. Other discovered IgGs heighten pain indirectly by T-cell-mediated inflammation or destruction of targets within the nociceptive pathways. Notable identified IgGs in pain include those against the components of channels and receptors involved in inhibitory or excitatory somatosensory synapses or their pathways: nodal and paranodal proteins (LGI1, CASPR1, CASPR2); glutamate detection (AMPA-R); GABA regulation and release (GAD65, amphiphysin); glycine receptors (GLY-R); water channels (AQP4). These disorders have other neurological manifestations of central/peripheral hyperexcitabability including seizures, encephalopathy, myoclonus, tremor and spasticity, with immunotherapy responsiveness. Other pain disorders, like complex regional pain disorder, have been associated with IgGs against β2-adrenergic receptor, muscarinic-2 receptors, AChR-nicotinic ganglionic α-3 receptors and calcium channels (N and P/Q types), but less consistently with immune treatment response. Here, we outline how the immune system contributes to development and regulation of pain, review specific IgG-mediated pain disorders and summarise recent development in therapy approaches. Biological agents to treat pain (anti-calcitonin gene-related peptide and anti-nerve growth factor) are also discussed., Competing Interests: Competing interests: DLHB reports that he has acted as a consultant on behalf of Oxford Innovation for Abide, Biogen, GSK, Lilly, Mitsubishi Tanabe, Mundipharma and TEVA over the last 3 years. LAQ reports that he has provided expert testimony for Grifols and CSL Behring and received research funds from Novartis Spain and Grifols. SRI reports that he is a coapplicant and receives royalties on patent application WO/2010/046716 (UK patent no. PCT/GB2009/051441) entitled ‘Neurological Autoimmune Disorders’. The patent has been licensed to Euroimmun AG for the development of assays for LGI1 and other VGKC-complex antibodies. The remaining authors report no relevant disclosures to this work., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

The process of e^{+}e^{-}→pp[over ¯] is studied at 22 center-of-mass energy points (sqrt[s]) from 2.00 to 3.08 GeV, exploiting 688.5  pb^{-1} of data collected with the BESIII detector operating at the BEPCII collider. The Born cross section (σ&#95;{pp[over ¯]}) of e^{+}e^{-}→pp[over ¯] is measured with the energy-scan technique and it is found to be consistent with previously published data, but with much improved accuracy. In addition, the electromagnetic form-factor ratio (|G&#95;{E}/G&#95;{M}|) and the value of the effective (|G&#95;{eff}|), electric (|G&#95;{E}|), and magnetic (|G&#95;{M}|) form factors are measured by studying the helicity angle of the proton at 16 center-of-mass energy points. |G&#95;{E}/G&#95;{M}| and |G&#95;{M}| are determined with high accuracy, providing uncertainties comparable to data in the spacelike region, and |G&#95;{E}| is measured for the first time. We reach unprecedented accuracy, and precision results in the timelike region provide information to improve our understanding of the proton inner structure and to test theoretical models which depend on nonperturbative quantum chromodynamics.

Using a total of 11.0  fb^{-1} of e^{+}e^{-} collision data with center-of-mass energies between 4.009 and 4.6 GeV and collected with the BESIII detector at BEPCII, we measure fifteen exclusive cross sections and effective form factors for the process e^{+}e^{-}→Ξ^{-}Ξ[over ¯]^{+} by means of a single baryon-tag method. After performing a fit to the dressed cross section of e^{+}e^{-}→Ξ^{-}Ξ[over ¯]^{+}, no significant ψ(4230) or ψ(4260) resonance is observed in the Ξ^{-}Ξ[over ¯]^{+} final states, and upper limits at the 90% confidence level on Γ&#95;{ee}B for the processes ψ(4230)/ψ(4260)→Ξ^{-}Ξ[over ¯]^{+} are determined. In addition, an excited Ξ baryon at 1820  MeV/c^{2} is observed with a statistical significance of 6.2-6.5σ by including the systematic uncertainty, and the mass and width are measured to be M=(1825.5±4.7±4.7)  MeV/c^{2} and Γ=(17.0±15.0±7.9)  MeV, which confirms the existence of the J^{P}=3/2^{-} state Ξ(1820).

Increased pro-inflammatory cytokine levels and proliferation of activated microglia have been found in Parkinson's disease (PD) patients and animal models of PD, suggesting that targeting of the microglial inflammatory response may result in neuroprotection in PD. Microglial proliferation is regulated by many factors, but colony stimulating factor-1 receptor (CSF1R) has emerged as a primary factor. Using data mining techniques on existing microarray data, we found that mRNA expression of the CSF1R ligand, CSF-1, is increased in the brain of PD patients compared to controls. In two different neurotoxic mouse models of PD, acute MPTP and sub-chronic LPS treatment, mRNA and protein levels of CSF1R and CSF-1 were significantly increased. Treatment with the CSF1R inhibitor GW2580 significantly attenuated MPTP-induced CSF1R activation and Iba1-positive cell proliferation, without a reduction of the basal Iba1-positive population in the substantia nigra. GW2580 treatment also significantly decreased mRNA levels of pro-inflammatory factors, without alteration of anti-inflammatory mediators, and significantly attenuated the MPTP-induced loss of dopamine neurons and motor behavioral deficits. Importantly, these effects were observed in the absence of overt microglial depletion, suggesting that targeting CSF1R signaling may be a viable neuroprotective strategy in PD that disrupts pro-inflammatory signaling, but maintains the beneficial effects of microglia., (© 2019 Federation of American Societies for Experimental Biology.)

Introduction: Microglial activation plays a crucial role in the pathology of ischemic stroke. Recently, we demonstrated that fingolimod (FTY720) exerted neuroprotective effects via immunomodulation in ischemic white matter damage induced by chronic cerebral hypoperfusion, which was accompanied by robust microglial activation. In this study, we assessed the pro-angiogenic potential of FTY720 in a murine model of acute cortical ischemic stroke., Methods: The photothrombotic (PT) method was used to induce cortical ischemic stroke in mice. We evaluated cortical damage, behavioral deficits, microglial polarization, and angiogenesis to identify the neuroprotective effects and possible molecular mechanisms of FTY720 in acute ischemic stroke., Results: In vivo, a reduction in neuronal loss and improved motor function were observed in FTY720-treated mice after PT stroke. Immunofluorescence staining revealed that robust microglial activation and the associated neuroinflammatory response in the peri-infarct area were ameliorated by FTY720 via its ability to polarize microglia toward the M2 phenotype. Furthermore, both in vivo and in vitro, angiogenesis was enhanced in the microglial M2 phenotype state. Behaviorally, a significant improvement in the FTY720-treated group compared to the control group was evident from days 7 to 14., Conclusions: Our research indicated that FTY720 treatment promoted angiogenesis via microglial M2 polarization and exerted neuroprotection in PT ischemic stroke., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

This study aimed to review clinical experiences using whole-field simultaneous integrated boost (SIB) intensity-modulated radiotherapy (IMRT) and sequential IMRT in postoperative patients with oral cavity cancer (OCC). From November 2006 to December 2014, a total of 182 postoperative patients with OCC who underwent either SIB-IMRT (n = 63) or sequential IMRT (n = 119) were enrolled retrospectively and matched randomly according to multiple risk factors by a computer. The differences were well balanced after patient matching ( P = .38). The median follow-up time was 65 months. For patients treated with the SIB technique and the sequential technique, the respective mortality rates were 36.8% and 20.0% ( P = .04). The primary recurrence rates were 26.3% and 10.0% ( P = .02), respectively. The respective marginal failure rates were 26.7% and 16.7%. A multivariate logistic regression analysis showed that patients who received the SIB technique had a 2.74 times higher risk of death than those who received the sequential technique (95% confidence interval = 1.10-6.79, P = .03). Sequential IMRT provided a significantly lower dose to the esophagus (5.2 Gy, P = .02) and trachea (4.6 Gy, P = .03) than SIB-IMRT. For patients with locally advanced OCC, postoperative sequential IMRT may overcome an unpredictable geographic miss, potentially with a lower marginal failure rate in the primary area. Patients treated by sequential IMRT show equal overall survival benefits to those treated by SIB-IMRT and a lower mortality rate than those treated by SIB-IMRT. Additionally, a reduced dose to the esophagus and trachea compared to sequential IMRT was noted.

By analyzing a 2.93  fb^{-1} data sample of e^{+}e^{-} collisions, recorded at a center-of-mass energy of 3.773 GeV with the BESIII detector operated at the BEPCII collider, we report the first observation of the semileptonic D^{+} transition into the axial-vector meson D^{+}→K[over ¯]&#95;{1}(1270)^{0}e^{+}ν&#95;{e} with a statistical significance greater than 10σ. Its decay branching fraction is determined to be B[D^{+}→K[over ¯]&#95;{1}(1270)^{0}e^{+}ν&#95;{e}]=(2.30±0.26&#95;{-0.21}^{+0.18}±0.25)×10^{-3}, where the first and second uncertainties are statistical and systematic, respectively, and the third originates from the input branching fraction of K[over ¯]&#95;{1}(1270)^{0}→K^{-}π^{+}π^{0}.

Objective: To study the relationship between the copy numbers of repetitive units at variable number tandem repeat (VNTR) loci of Mycobacterium tuberculosis complex (MTBC) with its diversity of protein profiles., Methods: The MTBC strains were subjected to genotyping using multiple locus variable number tandem repeat analysis (MLVA). Also, the principal component analysis (PCA) was performed for bacterial protein profiles of MTBC using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The relationship between the polymorphism of VNTR loci and PCA clustering was analyzed., Results: A total of 157 MTBC strains were collected. 146 MTBC strains (MS identification score values ≥1.700) were performed PCA and three clusters, clusterⅠ(61 strains), clusterⅡ(26 strains) and cluster Ⅲ(59 strains), were generated. Polymorphic diversities were observed in 24 VNTR loci, among them, 7 were highly various, 7 were moderately, and 10 were low various. The polymorphism of Mtub 39, QUB 26 and QUB 4156 loci were correlated with the results of MALDI-TOF MS clustering ( P =0.000, P =0.035, P =0.017)., Conclusion: The polymorphism of Mtub39, QUB26 and QUB4156 loci in MTBC was correlated with the difference of MALDI-TOF MS protein profiles, suggesting that these loci may play a role in regulating the composition of protein profiles of MTBC strains., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).)

Viewing sleep through a socioecological lens, maternal perceptions, and experiences of preschoolers' sleep were explored using semistructured interviews with 15 Māori (indigenous) and 16 non-Māori mothers, with low- and high socioeconomic position. Thematic analysis identified four themes: child happiness and health, maternal well-being, comfort and connection, and family functioning and harmony. Mothers perceived healthy preschooler sleep as supporting children's mental and physical health, parents' sleep/wake functioning, family social cohesion and emotional connectedness, and poor preschooler sleep as negatively influencing child, maternal and family well-being. Although many experiences were shared, some perceptions of sleep and sleep practices differed between mothers. Influences included health paradigms, socioeconomic circumstances, maternal autonomy, employment, parenting approaches, and societal expectations. Healthy preschooler sleep is valued by mothers and may play a protective role in family health and resilience. Preschooler sleep initiatives need to be responsive to maternal perspectives and address societal drivers of sleep experiences.

We report the first observation of D^{+}→τ^{+}ν&#95;{τ} with a significance of 5.1σ. We measure B(D^{+}→τ^{+}ν&#95;{τ})=(1.20±0.24&#95;{stat}±0.12&#95;{syst})×10^{-3}. Taking the world average B(D^{+}→μ^{+}ν&#95;{μ})=(3.74±0.17)×10^{-4}, we obtain R&#95;{τ/μ}=Γ(D^{+}→τ^{+}ν&#95;{τ})/Γ(D^{+}→μ^{+}ν&#95;{μ})=3.21±0.64&#95;{stat}±0.43&#95;{syst}., which is consistent with the standard model expectation of lepton flavor universality. Using external inputs, our results give values for the D^{+} decay constant f&#95;{D^{+}} and the Cabibbo-Kobayashi-Maskawa matrix element |V&#95;{cd}| that are consistent with, but less precise than, other determinations.

Seizures are common in humans with various etiologies ranging from congenital aberrations to acute injuries that alter the normal balance of brain excitation and inhibition. A notable consequence of seizures is the induction of aberrant neurogenesis and increased immature neuronal projections. However, regulatory mechanisms governing these features during epilepsy development are not fully understood. Recent studies show that microglia, the brain's resident immune cell, contribute to normal neurogenesis and regulate seizure phenotypes. However, the role of microglia in aberrant neurogenic seizure contexts has not been adequately investigated. To address this question, we coupled the intracerebroventricular kainic acid model with current pharmacogenetic approaches to eliminate microglia in male mice. We show that microglia promote seizure-induced neurogenesis and subsequent seizure-induced immature neuronal projections above and below the pyramidal neurons between the DG and the CA3 regions. Furthermore, we identify microglial P2Y12 receptors (P2Y12R) as a participant in this neurogenic process. Together, our results implicate microglial P2Y12R signaling in epileptogenesis and provide further evidence for targeting microglia in general and microglial P2Y12R in specific to ameliorate proepileptogenic processes. SIGNIFICANCE STATEMENT Epileptogenesis is a process by which the brain develops epilepsy. Several processes have been identified that confer the brain with such epileptic characteristics, including aberrant neurogenesis and increased immature neuronal projections. Understanding the mechanisms that promote such changes is critical in developing therapies to adequately restrain epileptogenesis. We investigated the role of purinergic P2Y12 receptors selectively expressed by microglia, the resident brain immune cells. We report, for the first time, that microglia in general and microglial P2Y12 receptors in specific promote both aberrant neurogenesis and increased immature neuronal projections. These results indicate that microglia enhance epileptogenesis by promoting these processes and suggest that targeting this immune axis could be a novel therapeutic strategy in the clinic., (Copyright © 2019 the authors.)

Purpose: The purpose of this study was to explore the central analgesia mechanism of moxibustion for chronic inflammatory visceral pain (CIVP)., Methods: A CIVP rat model was established by 2,4,6-trinitrobenzene sulfonic acid (TNBS) plus 50% ethanol via enema. The analgesic effect of moxibustion was evaluated using the abdominal withdrawal reflex (AWR), mechanical withdrawal threshold (MWT), and thermal withdrawal latency (TWL). The expression profile of phosphorylated proteins of the mitogen-activated protein kinase (MAPK) signaling pathway in the spinal cord was assayed by protein microarray. The differentially expressed proteins were examined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for functional clusters and corresponding signaling pathways., Results: Moxibustion exerted a significant analgesic effect for CIVP rats, mainly presenting as a decrease in the AWR score (all P<0.01) under different levels of distending pressure and an increase in MWT and TWL thresholds (all P<0.05). Compared with the normal group, 76 proteins were upregulated while 15 were downregulated, and MAPK signaling pathway was activated in the model group. Compared with the model group, there were 53 downregulated and 38 upregulated proteins in the moxibustion group, and MAPK signaling pathway was inhibited. Fold change (FC)>1.3 or <0.77 was taken as the screening standard to define the differentially expressed proteins. Fifteen differentially expressed proteins upregulated in the model group were downregulated in the moxibustion group. GO analysis showed that the differentially expressed proteins mainly controlled cellular metabolism regulation, transportation, and stress reactions. KEGG analysis revealed that these differentially expressed proteins were mostly involved in the ERK, JNK, and p38 pathways, and the ERK pathway was predominant., Conclusion: Moxibustion mitigates CIVP in rats and inhibits the phosphorylation of proteins in the spinal MAPK signaling pathway. The analgesic effect of moxibustion may be associated with the regulation of the spinal MAPK signaling pathway., Competing Interests: The authors report no conflicts of interest in this work., (© 2019 Huang et al.)

Microglia dynamically survey the brain parenchyma. Microglial processes interact with neuronal elements; however, what role neuronal network activity plays in regulating microglial dynamics is not entirely clear. Most studies of microglial dynamics use either slice preparations or in vivo imaging in anesthetized mice. Here we demonstrate that microglia in awake mice have a relatively reduced process area and surveillance territory and that reduced neuronal activity under general anesthesia increases microglial process velocity, extension and territory surveillance. Similarly, reductions in local neuronal activity through sensory deprivation or optogenetic inhibition increase microglial process surveillance. Using pharmacological and chemogenetic approaches, we demonstrate that reduced norepinephrine signaling is necessary for these increases in microglial process surveillance. These findings indicate that under basal physiological conditions, noradrenergic tone in awake mice suppresses microglial process surveillance. Our results emphasize the importance of awake imaging for studying microglia-neuron interactions and demonstrate how neuronal activity influences microglial process dynamics.

Aim: To explore and improve nursing care for infants after enterostomy., Methods: A total of 483 infants who underwent enterostomy from January 2014 to January 2019 were enrolled in this study., Results: During hospitalization and follow-up, there were 30 infants with peripheral skin complications, including 15 cases of allergic dermatitis, 13 cases of faecal dermatitis and two cases of avulsion injury., Conclusion: Without proper and effective nursing care, the peripheral skin complications of enterostomy-related can easily develop. Therefore, careful postoperative care and effective family follow-up and guidance are essential after discharge, and using WeChat to follow-up can provide timely and effective follow-up and guidance to patients., Implications for Nursing Management: This study summarizes the experience of nursing care for infants over a 5-year period. Nurses must provide sound care for infants after enterostomy, timely and effectively address complications, guide nursing care performed by family members and strengthen follow-up through the WeChat online support group to reduce the occurrence of complications., (© 2019 John Wiley & Sons Ltd.)

Objectives: As a rare systemic autoinflammatory disease, adult-onset Still's disease (AOSD) has heterogeneous clinical manifestations, response to treatment and outcome. This study tried to assess the clinical characteristics, laboratory tests, and treatments of Chinese AOSD patients, and make a retrospective analysis., Methods: We collected from 7 hospitals in China a total of 517 Chinese patients with AOSD who satisfied the Yamaguchi criteria. We retrospectively evaluated their clinical features, laboratory tests, treatments and compared them with published data from different studies. All the data in this study were from medical records and further statistic analyses., Results: We evaluated a total of 517 AOSD patients, 72% female, average age of onset was 37.7; spiking fever, rash and arthralgia occurred in 472 (91.3%), 413 (79.9%), 378 (73.1%) cases, respectively. There were 439/513 (85.6%) cases with leukocytosis and 456/476 (95.8%) cases with raised serum ferritin. The highest frequently used medications and regimens for remission were glucocorticoids (498/517, 96.3%), methotrexate (273/517, 52.8%) and hydroxychloroquine (174/517, 33.7%). 84.4%. 357/423 of AOSD cases were able to achieve initial remission with different regimens, mostly including glucocorticoids, methotrexate or hydroxychloroquine. 47.2% of them (244/517) received 30

Objective: To evaluate the diagnostic value of the serum Krebs von den Lungen-6 (KL-6) for the interstitial lung disease associated with connective tissue diseases (CTD-ILD). Methods: 84 patients with CTD-ILD (CTD-ILD group) and 91 patients with connective tissue disease (CTD group) who visited the department of rheumatology and immunology of People's Hospital of Xinjiang Uygur Autonomous Region between January, 2016 and December, 2017 were included. Serum KL-6 levels were measured by commercially available enzyme linked immunosorbent assay (ELISA) kits. Results: The significantly higher levels of KL-6 were determined in the CTD-ILD group than CTD group [1 239 (577, 2 094) vs 152 (89, 280) U/ml] ( P< 0.001). The optimal cutoff value of serum KL-6 for diagnosis of CTD-ILD was 402 U/ml, and the sensitivity and specificity were 82.1% and 86.8%, respectively. Area Under the Curve (AUC) was 0.905. Logistic regression analysis revealed that elevated KL-6 and decreased Carbon monoxide diffusion capacity were independently correlated with the occurrence of CTD-ILD, the decreased of DLcoSB% ( OR= 0.928, 95 %CI : 0.891-0.968) and increase of KL-6 level ( OR= 1.005, 95 %CI : 1.003-1.007) was the independent risk factor for the occurrence of ILD. Conclusion: The serum KL-6 is an important biomarker for the diagnosis of CTD-ILD and when the level of KL-6 is increased, the ILD should be alert.

Background: Corticosteroid is one of the main treatments for interstitial lung disease (ILD). Cryptogenic-organizing pneumonia (COP) is sensitive to corticosteroid therapy, whereas idiopathic pulmonary fibrosis (IPF) is not. Glucocorticoid receptor-α (GR-α) and histone deacetylase 2 (HDAC2) play critical roles in the sensitivity to corticosteroid therapy; however, it is unclear whether HDAC2 and/or GR-α are expressed in the lung tissues of patients with COP and/or IPF. Possible aberrant expressions of HDAC2 and GR-α in IPF and COP were investigated in the current study., Methods: Lung tissue samples were obtained from patients with COP (n = 9), IPF (n = 8), pulmonary abscesses (n = 7), or pulmonary inflammatory pseudotumors (n = 6) before corticosteroid treatment, as well as from control subjects (n = 10). The expression of GR-α, HDAC2, PI3K-δ, and NF-κBp65 in the samples was assessed by immunohistochemistry., Results: GR-α expression was the same in lung tissues from COP patients and control subjects, but was significantly lower in lung tissue from IPF. In addition, HDAC2 was significantly higher in lung tissues of COP patients compared to both IPF and control subjects. Furthermore, the transcription factor NF-κBp65 was significantly lower in lung tissues from both COP and control compared to IPF subjects, whereas there was no difference in NF-κBp65 when comparing tissues from COP patients to controls. HDAC2 and GR-α were negatively correlated with NF-κBp65 in COP lung tissue., Conclusion: HDAC2 and GR-α expression in lung tissues are potential biomarkers for predicting corticosteroid sensitivity when initially treating COP and IPF, as well as other forms of ILD., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Neuromyelitis optica spectrum disorder (NMOSD) refers to a range of autoimmune inflammatory demyelinating diseases affecting the optic nerves, spinal cord, and periependymal regions of the brain. Classical NMOSD is characterized by the presentation of autoantibodies against the water channel aquaporin-4 (AQP4). However, a subset of patients fulfilling the clinical criteria for NMOSD is negative for AQP4-IgG but positive for autoantibodies against myelin oligodendrocyte glycoprotein (MOG); these patients are associated with different clinical manifestations and pathogenesis., Methods: Patients who received a first diagnosis of NMOSD were reviewed retrospectively between April 2015 and December 2018. Patients were classified according to the presence of AQP4-IgG and MOG-IgG in serum and/or cerebrospinal fluid. Clinical characteristics, magnetic resonance imaging findings, disease severity, and serum C3 and C4 levels at the first episode were compared between the groups., Results: The NMOSD patients with AQP4-IgG and MOG-IgG demonstrated specific, differential clinical features. The AQP4-IgG group featured more women, the presentation of transverse myelitis attacks and simultaneous occurrence of optic neuritis and transverse myelitis were more common, and intrathecal synthesis was more evident. The MOG-IgG group featured younger patients, more acute disseminated encephalomyelitis (ADEM) or ADEM-like attacks, more frequent cerebrospinal fluid pleocytosis, and a better overall outcome. C3 levels were significantly lower in AQP4-IgG-positive patients and higher in MOG-IgG-positive patients relative to healthy controls. C4 levels were significantly lower in the AQP4-IgG-positive NMOSD group when compared to both MOG-IgG-positive patients and controls. C3 and C4 were then combined in a receiver operating characteristic model. The area under the curve of the model was calculated to differentiate the AQP4-IgG-positive group from the MOG-IgG-positive group was 0.787, which was considered moderately predictive., Conclusion: The combination of C3 and C4 could assist in the differential diagnosis of AQP4-IgG-positive NMOSD from MOG-IgG-positive NMOSD., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: To investigate potential sleep inequities in preschoolers in Aotearoa/New Zealand, by examining sleep durations and week/weekend sleep duration differences of Māori (indigenous) and non-Māori preschoolers; and independent associations between ethnicity (child and maternal), socioeconomic position (SEP) and preschoolers' sub-optimal and inconsistent week/weekend sleep durations., Design: Cross-sectional analysis of questionnaire data from the Moe Kura: Mother and Child, Sleep and Wellbeing in Aotearoa/New Zealand longitudinal study when children were 3 to 4 years old., Participants: 340 Māori and 570 non-Māori preschoolers and their mothers., Measurements: Measures included preschoolers' usual nighttime sleep duration on week nights (week nighttime sleep) and weekends (weekend nighttime sleep); usual sleep duration across 24 hours, including naps, on week nights (week sleep [24 h]) and weekends (weekend sleep [24 h]) (≪10 h/10-13 h/≫13 h); and the difference between week and weekend sleep durations per 24 hours (sleep [24 h] difference) (≫1 h/≤1 h). Log-binomial regression models investigated associations between child and maternal characteristics and sleep duration measures. Child models included child ethnicity, child gender and child SEP (area and individual socioeconomic deprivation). Maternal models included maternal ethnicity, maternal age and maternal SEP (area and individual socioeconomic deprivation)., Results: Ethnicity and low SEP were independently associated with week day sleep (24 h) ≪10 h, weekend sleep (24 h) ≪10 h, and with sleep (24 h) difference ≫1 h., Conclusions: Ethnic and socioeconomic inequities in sleep durations are evident as early as 3 to 4 years of age in NZ, highlighting the importance of addressing the socio-political drivers of sleep inequities early in the life course., (Copyright © 2019 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)