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Dysfunction of neuronal nitric oxide synthase contributes to neurotoxicity, which triggers cell death in various neuropathological diseases, including epilepsy. Studies have shown that inhibition of neuronal nitric oxide synthase activity increases the epilepsy threshold, that is, has an anticonvulsant effect. However, the exact role and potential mechanism of neuronal nitric oxide synthase in seizures are still unclear. In this study, we performed RNA sequencing, functional enrichment analysis, and weighted gene coexpression network analysis of the hippocampus of tremor rats, a rat model of genetic epilepsy. We found damaged hippocampal mitochondria and abnormal succinate dehydrogenase level and Na

Juvenile hormone (JH) absence induces photoperiod-mediated reproductive diapause, which is characterized by reproductive cessation. Although the role of methoprene-tolerant (Met)-mediated JH signaling in photoperiod-mediated female reproduction has been well documented, its role in male reproduction remains unclear. In this study, we investigated the role of JH in regulating photoperiod-mediated development of the male internal reproductive system (IRS) in the predatory ladybeetle Harmonia axyridis (Pallas). In a previous study, we found that adult male H. axyridis reared under either a short-day (SD) or long-day (LD) photoperiod had obvious differences in IRS development, but we were unable to identify the regulators of male reproductive diapause. In this study, we found that beetles reared under an SD photoperiod had significantly lower JH titer and a relatively undeveloped male IRS compared with those reared under an LD photoperiod. Additionally, application of the JH analog (JHA) methoprene promoted IRS development. Furthermore, Met knockdown strongly blocked JH signaling in males reared under the LD photoperiod, thereby slowing IRS development. Moreover, exogenous JHA did not reverse the suppressed development of the male IRS caused by Met knockdown. These results indicate that photoperiod regulates male IRS development in H. axyridis through a conserved Met-dependent JH signaling pathway.

Background. The aim of this study was to research the effects of glutamine synthetase (GS) and glutamate aspartate transporter (GLAST) in rat Müller cells and the effects of an adenosine A2AR antagonist (SCH 442416) on GS and GLAST in hypoxia both in vivo and in vitro. Methods. This study used RT-PCR and Western blotting to quantify the expressions of GS and GLAST under different hypoxic conditions as well as the expressions of GS and GLAST at different drug concentrations. A cell viability assay was used to assess drug toxicity. Results. mRNA and protein expression of GS and GLAST in hypoxia Group 24 h was significantly increased. mRNA and protein expressions of GS and GLAST both increased in Group 1 μM SCH 442416 compared with other groups. One micromolar SCH 442416 could upregulate GS and GLAST’s activity in hypoxia both in vivo and in vitro. Conclusions. Hypoxia activates GS and GLAST in rat retinal Müller cells in a short time in vitro. (2) A2AR antagonists upregulate the activity of GS and GLAST in hypoxia both in vivo and in vitro.

Hypophosphatemia might cause respiratory and heart failure and even death. We aimed to evaluate risk factors for hypophosphatemia and refeeding-related hypophosphatemia in patients requiring parental nutrition (PN).This was a single-center, retrospective study. Clinical parameters were obtained from medical records. Serum phosphate (inorganic phosphorus) was measured by photometric analysis. Hypophosphatemia was confirmed when serum phosphate level was less than 0.8 mmol/L (≈2.5 mg/dl). Refeeding related hypophosphatemia was confirmed if serum phosphate level had a decrease of 0.16 mmol/L or more from baseline and if the final assessment was below 0.65 mmol/L.A total number of 655 (426 men and 229 women, aged 62.8 ± 14.8 years) hospitalized patients requiring PN were included in the study, and 60.6% of them were patients with cancer. The average body mass index (BMI) was 21.1 ± 4.1 kg/mHypophosphatemia is common (37.6%) in hospitalized patients requiring PN. Monitoring of serum level of phosphorus is necessary to facilitate early treatment of hypophosphatemia.

To study the surgical effects of medial rectus recession (MRR) on divergence insufficiency esotropia (DIE).Nine DIE patients who were admitted to and had MRR at Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University between December 2017 and June 2020 were included in this retrospective study. All patients were followed up for 1 year at least. The postoperative esodeviation, near-distant disparity (NDD) and visual function were observed and compared.The mean age of the 9 patients was 28.8 years old (10-49 yr.), including 3 adolescent patients (≤18 yr.). The mean preoperative esodeviation was (19.8±13.2) PD for near and (32.6±15.3) PD at distance, while, the mean postoperative esodeviation 1 year after MMR was (-0.2±3.5) PD for near and (6.0±2.2) PD at distance, showing significant improvement over the mean preoperative esodeviation (Medial rectus muscle recession can effectively improve the NDD and the binocular function at distance of patients with divergence insufficiency esotropia. Postoperative esodeviations both for near and at distance tend to regress after the surgery. Therefore, it is recommended that the amount of MRR be increased in the treatment of DIE.

The Asian lady beetle Harmonia axyridis is an important predator of several agricultural pests, including aphids and whiteflies, and thus can contribute to pest management. Commercial viability as a pest control method requires that the beetle can be mass-reared, and that workable conditions for extended shelf-life can be guaranteed. One of the features of Harmonia's life cycle is that it enters diapause in the adult stage when the length of the photophase starts shortening in late summer. Reduction of juvenile hormone (JH) titer has been demonstrated to be the common endocrine mechanism inducing reproductive diapause in insects. However, whether H. axyridis enters diapause dependent on JH shutdown and how the JH level is regulated before diapause remains unknown.Like in other insects, the absence of JH triggers the induction and maintenance of reproductive diapause in H. axyridis, indicated by JH measurements and the knockdown of an intracellular JH receptor methoprene-tolerant (Met). Methoprene, a JH analog, significantly reversed diapause into reproduction via Met. Combined with RNA-sequencing and RNA interference, we also demonstrated that JH biosynthesis rather than the JH degradation pathway determines the reduction of JH titer in diapausing females.Our results reveal the vital role of JH in regulating reproductive diapause in female H. axyridis. Harmonia axyridis diapause could thus be manipulated by targeting JH production and JH signaling. © 2021 Society of Chemical Industry.

The association between neutrophil-to-lymphocyte ratio (NLR) with subclinical macrovascular and microvascular diseases has been less investigated. We sought to examine the association between NLR and new-onset subclinical macrovascular and microvascular abnormalities in the Chinese population.From a community cohort, we included 6,430 adults aged ≥ 40 years without subclinical macrovascular and microvascular diseases at baseline. We measured subclinical macrovascular and microvascular abnormalities separately using the ankle-brachial index (ABI), brachial-ankle pulse wave velocity (baPWV), and albuminuria.During a mean follow-up of 4.3 years, 110 participants developed incident abnormal ABI, 746 participants developed incident elevated baPWV, and 503 participants developed incident albuminuria. Poisson regression analysis indicated that NLR was significantly associated with an increased risk of new-onset abnormal ABI, elevated baPWV, and albuminuria. Compared to overweight/obese participants, we found a much stronger association between NLR and subclinical vascular abnormalities in participants with normal weight. Furthermore, we found an interaction between the NLR and body mass index (BMI) on the risk of new-onset abnormal ABI (NLR was associated with subclinical macrovascular and microvascular diseases in the Chinese population. Furthermore, in participants with normal weight, the association between NLR and subclinical vascular abnormalities was much stronger.

Recent clinical trials of lung adenocarcinoma with immune checkpoint inhibitors revealed that lung adenocarcinoma patients with EGFR mutations have a poor response to immunotherapy. However, the mechanisms have not been addressed. We performed immunohistochemistry analyses of resected lung adenocarcinoma tissues with and without EGFR mutations to investigate and compare the characteristics of the tumor microenvironment (TME). We retrospectively enrolled a total of 323 lung adenocarcinoma patients (164 had EGFR mutations), and their corresponding tissue samples were analyzed by the EGFR mutation test and immunohistochemistry. We selected the markers of the immune checkpoint molecule (PD1, PD-L1, and LAG-3) and immune cell (CD3, CD4, CD8, and Foxp3) as markers of the tumor microenvironment. Our results revealed that patients had a distinct tumor microenvironment between EGFR-mutant and wild-type lung adenocarcinomas; the expression of CD3, CD4, PD-L1, and Foxp3 in EGFR-mutant tumors was significantly higher than that in wild-type tumors, while the expression of LAG3 and PD-1 showed a positive correlation with EGFR-wild-type tumors. In survival analysis, EGFR-wild-type patients had longer disease-free survival (DFS) than EGFR-mutant patients ( P = 0.0065 ). Our research demonstrates significant differences in tumor microenvironment composition between EGFR-mutant and wild-type patients. Our findings provide novel evidence that contributes to understanding the mechanism underlying the poor efficacy of immune checkpoint inhibitors.

OBJECTIVE To determine serum bile acid (BA) and fatty acid (FA) profiles in Chinese children with non-alcoholic fatty liver disease (NAFLD). METHODS A total 76 children aged 4–17 years were categorized into three groups according to the presence and absence of as well as the severity of NAFLD, that is, non-NAFLD (control), mild and moderate to severe NAFLD groups, respectively, based on their liver ultrasonography findings. Serum BA and FA profiles were quantified separately by mass spectrometry and gas chromatography. General linear models were performed to assess the differences among the groups. RESULTS After adjusted for potential confounders, children with NAFLD had higher levels of chenodeoxycholic acid (CDCA), unconjugated primary BAs (CDCA + cholic acid) but lower levels of deoxycholic acid (DCA), taurodeoxycholic acid (TDCA), glycodeoxycholic acid (GDCA), total DCA (DCA + TDCA + GDCA), glycolithocholic acid (GLCA) and total lithocholic acid (GLCA + taurolithocholic acid) than children without NAFLD. As for FAs, children with mild and moderate to severe NAFLD had higher levels of n-7 monounsaturated FA. CONCLUSIONS Circulating BA and FA profiles may change in children with NAFLD. Further studies are needed to determine their associations and to understand the underlying mechanism of action.

Background Septic pulmonary embolism (SPE) is attracting more attention as a special pulmonary sign in severe infection. We aimed to describe the clinical and imaging features of Klebsiella pneumoniae (K. pneumonia)-associated SPE in the emergency department. Methods Records of patients with primarily extrapulmonary infection of K. pneumoniae who were admitted to the emergency department between 2014 and 2019 were retrieved. The identifications of K. pneumoniaeassociated SPE were mainly dependent on the clinical manifestations, typical imaging findings, and presence of a primary source of K. pneumoniae infection. Results A total of 33 cases were identified as SPE with extrapulmonary K. pneumoniae infection. The main clinical manifestations were a febrile/fragile state (100%), respiratory symptoms (18.2%), and digestive symptoms (33.3%). Eight patients (24.2%) developed septic shock, 2 (6.0%) experienced respiratory failure, and 2 (6.0%) complicated endophthalmitis. The major source of infection was liver abscess (n=26, 78.8%), followed by septicemia (n=8, 24.2%), intestinal infection (n=3, 9.1%), and ascites (n=1, 3.0%). The computed tomography (CT) features included the following: peripheral wedge-shaped opacity (n=12, 36.4%), a feeding vessel sign (n=3, 9.1%), multiple nodular lesions (n=5, 15.2%), multifocal lung ill-infiltrations (n=15, 45.5%), patchy ground-glass opacities (n=6, 18.2%), focal consolidations (n=9, 27.3%), lung abscesses (n=4, 12.1%), and pleural effusion (n=21, 63.6%). Re-examination of lung HRCT conducted in 7 patients demonstrated imaging improvement after treatment. Conclusions K. pneumonia-SPE presented special clinical and imaging characteristics, which bear similarities to the signs of pneumonia, but was potentially catastrophic. Identifying SPE in septic conditions is crucial to improving clinical outcomes.

Diapause control is one of the successful methods for long-term cold storage of biological control organisms without decreasing their fitness. Sufficient preparation before diapause is essential for successful diapause initiation and maintenance. Harmonia axyridis, an important biocontrol agent in its native place, can enter reproductive diapause for overwintering. However, the key preparatory events before diapause in H. axyridis, such as specific developmental trajectory, timing, and physiological changes, remain unclear. We compared differences in the development of internal reproductive organs, feeding amount and nutrient storage between pre-diapause and pre-reproductive adult H. axyridis which had been reared at 20 °C under a short-day (10L:14D) and long-day (14L:10D) condition, respectively. The results showed that there were obvious morphological differences in internal reproductive organs of diapause and reproductive H. axyridis. The development of internal reproductive organs was suppressed at early adult stage in pre-diapause beetles compared to pre-reproductive beetles. Feeding amount in both pre-diapause and pre-reproductive beetles increased for more than ten days after eclosion. The feeding amount of pre-diapause beetles sharply decreased from the 15th day after eclosion in females and the 14th day after eclosion in males, which implied the initiation of diapause. During the pre-diapause stage, carbohydrates and lipids were mainly accumulated by females, whereas males mainly accumulated carbohydrates. Our results not only provide basic information about the diapause process of pre-diapause stage, but also give tips to better utilization of diapause strategy during mass production and storage of H. axyridis.

With the growing demands for wide-band data processing capacity, accuracy and faster real-time processing speed, Channelized Receiver & Signal Processor as the key components of Passive Radar Seeker, heat dissipating capability gradually becomes one of the main factors that limit its further developments. This paper describes the thermal design of Channelized Receiver & Signal Processor in passive radar seeker. Detailed discussions were made about the basic heat transfer theory, heat transfer paths design from chips level to equipment level. Finally, steady thermal analysis was carried out based on ICEPAK, the results indicate that the maximum temperature rise is less than 60□, and having 11.8□ margins when flying in cruise flight mode (flying altitude 1000m, speed 0.9 Mach), it meets the cooling requirements of this passive radar seeker system.

ThFeAsN$_{1-x}$O$_x$ ($0\leq x\leq0.6$) system with heavy electron doping has been studied by the measurements of X-ray diffraction, electrical resistivity, magnetic susceptibility and specific heat. The non-doped compound exhibits superconductivity at $T_\mathrm{c}^\mathrm{onset}=30$ K, which is possibly due to an internal uniaxial chemical pressure that is manifested by the extremely small value of As height with respect to the Fe plane. With the oxygen substitution, the $T_\mathrm{c}$ value decreases rapidly to below 2 K for $0.1\leq x\leq0.2$, and surprisingly, superconductivity re-appears in the range of $0.25\leq x\leq0.5$ with a maximum $T_\mathrm{c}^\mathrm{onset}$ of 17.5 K at $x=0.3$. For the normal-state resistivity, while the samples in intermediate non-superconducting interval exhibit Fermi liquid behavior, those in other regions show a non-Fermi-liquid behavior. The specific heat jump for the superconducting sample of $x=0.4$ is $\Delta C/(\gamma T_\mathrm{c})=0.89$, which is discussed in terms of anisotropic superconducting gap. The peculiar phase diagram in ThFeAsN$_{1-x}$O$_x$ presents additional ingredients for understanding the superconducting mechanism in iron-based superconductors., Comment: 10 pages, 7 figures

Recently, we have found that a number of microRNAs (miRNAs) and proteins are involved in the response to acupuncture therapy in hypertensive rats. Our bioinformatics study suggests an association between these miRNAs and proteins, which include miR-339 and sirtuin 2 (Sirt2). In this paper, we aimed to investigate whether Sirt2 was a direct target of miR-339 in neurons. In human SH-SY5Y cells, the luciferase assay implied that Sirt2 was likely a target of miRNA-339. Overexpression of miR-339 downregulated Sirt2 expression, while knockdown of miR-339 upregulated Sirt2 expression in human SH-SY5Y cells and rat PC12 cells. In addition, overexpression of miR-399 increased the acetylation of nuclear factor-κB (NF-κB) and forkhead box protein O1 (FOXO1) in SH-SY5Y cells, which are known targets of Sirt2. Our findings demonstrate that miR-339 regulates Sirt2 in human and rat neurons. Since Sirt2 plays a critical role in multiple important cellular functions, our data imply that acupuncture may act through epigenetic changes and subsequent action on their targets, such as miRNA-339/Sirt2/NF-κB/FOXO1 axis. Some physiological level changes of neurons after altering the miR-339 levels are needed to validate the suggested therapeutic role of miR-339/Sirt2/NF-κB/FOXO1 axis in response to acupuncture therapy in the future work.

To determine serum bile acid (BA) and fatty acid (FA) profiles in Chinese children with non-alcoholic fatty liver disease (NAFLD).A total 76 children aged 4-17 years were categorized into three groups according to the presence and absence of as well as the severity of NAFLD, that is, non-NAFLD (control), mild and moderate to severe NAFLD groups, respectively, based on their liver ultrasonography findings. Serum BA and FA profiles were quantified separately by mass spectrometry and gas chromatography. General linear models were performed to assess the differences among the groups.After adjusted for potential confounders, children with NAFLD had higher levels of chenodeoxycholic acid (CDCA), unconjugated primary BAs (CDCA + cholic acid) but lower levels of deoxycholic acid (DCA), taurodeoxycholic acid (TDCA), glycodeoxycholic acid (GDCA), total DCA (DCA + TDCA + GDCA), glycolithocholic acid (GLCA) and total lithocholic acid (GLCA + taurolithocholic acid) than children without NAFLD. As for FAs, children with mild and moderate to severe NAFLD had higher levels of n-7 monounsaturated FA.Circulating BA and FA profiles may change in children with NAFLD. Further studies are needed to determine their associations and to understand the underlying mechanism of action.

Summary To date, acupuncture has been widely used despite a lack of solid clinical evidence in the East and West. However, there are few validated in vitro models for the mechanistic studies of acupuncture. We hypothesized that adenosine could be used as a probing tool in the mechanistic studies of acupuncture because of its critical role in the action of acupuncture. Subsequently, we tested this hypothesis using both in vitro and in vivo experiments. First, we found that adenosine stimulation mimicked the effect of acupuncture on microRNA profiling (including miR-339, miR-145 and miR-451) and protein level (including Sirt2) in nerve growth factor-induced differentiated PC12 cells. These miRNA and proteins have been found to be regulated by acupuncture treatment in the brain of spontaneously hypertensive rats. Next, we found that adenosine stimulation downregulated miR-339 expression through adenosine A1 receptor-mediated pathway. Finally, we showed that the concentration of adenosine was actually decreased in the brain of spontaneously hypertensive rats after acupuncture treatment at Taichong acupoint. Taken together, these findings suggest that adenosine could be used as a useful probing tool for acupuncture mechanistic studies, while more validation studies are certainly warranted.

The aim of the study is to explore whether monocyte–to-lymphocyte ratio (MLR) provides predictive value of the severity in patients with Klebsiella pneumonia infection (KPI). Patients in a tertiary medical center with Klebsiella pneumonia infection from 2014 to 2017 were recruited in this study. Patients with Klebsiella pneumonia infection were stratified into two groups based on the National Early Warning Score (NEWS). MLR was calculated by dividing monocytes count by lymphocytes count obtained from routine blood examination. The area under the curve (AUC) values was determined using the receiver-operating characteristic (ROC) curve. The correlation between the variables was tested with Pearson or Spearman correlation analysis. Ordinal logistic regression analysis was used to assess the relationship between MLR and the severity of Klebsiella pneumonia infection. One hundred fifty-two patients were finally enrolled for analysis. Among those, 43 (28.29%) cases had severe KPI. MLR was found to be an independent risk factor of the serious Klebsiella pneumonia infection (OR: 23.74, 95% CI: 5.41–104.11, P

During the period from December 2012 to December 2014, three dripping water sites (S1, S2, S3) and one pool water site (SC) have been selected for a long-term monitoring of geochemical indexes in Naduo Cave, Guanling county of Guizhou Province, China. Based on the local meteorological data, this paper analyzed the seasonal change of hydro-geochemical indicators and their feedbacks to climate events. The results indicated that the hydro-geochemical type of cave water was HCO₃⁻-Ca²⁺. Dripping water and pool water were in deposition all the year, except in the month with the maximum precipitation. There were some discrepancies of main ions' concentration among three dripping water sites due to the difference of the migration pathways and migration time. Affected by mixed water and high CO₂ concentration of cave air, the ion concentration of pool water was higher than dripping water, and there was considerable fluctuation. The geochemistry indexes of water in Naduo Cave showed extraordinary seasonal variation rules and could perfectly respond to the external climate environment. The concentration of ions was sensitive to the response of the annual precipitation change caused by extreme climate events. During the rainy season, the concentrations of Ca²⁺, Mg²⁺ and SO₄²⁻ in 2013 were relatively higher and more stable than those in 2014. The response time and susceptivity of each monitoring site were inconsistent.

MicroRNAs (miRNAs) are a group of endogenous noncoding RNAs that play important roles in many biological processes. This study aimed to check if miRNAs were involved in the response to acupuncture in rats. Microarray analysis was performed to compare the miRNA expression profiles of medulla in spontaneously hypertensive rats (SHRs) treated with or without acupuncture. Our microarray analysis identified 222 differentially expressed miRNAs in the medulla of SHRs treated with acupuncture at taichong acupoint. Among these miRNAs, 23 miRNAs with a significant difference were found in acupuncture-treated SHRs compared to untreated rats. These 23 miRNAs could regulate 2963 target genes which were enriched in at least 14 pathways based on our bioinformatic analysis. miRNA-339, miR-223, and miR-145 were downregulated in the medulla of SHRs compared to normotensive rats. Notably, these miRNAs were upregulated to basal levels in the medulla of SHRs treated with acupuncture at taichong in comparison with SHRs receiving acupuncture at nonacupoint group or SHRs without any treatment. Our findings have revealed significant changes of a panel of selective miRNAs in hypertensive rats treated at taichong acupoint. These data provide insights into how acupuncture elicits beneficial effects on hypertension.

To compare the prevalence rates of metabolic syndrome (MS) in obese children, according to three commonly used 'Pediatric MS definitions': (1) the International Diabetes Federation (IDF), (2) Cook, et al, and(3)da Silva, et al, in order to choose an appropriate one for the Chinese obese children. It was also intended to assess the variances of American or Chinese cutoff values on MS prevalence.A retrospective study was performed in obese children from Obesity Outpatient Service Program from January 2004 to December 2008. Subjects were eligible if they met the following criteria: (1) aged 7 to 18 years, (2) with no following conditions as hereditary endocrine or metabolic diseases, secondary obesity, hepatic or renal disease, using medication that alters blood pressure or glucose or lipid metabolism etc., (3) data were complete on the variables of interest. Height, weight and waist circumference, systolic and diastolic blood pressure, fasting lipid profiles, blood sugar and insulin were measured. Insulin resistance was evaluated by homeostasis model assessment (HOMA). American or Chinese cutoff values were used to identify central obesity and hypertension. The prevalence rates of MS under three definitions were calculated and compared by Kappa test to determine the degree of agreement.136 patients with 103 males and 33 females were enrolled in the study. According to the American cutoff value, 19.2%, 34.6%, 52.9% of the subjects were classified as MS under definitions of IDF, Cook, et al, da Silva, et al respectively, matching well with 19.2%, 43.4%, 58.1% when the Chinese cutoff value was used (Kappa = 1, 0.79, 0.90). The degrees of agreement according to the Kappa statistics between Cook, et al and da Silva, et al (0.52, American cutoff value/0.51, Chinese cutoff value) were better than the others (0.24 - 0.4). Children who were diagnosed as MS under the definitions of Cook, et al. or da Silva, et al. appeared to have had serious insulin resistance when compared to those without MS.Prevalence of the metabolic syndrome appeared to be high among the obese pediatric outpatients, which was probably due to the definition being chosen. The use of definitions provided by Cook, et al and da Silva, et al might be more suitable for MS diagnosis in obese children in the outpatient department, if insulin resistance was under consideration. Both American and Chinese cutoff value could be used for MS diagnosis in the Chinese obese children.