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In the context of rapid urbanization, metropolitan areas are facing the risk of supply-demand mismatches among ecosystem services. Investigating the patterns, relationships, and driving factors of multiple supply-demand risks is of great significance to support the efficient management of regional ecological risks. We quantified the single/comprehensive supply-demand risk rates of six ecosystem services in Wuhan Metropolitan Area at the township scale in 2000, 2010, and 2020. By applying the self-organizing feature map network and optimal parameter geo-detector, we identified supply-demand risks bundles of ecosystem services and influencing factors of comprehensive risks. The results showed significant spatial variations in the supply-demand risks of typical ecosystem services from 2000 to 2020. The supply-demand risk associated with grain production, water yield, carbon sequestration, and green space recreation increased, while soil conservation and water purification risks decreased. The comprehensive ecosystem services supply-demand risk increased from 0.41 to 0.45, indicating a 'core area increase and periphery decrease' trend. Throughout the study period, the area exhibited bundles of comprehensive extremely high-risk bundles (B 1 ), comprehensive high-risk bundles (B 2 ), water purification high-risk bundles (B 3 ), and grain production-soil conservation risk bundles (B 4 ). The transition of risk types from B 3 to B 2 and from B 2 to B 1 suggested an increase in the combination and intensity of supply-demand risk. Vegetation cover, nighttime light index, and population density were the main driving factors for spatial variations in comprehensive supply-demand risk. Ecologi-cal risk assessment based on ecosystem services supply-demand bundles could provide an effective and reliable way to regulate multiple regional risk issues.

The urea-assisted water splitting not only enables a reduction in energy consumption during hydrogen production but also addresses the issue of environmental pollution caused by urea. Doping heterogeneous atoms in Ni-based electrocatalysts is considered an efficient means for regulating the electronic structure of Ni sites in catalytic processes. However, the current methodologies for synthesizing heteroatom-doped Ni-based electrocatalysts exhibit certain limitations, including intricate experimental procedures, prolonged reaction durations, and low product yield. Herein, Fe-doped NiO electrocatalysts were successfully synthesized using a rapid and facile solution combustion method, enabling the synthesis of 1.1107 g within a mere 5 min. The incorporation of iron atoms facilitates the modulation of the electronic environment around Ni atoms, generating a substantial decrease in the Gibbs free energy of intermediate species for the Fe-NiO catalyst. This modification promotes efficient cleavage of C-N bonds and consequently enhances the catalytic performance of UOR. Benefiting from the tunability of the electronic environment around the active sites and its efficient electron transfer, Fe-NiO electrocatalysts only needs 1.334 V to achieve 50 mA cm -2 during UOR. Moreover, Fe-NiO catalysts were integrated into a dual electrode urea electrolytic system, requiring only 1.43 V of cell voltage at 10 mA cm -2 .

Background: Studies have shown that the absolute lymphocyte count (ALC) and the neutrophil-to-lymphocyte ratio (NLR) are related to the outcomes in patients with breast cancer receiving specific chemotherapies. However, the reports have focussed on the initial blood test and there is a lack of evidence or data to support that dynamic changes of ALC or NLR are associated with the patients' survival outcomes., Methods: We retrospectively reviewed electronic medical records from patients with breast cancer treated with eribulin from 2015 to 2019 at our institution. Blood test data were available prior to starting eribulin (baseline), and at 1, 3 and 6 months after initiating eribulin. We classified the patients into ALC and NLR high and low groups using the following cut-offs: 1000/µl for ALC and 3 for NLR. We defined ALC and NLR trends as increasing or decreasing compared with the initial data. We assessed the associations between the ALC and NLR with progression-free survival and overall survival., Results: There were 136 patients with breast cancer treated with eribulin. Of these patients, 60 had complete blood tests and follow-up data. Neither a high ALC nor a low baseline NLR was associated with the survival outcome. One month after initiating eribulin treatment, a high ALC and a low NLR were significantly associated with longer progression-free survival (p = 0.044 for each). Three months after initiating eribulin, a high ALC was significantly associated with better overall survival (p = 0.006). A high NLR at 3 or 6 months after initiating eribulin was associated with worse overall survival (p = 0.017 and p = 0.001, respectively). The ALC and NLR trends across times were not associated with survivals., Conclusion: We showed that 1, 3 and 6 months after initiating eribulin, a high ALC and a low NLR may be related to the patients' survival outcomes. The ALC and NLR trends were not associated with survival. Accordingly, we believe patients who maintain a high ALC and a low NLR may have better clinical outcomes after initiating eribulin., (© 2024. The Author(s).)

More than 30% of fruits of Chinese Quince (Chaenomeles speciosa) and peach (Prunus persica) showed circular, water-soaked and brown spots in July 2022 in Kunming, Yunnan, China. The center of these spots was covered by a large number of earthy brown and oblate sporogeneous mycelium containing conidiophore and conidia, which were one-celled, limoniform, hyaline (13.73 to 22.77 x 8.17 to 12.84 µm, n=50). By September 2022, almost 100% of fruits showed symptoms. Later, most of them fell or a few stiff, black and mummified fruits were left on the trees. Fungal isolates were isolated by single-spore technique on Potato Dextrose agar (PDA) from the diseased fruits, and incubated at room temperature (20-28 °C) in darkness for 14 days. The colony was gray, smooth at margins, 7.6-8.0 cm in diameter. To fullfill Koch's postulates, mycelial plugs of one representative isolate YHD611 from Chinese Quince and another YHD610 from peach were used to inoculate three wounded and three non-wounded surface-disinfected fruits of both hosts at room temperature (19-27 °C), respectively. Three wounded and three non-wounded fruits inoculated with sterile PDA plugs served as the control. The wounded peaches appeared water-soaked and had brown lesions after three days of inoculation, then completely decayed after nine days, while non-wounded fruits showed symptoms after five days. The wounded fruits of Chinese Quince developed similar symptoms after eight days of inoculation, and completely decayed after 13 days, while non-wounded fruits showed obvious symptoms after 15 days. In a subsequent study, isolate YHD611 was inoculated to peach while isolate YHD610 was inoculated to Chinese Quince to understand host specificity of the isolates. The results showed that when peaches were infected with YHD611, symptoms were observed on wounded fruits after three days while on non-wounded fruits after five days. When Chinese Quince was infected with YHD610, symptoms were observed on wounded fruits after 14 days while on non-wounded fruits after 21 days. Fungal isolates from symptomatic fruits were identical to the original isolates. There were no symptoms on the control fruits of both hosts. Molecular identification was confirmed based on the sequences of internal transcribed spacer (ITS, primers ITS1 and ITS4) and β-tubulin (TUB2, primers Bt2a and Bt2b) genes (Niu et al. 2016). BLASTn analysis of the ITS (OQ15519and OQ155196) and TUB2 (OQ185202 and OQ185201) of YHD611 and YHD610 revealed a 100% sequence identity, respectively, to Monilia yunnanensis AH7-2 (KT735924.1 for ITS, KT736008.1 for TUB2). In the phylogenetic analyses based on ITS and TUB2 sequence data, the isolates YHD611 and YHD610 belonged to the M. yunnanensis clade. Based on morphological and molecular identification, both isolates were identified as M. yunnanensis, which was reported as the pathogen causing brown rot of plum, peach, apple and pear in Yunnan, China (Hu et al. 2011; Yin et al. 2015). To our knowledge, this is the first report of M. yunnanensis causing brown rot on the fruits of Chinese Quince in Yunnan, China. This study also reports that M. yunnanensis from Chinese Quince can infect peach, and the pathogen from peach can infect Chinese Quince. These findings suggest that M. yunnanensis can transfer from one host to another and causing serious economic losses in multiple fruit crops in Yunnan, China. References: Hu, M. J., et al. 2011. PLoS One. 6:e24990. Niu, C. W., et al. 2016. Mycosystema, 35(10):1. Yin, L. F., et al. 2015. Plant Dis. 99:1775.

Imbibition dynamics in a rectangular U-groove that is connected to a sudden enlargement and complicated by the presence of Concus-Finn (CF) filaments is investigated using many-body dissipative particle dynamics. For open-ended sudden enlargement, four flow types are identified and depend on the contact angle θ y , the critical angle θ f associated with the occurrence of CF filaments, and the critical angle θ c associated with the occurrence of main flow. First, for θ y > θ f and θ y > θ c , the corner flow is absent, and the main flow stops at the end of the small U-groove. Second, for θ c > θ y > θ f , the corner flow vanishes, but the main flow occurs. Third, for θ f > θ y > θ c , the corner flow takes place in the large U-groove, but the main flow is still absent. Fourth, for θ y < θ f and θ y < θ c , both the corner and main flows appear in the large U-groove. Additionally, the flow dynamics is greatly influenced by the length of the large U-groove ( l e ). For closed-ended sudden enlargement, similar findings can be obtained. However, the outcome of the third case is altered for sufficiently small l e , and the sudden enlargement can eventually be filled.

Summary: We developed the eccDB database to integrate available resources for extrachromosomal circular DNA (eccDNA) data. eccDB is a comprehensive repository for storing, browsing, searching, and analyzing eccDNAs from multispecies. The database provides regulatory and epigenetic information on eccDNAs, with a focus on analyzing intrachromosomal and interchromosomal interactions to predict their transcriptional regulatory functions. Moreover, eccDB identifies eccDNAs from unknown DNA sequences and analyzes the functional and evolutionary relationships of eccDNAs among different species. Overall, eccDB offers web-based analytical tools and a comprehensive resource for biologists and clinicians to decipher the molecular regulatory mechanisms of eccDNAs., Availability and Implementation: eccDB is freely available at http://www.xiejjlab.bio/eccDB., (© The Author(s) 2023. Published by Oxford University Press.)

Background: Colonic diverticulitis is a leading cause of abdominal pain. The monocyte distribution width (MDW) is a novel inflammatory biomarker with prognostic significance for coronavirus disease and pancreatitis; however, no study has assessed its correlation with the severity of colonic diverticulitis., Methods: This single-center retrospective cohort study included patients older than 18 years who presented to the emergency department between November 1, 2020, and May 31, 2021, and received a diagnosis of acute colonic diverticulitis after abdominal computed tomography. The characteristics and laboratory parameters of patients with simple versus complicated diverticulitis were compared. The significance of categorical data was assessed using the chi-square or Fisher's exact test. The Mann-Whitney U test was used for continuous variables. Multivariable regression analysis was performed to identify predictors of complicated colonic diverticulitis. Receiver operator characteristic (ROC) curves were used to test the efficacy of inflammatory biomarkers in distinguishing simple from complicated cases., Results: Of the 160 patients enrolled, 21 (13.125%) had complicated diverticulitis. Although right-sided was more prevalent than left-sided colonic diverticulitis (70% versus 30%), complicated diverticulitis was more common in those with left-sided colonic diverticulitis (61.905%, p = 0.001). Age, white blood cell (WBC) count, neutrophil count, C-reactive protein (CRP) level, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and MDW were significantly higher in the complicated diverticulitis group (p < 0.05). Logistic regression analysis indicated that the left-sided location and the MDW were significant and independent predictors of complicated diverticulitis. The area under the ROC curve (AUC) was as follows: MDW, 0.870 (95% confidence interval [CI], 0.784-0.956); CRP, 0.800 (95% CI, 0.707-0.892); NLR, 0.724 (95% CI, 0.616-0.832); PLR, 0.662 (95% CI, 0.525-0.798); and WBC, 0.679 (95% CI, 0.563-0.795). When the MDW cutoff was 20.38, the sensitivity and specificity were maximized to 90.5% and 80.6%, respectively., Conclusions: A large MDW was a significant and independent predictor of complicated diverticulitis. The optimal cutoff value for MDW is 20.38 as it exhibits maximum sensitivity and specificity for distinguishing between simple and complicated diverticulitis The MDW may aid in planning antibiotic therapy for patients with colonic diverticulitis in the emergency department., (© 2023. The Author(s).)

Chronic pruritus is an unpleasant sensory perception that negatively affects quality of life and is common among patients with type 2 diabetes mellitus. Current antipruritic therapies are insufficiently effective. Thus, the mediation of diabetic pruritus by histamine-independent pathways is likely. The aim of this study was to identify possible mediators responsible for diabetic pruritus. A total of 87 patients with type 2 diabetes mellitus were analysed, of whom 59 had pruritus and 28 did not. The 2 groups were assessed for baseline demographics, serum biochemistry parameters, cytokines, and chemokines. This study also investigated the associations of these factors with the severity of itching. Neither haemoglobin A1c nor serum creatinine levels were correlated with severity of itching. Significantly higher levels of interleukin-4 (p = 0.004), interleukin-13 (p = 0.006), granulocyte-macrophage colony-stimulating factor (p < 0.001) and C-X-C motif chemokine ligand 10 (p = 0.028) were observed in the patients with pruritus than in those without pruritus. Moreover, the levels of these mediators were positively correlated with the severity of itching. Thus, novel antipruritic drugs can be developed to target these molecules. This is the first study to compare inflammatory mediators comprehensively in patients with diabetes mellitus with pruritus vs those without pruritus.

Background: This study aimed to examine the effectiveness and safety of eribulin used as an early-line (EL, i.e., first-/second-line) versus late-line (LL, i.e., third-line and beyond) chemotherapy for recurrent advanced or metastatic breast cancer (A/MBC) patients., Methods: This study conducted a retrospective observation of A/MBC patients initiating eribulin between January 1, 2015, and June 30, 2019, using medical database at a university-affiliated teaching hospital in Taiwan. Patients were assigned into either the EL or LL group based on the timing of respective eribulin treatments and were observed for at least 6 months up to December 2019 for progression-free survival (PFS), time to treatment failure (TTF), overall survival (OS), disease response, and occurrence of adverse events. The Kaplan-Meier and Cox proportional hazard regression survival analyses were performed., Results: Of 127 patients, 23.6% (n = 30) and 76.4% (n = 97) were assigned to the EL and LL groups, respectively, between which no difference in patient characteristics was noted. Median PFS and TTF were 6.5 months and 5.0 months for the EL and 4.2 months and 3.4 months for the LL, respectively. Median OS could not be estimated in the EL group and was 20.5 months in the LL group. Eribulin as an EL treatment was the only factor associated with longer TTF and OS, whereas the number of metastatic sites was additionally associated with PFS in the multivariate analysis. No complete response was reported in either group, but a partial response was obtained in 6.7% in the EL group and 3.1% in the LL group. The common adverse events between two groups were similar, including leukopenia (80.0%), neutropenia (76.7%), and anemia (60.0%)., Conclusions: The eribulin used as an EL of chemotherapy was effective for A/MBC patients with known toxicities in this study, while eribulin as the LL chemotherapy showed consistent results with previous reports., (© 2022 S. Karger AG, Basel.)

Objective: To investigate the effect of perioperative blood pressure variability on cerebral hyperperfusion syndrome after carotid artery stenting., Methods: A retrospective analysis was conducted of data collected from 418 patients who underwent carotid artery stenting in Guangxi Zhuang Autonomous Region People's Hospital in China. The blood pressure data were collected during operation (after balloon dilation, before stent release, after stent release) and within 3 days after the operation. The blood pressure variability was evaluated by measuring the mean, maximum, minimum, max-min, standard deviation (SD) of systolic blood pressure (SBP) and diastolic blood pressure (DBP). The correlation between blood pressure variability and cerebral hyperperfusion syndrome was analysed., Results: Blood pressure data from 418 patients were analysed. Twenty patients (4.8%) developed cerebral hyperperfusion syndrome. The parameters of blood pressure variability were divided into four groups according to quartile. After adjusting for age, symptomatic carotid stenosis, unilateral carotid stenosis, bilateral carotid stenosis, collateral circulation, diabetes mellitus and chronic kidney disease, multivariate analysis showed that SBP Max , SBP Min , SBP Max-Min , SBP CV , DBP SD , DBP Max , DBP Min , DBP Max-Min and DBP CV were associated with the occurrence of cerebral hyperperfusion syndrome ( P  < 0.05), respectively., Conclusion: This study suggests that blood pressure variability during the perioperative period may increase the risk of cerebral hyperperfusion syndrome.

Background & Aims: Aging is a pathophysiological process driven by a diverse set of complex biological processes, and environmental pollution plays an important role in this process. This study aimed to explore the association between serum α-Klotho levels and urinary perchlorate, nitrate, and thiocyanate levels., Methods: This secondary dataset analysis included 4875 participants (mean age, 57.69 year; male, 49.58%; non-Hispanic White, 47.67%) from the US National Health and Nutrition Examination Survey (2007-2014). Enzyme-linked immunosorbent assay was used to quantify α-Klotho levels, and ion chromatography coupled with electrospray tandem mass spectrometry was used to quantify thiocyanate, nitrate, and perchlorate levels. Multivariate linear regression models were applied to estimate the association between perchlorate, nitrate, and thiocyanate levels and serum α-Klotho levels., Results: Urinary thiocyanate levels were negatively associated with α-Klotho levels (β = - 0.006; 95% confidence interval, - 0.010 to - 0.003; P = 0.0004) after adjusting for age, sex, body mass index, race, alcohol consumption, estimated glomerular filtration rate, underlying disease, physical activity, smoking status, usual energy intake, and urinary creatinine and serum cotinine levels and mutual adjustment of urinary perchlorate, urinary nitrate, and urinary thiocyanate levels. The α-Klotho level in participants in the highest quartile was higher by 50.567 ng/mL (β = 50.567; 95% confidence interval, 14.407 to 86.726; P = 0.009) than that in participants in the lowest quartile of urinary perchlorate. A linear relationship was observed between urinary thiocyanate and α-Klotho levels., Conclusions: Urinary thiocyanate levels were negatively associated with serum α-Klotho levels. Urinary thiocyanate should be further investigated as a potential mediator of aging and age-related diseases., (© 2022. The Author(s).)

Objectives: To analyze the case, scene and forensic pathological characteristics of sudden unexpected death in epilepsy (SUDEP), to provide a practical basis for forensic identification., Methods: A total of 9 autopsy cases of SUDEP were collected. The basic information of the cases, the scene characteristics, the forensic pathological changes, the common drugs and antiepileptic drug test results, and pericardial fluid biochemical test results were analyzed., Results: All of the 9 cases were male epilepsy patients died during sleep at night, the age of death was (37.1±8.6) years, and the course of epilepsy was (21.3±5.6) years. Six corpses were in prone position and three in left lateral position. The hemorrhage of the sternocleidomastoid muscle, sternal thyroid muscle and sternohyoid muscle were found with 8 cases, 5 cases and 4 cases, respectively, all of them were unilateral. Six cases had bilateral hemorrhage of pectoralis minor muscle. Brain edema, phagocytosis of frontotemporal neurons and gliosis, cardiac fibers bend in wavy patterns and eosinophilic staining enhancement, pulmonary edema, pulmonary congestion, alveolar hemorrhage, pulmonary small bronchiole wall shrinking, tubular proteinuria and pancreatic parenchymal hemorrhage were the common histopathological changes. The biochemical test results of pericardial fluid indicated that there were myocardial ischemic damage., Conclusions: Young male, early onset, long course of disease, sleep in the prone position, poor drug compliance or combination, epileptic seizure may be the risk factors of SUDEP. Cardiac dysfunction and respiratory depression might be the main death mechanism of SUDEP.

Background: Ischemic stroke is one of the leading causes of mortality worldwide. The available treatments are not effective. Phosphodiesterase 9A (PDE9A) is an intracellular cyclic guanosine monophosphate (cGMP) hydrolase considered to be a promising therapeutic target for brain diseases. This study explored neuroprotective effects and the underlying mechanism of LW33, a novel PDE9A inhibitor, on ischemic stroke in vitro and in vivo., Methods: A middle cerebral artery occlusion (MCAO) model was established in adult male Sprague-Dawley rats and an oxygen-glucose deprivation/reoxygenation (OGD/R) model was established in human SH-SY5Y cells to mimic ischemia-reperfusion injury in vitro., Results: LW33 increased cell viability, reduced lactate dehydrogenase activity, and OGD/R-induced apoptosis of SH-SY5Y cells. The protective effects of LW33 against stroke occurred in the recovery phase. LW33 administration significantly reduced cerebral infarction volume in MCAO rats, without causing significant deformation or necrosis of neurons in the cortex. LW33 also improved learning and cognitive dysfunction and reduced other pathological changes in MCAO rats in the recovery period. Moreover, LW33 stimulated the cGMP/PKG/CREB pathway and up-regulated the expression of the apoptosis-related proteins, and this effect was reversed by KT5823 treatment., Conclusion: LW33 inhibited cell apoptosis and promoted neuronal repair to alleviate OGD/R and MCAO induced pathological alterations via the cGMP/PKG/CREB pathway, indicating that LW33 may be a promising therapeutic target for ischemic stroke., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To investigate the feasibility of multi-slice spiral CT(MSCT) imaging features of gastric stromal tumor (GST) in predicting pathological NIH risk classification, providing imaging basis for patients with GST before treatment. Methods: The clinical and CT imaging data of 504 patients(506 GST lesions), 259males and 245 females, aged from 13 to 85(60±11) years, with GST confirmed by surgery and pathology collected in the Zhongshan Hospital Affiliated to Fudan University and the Affiliated TCM Hospital of Southwest Medical University. According to pathological NIH risk classification, 506 lesions were divided into low risk group (very low and low risk degree, 277 lesions) and high risk group (medium and high risk degree, 229 lesions).Clinical data and imaging characteristics were compared between two groups. Multivariate logistic regression analysis was performed to screen out independent risk factors for statistically significant imaging indicators. Receiver operating curve (ROC) was used to evaluate the predictive value of tumor length for risk classification. Resulst: Between low risk group and high risk group,there were significant differences in gender(male/female:131/146 vs 129/100), gastrointestinal bleeding(present/absent:39/238 vs 59/170), morphology(regular/Irregular:218/59 vs 95/134), calcification(present/absent:36/241 vs 53/176), degree of necrosis(0°/Ⅰ°/Ⅱ°/Ⅲ°:197/61/16/3 vs 58/98/32/41), ulceration(present/absent:32/245 vs 94/135), growth pattern(endophytic/exophytic/mixed:102/105/70 vs 44/98/87), tumor location(fundus/cardia/body/angle/antrum:98/7/135/12/25 vs 98/6/114/5/6), feeding artery(present/absent:32/245 vs 104/125), vascular enhancement(present/absent:19/258 vs 88/141), effusion of around the disease(present/absent:0/277 vs 13/216), positive sign of fat around the disease(present/absent:0/277 vs 30/199),maximum long diameter[2.82(2.04,3.80) cm vs 5.93(4.06,8.29) cm] and short diameter [2.31(1.60,2.88) cm vs 4.40(3.21,6.37) cm]of tumor(all P <0.05).The maximum long diameter of tumor ( OR =2.08,95% CI :1.35-3.20) and ulceration positive( OR =2.01,95% CI :1.03-3.92) were independent risk factors of risk classification(all P <0.05).Gastric antrum was used as the reference for tumor location, gastric fundus( OR =7.77,95% CI :2.00-30.24) and gastric body( OR= 3.93,95% CI :1.03-15.01) were independent risk factors of risk classification(all P <0.05).The area under curve(AUC) of the maximum long diameter of tumor for predicting risk classification was 0.87, and the optimal critical value, sensitivity and specificity were 4.98cm, 62.9% and 95.3% respectively. Conclusions: MSCT image features of GST had certain characteristics. MSCT has certain predictive value for pathological NIH risk classification of GST, which can provide certain imaging basis for patients before treatment.

Background: Tai Chi has been shown to improve motor symptoms in Parkinson's disease (PD), but its long-term effects and the related mechanisms remain to be elucidated. In this study, we investigated the effects of long-term Tai Chi training on motor symptoms in PD and the underlying mechanisms., Methods: Ninety-five early-stage PD patients were enrolled and randomly divided into Tai Chi (n = 32), brisk walking (n = 31) and no-exercise (n = 32) groups. At baseline, 6 months and 12 months during one-year intervention, all participants underwent motor symptom evaluation by Berg balance scale (BBS), Unified PD rating-scale (UPDRS), Timed Up and Go test (TUG) and 3D gait analysis, functional magnetic resonance imaging (fMRI), plasma cytokine and metabolomics analysis, and blood Huntingtin interaction protein 2 (HIP2) mRNA level analysis. Longitudinal self-changes were calculated using repeated measures ANOVA. GEE (generalized estimating equations) was used to assess factors associated with the longitudinal data of rating scales. Switch rates were used for fMRI analysis. False discovery rate correction was used for multiple correction., Results: Participants in the Tai Chi group had better performance in BBS, UPDRS, TUG and step width. Besides, Tai Chi was advantageous over brisk walking in improving BBS and step width. The improved BBS was correlated with enhanced visual network function and downregulation of interleukin-1β. The improvements in UPDRS were associated with enhanced default mode network function, decreased L-malic acid and 3-phosphoglyceric acid, and increased adenosine and HIP2 mRNA levels. In addition, arginine biosynthesis, urea cycle, tricarboxylic acid cycle and beta oxidation of very-long-chain fatty acids were also improved by Tai Chi training., Conclusions: Long-term Tai Chi training improves motor function, especially gait and balance, in PD. The underlying mechanisms may include enhanced brain network function, reduced inflammation, improved amino acid metabolism, energy metabolism and neurotransmitter metabolism, and decreased vulnerability to dopaminergic degeneration. Trial registration This study has been registered at Chinese Clinical Trial Registry (Registration number: ChiCTR2000036036; Registration date: August 22, 2020)., (© 2022. The Author(s).)

This study aimed to explore the characteristic role of Puerariae Lobatae Radix(PLR) in Gegen Decoction for the treatment of primary dysmenorrhea(PD). Estrogen(E&#95;2) was combined with oxytocin to establish a mouse model of PD. The mice were randomly divided into a normal group, a model group, a Gegen Decoction group, a PLR-free Gegen Decoction group, a PLR group, and a positive drug group(ibuprofen). Writhing response times and writhing incubation of mice in each group were tested by behavio-ral assessment, and the serum levels of prostaglandin F&#95;(2α)(PGF&#95;(2α)), prostaglandin E&#95;2(PGE&#95;2), E&#95;2, and progesterone(PROG) were detected by ELISA kits. Western blot method was adopted to detect cyclooxygenase-2(COX-2) and estrogen receptor alpha(ER&#95;α) expression levels in uterine tissues. Doppler ultrasound was employed to detect changes in uterine artery blood flow in mice, including peak systolic blood flow velocity(maximum velocity), end-diastolic velocity(minimum velocity), peak systolic blood flow velocity/end-diastolic velocity(S/D), pulsatility index(PI), and resistive index(RI). Histopathological changes in the uterus were detected by HE staining. Based on the oxytocin-induced isolated uterine contraction model, the effects of Gegen Decoction, PLR-free Gegen Decoction, and PLR on the amplitude, frequency, and activity of isolated uterine contraction were compared to investigate the role of PLR in Gegen Decoction for the treatment of PD. The results showed that compared with the Gegen Decoction group, the PLR-free Gegen Decoction improved the indicators of PD except for E&#95;2 content, ER&#95;α expression, and uterine artery blood flow. PLR could significantly down-regulate the serum content of E&#95;2 and the protein expression of uterine ER&#95;α, and improve the uterine artery blood flow. The data suggested that PLR, as the sovereign drug of Gegen Decoction, might function in Gegen Decoction for the treatment of PD by mediating E&#95;(2 )and improving the uterine artery blood flow.

Objective: To explore the imaging features and clinical effect of accordion maneuver in promoting the bone healing at the docking site after tibial transport under ultrasonic monitoring. Methods: Retrospective analysis was conducted on the clinical data of 16 patients with tibial bone transport who were admitted to the Department of Orthopedics, the second Hospital of Shanxi Medical University from May 2018 to October 2019. All the patients were treated with accordion maneuver to promote bone healing at the docking site under ultrasound monitoring. There were 14 males and 2 females, aged (45.3±14.3) years (range: 6 to 61 years). Before tibial bone transport, the length of the tibial defect of 16 patients was (6.0±2.6) cm (range: 2.0 to 12.1 cm). The operation steps of accordion maneuver were as follows: pressurization for 2 weeks, suspension for 12 days, distraction for 2 weeks, retraction for 2 weeks, and then stop the operation to consolidate the bone mineralization. During accordion treatment, ultrasound was used to monitor the size of hematoma, Adler grade of blood flow signal and the changes of new callus in and around the docking site. X-ray was performed to monitor bone healing at the docking site. Pearson correlation coefficient was used to analyze the correlation between the size of hematoma, the resistance index of blood flow signal and the bone healing time of the docking site. Paley healing criterion was used to evaluate the bone healing and functional recovery of the patients. Results: During accordion maneuver, ultrasound examination showed that the Adler grade of blood flow signals around the docking site increased gradually before retraction and then decreased gradually, but the degree of callus mineralization continued to increase gradually. After 2 weeks of pressure on the docking site, hematoma was observed in 14 patients by ultrasound examination. X-ray showed that all docking sites had bony healing, with the healing time of (30.8±4.9) weeks (range: 23 to 40 weeks).The size of the hematoma was negatively correlated with the healing time of the docking site ( r =-0.819, P <0.01). No hematoma was found in 2 patients, and after continuous observation for 20 weeks, there was still no obvious callus connection at the docking site. After bone cortical removal, ultrasound examination showed hematoma formed at the docking site. Accordion maneuver was continued, and the docking site healed at 30 and 32 weeks after surgery, respectively. There was a negative linear correlation between hematoma size at 2 weeks of compression and the blood flow resistance index at 2 weeks of retraction in 16 patients ( r =-0.801, P <0.01). The patients were followed-up for (14.5±3.2) months (range: 10.6 to 20.2 months). At the last follow-up, 12 patients were evaluated as excellent and 4 were evaluated as good by Paley healing criteria. Conclusion: The distraction and compression stress applied in accordion maneuver can promote bone healing at the docking site, and ultrasound can monitor early signs of bone healing at the docking site to help determine the tendency of bone healing.

Objective: To analyze effect of accordion technique on bone mineralization of extended bone segment in treating tibial bone defect with bone transport., Methods: From May 2017 to October 2019, 22 patients with tibial bone defects were treated with Ilizarov bone-transport technique, and divided into two groups after bone-transport was completed, 11 patients in each group. In observation group, there were 9 males and 2 females aged from 20 to 60 years old with an average of (42.6± 13.3) years old;the length of bone defect ranged from 3 to 13 cm with an average of(6.4±2.6) cm;2 patients were suffered from upper tibial bone defects, 3 patients were middle and 6 patients were lower;patients were treated with accordion technique for 35 days. In control group, there were 10 males and 1 female aged from 41 to 60 years old with an average of (51.6±6.4) years old;the length of bone defect ranged from 3 to 10.7 cm with an average of (6.6±2.5) cm;1 patient was suffered from upper tibial bone defects, 3 patients were middle and 7 patients were lower;patients were treated with lock external fixator to waiting bone mineralization. The content of hydroxyapatite (HAP) extended bone segment was measured after bone-transport completed immediately, 35, 65 and 95 days after bone-transport was completed, respectively, then the mineralization time and healing time were compared between two groups, and the therapeutic effect of bone defect was evaluated by using Paley scoring criteria., Results: Twenty-two patients were followed up from 18 to 36 months with an average of (27.0±6.3) months. The wounds on the bone defects healed spontaneously during bone transport, and there were no wound complications such as skin infection or skin necrosis occurred. There were statisticaldifference in the content of HAP of the extended bone segments at 35, 65 and 95 days after bone-transport between two groups ( P <0.05). There were difference in mineralization time and healing time between two groups ( P <0.05). According to Paley standard evaluation, 10 patients got excellent results, and 1 good in observation group; while 9 patients got excellent results, 2 good in control group;and there was no differences between two groups ( Z =-0.607, P = 0.544)., Conclusion: Accordion technique and locking external fixator mineralization in prolonging bone segment healing after bone-transport have the equal clinical effect, while the accordion technique could significantly accelerate the growth rate of HAP and shorten the mineralization time and healing time.

Introduction: S100 calcium-binding protein A8 (S100A8) is also known as macrophage-related protein 8, which is involved in various pathological processes in the central nervous system post-traumatic brain injury (TBI), and plays a critical role in inducing inflammatory cytokines. Accumulating evidences have indicated that toll-like receptor 4 (TLR4) is considered to be involved in inflammatory responses post TBI. The present study was designed to analyze the hypothesis that S100A8 is the key molecule that induces inflammation via TLR4 in TBI., Methods: The weight-drop TBI model was used and randomly implemented on mice that were categorized into six groups: Sham, NS, S100A8, S100A8+TAK-242, TBI, and TBI+TAK-242 groups. In the S100A8+TAK-242 and TBI+TAK-242 groups, at half an hour prior to the intracerebroventricular administration of S100A8 or TBI, mice were intraperitoneally treated with TAK-242 that acts as a selective antagonist and inhibitor of TLR4. Furthermore, the protein recombinant of S100A8 was injected into the lateral ventricle of the brain of mice in the S100A8 and S100A8+TAK-242 groups. Sterile normal saline was injected into the lateral ventricle in the NS group. To evaluate the association between S100A8 and TLR4, Western blot, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and Nissl staining were employed. Simultaneously, the neurological score and brain water content were assessed. In the in vitro analysis, BV-2 microglial cells were stimulated with lipopolysaccharide LPS or S100A8 recombinant protein, with or without TAK-242. The expression of the related proteins was subsequently detected by Western blot or enzyme-linked immunosorbent assay., Results: The levels of S100A8 protein and pro-inflammatory cytokines were significantly elevated after TBI. There was a reduction in the neurological scores of non-TBI animals with remarkable severe brain edema after the intracerebroventricular administration of S100A8. Furthermore, the TLR4, p-p65, and myeloid differentiation factor 88 (MyD88) levels were elevated after the administration of S100A8 or TBI, which could be restored by TAK-242. Meanwhile, in the in vitro analysis, due to the stimulation of S100A8 or LPS, there was an upregulation of p-p65 and MyD88, which could also be suppressed by TAK-242., Conclusion: The present study demonstrated that the TLR4-MyD88 pathway was activated by S100A8, which is essential for the development of inflammation in the brain after TBI., Competing Interests: 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 © 2021 He, Zhao, Wu, Cheng, Sun, Zhang, Yang, Fan, Di and Jiang.)

Aims: To explore the biological function and mechanism of Syntaxin2 (STX2) in Colorectal cancer (CRC) proliferation., Main Methods: A series of gain- and loss-of-function analysis were conducted the to explore the biological function of STX2 in CRC proliferation in vivo and in vitro. Western blot, Co-immunoprecipitation (Co-IP) and the functional analyses were taken to analyze the regulative role of STX2 on Exosome Complex 4 (EXOSC4) in CRC proliferation; Immunohistochemistry (IHC) and Real-time quantitative polymerase chain reaction (qPCR) were used to further verify the relationship between the expression of STX2 and EXOSC4 in human CRC samples., Key Findings: Our study revealed that the over-expression of STX2 promoted CRC proliferation, while knockdown of STX2 repressed CRC proliferation; STX2 promoted CRC proliferation via increasing EXOSC4 protein; There was a positive correlation between STX2 and EXOSC4 expression., Significance: The current data verify that STX2 drives the proliferation of CRC via increasing the expression of EXOSC4., (Copyright © 2020. Published by Elsevier Inc.)

In this study, the physiological values of volumes of plasma, cells, total blood and the F blood factors were identified in 24 adult tree shrews (Tupaia belangeri; 12 male and 12 female; average BW of 123.9±19.19 g). The two-compartment model method of Evans Blue dye was used to obtain the plasma volume and the venous hematocrit was measured by microhematocrit method. To establish the relationship between body weight (BW) and blood volume of tree shrews, We performed linear fitting for these two datasets. Results were analyzed according to gender and weight (<120g vs.>120g). Statistical significance was assessed using the unpaired student t test and one-way ANOVA. The average volumes per 100g body weight of plasma, red blood cell (RBC) and total blood were 5.42±0.543, 3.24±0.445, and 8.66±0.680ml respectively. The mean body hematocrit, cardiac hematocrit, jugular vein hematocrit, femoral vein hematocrit, and tail vein hematocrit was 37.43±4.096, 39.72±3.219, 43.04±4.717, 40.84±3.041, and 38.71±3.442% respectively. The F cardiac was 0.94±0.072, F jugular vein 0.88±0.118, F femoral vein 0.92±0.111, and the F tail vein 0.97±0.117. Blood volume (ml) was 85.89103×BW (kg). This is the first study to provide the parameters of plasma volume, cell volume, total blood volume and F factor and a baseline for future research on blood physiology of tree shrews., Competing Interests: The authors have declared that no competing interests exist.

Background: Paclitaxel plays a pivotal role in the chemotherapy of breast cancer, but resistance to this drug is an important obstacle in the treatment. It is reported that microRNA-152-3p (miR-152-3p) is involved in tamoxifen resistance in breast cancer, but whether it is involved in paclitaxel resistance in breast cancer remains unknown. Materials and methods: We examined the expression of miR-152-3p in breast cancer tissues and cells by qRT-PCR. After transfecting paclitaxel-resistant MCF-7/TAX cells with miR-152-3p mimics, we analyzed the function of miR-152-3p in these cells by MTT assay and flow cytometry. We screened the target gene, endothelial PAS domain-containing protein 1 ( EPAS1 ), using bioinformatics analysis and verified it with the dual luciferase reporter gene experiment. The relationship between EPAS1 and miR-152-3p and their roles in paclitaxel resistance of breast cancer were further investigated using RNA interference and transfection techniques. Results: The expression of miR-152-3p in normal breast tissues and cells was markedly higher than that in breast cancer. Overexpression of miR-152-3p decreased the survival rate and increased the apoptosis rate and sensitivity of MCF-7/TAX cells to paclitaxel. We confirmed that EPAS1 is the target of miR-152-3p and is negatively regulated by this miRNA. Moreover, transfection with EPAS1 siRNA enhanced the susceptibility and apoptosis rate of MCF-7/TAX cells to paclitaxel. Co-transfection of miR-152-3p mimics and EPAS1 increased paclitaxel sensitivity and apoptosis induced by the drug. Conclusion: miR-152-3p inhibits the survival of MCF-7/TAX cells and promotes their apoptosis by targeting the expression of EPAS1 , thereby, enhancing the sensitivity of these breast cancer cells to paclitaxel., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

A new organic small-molecule family comprising tetracyanoquinodimethane-substituted quinoidal dithioalky(SR)terthiophenes ( DSTQ s) ( DSTQ-6 ( 1 ); SR = SC 6 H 13 , DSTQ-10 ( 2 ); SR = SC 10 H 21 , DSTQ-14 ( 3 ); SR = SC 10 H 21 ) was synthesized and contrasted with a nonthioalkylated analogue ( DRTQ-14 ( 4 ); R = C 14 H 29 ). The physical, electrochemical, and electrical properties of these new compounds are thoroughly investigated. Optimized geometries obtained from density functional theory calculations and single-crystal X-ray diffraction reveal the planarity of the SR-containing DSTQ core. DSTQ s pack in a slipped π-π stacked two-dimensional arrangement, with a short intermolecular stacking distance of 3.55 Å and short intermolecular S···N contacts of 3.56 Å. Thin-film morphological analysis by grazing incident X-ray diffraction reveals that all DSTQ molecules are packed in an edge-on fashion on the substrate. The favorable molecular packing, the high core planarity, and very low lowest unoccupied molecular orbital (LUMO) energy level (-4.2 eV) suggest that DSTQ s could be electron-transporting semiconductors. Organic field-effect transistors based on solution-sheared DSTQ-14 exhibit the highest electron mobility of 0.77 cm 2 V -1 s -1 with good ambient stability, which is the highest value reported to date for such a solution process terthiophene-based small molecular semiconductor. These results demonstrate that the device performance of solution-sheared DSTQ s can be improved by side chain engineering.

Nuclear protein LaeA is known as the global regulator of secondary metabolism in Aspergillus . LaeA connects with VeA and VelB to form a heterotrimeric complex, which coordinates fungal development and secondary metabolism. Here, we describe a new interaction partner of LaeA, the kinetochore protein Spc105, from the aflatoxin-producing fungus Aspergillus flavus . We showed that in addition to involvement in nuclear division, Spc105 is required for normal conidiophore development and sclerotia production of A. flavus . Moreover, Spc105 positively regulates the production of secondary metabolites such as aflatoxin and kojic acid, and negatively regulates the production of cyclopiazonic acid. Transcriptome analysis of the Δspc105 strain revealed that 23 backbone genes were differentially expressed, corresponding to 19 of the predicted 56 secondary metabolite gene clusters, suggesting a broad regulatory role of Spc105 in secondary metabolism. Notably, the reduced expression of laeA in our transcriptome data led to the discovery of the correlation between Spc105 and LaeA, and double mutant analysis indicated a functional interdependence between Spc105 and LaeA. Further, in vitro and in vivo protein interaction assays revealed that Spc105 interacts directly with the S -adenosylmethionine (SAM)-binding domain of LaeA, and that the leucine zipper motif in Spc105 is required for this interaction. The Spc105-LaeA interaction identified in our study indicates a cooperative interplay of distinct regulators in A. flavus , providing new insights into fungal secondary metabolism regulation networks.

Despite the success and advantages over traditional chemotherapeutic strategies, photothermal therapy (PTT) suffers from certain limitations, such as poor stability, low therapeutic efficacy of PTT agents in vivo , and their affinity loss during the multistep synthesis process of delivery carriers, among others. To address these limitations, we designed a stable, biocompatible, and dual-triggered formulation of indocyanine green (ICG)-encapsulated silk fibroin (SF) (ICG-SF) nanoparticles using supercritical fluid (SCF) technology. We demonstrated that ICG encapsulation in SF through this environmental-friendly approach has offered excellent photothermal stability, the pH-responsive release of ICG from SF specifically in the tumor acidic environment, and its substantial activation with near-infrared (NIR) light at 808 nm significantly enhanced the PTT efficiency. In vitro and in vivo photothermal experiments have shown that these ICG-SF nanoparticles were capable of devastating tumor cells merely under light-induced hyperthermia. Together, these results have suggested that the biocompatible ICG-SF nanoparticles prepared by the SCF process resulted in high PTT efficiency and may have a great potential as a delivery system for sustained cancer therapy.

We reported the acceleration of skin wound healing in diabetic rats by repeated exposure to low-dose radiation (LDR). Here, we explored whether the wound healing could be further improved when LDR was combined with a topical application of basic fibroblast growth factor (bFGF) or zinc. Wounds were established on the backs of type 1 diabetic rats induced by a single injection of streptozotocin. Rats were treated daily with normal saline (Diabetes), LDR, bFGF, zinc, or combined 3 treatments for 5 consecutive days with a 2-day break between each consecutive 5-day treatment. Changes in wound size, histopathology, and microvessel density were assessed on days 5, 10, and 15, respectively, once treatment is started. All treatment regimens significantly accelerated skin wound healing, tissue remodeling, and new vessel formation compared to diabetes group. However, the combined LDR plus bFGF and zinc provided a better beneficial effect on wound healing than either one of these treatments alone. Further, we found that the effects of LDR and bFGF were similar, whereas zinc alone induced a weaker response. Our results suggest that whole-body LDR plus the topical application of bFGF and zinc can further accelerate wound healing in diabetic rats., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Patients with chronic spontaneous urticaria (CSU) often have sleep disorders (SDs) because of pruritus. However, SDs might also contribute to the development of CSU. Here, we present the first population-based cohort study on the association between SDs and subsequent CSU development.This study investigated whether SDs increase the risk of CSU by using a population-based database in Taiwan.This retrospective matched-cohort study included 105,892 patients with new-onset SDs (SD cohort) and 105,892 randomly selected controls (control cohort). Each patient was monitored for 10 years to individually identify patients who were subsequently diagnosed as having CSU during the follow-up period. A Cox proportional hazard regression analysis was conducted to determine the risk of CSU in patients with SDs compared with the controls.All relevant comorbidities were more prevalent in the SD cohort than in the control cohort (P < .001). During the follow-up period, the incidence rates of CSU among the patients with SDs and controls were 53.4 and 28.3 per 10,000 person-years, respectively. After adjustment for age, sex, and comorbidities, the adjusted hazard ratio for CSU in the SD cohort was 1.83 (95% confidence interval = 1.73-1.93, P < .001).The risk of CSU was higher in the patients with SDs than in the controls.

Excitation-emission matrix fluorescence spectroscopy combined with fluorescence regional integration (FRI) analysis were adopted to analyze the water samples collected from the Lujiang River, which flows through the rapidly urbanizing areas of Beilun, Ningbo, in order to illuminate the composition and characteristics of the spatial distribution of fluorescent dissolved organic matter (FDOM), and further to explain its correlation with water quality in the urban river. The results showed that FDOM was composed of tyrosine-like, tryptophan-like, soluble microbial by-product-like, fulvic-like, and humic-like materials, and FDOM was dominated by protein-like components, accounting for 83.8% of the total fluorescence intensity, while humic-like components accounted for much less. The concentrations of the water quality parameters, such as total nitrogen, total phosphorus, and metals, were linearly correlated with the total fluorescence intensity of all components, indicating that FDOM was significantly related to the removal and transformation of nitrogen and phosphorus. The distribution of FDOM in different areas has the following characteristics:FDOM was low and not distinctly influenced by human activities in the upstream, while in the downstream, FDOM was high and showed the characteristics typical of that in urbanized rivers. Therefore, anthropogenic activities can greatly influence river water quality and the concentration and composition of FDOM.

Radioresistance hampers success in the treatment of patients with advanced colorectal cancer (CRC). Improving our understanding of the underlying mechanisms of radioresistance could increase patients' response to irradiation (IR). MicroRNAs are a class of small RNAs involved in tumor therapy response to radiation. Here we found that miR-214 was markedly decreased in CRC cell lines and blood of CRC patients after IR exposure. Meanwhile, autophagy was enhanced in irradiated CRC cells. Mechanically, ATG12 was predicted and identified as a direct target of miR-214 by dual luciferase assay, qPCR, and Western blot. In vitro and in vivo experiments showed that miR-214 promoted radiosensitivity by inhibiting IR-induced autophagy. Restoration of ATG12 attenuated miR-214-mediated inhibition of cell growth and survival in response to IR. Importantly, miR-214 was highly expressed in radiosensitive CRC specimens and negatively correlated with plasma level of CEA. Moreover, ATG12 and LC3 expressions were increased in radioresistant CRC specimens. Our study elucidates that miR-214 promotes radiosensitivity by inhibition of ATG12-mediated autophagy in CRC. Importantly, miR-214 is a determinant of CRC irradiation response and may serve as a potential therapeutic target in CRC treatment.

Background: MiR-214 is aberrantly regulated in several tumours, but its underlying mechanisms in colorectal cancer (CRC) metastasis remain largely unknown. This study aimed to demonstrate the function and potential mechanism of miR-214 in regulating invasion and metastasis of CRC., Methods: The transcription factor and targets of miR-214 were predicted by bioinformatics and validated using ChIP and dual-luciferase reporter assay. DNA methylation status was explored using bisulphite sequencing PCR. The in vitro and in vivo function of miR-214 in CRC was evaluated using MTT, plate colony formation, Matrigel invasion and animal models. Real-time PCR or western blotting was performed to detect FOXD3, miR-214 and MED19 expressions in CRC cells and clinical specimens., Results: MiR-214 was downregulated in CRC and was significantly correlated with lymphatic metastasis. Downregulation of miR-214 might due to promoter hypermethylation in CRC. FOXD3 was validated as a transcription factor of miR-214 by ChIP assay. Dual-luciferase assay identified MED19 as a target of miR-214 in CRC. In vitro and in vivo experiments showed that miR-214 mediated the inhibiting effect of FOXD3 on proliferation, invasion and metastasis by targeting MED19. Spearman's correlation analysis showed a positive correlation between FOXD3 and miR-214, and negative correlations between FOXD3 and MED19, miR-214 and MED19 in CRC cells and clinical specimens., Conclusions: FOXD3/miR-214/MED19 axis is important for the regulation of growth, invasion and metastasis of CRC. Targeting the miR-214-mediated axis might be helpful for the treatment of CRC.

Purpose: This study investigated whether alcoholic intoxication (AI) increases the risk of inflammatory bowel disease (IBD) by using a population-based database in Taiwan., Methods: This retrospective matched-cohort study included 57 611 inpatients with new-onset AI (AI cohort) and 230 444 randomly selected controls (non-AI cohort). Each patient was monitored for 10 years to individually identify those who were subsequently diagnosed with Crohn disease (CD) and ulcerative colitis (UC) during the follow-up period. Cox proportional hazard regression analysis was conducted to determine the risk of IBD in patients with AI compared with controls without AI., Results: The incidence rate of IBD during the 10-year follow-up period was 2.69 per 1 000 person-years and 0.49 per 1 000 person-years in the AI and non-AI cohorts, respectively. After adjustment for age, sex, and comorbidity, the AI cohort exhibited a 3.17-fold increased risk of IBD compared with the non-AI cohort (hazard ratio [HR] = 3.17, 95% confidence interval [CI] = 2.19-4.58). Compared with the non-AI cohort, the HRs of CD and UC were 4.40 and 2.33 for the AI cohort, respectively. After stratification for the severity of AI according to the duration of hospital stay, the adjusted HRs exhibited a significant correlation with the severity; the HRs of IBD were 1.76, 6.83, and 19.9 for patients with mild, moderate, and severe AI, respectively (p for the trend < .0001)., Conclusion: The risk of IBD was higher in patients with AI and increased with the length of hospital stay., Competing Interests: All authors declare that they have no conflict of interest. All authors have declared that no competing interest exists.

Objectives: Study the gene and protein expression of NACHT-PYD-containing protein 3 (NALP3) inflammasome and extracellular regulated protein kinase (ERK), the intervention effects of sodium ferulate (SF) in human lung epithelial cells A549 under oxidative stress, and to investigate the possible mechanism., Methods: Human lung epithelial cells A549 cultured in vitro were divided into 6 groups, including control group,H₂O₂(200 umol/L) group, SF group (400 ug/mL), caspase-1 blockers (Z-VAD) group (Z-VAD 20 umol/L+H₂O₂200 umol/L), ERK blockers (PD98059) group (PD98059 50 umol/L+H₂O₂ 200 umol/L), and SF+H₂O₂ group (SF 400 ug/mL+H₂O₂ 200 umol/L). Fluorescent quantitative real-time PCR (qRT-PCR) was performed to detect the mRNA levels of caspase-1 and NALP3 , the expression of caspase-1, NALP3, phosphorylated ERK p-ERK, ERK protein were evaluated by Western blot. The level of interleukin-1 β (IL-1β) were detected by ELISA., Results: Compared with the control group,H₂O₂ not only increased the mRNA and protein expression levels of caspase-1 and NALP3 and the protein expression levels of p-ERK/ERK, but also enhanced the secretion of IL-1β in human lung epithelial cells A549 ( P <0.05),while SF group showed no statistic significance of those indicators above ( P >0.05). The Z-VAD group, the PD98059 group and the SF+H₂O₂ group resisted the effects of H₂O₂ on A549 cells by decreasing the mRNA and protein expressions of caspase-1 and NALP3,and the protein expression of p-ERK/ERK, as well as reducing the secretion of IL-1β( P <0.05),when compared with the H₂O₂ group., Conclusions: SF may reduce the expression of caspase-1, NALP3 and IL-1β by inhibiting ERK, so as to reduce the inflammation caused by oxidative stress.

To study the pollution characteristics of water-soluble ions in atmospheric particulate matter in Chengdu Plain, and identify the composition, distribution, time and spatial variation, achieve targeted control of heavy pollution and haze days, 1476 samples were collected at five monitoring sites during August 2013-July 2014, in which eight kinds of inorganic water-soluble ions (SO 4 2- , NO 3 - , NH 4 + , K + , Na + , Ca 2+ , Mg 2+ , Cl - ) were determined by ion chromatography. The results showed that the total mass concentrations of 8 ions in PM 2.5-10 and PM 2.5 were 11.35 and 36.93μg·m -3 , accounting for 37.8% and 46.6% respectively, and SNA (SO 4 2- , NO 3 - and NH 4 + ) in PM 2.5-10 and PM 2.5 contributed 81.1% and 89.9% to the total ions, respectively. The concentration of water-soluble ions was highest in winter and lowest in summer. ρ (SO 4 2- )/ ρ (PM 2.5 ) was highest in summer and autumn, while ρ (NO 3 - )/ ρ (PM 2.5 ) was highest in winter and lowest in summer. SNA, Cl - , K + mostly distributed in PM 2.5 , Ca 2+ and Mg 2+ in PM 2.5-10 . PM 2.5 was generally neutral, the water-soluble ions in which existed as (NH 4 ) 2 SO 4 , NH 4 NO 3 , KNO 3 , NaCl, KCl and so on. ρ (NO 3 - )/ ρ (SO 4 2- ) revealed that the main source of PM 2.5 was given priority to fixed sources. Sulfur oxidation ratio (SOR) and nitrogen oxidation ratio (NOR) were 0.31 and 0.13, respectively, which had opposite changing trend with a highest SOR in summer and NOR in winter. PM 2.5 had the characteristics of regional pollution complex, and SNA was the dominant factor causing the increase of ρ (PM 2.5 ).

Nasopharyngeal carcinoma is one of the most common of head and neck malignant tumors in southern region of China. Till date radiotherapy is considered as the first choice of treatment this disease.Although the rate of occurrence of pseudoaneurysms of the internal carotid artery in post radiation treatment of nasopharyngeal carcinoma is low, it is also a hot topic in department of otolaryngology and doctors because of its dangerous and lifethreatening emergencies.In order to improve the level of diagnosis and treatment of the disease, diagnosis, risk, treatment, prognosis and prevention are current summarized in this report., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: To investigate the positive effects of mouse nerve growth factor(mNGF) on cognitive impairment in whole brain irradiation rats., Methods: Fifty-five male Sprague-Dawley rats were randomly divided into normal control group, mNGF treated group, saline treated group.mNGF treated group and saline treated group were cranial irradiated at a single dose of 12 Gy by X-ray.30 days after radiation each group were treated with correspondent drugs.60 days after radiation, Morris water maze experiment, EB leakage of the brain, and expressions of neuN, vWF, ZO-1 in hippocampus by immunofluorescence, and expressions of neuN, vWF, ZO-1, VEGF and GFAP in hippocampus by Western blot were tested and analyzed., Results: The escape latencies: normal control group< mNGF treated group< saline treated group; the numbers of crossing hidden platform in these 3 groups were 3.00± 1.08, 1.50± 1.08, 0.38± 0.48 times (P<0.01). EB leakage of these 3 groups were 0.14±0.14, 0.66±0.20 and 1.36±0.27 μg/g (P<0.05). In immunofluorescence, expressions of neuN, vWF and ZO-1: normal control group> mNGF treated group> saline treated group.In Western blot, expressions of neuN, vWF and ZO-1: normal control group> mNGF treated group> saline treated group, yet the expressions of VEGF and GFAP: normal control group< mNGF treated group< saline treated group., Conclusion: mNGF ameliorates cognitive impairment after whole brain irradiation.

Background: Colorectal cancer (CRC) is one of the most common cancers in the world. MicroRNAs play important roles in the progression of CRC. This study aimed to investigate the role of miR-206 and its novel mechanism in the invasion and metastasis of CRC., Methodology: Real-time RT-PCR or Western blotting was used to detect the expressions of miR-206, FMNL2 and c-MET in CRC cell lines and tissues. Luciferase reporter assays were conducted to detect the associations between miR-206 and 3'UTRs of FMNL2 and c-MET. A series of loss-of-function and gain-of-function assays were performed to evaluate the effect of miR-206 on the proliferation, invasion and metastasis of CRC cells., Results: miR-206 was significantly down-regulated in CRC tissues and correlated closely with differentiation, lymphatic metastasis and serosal invasion. miR-206 suppressed CRC cell proliferation by arresting CRC cells in the G1/G0 phase and accelerating apoptosis. miR-206 also inhibited cell invasion and lung metastasis in CRC cells. Mechanically, FMNL2 and c-MET were identified as direct targets of miR-206. And FMNL2 rescued the suppression of miR-206 in the proliferation and invasion of CRC cells., Conclusions: This study revealed functional and mechanistic links between miR-206 and oncogene FMNL2 and c-MET in the progression of CRC. miR-206 functioned as a tumor suppressor in the progression of CRC by targeting FMNL2 and c-MET. Restoration of miR-206 expression may represent a promising therapeutic approach for targeting malignant CRC.

Key Message: Six foxtail millet ASR genes were regulated by various stress-related signals. Overexpression of ASR1 increased drought and oxidative tolerance by controlling ROS homeostasis and regulating oxidation-related genes in tobacco plants. Abscisic acid stress ripening (ASR) proteins with ABA/WDS domains constituted a class of plant-specific transcription factors, playing important roles in plant development, growth and abiotic stress responses. However, only a few ASRs genes have been characterized in crop plants and none was reported so far in foxtail millet (Setaria italic), an important drought-tolerant crop and model bioenergy grain crop. In the present study, we identified six foxtail millet ASR genes. Gene structure, protein alignments and phylogenetic relationships were analyzed. Transcript expression patterns of ASR genes revealed that ASRs might play important roles in stress-related signaling and abiotic stress responses in diverse tissues in foxtail millet. Subcellular localization assays showed that SiASR1 localized in the nucleus. Overexpression of SiASR1 in tobacco remarkably increased tolerance to drought and oxidative stresses, as determined through developmental and physiological analyses of germination rate, root growth, survival rate, relative water content, ion leakage, chlorophyll content and antioxidant enzyme activities. Furthermore, expression of SiASR1 modulated the transcript levels of oxidation-related genes, including NtSOD, NtAPX, NtCAT, NtRbohA and NtRbohB, under drought and oxidative stress conditions. These results provide a foundation for evolutionary and functional characterization of the ASR gene family in foxtail millet.

Alcohol use disorder (AUD) is considered a possible risk factor for irritable bowel syndrome (IBS); however, previous studies investigating the association between AUD and IBS have yielded inconsistent results. The study investigated whether AUD increases the risk of IBS by using a population-based database in Taiwan.This retrospective matched-cohort study included the health insurance claims data of 56,355 AUD inpatients and 225,420 randomly selected controls by frequency-matched for sex, age, and index year. Cox proportional hazards regression analysis was performed to measure the risk of IBS among AUD patients compared with non-AUD patients.During the follow-up period, the incidence rate ratio (IRR) of IBS had 12.3-fold (95% CI: 11.9-12.7) in the AUD patients than non-AUD patients and the adjusted hazard ratio (aHR) for IBS in the AUD patients was 5.51 (95% CI: 4.36-6.96). For several comorbidities, the risk of IBS was significantly higher in the AUD patients than in non-AUD patients, with aHRs of 2.14 (95% confidence interval [CI]: 1.19-3.84), 2.05 (95% CI: 1.06-3.96), and 2.91 (95% CI: 1.26-6.72) for sleep disorders, acute pancreatitis, and hepatitis B, respectively. When we stratified the severity of AUD according to the length of hospital stay, the aHRs exhibited a significant correlation (P < 0.001) with severity, yielding aHRs of 3.24 (95% CI: 2.49-4.22), 11.9 (95% CI: 8.96-15.9), and 26.1 (95% CI: 19.4-35.2) for mild, moderate, and severe AUD, respectively.The risk of IBS was higher among AUD patients, and increased with the length of hospital stay.

Bavachinin (BCI), a major bioactive compound in Chinese herbal Psoralea corylifolia, possesses a wide range of biological activities. In this study, the glucuronidation pathway of BCI was characterized for the first time, by using pooled human liver microsomes (HLM), pooled human intestine microsomes (HIM) and recombinant human UDP-glucosyltransferases (UGTs). One mono-glucuronide was detected in HLM in the presence of uridine-diphosphate glucuronic acid (UDPGA), and it was biosynthesized and well-characterized as BCI-4'-O-glucuronide (BCIG). Reaction phenotyping assay showed that UGT1A1, UGT1A3 and UGT1A8 were involved in BCI-4'-O-glucuronidation, while UGT1A1 and UGT1A8 displayed the higher catalytic ability among all tested UGT isoforms. Kinetic analysis demonstrated that BCI-4'-O-glucuronidation in both HLM and UGT1A1 followed sigmoidal kinetic behaviors and displayed much close Km values (12.4 μM in HLM & 9.7 μM in UGT1A1). Both chemical inhibition assays and correlation analysis demonstrated that UGT1A1 displayed a predominant role in BCI-4'-O-glucuronidation in HLM. Both HIM and UGT1A8 exhibited substrate inhibition at high concentrations, and Km values of HIM and UGT1A8 were 3.6 and 2.3 μM, respectively. Similar catalytic efficiencies were observed for HIM (199.3 μL/min/mg) and UGT1A8 (216.2 μL/min/mg). These findings suggested that UGT1A1 and UGT1A8 were the primary isoforms involved in BCI-4'-O-glucuronidation in HLM, and HIM, respectively., (Copyright © 2015 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.)

Conclusion: Electromyography of the tensor veli palatine (TVP) was abnormal and showed mainly myogenic impairment in patients with nasopharyngeal carcinoma (NPC) with secretory otitis media (SOM) after radiotherapy. The diseased ears showed impairment in opening functions of the eustachian tubes (ETs)., Objectives: To characterize electrophysiology of the TVP muscle using electromyography (EMG) in patients with SOM after radiotherapy of NPC., Methods: Twenty healthy volunteers and 20 patients with NPC and SOM after radiotherapy were chosen for assessment of EMG of the TVP during swallowing., Results: The measurements of average duration and amplitude of action potential, swallowing contraction duration, and peak voltage in NPC patients with both SOM (n = 25) and healthy ears (n = 6) were significantly lower than those of ears (n = 38) in healthy controls (p < 0.01). In patients with NPC, the average action potential duration and swallowing contraction duration in ears with SOM were lower than those of subjects with healthy ears (p < 0.05), whereas no significant difference was found in average amplitude of action potential and peak voltage between them.

Objective: To study the effects of sodium ferulate on inflammation in human lung epithelial cells (A549) under oxidative stress and itsinfluence onthe expression of inflammasome NACHT-PYD-containing protein 3 (NALP3) and nuclear factor kappa B (NF-κB)., Methods: Human lung epithelial cells A549 cultured in vitro were divided into 4 groups, including control group, H2O2 (100µmol/L) stress group, NF-κB blockers group (PDTC 100 µmol/L+ H2O2 100 µmol/L), sodium ferulate (SF) intervention group (SF 400µg/mL+ H2O2 10µmol/L). The expression of NALP3,IκBα protein were evaluated by Western blot, while mRNA levels of NALP3, NF-κB (P65) were measured by qRT-PCR. The level of interleukin-1beta (ILβ1) were detected by ELISA., Results: H2O2 not only increased the mRNA and protein expression levels of NALP3, but also enhanced the secretion of ILβ1p in human lung epithelial cells A549 (P<0. 05) when compared with control group. NF-κB blockers PDTC and sodium ferulateresisted the effects of H2O2 on A549 cells, that decreased the mRNA and protein expression of NALP3 and the mRNA expression of NF-κB (P65), reduced the degeneration of IκBα and the secretion of IL-1β (P<0. 05) when compared to H2O2 stress group., Conclusion: SF may reduce the expression of NALP3 and IL-1β by inhibiting NF-κB, so as to reduce the inflammation caused by oxidative stress.

Objective: To discuss the role of Litchi chinensis seed saponins on hyperplasia of mammary glands(HMG) and the influence of estrogen signaling pathways in rats., Methods: In addition to eight non-pregnant female SD rats in normal control group, the other 32 pathologic models of HMG rat model were randomly divided into other four groups: model control group, low and high dose groups, which were given experimental drug of Litchi chinensis seed saponins (LSE) 0. 1 g/kg and 0. 2 g/kg, and the positive control group with experimental drug of tamoxifen 4 mg/kg. Then all model rats were orally administrated for four weeks. The diameter and height of nipple were measured, and the content changes of estradiol(E2) and progestrogen(P) in serum were detected with ELISA method. The HMG were detected by the morphology examination. The expression of estrogen receptor(ER) and progesterone receptor(PR) in the mammary glands were investigated by immunohistochemical staining., Results: According to LSE in the low and high dose groups, it was discovered that the nipple diameter and height of HMG rats, the expression of ER and PR in HMG and the content of serum E2 were reduced, the content of serum P were improved, and the hyperplasia of mammary glands was inhibited., Conclusion: LSE can obviously inhibit the rat hyperplasia of mammary gland, and its possible mechanism is related to adjusting the transduction pathway of estrogen signal to lower estrogen levels.

Drought-induced (Di19) proteins played important roles in plant growth, development, and abiotic stress responses. In the present study, a total of seven Di19 genes were identified in soybean. Each soybean Di19 gene showed specific responses to salt, drought, oxidative, and ABA stresses based on expression profiles. With a relatively higher transcript level among Di19 members under four stress treatments, GmDi19-5 was selected for detailed analysis. Inhibitor assays revealed that ABA inhibitor (Fluridone) or H2O2 inhibitor (DMTU) was involved in the drought- or salt-induced transcription of GmDi19-5. The GUS activity driven by the GmDi19-5 promoter was induced by salt, PEG, ABA, and MV treatments and tended to be accumulated in the vascular bundles and young leaves. A subcellular localization assay showed that GmDi19-5 protein localized in the nucleus. Further investigation showed that GmDi19-5 protein was involved in the interaction with GmLEA3.1. Overexpression of GmDi19-5 increased sensitivity of transgenic Arabidopsis plants to salt, drought, oxidative, and ABA stresses and regulated expression of several ABA/stress-associated genes. This present investigation showed that GmDi19-5 functioned as a negative factor under abiotic stresses and was involved in ABA and SOS signaling pathway by altering transcription of stress-associated genes.

Icaritin, a prenylflavonoid derivative from Epimedium Genus, has been shown to exhibit many pharmacological and biological activities. However, the function and the underlying mechanisms of icaritin in human non-small cell lung cancer have not been fully elucidated. The purpose of this study was to investigate the anticancer effects of icaritin on A549 cells and explore the underlying molecular mechanism. The cell viability after icaritin treatment was tested by MTT assay. The cell cycle distribution, apoptosis and reactive oxygen species (ROS) levels were analyzed by flow cytometry. The mRNA and protein expression levels of the genes involved in proliferation and apoptosis were respectively detected by RT-PCR and Western blotting. The results demonstrated that icaritin induced cell cycle arrest at S phase, and down-regulated the expression levels of S regulatory proteins such as Cyclin A and CDK2. Icaritin also induced cell apoptosis characterized by positive Hoechst 33258 staining, accumulation of the Annexin V-positive cells, increased ROS level and alteration in Bcl-2 family proteins expression. Moreover, icaritin induced sustained phosphorylation of ERK and p38 MAPK. These findings suggested that icaritin might be a new potent inhibitor by inducing S phase arrest and apoptosis in human lung carcinoma A549 cells.

Objective: To investigate the expressions of plasminogen activator inhibitor-1 (PAI-1), activated protein C (APC) and the histology structures of the rat lung tissues in the different hypoxia time; and to investigate the effects of breviscapine to the above changes., Methods: Eighty SD rats were randomly divided into A (control), B (hypoxia), C (hypoxia + low-dose breviscapine) and D (hypoxia + high-dose breviscopine) groups with 20 rats in each group. Each hypoxia group placed daily pressure (101 kpa, 10% O2) environment for 8 h, low-dose and high-dose breviscapine groups were given of 10 mg/kg, 40 mg/kg breviscapine by intraperitoneal injection. On the 3rd, 7th, 14th and 21st d, 5 rats were randomly taken from each group and were killed for examination. The hematoxylin and eosin stain (HE stain) was performed for observation on pathological changes in the rat lung tissues. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was performed for detection of the mRNA levels of transforming growth factor (TGF-beta1) and Plasminogen activator inhibitor-1 (PAI-1). Western blot analysis was applied for detection of the expression of PAI-1. Besides, APC in the bronchoalveolar lavage fluid (BALF) was determined by ELISA., Results: (1) The HE stain demonstrated that compared with A group, the degree of thickening of alveolar septal the mRNA expressions of TGF-beta1 and PA-1, and the protein expressions of PAI-1 in B group were increased (P < 0.05), and the expression of APC in the BALF was decreased (P < 0.05). And with prolonged hypoxia, the more significant of these changes were observed. Positive correlation was found between the mRNA levels of PAI-1 and TGF-beta1 (r = 0.936, P < 0.05). (2) Compared with B group, the increased thicknesses of alveolar septal in C and D groups were lightened, the mRNA expressions of TGF-beta1 and PAI-1, and the protein expression of PAI-1 were decreased (P < 0.05), and the expressions of APC in the BALF was increased (P < 0.05). With increasing dose, the expression levels of each factor gradually reduced or increased., Conclusion: Hypoxia may cause coagulant function abnormality to increase clotting activity and reduce fibrinolytic activity and the anticoagulant activity, inducing alveolar septal thickening, and the mechanism of above changes may related to the TGF-beta1 signaling pathways. Breviscapine could improve hypoxia-induced hypercoagulable state that alleviate alveolar septal thickening.

Fucoidan is one of the main bioactive components of polysaccharides. The current study was focused on the anti-tumor effects of fucoidan on human heptoma cell line HepG2 and the possible mechanisms. Fucoidan treatment resulted in cell cycle arrest and apoptosis of HepG2 cells in a dose-dependent manner detected by MTT assay, flow cytometry and fluorescent microscopy. The results of flow cytometric analysis revealed that fucoidan induced G2/M arrest in the cell cycle progression. Hoechst 33258 and Annexin V/PI staining results showed that the apoptotic cell number was increased, which was associated with a dose-dependent up-regulation of Bax and down-regulation of Bcl-2 and p-Stat3. In parallel, the up-regulation of p53 and the increase in reactive oxygen species were also observed, which may play important roles in the inhibition of HepG2 growth by fucoidan. In the meantime, Cyclin B1 and CDK1 were down-regulated by fucoidan treatment. Down-regulation of p-Stat3 by fucoidan resulted in apoptosis and an increase in ROS in response to fucoidan exposure. We therefore concluded that fucoidan induces apoptosis through the down-regulation of p-Stat3. These results suggest that fucoidan may be used as a novel anti-cancer agent for hepatocarcinoma.

The relationship between sexual reproduction and clonal growth in clonal plants often shows up at the ramet level. However, only a few studies focus on the relationship at the genet level, which could finally account for evolution. The sexual reproduction and clonal growth of Ligularia virgaurea, a perennial herb widely distributed in the alpine grasslands of the Qinghai-Tibetan Plateau of China, were studied under different competition intensities and light conditions at the genet level through a potted experiment. The results showed that: (1) sexual reproduction did not depend on density or light, and increasing clonal growth with decreasing density and increasing light intensity indicated that intraspecific competition and light intensity may affect the clonal life history of L. virgaurea; (2) both sexual reproduction and clonal growth show a positive linear relationship with genet size under different densities and light conditions; (3) a threshold size is required for sexual reproduction and no evidence of a threshold size for clonal growth under different densities and light conditions; (4) light level affected the allocation of total biomass to clonal and sexual structures, with less allocation to clonal structures and more allocation to sexual structures in full sunlight than in shade; (5) light determined the onset of sexual reproduction, and the genets in the shade required a smaller threshold size for sexual reproduction to occur than the plants in full sunlight; and (6) no evidence was found of trade-offs between clonal growth and sexual reproduction under different densities and light conditions at the genet level, and the positive correlation between two reproductive modes indicated that these are two integrated processes. Clonal growth in this species may be viewed as a growth strategy that tends to maximize genet fitness.

Overactivated microglia contribute to a variety of pathological conditions in the central nervous system. The major goal of the present study is to evaluate the potential suppressing effects of a new type of Ginko biloba extract, GBE50, on activated microglia which causes proinflammatory responses and to explore the underlying molecular mechanisms. Murine BV2 microglia cells, with or without pretreatmentof GBE50 at various concentrations, were activated by incubation with lipopolysaccharide (LPS). A series of biochemical and microscopic assays were performed to measure cell viability, cell morphology, release of tumor necrosis factor- α (TNF- α ) and interleukin-1 β (IL-1 β ), and signal transduction via the p38 MAPK and nuclear factor-kappa B (NF- κ B) p65 pathways. We found that GBE50 pretreatment suppressed LPS-induced morphological changes in BV2 cells. Moreover, GBE50 treatment significantly reduced the release of proinflammatory cytokines, TNF- α and IL-1 β , and inhibited the associated signal transduction through the p38 MAPK and NF- κ B p65 pathways. These results demonstrated the anti-inflammatory effect of GBE50 on LPS-activated BV2 microglia cells, and indicated that GBE50 reduced the LPS-induced proinflammatory TNF- α and IL-1 β release by inhibiting signal transduction through the NF- κ B p65 and p38 MAPK pathways. Our findings reveal, at least in part, the molecular basis underlying the anti-inflammatory effects of GBE50.