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We present a computational study of isochoric heating in multi-layered (ML) targets at ultra-high intensity laser irradiation ( ∼ 10 20 W c m − 2 ). Previous studies have shown enhanced ion heating at interfaces, but at the cost of large temperature gradients. Here, we study ML targets to spread this enhanced interface heating to the entirety of the target and find heating parameters at which the temperature distribution is more homogeneous than at a single interface while still exceeding the mean temperature of a non-layered target. Further, we identify a limiting process of pressure oscillations that causes the layers to alternate between expanding and being compressed and leads to lower ion temperatures. Based on that, we derive an analytical model estimating the oscillation period to find target conditions that optimize heating and temperature homogeneity. This model can also be used to infer the electron energy from the oscillation period which can be measured e.g. by XFEL probing.

D-Allulose 3-epimerase (DAE) is a vital biocatalyst for the industrial synthesis of D-allulose, an ultra-low calorie rare sugar. However, limited thermostability of DAEs hinders their use at high-temperature production. In this research, hyperthermophilic TI-DAE (Tm = 98.4 ± 0.7 ℃) from Thermotoga sp. was identified via in silico screening. A comparative study of the structure and function of site-directed saturation mutagenesis mutants pinpointed the residue I100 as pivotal in maintaining the high-temperature activity and thermostability of TI-DAE. Employing TI-DAE as a biocatalyst, D-allulose was produced from D-fructose with a conversion rate of 32.5%. Moreover, TI-DAE demonstrated excellent catalytic synergy with glucose isomerase CAGI, enabling the one-step conversion of D-glucose to D-allulose with a conversion rate of 21.6%. This study offers a promising resource for the enzyme engineering of DAEs and a high-performance biocatalyst for industrial D-allulose production., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Chronic periodontitis, an inflammation-related disorder affecting global populations, has been revealed to be linked to diverse cancers. Numerous epidemiological studies have not shown a link between chronic periodontitis and blood cancers in Taiwan., Methods: This study included 601,628 patients, diagnosed with newly chronic periodontitis by the ICD-9-CM classification, who were enrolled from 2001 to 2021 in the National Health Insurance Research Database (NHIRD) in Taiwan. In this study, we employed comprehensive statistical analyses to investigate the association between chronic periodontitis and hematologic cancers. Initially, we calculated incidence density and used a Poisson regression to analyze relative risk. Subsequently, we compared the cumulative incidence of hematological cancer in both chronic and non-chronic periodontitis groups using the Kaplan-Meier method., Results: The results revealed a significantly lower cumulative incidence of hematologic cancer in individuals with non-chronic periodontitis over a 12-year follow-up period. To further explore the risk factors, a Cox proportional hazard regression analysis was conducted. Being male (adjusted hazard ratio [aHR] = 1.21, 95% CI: 1.04 to 1.42; p = 0.014) and having hypertension (aHR = 1.34, 95% CI: 1.06 to 1.69; p = 0.015) were demonstrated to be associated with an increased risk of hematologic cancers, respectively. In addition, in a subtype multivariate analysis for categorizing hematologic cancers into lymphoma and leukemia, the aHR for leukemia was 1.48 (95% CI: 1.13 to 1.93; p = 0.004) and aHR for lymphoma was 1.15 (95% CI: 0.96 to 1.37; p = 0.140)., Conclusions: This study found that being male and having hypertension were the significant risk factors for hematological malignancies. Moreover, the association between chronic periodontitis and specific subtypes of hematologic cancers was confirmed., Competing Interests: The authors declare no conflicts of interest.

Background: In the advent of increasing antibiotic resistance, several studies sought to determine antibiotic prescription trends; however, no pattern has been firmly identified particularly for the burned population. We performed a query of burned patients in a large established database to understand differences in antibiotic use related to patient-specific factors., Methods: Burned patients with systemic antibiotics given within 7 days of injury were identified on the TriNetX database. The patient population was stratified by age, 1-year time intervals of antibiotic prescription from 2004 to 2019, time of antibiotic prescription in 1-day intervals after injury, and % TBSA burned in 10% intervals ranging from < 10% to > 90%. Data were analyzed using χ 2 with p < 0.05 considered significant. Pearson coefficients (r 2 ) values were used to correlate differences in antibiotic prescription between age groups and to changes over time., Results: Stratification by age revealed higher use of antibiotics in older burned patients compared to younger patients. Surprisingly, 87.6% of burn patients of those who received antibiotic therapy was on the day of injury. Penicillins and beta-lactam antimicrobials were used most often at a frequency of 64%. No statistically significant differences in rates of antibiotic therapy were observed in burned patients when stratified by %TBSA burned., Conclusions: The study elucidates current patterns of antibiotic use in burn care in the United States, allowing for improved understanding of both past and present patterns of antibiotic prescription., (Copyright © 2023 Elsevier Ltd and ISBI. All rights reserved.)

The application of (R)-ω-transaminases as biocatalysts for chiral amine synthesis has been hampered by inadequate stereoselectivity and narrow substrate spectrum. Herein, an effective evolution strategy for (R)-ω-transaminase designing for the asymmetric synthesis of sitagliptin intermediate is presented. Since natural transaminases lack activity toward bulky prositagliptin ketone, transaminase scaffolds with catalytic machinery and activity toward the truncated prositagliptin ketone were firstly screened based on substrate walking principle. A transaminase chimera was established synchronously conferring catalytic activity and (R)-selectivity toward prositagliptin ketone through motif swapping, followed by stepwise evolution. The process resulted in a "best" engineered variant MwTA M8 , which exhibited 79.2-fold higher activity than the chimeric scaffold MwTA Mc . Structural analysis revealed that the heightened activity is mainly due to the enlarged and adaptive substrate pocket and tunnel. The novel (R)-transaminase exhibited unsatisfied industrial operation stability, which is expected to further modify the protein to enhance its tolerance to temperature, pH, and organic solvents to meet sustainable industrial demands. This study underscores a useful evolution strategy of engineering biocatalysts to confer new properties and functions on enzymes for synthesizing high-value drug intermediates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this work., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Cajanus cajan (L.) Millsp., also known as pigeon pea, has roots that have exhibited much pharmacological potential. The present study was conducted to assess the safe dose of the ethanolic extract of C. cajan roots (EECR95) and to analyze the main soy isoflavones contents. In vitro, we investigated the mutagenicity and cytotoxic effect of EECR95 on Salmonella typhimurium -TA98 and TA100 (by Ames tests) and RAW 264.7, L-929, and HGF-1 cell lines (by MTT tests) for 24 h of incubation. We found no mutagenic or cytotoxic effects of EECR95. After administration of 0.2 or 1.0 g/kg bw of EECR95 to both male and female Wistar rats for 90 days, there were no significant adverse effects on the behaviors (body weight, water intake, and food intake), organ/tissue weights, or immunohistochemical staining, and the urine and hematological examinations of the rats were within normal ranges. EECR95 potentially decreases renal function markers in serum (serum uric acid, BUN, CRE, and GLU) or liver function markers (cholesterol, triglyceride, and glutamic-pyruvate-transaminase (GPT)). We also found that EECR95 contained five soy isoflavones (genistein, biochanin A, daidzein, genistin, and cajanol), which may be related to its hepatorenal protection. Based on the high dose (1.0 g/kg bw) of EECR95, a safe daily intake of EECR95 for human adults is estimated to be 972 mg/60 kg person/day.

Promotion of new blood vessel formation is a new strategy for treating ischemic stroke. Non-coding miRNAs have been recently considered potential therapeutic targets for ischemic stroke. miR-181b has been shown to promote angiogenesis in hypoxia and traumatic brain injury model, while its effect on ischemic stroke remains elusive. In this study, we found that overexpression of miR-181b in brain microvascular endothelial cells subjected to oxygen-glucose deprivation in vitro restored cell proliferation and enhanced angiogenesis. In rat models of focal cerebral ischemia, overexpression of miR-181b reduced infarction volume, promoted angiogenesis in ischemic penumbra, and improved neurological function. We further investigated the molecular mechanism by which miR-181b participates in angiogenesis after ischemic stroke and found that miR-181b directly bound to the 3'-UTR of phosphatase and tensin homolog (PTEN) mRNA to induce PTEN downregulation, leading to activation of the protein kinase B (Akt) pathway, upregulated expression of vascular endothelial growth factors, down-regulated expression of endostatin, and promoted angiogenesis. Taken together, these results indicate that exogenous miR-181b exhibits neuroprotective effects on ischemic stroke through activating the PTEN/Akt signal pathway and promoting angiogenesis., Competing Interests: None

Erythritol is a novelty 4-carbon sugar polyol and has great potential to be used as the precursor of some platform chemicals. The increasing cost of glucose poses researchers shifting insights to the cheaper biodiesel raw materials. Herein, we engineered a non-degradation, non-byproducts Yarrowia lipolytica for the erythritol production with high-titer from glycerol. Initially, the degradation and competition modules were blocked by URA3 counter-selection marker. Subsequently, a shortened biosynthetic pathway was explored to elevate its synthetic flux by multi-modules combination expression of functional genes. Furthermore, a screened glycerol transporter ScFPS1 was integrated into ERY6 genome to promote the glycerol uptake. The constructed strain ERY8 produced 176.66 g/L erythritol in the 5-L bioreactor with a yield and productivity of 0.631 g/g and 1.23 g/L/h, respectively, which achieved the highest fermentation production efficiency till date. This study proposed a novel multi-modules combination strategy for effectively engineering Y. lipolytica to produce erythritol using glycerol., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: This investigation aimed to evaluate the impact of continuous pericapsular nerve group (PENG) block and continuous fascia iliac compartment block (FICB) on postoperative pain following total hip arthroplasty (THA)., Methods: This prospective, randomized, and controlled trial recruited a cohort of fifty-seven patients with unilateral femoral neck fractures from Xi'an Aerospace General Hospital in northwest China between July 2020 and November 2021. These patients were randomly assigned to two groups: the continuous PENG block group (PENG group, n = 29) and the continuous FICB group (FICB group, n = 28). Under ultrasound guidance, PENG block and FICB procedures were performed prior to spinal anesthesia, utilizing 20 ml of 0.25% ropivacaine for PENG block and 30 ml of 0.25% ropivacaine for FICB. Subsequently, a catheter was inserted. All study participants received a standardized postoperative multimodal analgesic regimen, including intravenous administration of 30 mg Ketorolac tromethamine every eight hours and patient-controlled neural analgesia (PCNA) after surgery. Numerical rating scale (NRS) scores at rest and during exercise were recorded at various time points: prior to block (T0), 30 min post-blockade (T1), and 6 h (T2), 12 h (T3), 24 h (T4), and 48 h (T5) postoperatively. Additional data collected encompassed postoperative quadriceps muscle strength, the time of initial ambulation after surgery, the number of effective PCNA activations, rescue analgesia requirements, and occurrences of adverse events (such as nausea and vomiting, hematoma, infection, catheter detachment, or displacement) within 48 h following surgery., Results: In the PENG group, the resting NRS pain scores exhibited lower values at T1, T4, and T5 than those at T0. Furthermore, exercise NRS pain scores at T1-T5 were lower in the PENG group than in the FICB group. Similarly, during the same postoperative period, the PENG group demonstrated enhanced quadriceps strength on the affected side compared to the FICB group. Additionally, the PENG group displayed earlier postoperative ambulation and reduced occurrences of effective PCNA activations and rescue analgesia requirements compared to the FICB group., Conclusion: Continuous PENG block exhibited superior analgesic efficacy after THA compared to continuous FICB, promoting recovery of quadriceps strength on the affected side and facilitating early postoperative ambulation., Trial Registration: This clinical trial was registered in the China Clinical Trials Center ( http://www.chictr.org.cn ) on 20/07/2020, with the registration number ChiCTR2000034821., (© 2023. The Author(s).)

O -Acetyl-L-homoserine (OAH) is a potentially important platform metabolic intermediate for the production of homoserine lactone, methionine, 1,4-butanediol and 1,3-propanediol which have giant market value. Currently, multiple strategies have been adopted to explore sustainable production of OAH. However, the production of OAH by consuming cheap bio-based feedstocks with Escherichia coli as the chassis is still in its infancy. Construction of high yield OAH-producing strains is of great significance in industry. In this study, we introduced an exogenous metA from Bacillus cereus ( metXbc ) and engineered an OAH-producing strain by combinatorial metabolic engineering. Initially, exogenous metXs/metA were screened and used to reconstruct an initial biosynthesis pathway of OAH in E. coli . Subsequently, the disruption of degradation and competitive pathways combined with optimal expression of metXbc were carried out, accumulating 5.47 g/L OAH. Meanwhile, the homoserine pool was enriched by overexpressing metL with producing 7.42 g/L OAH. Lastly, the carbon flux of central carbon metabolism was redistributed to balance the metabolic flux of homoserine and acetyl coenzyme A (acetyl-CoA) in OAH biosynthesis with accumulating 8.29 g/L OAH. The engineered strain produced 24.33 g/L OAH with a yield of 0.23 g/g glucose in fed-batch fermentation. By these strategies, the key nodes for OAH synthesis were clarified and corresponding strategies were proposed. This study would lay a foundation for OAH bioproduction., Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03564-5., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest in the publication., (© King Abdulaziz City for Science and Technology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

This study aimed to directly compare the contents and the clinical efficacy of the two autologous blood-derived products, platelet-rich plasma (PRP) and autologous conditioned serum (ACS) for osteoarthritis (OA) treatment. The contents of standard-prepared PRP and ACS prepared at 37 °C for 1 h, 3 h, 6 h, and 24 h from healthy volunteers were compared. The clinical efficacy of pain relief in patients with Stage III knee OA was evaluated by a patient-reported visual analog scale (VAS) pain rating. PDGF-BB levels in ACS 1 h were significantly higher than those in PRP, and the levels in ACS preparations remained stable. IGF-1 level of ACS 24 h showed a significant increase compared to those of other ACS preparations and PRP. ACS 3 h showed a turning of IL-1Ra level and revealed a time-dependent increase up to 24 h. ACS 6 h showed a turning increase in TNF-α levels. ACS 3 h was chosen for clinical comparison with PRP. The reduction in pain VAS in the ACS group was significantly more compared to those of the PRP group ( p = 0.028). However, PRP showed significant earlier improvement ( p < 0.001). Conclusion: ACS contained higher levels of PDGF-BB and IL-1Ra and provided better improvement in pain relief compared to PRP.

Gibberellic acid (GA 3 ) is one of natural phytohormones, widely used in agriculture and downstream fields. Qualified for the nature productivity, Fusarium fujikuroi was currently employed for the industrial biotransformation from agriculture residues into GA 3 . Herein, Multivariate modular metabolic engineering (MMME) was assigned to reconstitute the metabolic balance in F. fujikuroi for enhancing GA 3 production. Three modules including precursor pool, cluster-specific channel and P450-mediated oxidation in GA 3 biosynthetic pathway were defined and optimized separately. The enhancement of both precursor pool and cluster-specific channel pushed metabolic flux transfer into the GA 3 -specific pathway. Moreover, both introduction of Vitreoscilla hemoglobin and reinforcement of NADPH-dependent cytochrome P450 reductase facilitated oxidation cofactor transfer and subsequently boosted mycelium growth and GA 3 biosynthesis. Integration of three modules in the engineered strain accumulated 2.89 g/L GA 3 in shake flask via submerged fermentation, presenting a promising modular metabolic engineering model for efficient microbial transformation in agro-industrial application., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To explore the feasibility of applying quantitative analysis of the facial skin color to evaluate the severity of motion sickness objectively and to seek objective indicators that can reflect the severity of motion sickness. Methods: Motion sickness was induced in 51 male adult subjects recruited at the Air Force Medical University by Coriolis acceleration stimulation, and facial skin colorimetric values were acquired using a portable spectrophotometer at five time points: before stimulation and at 0 min, 10 min, 20 min and 30 min after the end of stimulation. The Graybiel rating scales were applied to assess the severity of motion sickness in subjects at each time point after stimulation, and the correlation between the magnitude of change in each colorimetric value and the maximum Graybiel's score was analyzed. The ROC curves were used to compare the evaluation performance of colorimetric value indicators which could reflect the severity of motion sickness. Results: Each colorimetric value in the CIE-L * a * b * color system changed significantly after exposure to provocative motion stimuli, and the trend was consistent with the typical sign of pallor in motion sickness. The magnitudes of the increase in the colorimetric value CIE-L * , the decrease in CIE-a * , and the increase in CIE-b * were all significantly and positively correlated with the maximum of Graybiel's scores ( r =0.490 0, P =0.000 3; r =0.549 3, P <0.000 1; r =0.540 9, P <0.000 1). Comparing the performance of three colorimetric indicators to assess the severity of motion sickness, CIE-a * had an area under the ROC curve of 0.875 0, a sensitivity of 85.71%, and a specificity of 87.50%, which was better than CIE-L * and CIE-b * . Conclusions: The CIE-L * a * b * colorimeter values can be considered as objective indicators of the severity of motion sickness, among which the colorimetric indicator CIE-a * has the most diagnostic significance, and the method of quantitative analysis of the facial skin color can provide a new reference for the objective evaluation of the severity of motion sickness.

Objective: To establish an animal model of noise-induced hidden hearing loss (NIHHL), evaluate the dynamic changes in cochlear ribbon synapses and cochlear hair cell morphology, and observe the involvement of the SIRT1/PGC-1α signaling pathway in NIHHL. Methods: Male guinea pigs were randomly divided into three groups: control group, noise exposure group, and resveratrol treatment group. Each group was divided into five subgroups: the control group and 1 day, 1 week, 2 weeks, and 1 month post noise exposure groups. The experimental groups received noise stimulation at 105 dB SPL for 2 h. Hearing levels were examined by auditory brainstem response (ABR). Ribbon synapses were evaluated by inner ear basilar membrane preparation and immunofluorescence. The cochlear morphology was observed using scanning electron microscopy. Western blotting analysis and immunofluorescence was performed to assess the change of SIRT1/PGC-1α signaling. Levels of superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), ATP and SIRT1 activity were measured using commercial testing kits. Results: In the noise exposure group, hearing threshold exhibited a temporary threshold shift (TTS), and amplitude of ABR wave I decreased irreversibly. Ribbon synapse density decreased after noise exposure, and the stereocilia were chaotic and then returned to normal. The expression and activity of SIRT1 and PGC-1α protein was lower than that in the control group. SOD, CAT and ATP were also influenced by noise exposure and were lower than those in the control group, but MDA showed no statistical differences compared with the control group. After resveratrol treatment, SIRT1 expression and activity showed a significant increase after noise exposure, compared with the noise exposure group. In parallel, the PGC-1α and antioxidant proteins were also significantly altered after noise exposure, compared with the noise exposure group. The damage to the ribbon synapses and the stereocilia were attenuated by resveratrol as well. More importantly, the auditory function, especially ABR wave I amplitudes, was also promoted in the resveratrol treatment group. Conclusion: The SIRT1/PGC-1α signaling pathway and oxidative stress are involved in the pathogenesis of NIHHL and could be potential therapeutical targets in the future., 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 © 2022 Liu, Jiang, Li, Chen, Huang, Zhang, Ruan and Wang.)

Background/purpose: Pulp stones are discrete calcified masses appearing in the dental pulp of healthy, disease and unerupted teeth. They are presented freely within the pulp tissue or attached and embedded in any part of coronal and radicular dentin. Here, the purposes of this study were to identify the presence of pulp stones in periodontal patients using digital panoramic and periapical radiographies, and to determine the association with gender, age, tooth type and dental arch., Materials and Methods: This is a retrospective study on selected records of 465 dental samples obtained between January and December, 2020. Data were collected from patients diagnosed with generalized chronic periodontitis and accepted the full periodontal treatment covered by the Government's Periodontal Health Care Program. Their digital panoramic (DPR) examination and full mouth periapical radiographic (DPA) examination (including 12 periapical and 4 bitewing images) were performed at the Outpatient Clinics of the Department of Stomatology, Taichung Veterans General Hospital. Patients were segregated into various groups according to their age, gender and tooth locations. All radiographic images were examined by a dental radiologist and two dentists to identify the presence of pulp stone calcifications and their associated factors using the Sirona applications software. Records were analyzed using SPSS version 22.0 based on tests of Pearson Chi-square and McNemar correlation., Results: From 271 males and 194 females, a total of 465 DPR and 7440 DPA radiographs were studied. Pulp stone calcifications were identified in 270 (58.0%) subjects in DPR images and 348 (74.8%) subjects in DPA images (for 1 or more teeth per subject). We detected calcified opacities in 1031 teeth with DPR images and in 1326 teeth with DPA images from a total of 12,407 teeth. The incidence of pulp stones was similar across genders, but different in tooth locations and dental arch sextant. Moreover, pulp stones were detected more often on maxillary molars and subjects of old ages (>40 years). Digital panoramic and periapical radiography showed significant differences in the detection of pulp stone calcifications (P < 0.05), and detected better with digital periapical radiography examination., Conclusion: We found 58.0% (n = 645) of our patients with pulp stones using digital panoramic radiography, and 74.8% using digital periapical radiography. Regarding individual teeth, only 8.5% of pulp stones were observed in digital panoramic radiography and 10.6% in digital periapical radiography. Pulp stones were more often seen in maxillary molar teeth and old patients of ages >40 years old using periapical radiography examination especially in those patients with periodontally condition. As a two-dimensional imaging system, digital periapical radiography is recommended for a definitive and routine assessment in patients suspected of hard tissue abnormality and pulp calcification formation., Competing Interests: The authors gave no conflicts of interest relevant to this article., (© 2022 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Background: Citation analysis can provide a historical perspective in the advancement of research, evolution, and areas of research. Taiwan exhibits rigorous academic and scientific activities in dentistry; however, based on its empirical contribution in research, there is no report in the literature analyzing the top-cited articles published by authors affiliated with Taiwan institutes. The purpose of this study was to analyze the citation characteristics of the top 100 most-cited articles published in dentistry with author(s) affiliated with Taiwan institutes., Methods: The Scopus database was used to search the qualified articles with authors from Taiwan published in journals. The bibliometric parameters, including year of publication, study design, research fields, citation half-life, self-citation, institute of origin, and international collaboration were analyzed. Multivariable linear regression in generalized linear model was used to find associate factors related to trends of citation counts., Results: The top 100 most-cited articles were determined by analyzing 7667 articles from the Scopus database. The steadily increasing trends were observed in the number and percentage of articles of author(s) affiliated with Taiwan institutes to the world. The most common study design was the in vitro research (55 %). The majority citation half-life is 3-5 and 6-8 years, and self-citation counts were between one to five times (n = 26). The percentage of international collaboration of these most-cited articles was 32%, and the main collaboration country was the United States. By using multivariable linear regression in the generalized linear model, the associated factors, study design, and self-citation were significantly associated with the escalating trends of citation counts., Conclusion: This is the first study that provides valuable information in the dentistry regarding the academic activity, and empirical contribution of author(s) affiliated with Taiwan institutes in the world. The trends of citation characteristics were significantly correlated with study design and self-citation of these articles., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2021, the Chinese Medical Association.)

This study aimed to establish nomograms to preoperatively predict the possibility of testicular salvage (TS) in patients with testicular torsion. The clinical data of 204 patients with testicular torsion diagnosed at Xijing Hospital and Tangdu Hospital (Xi'an, China) between August 2008 and November 2019 were retrospectively analyzed. Univariate and multivariate logistic regression analyses were used to determine the independent predictors of TS. Based on multivariate regression coefficients, nomograms to predict possibility of TS were established. The predictive ability of the nomograms was internally validated by receiver operating characteristic (ROC) curves and calibration plots. The duration of symptoms ranged from 2 h to 1 month, with a median of 3.5 days. Thirty (14.7%) patients underwent surgical reduction and contralateral orchiopexy, while the remaining 174 (85.3%) underwent orchiectomy and contralateral orchiopexy. Finally, long symptom duration was an independent risk predictor for TS, while visible intratesticular blood flow and homogeneous testicular echotexture under color Doppler ultrasound were independent protective predictors. Internal validation showed that the nomograms, which were established by integrating these three predictive factors, had good discrimination ability in predicting the possibility of TS (areas under the ROC curves were 0.851 and 0.828, respectively). The calibration plots showed good agreement between the nomogram-predicted possibility of TS and the actual situation. In conclusion, this brief preoperative prediction tool will help clinicians to quickly determine the urgency of surgical exploration., Competing Interests: None

Background: To explore an expression profile in plasma exosomal miRNAs of mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE + HS) patients and investigate the associated clinical significance and putative pathways involved., Methods: Plasma exosomal miRNAs were measured in six mTLE + HS patients who were confirmed with pre-surgical stereo-electroencephalography and six without hippocampal sclerosis (mTLE-HS) using Illumina HiSeq 2500. Then six dysregulated miRNAs were chosen for validation in an independent sample of 18 mTLE + HS patients and 18 mTLE-HS controls using RT-qPCR. Receiver operating characteristic curve was conducted to evaluate the diagnostic value of miRNAs in HS. Bioinformatic analyses were conducted to reveal in which pathways these miRNAs were involved., Results: We revealed that a total of 42 exosomal miRNAs were differentially expressed in mTLE + HS. Among them, 25 were increased and 17 decreased. After validation, hsa-miR-129-5p, -214-3p, -219a-5p, and -34c-5p were confirmed as being upregulated, while hsa-miR-421 and -184 were significantly downregulated in mTLE + HS. Moreover, hsa-miR-184 had the best diagnostic value for discriminating mTLE + HS with 88.9% sensitivity and 83.3% specificity. These six miRNAs regulated several genes from neurotrophin-, hippo-, p53-, TGF- beta-, HIF- 1-, mTOR-related pathways., Conclusion: Six miRNAs were dysregulated in mTLE + HS patients and targeted several genes. This result might facilitate pathological mechanistic studies of miRNAs in HS and represent potential diagnostic biomarkers. These provided the rationale for further confirmation studies in larger cohorts of prospective patients., (Copyright © 2020 Huang, Luo, Xu and Lu.)

To investigate the clinical value of changes in the subtypes of peripheral blood lymphocytes and levels of inflammatory cytokines in patients with COVID-19, the total numbers of lymphocytes and CD4+ lymphocytes and the ratio of CD4+/CD8+ lymphocytes were calculated and observed in different groups of patients with COVID-19. The results show that the lymphocytopenia in patients with COVID-19 was mainly manifested by decreases in the CD4+ T lymphocyte number and the CD4+/CD8+ ratio. The decreased number of CD4+ T lymphocytes and the elevated levels of TNF-α and IL-6 were correlated with the severity of COVID-19 disease., Competing Interests: The authors have declared that no competing interests exist.

Aim: To assess the association between periodontitis (PD) and inadequate disease control (IDC) in patients with rheumatoid arthritis (RA) receiving biological therapy., Materials and Methods: In total, 111 RA patients receiving biological therapy for at least 3 months were assessed for periodontal disease at baseline. RA disease activity was assessed at baseline and at 3 months of follow-up. A multivariable logistic regression analysis was used to estimate the association between PD and IDC, adjusting for age, sex, smoking, diabetes, and baseline RA disease activity. An additional exploratory model further controlled for disease characteristics and other medications., Results: Among 111 patients, 84 (75.7%) had PD, of whom 37 (44.0%) received periodontal treatment. Thirty-four (40.5%) of PD patients had IDC; 12 (32.4%) of treated PD patients and 22 (46.8%) of untreated patients had IDC, respectively. The ORs (95% CIs) for IDC were 1.45 (0.50-4.23) in PD patients and 1.84 (0.59-5.76) in untreated PD patients. In the exploratory model, the ORs (95% CIs) for IDC were 5.00 (1.19-21.03) in PD patients and 6.26 (1.34-29.34) in untreated PD patients., Conclusion: This single-centre, prospective study failed to demonstrate a consistently positive correlation between PD and IDC in RA patients receiving biological treatment., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: The purpose of this pilot study was to evaluate the effects of the Bass brushing method on dental plaque and pneumonia in older adults hospitalized with pneumonia after discharge., Background: Poor oral hygiene may lead to pneumonia. Complications of pneumonia in older adults can be life-threatening during hospitalization and after discharge., Methods: Older adults hospitalized with pneumonia (n = 30) were randomly assigned to intervention (with the Bass brushing method; n = 15) or control (with usual care; n = 15) groups. Dental plaque index and pneumonia as detected on chest x-rays were evaluated prior to the intervention (baseline) and every month for six months after discharge., Results: Participants in the intervention group experienced a sustained reduction in dental plaque from the fourth to the sixth months (p = .024; p = .025; p = .000, respectively) that was not found in the control group. There were no group differences in detected pneumonia throughout the follow-up period. Pneumonia as detected on the chest x-rays at baseline (p = .001) and dental plaque index (p = .021) were significant predictors of the risk of pneumonia across groups., Conclusions: The Bass brushing method is a simple and effective oral hygiene practice that reduces dental plaque in older adults hospitalized with pneumonia after discharge., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: A precise positioning for dental implant placement is important for further prosthesis fabrication and maintenance. Computer-aided surgery has been developed to transfer digitally planned implant positioning to the patient over the past decades. This study aimed to evaluate the accuracy of a computer-aided laboratory-fabricated surgical template. A further objective was to compare the accuracy between in vivo and in vitro groups., Methods: A total of 20 implants were placed in the posterior tooth region through the aid of surgical templates on 17 partially edentulous patients in the in vivo group. The surgical template was fabricated in laboratory after virtual implant planning was completed using computer software. In the in vitro group, the same procedures were performed on the models without placing fixture with the same templates used in surgery. Deviations of the implant access at the implant platform level and apical region, as well as the angle deviations between the virtual planning data and the surgical results, were measured using a follow-up Cone Beam Computerized Tomography (CBCT) investigation, and image fusion with planning data., Result: The median deviation at platform level, apex and angulation was 0.95 mm (0.3-1.3 mm),1.35 mm (0.1-3.6 mm) and 3.92° (0.44-11.66°) respectively in the in vivo group; and 0.4 mm (0-1.0 mm), 0.65 mm (0.1-1.9 mm), 2.16° (0.17-6.91) respectively in the in vitro group. The in vitro group displayed significantly less deviation (p < 0.05)., Conclusion: The data from this study shows that computer-aided laboratory-fabricated template may be a reliable tool for implant placement. However, the clinical conditions seem to affect the accuracy of the template., (Copyright © 2018. Published by Elsevier Taiwan LLC.)

Objective: To study whether the antibiotics should be used in the patients with or without chronic nasal sinusitis after the nasal surgery,and how to rationally use it. Method： Study design:prospective stratified randomized controlled study.Patients with sinusitis were divided into three groups.A group was without antibiotics,B group was with standard antibiotics using ,and C group was with prolonged antibiotics using.Patients without sinusitis were divided into D group without antibiotics,E group with standard antibiotics using,and F group with prolonged antibiotics using. Observe the postoperative infection rate in each group and compare them. Result： The infection rates were 3.53%,2.67%,0.00% in A,B and C group, and there was no significant differences between three groups. The infection rates were 1.22%,0.00%,1.39% in D,E and F group,and there was no significant differences between them. Conclusion： There was no influence in patients with or without using antibiotics,standard or prolonged using antibiotics after nasal surgery. Recommend not to use antibiotics after nasal surgery,and appropriately use antibioctics within 48 hours.Prolonged using is not recommended., 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.)

Temporal lobe epilepsy (TLE) is a chronic neurological disease characterized by recurrent spontaneous seizures. MicroRNAs are dysregulated in various pathological conditions including epilepsy. Therefore, we hypothesized that the dysregulation of these microRNAs might also be associated with the pathogenesis of TLE. In this study, we found that a microRNA, hsa-miR-155-5p, was upregulated in patients with TLE post-surgery, and hence associated with clinical and pathological manifestations and seizure outcomes. We then used a rat model of experimental epilepsy induced by pilocarpine and revealed that the rat homologue was upregulated as well. Importantly, injection of an antagomiR of rno-miR-155-5p in vivo resulted in a reduction of the pathophysiological features associated with the status epilepticus, which was accompanied by decrease of apoptosis in the hippocampus. This effect was correlated with an increase in rat Sestrin-3 expression, which was a gene known to counteract oxidative stress. This rescue was also observed after injection of a lentivirus carrying the small interfering RNA of rat Sestrin-3 gene in the hippocampus. In addition, rno-miR-155-5p as well as rat Sestrin-3 mRNA and protein expression were partly dependent on oxidative stress induced by H 2 O 2 in PC12 cells . Taken together, our data suggest that rno-miR-155-5p is a potent post-transcriptional regulator of rat Sestrin-3 and it may be one of the molecular links between brain damage and increased risk for seizures during damage by oxidative stress., (Copyright © 2017. Published by Elsevier B.V.)

Objective: Wilms' tumor (WT) is the most common malignant tumor in the children's urogenital system. MiR-190b was found to participate in the development and progression of several cancers. However, the molecular mechanism of miR-190b in WT is still unclear., Patients and Methods: We detected the miR-190b in WT tissue samples compared to adjacent normal samples as well as in WT patients' blood sample compared to normal volunteers using qRT-PCR. With over-expression and knockdown of miR-190b in WT-derived cell line SK-NEP-1, we next studied cell proliferation, cell circle, apoptosis, invasion and migration abilities change caused by miR-190b ectopic expression. Dual-luciferase assay and Western-blot analysis were used to explain the mechanism of miR-190b in WT., Results: MiR-190b was over-expressed in WT tissue and blood samples compared to normal group, relatively. Up-regulation of miR-190b in SK-NEP-1 cells significantly increased the growth and decreased the apoptosis of cells, while its down-regulation reduced cell proliferation and promoted cell apoptosis of SK-NEP-1. Also, cell invasion and migration abilities were significantly improved after miR-190b over-expression. Moreover, PTEN was proved to be a direct target of miR-190b and its protein level was remarkably decreased after miR-190b up-regulation., Conclusions: miR-190b over-expressed in WT and promoted cell proliferation, invasion and migration while reduced cell apoptosis of WT cells by repressing PTEN repression, which might provide a potential target for WT diagnosis and therapy.

Several monotonicity and concavity results related to the generalized digamma and polygamma functions are presented. This extends and generalizes the main results of Qi and Guo and others., Competing Interests: The authors declare that they have no competing interests.

The authors obtain some Wilker and Cusa type inequalities for generalized trigonometric and hyperbolic functions and generalize some known inequalities., Competing Interests: The authors declare that they have no competing interests.

Gingival disase and rheumatoid arthritis (RA) are linked at both the epidemiologic and pathogenesis levels. In this study, we aimed to identify environmental factors associated with RA and gingival disease and to investigate factors that protect the gingival tissue in RA patients. This retrospective study analyzed 754 RA patients with gingival disease selected from the NHANES database who completed the mobile examination center interview/examination between 1999 and 2004. Data collected included demographics, lifestyle, dietary intake, and biomarkers. The study included 173 RA patients with gingival disease. Multivariate logistic regression analysis showed that the odds of gingival disease were significantly increased with male gender. However, the odds of gingival disease was significantly decreased with increased vitamin C intake (OR = 0.996, p = 0.041), and higher serum vitamin D levels (OR = 0.979, p = 0.011). Given the significant association between the prevalence of gingival disease and RA, identification of risk factors of gingival disease will be useful as a screening tool in national health surveys to improve the management of periodontal disease in patients with RA.

Study Design: Experimental study., Objectives: To investigate the expression of autophagy in different stages of the neurogenic bladder after spinal cord injury (SCI) in rats., Setting: Second Hospital of Shandong University, Jinan, China., Methods: A total of 36 Wistar rats were divided into the SCI and control groups. In total, six animals were killed and sampled from each group at 1, 4 and 14 days after surgery of T10-T11 level. BBB scale, residual urine volume and urinary bladder function score were estimated at each time point. The expression of microtubule-associated protein 1 light chain 3 (LC3) and P62 was detected using western blot analysis, immunofluorescence staining or real-time PCR (RT-PCR)., Results: The locomotor functions of the hindlimbs and the bladder function of the SCI group rats were lost after surgery, but gradually recovered from 1 day. Western blot showed that the LC3-II/actin was higher in the SCI than in the control group. Immunofluorescence staining revealed that LC3 and P62 were expressed in bladder smooth muscle cell. RT-PCR showed a remarkably increased LC3 mRNA expression at 1, 4 and 14 days in the SCI than in the control group. The P62 mRNA level of the SCI bladder tissues did not differ from that of the control group at 1 day but decreased at 4 and 14 days after surgery., Conclusions: Autophagy is activated during the recovery of the bladder after SCI and sustained. Autophagy may play an important role in bladder neurogenesis and may represent one of the mechanisms of bladder self-repair.

Background: miR-146a, a strong pro-apoptotic factor in some pathophysiological processes, is reported to be involved in ischemic stroke (IS), though its role remains unclear. Fbxl10 is an active anti-apoptotic factor and a predicted target of miR-146a. We hypothesized that dysregulation of miR-146a contributes to ischemic injury by targeting Fbxl10., Methods: Circulating miRNAs were detected by miRNA microarray and qRT-PCR. miR-146a targets were predicted using bioinformatics and confirmed with a dual luciferase reporter assay. We used an in vitro ischemic model of oxygen-glucose deprivation and reperfusion (OGD/R) to mimic cerebral ischemia/reperfusion (I/R) conditions. Expression of miR-146a, Fbxl10 and Bcl2l2 mRNAs, and Fbxl10 and Bcl2l2 proteins was verified by qRT-PCR and Western blotting. The effects of miR-146a on neuronal cell apoptosis were evaluated by flow cytometry., Results: A significant reduction in miR-146a expression was observed in acute ischemic stroke (AIS). A dual-luciferase reporter assay showed that Fbxl10, but not Bcl2l2, is a target of miR-146a. Transfection with miR-146a mimics promoted apoptosis in SK-N-SH cells and significantly reduced expression of Fbxl10. Conversely, miR-146a inhibition attenuated OGD/R-induced neuronal cell death and significantly up-regulated Fbxl10 expression., Conclusions: miR-146a expression was significantly down-regulated in AIS, and Fbxl10 was identified as a target of miR-146a. Moreover, up-regulation of Fbxl10, a miR-146a target, likely protects neurons from ischemic death., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

To investigate the effects and mechanism of diosmetin on acute hepatic failure (AHF), an AHF murine model was established through administration of lipopolysaccharides/D-galactosamine (LPS/D-GalN). In vitro, diosmetin scavenged free radicals. In vivo, diosmetin decreased mortality among mice, blocked the development of histopathological changes and hepatic damage, and suppressed levels of inflammatory mediators and cytokines. In addition, diosmetin prevented the expression of phosphorylated IKK, IκBα, and NF-κB p65 in the NF-κB signaling pathway, and JNK and p38 in the MAPK signaling pathway. Diosmetin also inhibited hepatocyte apoptosis. Thus, diosmetin exerts protective effects against endotoxin-induced acute hepatic failure in mice. The underlying mechanisms are antioxidation, NF-κB signaling inhibition, inflammatory mediator/cytokine attenuation, and hepatocyte apoptosis suppression. Diosmetin is thus a potential drug candidate for use in the treatment of acute hepatic failure.

In this paper, we show an elegant inequality involving the ratio of generalized complete elliptic integrals of the first kind and generalize an interesting result of Alzer., Competing Interests: The authors declare that they have no competing interests.

Background/purpose: The prevalence of pulpal calcifications was widely studied in the past. The purposes of this study were to investigate the incidence of pulpal calcifications of periodontally involved teeth in a Taiwan Chinese population using radiographic and histological examinations, and to find out any association of pulpal calcification with systemic disease and dental conditions., Materials and Methods: A total of 197 teeth freshly extracted because of severe periodontal destruction were collected and prepared for histological and radiographic studies of the incidence of pulpal tissue calcifications. The occurrences of calcifications were recorded based on the different types of classifications proposed by Seltzer (1972). The number of examined teeth with pulpal calcifications was calculated, and they were statistically analyzed with the Chi-square test., Results: The patient population ranged in age from 16 years to 85 years. Of them, 165 (84%) were male and 32 (17%) were female. The results show that the incidence of pulpal calcifications of periodontally involved teeth was 62% in histological and 30% in radiographic examinations. The occurrences were slightly higher than that reported in some previous studies and significantly different between the two examined methods. No significant association of pulpal calcification with age and systemic disease was found. Moreover, molars were observed to have more pulpal calcifications than bicuspids and incisors statistically (P < 0.001)., Conclusion: The true incidence of pulpal calcifications of periodontally involved teeth is likely to be higher in histological examination because pulpal calcifications with a small diameter may not be seen on radiographs. The prevalence of pulpal calcifications was found to increase significantly in molar teeth, and the results indicated that localized calcifications occur mostly in the radicular area of the pulp tissue.

Objective: Leptin has been found highly expressed in human osteoarthritis. We aimed to explore the possible effects and mechanisms of leptin on the apoptosis and autophagy of chondrocytes during osteoarthritis pathogenesis., Methods: Gene expression profile from osteoarthritis affected and preserved cartilage were downloaded from NCBI's Gene Expression Omnibus database (GSE57218). Lysyl oxidase-like 3 (LOXL3) mRNA expression in cartilage tissues and leptin concentration in joint synovial fluid (SF) was measured in samples from 45 osteoarthritis patients and 25 healthy donors by real-time PCR and radioimmunoassay, respectively. Rat osteoarthritis model was induced by anterior cruciate ligament transection (ACLT). The expression of apoptosis regulators and autophagy markers were detected by Western blot. Cell survival and cell apoptosis were identified by CCK-8 and flow cytometry, respectively., Results: Re-analysis on GSE57218 indicated that LOXL3 mRNA was upregulated in osteoarthritis affected cartilage. LOXL3 mRNA was upregulated in osteoarthritis patients, which was positively correlated with SF leptin concentration. Similar results were obtained in rat osteoarthritis model. Moreover, ACLT surgery led to a significant increase in the protein levels of cleaved caspase 3, and a notable decrease in the protein levels of Bcl-2, LC3 II/LC3 I and Beclin1. Silencing of LOXL3 in ACLT and leptin treated primary chondrocytes significantly inhibited cell apoptosis, and promoted cell proliferation and autophagy. Moreover, overexpression of LOXL3 remarkably inhibited autophagy of chondrocytes via activating mTORC1., Conclusions: LOXL3, a downstream of leptin, stimulated the apoptosis, but inhibited the autophagy of chondrocytes. LOXL3 is a potential therapy target for osteoarthritis., (Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Background: Neurogenic neuroprotection is a promising approach for treating patients with ischemic brain lesions. Fastigial nucleus stimulation (FNS) has been shown to reduce the tissue damage resulting from focal cerebral ischemia in the earlier studies. However, the mechanisms of neuroprotection induced by FNS remain unclear. MicroRNAs (miRNAs) are a newly discovered group of non-coding small RNA molecules that negatively regulate target gene expression and involved in the regulation of pathological process. To date, there is a lack of knowledge on the expression of miRNA in response to FNS. Thus, we study the regulation of miRNAs in the rat ischemic brain by the neuroprotection effect of FNS., Methods: In this study, we used an established focal cerebral ischemia/reperfusion (IR) model in rats. MiRNA expression profile of rat ischemic cortex after 1 h of FNS were investigated using deep sequencing. Microarray was performed to study the expression pattern of miRNAs. Functional annotation on the miRNA was carried out by bioinformatics analysis., Results: Two thousand four hundred ninety three miRNAs were detected and found to be miRNAs or miRNA candidates using deep sequencing technology. We found that the FNS-related miRNAs were differentially expressed according microarray data. Bioinformatics analysis indicated that several differentially expressed miRNAs might be a central node of neuroprotection-associated genetic networks and contribute to neuroprotection induced by FNS., Conclusions: MiRNA acts as a novel regulator and contributes to FNS-induced neuroprotection. Our study provides a better understanding of neuroprotection induced by FNS.

We established a necrotizing enterocolitis (NEC) rat model and explored the role of bifidobacteria in the intestines of the rats and its regulation on intestinal Toll-like receptors (TLRs). Seventy-five newborn Sprague-Dawley rats were randomly divided into 5 groups (15 rats/group): group A, artificial feeding group (formula-fed); group B, NEC model (LPS + formula-fed); group C, bifidobacterium (LPS + formula-fed + bifidobacterium microcapsules, intragastric administration); group D, artificial feeding + bifidobacterium (formula-fed + bifidobacterium microcapsules gavage); group E, rat breast-feeding group (rat breast-feeding). After 3 days of feeding, rats were placed in incubators, fasted for 12 h, and killed by decapitation. The ileocecal proximal segment ileum was fixed and sliced; pathological examination was conducted, and TLR2, TLR4, and nuclear factor-kB p65 protein expression in the intestinal tissue was detected by immunohistochemistry. There was a statistically significant difference in pathological scores between groups C and B (H = 21.789, P = 0.000), and the former was lower than the latter. TLR2, TLR4, and nuclear factor-kB p65 expression in intestinal tissue was determined in groups A-E. There were statistically significant differences between groups C and B (P = 0.001; P = 0.000; P = 0.000). Bifidobacteria had a protective effect on the intestines of newborn rats with NEC, which showed reduced NEC and intestinal damage severity. This observation may be related to the reduced levels of TLR2, TLR4, and nuclear factor-kB P65 observed during the inflammatory response.

We investigated the effect of inactivated Bifidobacterium on the mRNA expression of TRAF6, GSK-3β, and microRNA-146a in lipopolysaccharide (LPS)-stimulated rat small intestinal epithelial cells (IEC-6s). IEC-6s were randomly divided into an LPS group, a culture supernatant group, and an inactivated bacteria group. After stimulation with LPS for 5 h, the three groups were treated as follows: the LPS group was cultured for 24 h with sterile saline; the culture supernatant group was cultured with Bifidobacterium (infantis strain) culture supernatant for 24 h; and the inactivated bacteria group was cultured with inactivated infantis Bifidobacterium for 24 h. Reverse transcription polymerase chain reaction was used to determine mRNA expression levels. The mRNA expression levels of TRAF-6 and GSK-3β in the culture supernatant group were lower, and microRNA-146a expression was higher, compared with the LPS group (t = 5.278, P = 0.000; t = 6.316, P = 0.000; t = 13.218, P = 0.000, respectively). GSK-3β mRNA expression in the inactivated bacteria group was lower than in the LPS group (t = 4.837, P = 0.000). There was no difference in the mRNA expression levels of TRAF-6 and microRNA-146a between the two groups (t = 0.732, P = 0.472 and t = 1.463, P = 0.164). Both the culture supernatant and the inactivated Bifidobacterium had a protective effect on LPS-stimulated IEC-6s. The protective effect of Bifidobacterium may be achieved through increased microRNA-146a by reducing levels of TRAF6 and GSK-3β; the protective effect of inactivated Bifidobacterium may be achieved by reducing levels of GSK-3β.

[Purpose] This study investigated the effects of a 12-hour neuromuscular electrical stimulation program in the evening hours on upper extremity function in sub-acute stroke patients. [Subjects and Methods] Forty-five subjects were randomized to one of three groups: 12-hour neuromuscular electrical stimulation group (n=15), which received 12 hours of neuromuscular electrical stimulation and conventional rehabilitation for the affected upper extremity; neuromuscular electrical stimulation group (n=15), which received 30 min of neuromuscular electrical stimulation and conventional rehabilitation; and control group (n=15), which received conventional rehabilitation only. The Fugl-Meyer assessment, Action Research Arm Test, and modified Ashworth scale were used to evaluate the effects before and after intervention, and 4 weeks later. [Results] The improvement in the distal (wrist-hand) components of the Fugl-Meyer assessment and Action Research Arm Test in the 12-hour neuromuscular electrical stimulation group was more significant than that in the neuromuscular electrical stimulation group. No significant difference was found between the two groups in the proximal component (shoulder-elbow) of the Fugl-Meyer assessment. [Conclusion] The 12-hour neuromuscular electrical stimulation group achieved better improvement in upper extremity motor function, especially in the wrist-hand function. This alternative therapeutic approach is easily applicable and can be used in stroke patients during rest or sleep.

Aims: Studies showed fastigial nucleus stimulation (FNS) reduced brain damage, but the mechanisms of neuroprotection induced by FNS were not entirely understood; MicroRNAs are noncoding RNA molecules that regulate gene expression in a posttranscriptional manner, but their functional consequence in response to ischemia-reperfusion (IR) remains unknown. We investigated the role of microRNA-29c in the neuroprotection induced by FNS in rat., Methods: The IR rat models were conducted 1 day after FNS. Besides, miR-29c antagomir (or agomir or control) was infused to the left intracerebroventricular 1 day before IR models were conducted. We detected differential expression of Birc2 mRNA (also Bak1mRNA and miR-29c) level among different groups by RT-qPCR. The differential expression of Birc2 protein (also Bak1 protein) level among different groups was surveyed via Western blot. The neuroprotective effects were assessed by infarct volume, neurological deficit, and apoptosis., Results: MiR-29c was decreased after FNS. Moreover, miR-29c directly bound to the predicted 3'-UTR target sites of Birc2 and Bak1 genes. Furthermore, over-expression of miR-29c effectively reduced Birc2 (also Bak1) mRNA and protein levels, increased infarct volume and apoptosis, and deteriorated neurological outcomes, whereas down-regulation played a neuroprotective role., Conclusions: MiR-29c correlates with the neuroprotection induced by FNS by negatively regulating Birc2 and Bak1., (© 2015 John Wiley & Sons Ltd.)

Previous studies have shown that fastigial nucleus stimulation (FNS) reduces tissue damage resulting from focal cerebral ischemia. Although the mechanisms of neuroprotection induced by FNS are not entirely understood, important data have been presented in the past two decades. MicroRNAs (miRNAs) are a newly discovered group of non-coding small RNA molecules that negatively regulate target gene expression and are involved in the regulation of cell proliferation and cell apoptosis. To date, no studies have demonstrated whether miRNAs can serve as mediators of the brain's response to FNS, which leads to endogenous neuroprotection. Therefore, this study investigated the profiles of FNS-mediated miRNAs. Using a combination of deep sequencing and microarray with computational analysis, we identified a novel miRNA in the rat ischemic cortex after 1 h of FNS. This novel miRNA (PC-3p-3469&#95;406), herein referred to as rno-miR-676-1, was upregulated in rats with cerebral ischemia after FNS. In vivo observations indicate that this novel miRNA may have antiapoptotic effects and contribute to neuroprotection induced by FNS. Our study provides a better understanding of neuroprotection induced by FNS. MicroRNA (miRNA) is defined as a small non-coding RNA that fulfills both the expression and biogenesis criteria. Here, we describe a novel miRNA in the rat ischemic cortex expressed after 1 h of fastigial nucleus stimulation (FNS). The miRNA was functionally characterized by secondary structure, quantitative expression, the conservation analysis, target gene analysis, and biological functions. We consider rno-miR-676-1 to be a true microRNA and present evidence for its neuroprotective effects exerted after induction by FNS., (© 2015 International Society for Neurochemistry.)

The chemical consituents from Psychotria straminea were separated and purified by column chromatographies on silica gel, Sephadex LH-20, ODS and RP-HPLC. The strictures of the isolated compounds were identified on the basis of physicochemical properties and spectroscopic analysis, as well as comparisons with the data in literature. Sixteen compounds were isolated and elucidated as tectochrysin (1), apigenin (2), kaempferol (3), luteolin (4), diosmetin (5), quercetin (6), kaempferol-4'-O-methylether (7), rhamnetin (8), 7-hydroxycoumarin (9), 7-methoxycoumarin (10), scopoletin (11), lupeol (12), 30-oxo-lupeol (13), lupenyl acetate (14), α-amyrin (15), and ursolic acid (16). This is the first study on the chemical composition of P. Straminea, and all compounds were isolated from P. straminea for the first time. In addition to compounds 6 and 9, the other compounds were isolated from the genus Psychotria for the first time.

The chemical consituents from Ochrosia elliptica were separated and purified by column chromatographies on silica gel, Sephadex LH-20, ODS and RP-HPLC. The structures of the isolated compounds were identified on the basis of physicochemical properties and spectroscopic analysis, as well as comparisons with the data in the literature. 18 compounds were isolated and elucidated as (+) -pinoresinol(1), (+) -medioresinol (2), (+) -lariciresinol (3), (+) -5'-methoxy lariciresinol(4), (+) -isolariciresinol (5), syringaresinol(6), episyringaresinol (7), ciwujiatone (8), zhebeiresinol (9), 7-hydroxycoumarin (10), 7-methoxycoumarin (11), scopoletin(12), isofraxidin(13), caffeic acid ethyl ester (14), ferulic acid (15), p-hydroxybenzaldehyde (16), vanillin (17), and vanillic acid(18). All compounds were isolated from the genus Ochrosia for the first time.

The study of soliton interactions is of significance for improving pulse qualities in nonlinear optics. In this paper, interaction between two solitons, which is governed by the Hirota equation, is considered. Via use of the Hirota method, an analytic soliton solution is obtained. Then a two-period vibration phenomenon is observed. Moreover, turning points of the coefficients of higher-order terms, which are related with sudden delaying or leading, are found and analyzed. With different coefficient constraints, soliton interactions are discussed by different frequency separation with the split-step Fourier method, and characteristics of soliton interactions are exhibited. Through turning points, we get a pair of solitons which tend to be bound solitons but not exactly. Furthermore, we control a pair of solitons to emit at different emission angles. The stability of the two-period vibration is analyzed. Results in this paper may be helpful for the applications of optical self-routing, waveguiding, and faster switching.

Objectives: Angiotensin-converting enzyme (ACE) I/D polymorphism has been implicated in aortic aneurysm risk, but individual published studies show inconclusive results. The aim of this study was to explore a more precise estimation of its relation with aortic aneurysm using meta-analysis., Methods: Electronic searches of PubMed and EMBASE databases were conducted for all publications through February 2014. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to access the strength of this association in the random-effects model or fixed-effects model., Results: Fourteen case-control studies, including a total of 3938 cases and 5748 controls, were included. This meta-analysis showed a significant association between ACE I/D polymorphism and aortic aneurysm risk (OR = 1.53, 95% CI 1.26-1.87, P <0.01). In the subgroup analysis by ethnicity, a statistically significant association was found in Caucasians (OR = 1.46, 95% CI 1.20-1.77, P <0.01), but not in Asians. In the subgroup analysis by type of aortic aneurysm, this polymorphism was significantly associated with abdominal aortic aneurysm risk (OR = 1.38, 95% CI 1.10-1.74, P <0.01), thoracic aortic aneurysm risk (OR = 1.59, 95% CI 1.11-2.29, P = 0.01) and aortic dissection risk (OR = 2.43, 95% CI 1.07-5.52, P = 0.03). Stratification by hypertension status showed that hypertensive patients with this polymorphism were associated with increased aortic aneurysm risk (OR = 1.47, 95% CI 1.03-2.09, P = 0.03), whereas normotensive individuals with this polymorphism did not have an increased aortic aneurysm risk., Conclusions: This meta-analysis suggested that ACE I/D polymorphism was associated with aortic aneurysm risk., (© Crown copyright 2014.)

Objective: To observe the effect of tensile stress on human heel skin fibroblast proliferation in vitro, providing a theoretical basis for preventing the wound edge skin necrosis and nonunion after calcaneal fracture surgery., Methods: Fibroblast cells were taken from lateral heel skin of a 40 year-old-man, then cultured and subcultured in vitro. After that, they were divided into three groups: 0 hours group, 6 hours group and 24 hours group and were tested by tensile stress testing. The levels of TGF-β1 and IL-6 in nutrient fluid were measured. Transmission electron microscope and light microscope was applied for observe mitochondria and nucleus., Results: Under 10% of the tensile stress, mitochondria decreased, the levels of TGF-β1 and IL-6 in nutrient fluid were decreased and cell proliferation was inhibited gradually with time increasing., Conclusion: The human lateral heel skin in a long-time tensile stress state is an important cause of wound edge skin necrosis and nonunion after calcaneus fracture surgery.

Background: We conducted an independent external validation of three cardiovascular risk score models (Framingham risk score model and SCORE risk charts developed for low-risk regions and high-risk regions in Europe) on a prospective cohort of 4487 Australian women with no previous history of heart disease, diabetes or stroke. External validation is an important step to evaluate the performance of risk score models using discrimination and calibration measures to ensure their applicability beyond the settings in which they were developed., Methods: Ten year mortality follow-up of 4487 Australian adult women from the National Heart Foundation third Risk Factor Prevalence Study with no baseline history of heart disease, diabetes or stroke. The 10-year risk of cardiovascular mortality was calculated using the Framingham and SCORE models and the predictive accuracy of the three risk score models were assessed using both discrimination and calibration., Results: The discriminative ability of the Framingham and SCORE models were good (area under the curve > 0.85). Although all models overestimated the number of cardiovascular deaths by greater than 15%, the Hosmer-Lemeshow test indicated that the Framingham and SCORE-Low models were calibrated and hence suitable for predicting the 10-year cardiovascular mortality risk in this Australian population. An assessment of the treatment thresholds for each of the three models in identifying participants recommended for treatment were found to be inadequate, with low sensitivity and high specificity resulting from the high recommended thresholds. Lower treatment thresholds of 8.7% for the Framingham model, 0.8% for the SCORE-Low model and 1.3% for the SCORE-High model were identified for each model using the Youden index, at greater than 78% sensitivity and 80% specificity., Conclusions: Framingham risk score model and SCORE risk chart for low-risk regions are recommended for use in the Australian women population for predicting the 10-year cardiovascular mortality risk. These models demonstrate good discrimination and calibration performance. Lower treatment thresholds are proposed for better identification of individuals for treatment.

Oxidative stress is believed to be an important inducer of cellular senescence and aging. Zinc finger protein 637 (Zfp637), which belongs to the Krüppel-like protein family, has been hypothesized to play a role in oxidative stress. Nevertheless, the precise function of Zfp637 has seldom been reported, and it remains unclear whether Zfp637 is involved in oxidative stress-induced premature senescence. In this study, we show that the endogenous expression levels of Zfp637 and mouse telomerase reverse transcriptase (mTERT) are downregulated during oxidative stress-induced premature senescence and in senescent tissues from naturally aged mice. The overexpression of Zfp637 markedly increases mTERT expression and telomerase activity, maintains telomere length, and inhibits both H2O2 and D-galactose-induced senescence accompanied by a reduction in the production of reactive oxygen species (ROS). In contrast, the knockdown of Zfp637 significantly aggravates cellular senescence by downregulating mTERT and telomerase activity, accelerating telomere shortening, and increasing ROS accumulation. In addition, the protective effect of Zfp637 against premature senescence is abrogated in the absence of mTERT. We further confirm that Zfp637 binds to and transactivates the mTERT promoter (-535/-502) specifically. As a result, the mTERT-mediated telomerase activity and telomere maintenance are responsible for the protective effect of Zfp637 against oxidative stress-induced senescence. We therefore propose that Zfp637 prevents oxidative stress-induced premature senescence in an mTERT-dependent manner, and these results provide a new foundation for the investigation of cellular senescence and aging.

Background/purpose: Toll-like receptor (TLR)-4 and TLR-2 play an essential role in the pathogenesis of necrotizing enterocolitis (NEC). In this study, we investigated the protective effect of glutamine (Gln) in an NEC neonatal rat model, and the potential association with TLR-4 and TLR-2 expression in local intestinal tissues., Methods: Preterm neonatal rats were randomly divided into 3 groups: normal control; NEC model; and NEC plus Gln intervention. NEC was induced by feeding with artificial milk substitutes, plus exposure to hypoxia and cold stress. All preterm rats were sacrificed at 3 days after birth. The intestinal tissues were taken for pathological analysis. Protein and mRNA expression of TLR-2, TLR-4, and caspase-3 was examined by immunohistochemistry and real-time RT-PCR, respectively., Results: Compared with the normal control, the NEC neonatal rats showed mucosal injury and upregulated mRNA and protein expression of TLR-2, TLR-4, and caspase-3 in ileum and colon. Gln intervention significantly reduced the mucosal injury and suppressed the upregulated expression of TLR-2, TLR-4, and caspace-3 in the ileum and colon of NEC neonatal rats., Conclusions: Gln protects the intestinal tract of NEC neonatal rats, which may be associated with the reduction of TLR-2 and TLR-4 expression in intestines., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Using a two-layer structure consisting of polyethylene terephthalate (PET) and polydimethylsiloxane (PDMS) to support graphene grown by chemical vapor deposition (CVD), we demonstrate a flexible integrated graphene saturable absorber (SA) on microfiber for passive mode-locked soliton fiber laser. This method can optimize the light-graphene interaction by using evanescent field in the integration structure. Moreover, the fiber laser with the in-line microfiber-to-graphene SA can realize the tunabilities of both the 3dB bandwidth of output optical spectrum and the pulse width of soliton. This tunable mode-locked soliton laser has potential applications in optical communication, optical microscopy, and so on.