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Background/Aims: Hypoxia has recently been proposed as one of the most important factors in progressive renal injury. Hypoxia-induced vascular endothelial growth factor (VEGF) expression may play a critical role in maintaining peritubular capillary endothelium in renal disease. This study was designed to investigate the effect and underlying mechanism of all-trans retinoic acid (ATRA) on hypoxia-induced injury in NRK52E cells. Methods: For mimicking hypoxia, cells were treated with 100 µM of cobalt chloride (CoCl2). The cell viability, expression of VEGF, p65, transforming growth factor-β2 (TGF-β2) and serine carboxypeptidase 1 (Scpep1), and nuclear factor of kappaB (NF-κB) activities after ATRA treatment were determined by MTT, western blot and electrophoretic mobility shift assay. Co-immunoprecipitation analysis was performed to demonstrate whether Scpep1 interacted with TGF-β2. Results: It was found that CoCl2 triggered hypoxia injury and significantly reduced cell viability. ATRA pretreatment increased the cell survival rate. Under hypoxic conditions, the expression of VEGF, p65 and TGF-β2 increased. Addition of ATRA significantly attenuated the expression of VEGF, p65 and TGF-β2. There was a corresponding variation of NF-κB/DNA binding activities. In addition, ATRA stimulated Scpep1 expression under normoxic and hypoxia condition. Furthermore, TGF-β2 interacted with Scpep1. Conclusions: This study indicated that ATRA may attenuate hypoxia-induced injury in NRK52E cells via inhibiting NF-κB/VEGF and TGF-β2/VEGF pathway.

Objective: To provide a broad overview of the current state of research regarding the effects of 7 commonly used motor learning strategies to improve functional tasks within older neurologic and geriatric populations. Data Sources: PubMed, CINAHL, and Embase were searched. Study Selection: A systematic mapping review of randomized controlled trials was conducted regarding the effectiveness of 7 motor learning strategies—errorless learning, analogy learning, observational learning, trial-and-error learning, dual-task learning, discovery learning, and movement imagery—within the geriatric and neurologic population. Data Extraction: Two thousand and ninety-nine articles were identified. After screening, 87 articles were included for further analysis. Two reviewers extracted descriptive data regarding the population, type of motor learning strategy/intervention, frequency and total duration intervention, task trained, movement performance measures, assessment time points, and between-group effects of the included studies. The risk of bias 2 tool was used to assess bias; additionally, papers underwent screening for sample size justification. Data Synthesis: Identified articles regarding the effects of the targeted motor learning strategies started around the year 2000 and mainly emerged in 2010. Eight populations were included, for example, Parkinson's and stroke. Included studies were not equally balanced: analogy learning (n=2), errorless learning and trial-and-error learning (n=5), mental practice (n=19), observational learning (n=11), discovery learning (n=0), and dual-tasking (n=50). Overall studies showed a moderate-to-high risk of bias. Four studies were deemed sufficiently reliable to interpret effects. Positive trends regarding the effects were observed for dual-tasking, observational learning, and movement imagery. Conclusions: Findings show a skewed distribution of studies across motor learning interventions, especially toward dual-tasking. Methodological shortcomings make it difficult to draw firm conclusions regarding the effectiveness of motor learning strategies to improve functional studies. Future researchers are strongly advised to follow guidelines that aid in maintaining methodological quality. Moreover, alternative designs fitting the complex practice situation should be considered.

Background: Thromboelastogram (TEG) is an effective indicator that monitors the dynamic changes of blood coagulation in real-time. It still remains controversial about the performance and influence of coagulation at high altitude. The present study intends to describe comprehensively the clinical features of TEG in populations exposed to or transferring from high altitude. Methods: Two groups were recruited in the present study. Group A included young males who worked at high-altitude (4888 m or 5418 m) areas for some time, while Group B included young males who had recently returned from high-altitude (4888 m or 5418 m) areas. Medical examinations were performed using portable devices. Spearman's test was used to evaluate the correlations between thromboelastogram (TEG) variables and other variables. Logistic regression analysis was used to analyze the factors affecting various abnormal TEG variables. Results: A total of 51 adult males were included in the two groups. Significantly increased reaction time (R) and decreased maximum amplitude (MA) were found in group B (P

The close-in weapon system (CIWS) is a combat system that faces a complex environment full of dynamic and unknown challenges, whose construction and planning require a systematic design method. Multi-living agent (MLA) theory is a methodology for the combat system design, which uses the livelihood degree to evaluate the multi-dimensional long-term operational effectiveness of the system; whereas, there is still no uniform quantization framework for the livelihood degree, and the adjustment methods of livelihood degree need to be further improved. In this paper, we propose the uniform quantization framework for the livelihood degree and detailed discuss the methods of livelihood adjustment. Based on the MLA theory, the multi-dimensional operational effectiveness of the missile-gun integrated weapon system (MGIWS) is analyzed, and the long-term combat effectiveness against the saturation attack is assessed. Furthermore, the planning problem of the equipment deployment and configuration is investigated. Two objectives, including the overall livelihood degree and cost-effectiveness (CE), are proposed, and the optimization method based on genetic algorithm (GA) is studied for the planning problem.

BackgroundOsteoporosis has already been a growing health concern worldwide. The influence of living area, lifestyle, socioeconomic, and medical conditions on the occurrence of osteoporosis in the middle-aged and elderly people in China has not been fully addressed.MethodsThe study was a multicenter cross-sectional study on the middle-aged and elderly permanent residents, which gathered information of 22,081 residents from June 2015 to August 2021 in seven representative regions of China. The bone mineral density of lumbar vertebrae and hip were determined using the dual-energy X-ray absorptiometry densitometer instruments. Serum levels of bone metabolism markers were also measured. Information about education, smoking, and chronic diseases were also collected through face-to-face interviews. Age-standardized prevalence and 95% confidence intervals (CIs) of osteopenia and osteoporosis by various criteria were estimated by subgroups and overall based on the data of China 2010 census. The relationships between the osteoporosis or osteopenia and sociodemographic variables or other factors were examined using univariate linear models and multivariable multinomial logit analyses.ResultsAfter screening, 19,848 participants (90%) were enrolled for the final analysis. The age-standardized prevalence of osteoporosis was estimated to be 33.49%(95%CI, 32.80–34.18%) in the middle-aged and elderly Chinese permanent residents, for men and women was 20.73% (95% CI, 19.58–21.87%) and 38.05% (95% CI, 37.22–38.89%), respectively. The serum concentrations of bone metabolic markers, and calcium and phosphorus metabolism were influenced by age, body mass index (BMI), gender, education level, regions, and bone mass status. Women, aged 60 or above, BMI lower than 18.5 kg/m2, low education level including middle school, primary school and no formal education as well as current regular smoking, a history of fracture were all significantly associated with a higher risk of osteoporosis and osteopenia in the middle-aged and elderly people.ConclusionsThis study revealed dramatic regional differences in osteoporosis prevalence in China, and female, aged 60 or older, low BMI, low education level, current regular smoking, and a history of fracture were associated with a high risk of osteoporosis. More prevention and treatment resources should be invested into particular population exposed to these risk factors.

Objective: To examine the association between serum β2-microglobulin (B2M) levels and frailty in an elderly Chinese population. Design: A population-based cohort study. Setting and participants: We used data on 1,663 elderly participants (aged 70-84 years) from the aging arm of the Rugao Longevity and Ageing study, a population-based observational two-arm cohort study conducted in Rugao, China. Measurements: The serum B2M was measured with chemiluminescence immunoassay by a technician in the biochemistry laboratory of the Rugao People's Hospital. Information on the frailty index and phenotype was collected. Results: The mean B2M levels and frailty index were 1.8 mg/L and 0.16, respectively; 188 (11.3%) participants were classified as frail (frailty phenotype). For a standard deviation increase in B2M, the adjusted odds ratio for frailty phenotype was 1.20 (95% CI: 1.05, 1.39; P=0.009) and the standardized coefficient for frailty index was 0.07 (95% CI: 0.02, 0.11; P=0.004). Relative to the lowest quartile, the highest B2M quartile had a greater risk of prevalent frailty with adjusted odds ratios of 1.68 (95% CI: 1.04, 2.71; P=0.034) for frailty phenotype and 1.51 (95% CI: 1.01, 2.27; P=0.044) for frailty index (≥0.25). In addition, estimated glomerular filtration rate (based on B2M) or chronic kidney disease (estimated glomerular filtration rate 60 mL/min/1.73 m2) was significantly associated with frailty phenotype and index. Conclusion: B2M was significantly associated with both frailty phenotype and index in elderly Chinese population. The findings underscore the promising kidney relevant biomarkers for identifying vulnerable elderly Chinese population Objective: To examine the association between serum β2-microglobulin (B2M) levels and frailty in an elderly Chinese population. Design: A population-based cohort study. Setting and participants: We used data on 1,663 elderly participants (aged 70-84 years) from the aging arm of the Rugao Longevity and Ageing study, a population-based observational two-arm cohort study conducted in Rugao, China. Measurements: The serum B2M was measured with chemiluminescence immunoassay by a technician in the biochemistry laboratory of the Rugao People's Hospital. Information on the frailty index and phenotype was collected. Results: The mean B2M levels and frailty index were 1.8 mg/L and 0.16, respectively; 188 (11.3%) participants were classified as frail (frailty phenotype). For a standard deviation increase in B2M, the adjusted odds ratio for frailty phenotype was 1.20 (95% CI: 1.05, 1.39; P=0.009) and the standardized coefficient for frailty index was 0.07 (95% CI: 0.02, 0.11; P=0.004). Relative to the lowest quartile, the highest B2M quartile had a greater risk of prevalent frailty with adjusted odds ratios of 1.68 (95% CI: 1.04, 2.71; P=0.034) for frailty phenotype and 1.51 (95% CI: 1.01, 2.27; P=0.044) for frailty index (≥0.25). In addition, estimated glomerular filtration rate (based on B2M) or chronic kidney disease (estimated glomerular filtration rate 60 mL/min/1.73 m2) was significantly associated with frailty phenotype and index. Conclusion: B2M was significantly associated with both frailty phenotype and index in elderly Chinese population. The findings underscore the promising kidney relevant biomarkers for identifying vulnerable elderly Chinese population. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) which are continuously generated mainly by mitochondria, have been proved to play an important role in the stress signaling of cancer cells. Moreover, pentatricopeptide repeat (PPR) proteins have been suggested to take part in mitochondrial metabolism. However, the mechanisms integrating the actions of these distinct networks in urothelial carcinoma of the bladder (UCB) pathogenesis are elusive. In this study, we found that leucine rich pentatricopeptide repeat containing (LRPPRC) was frequently upregulated in UCB and that it was an independent prognostic factor in UCB. We further revealed that LRPPRC promoted UCB tumorigenesis by regulating the intracellular ROS homeostasis. Mechanistically, LRPPRC modulates ROS balance and protects UCB cells from oxidative stress via mt-mRNA metabolism and the circANKHD1/FOXM1 axis. In addition, the SRA stem-loop interacting RNA binding protein (SLIRP) directly interacted with LRPPRC to protect it from ubiquitination and proteasomal degradation. Notably, we showed that LRPPRC modulated the tumorigenesis of UCB cells in a circANKHD1-FOXM1-dependent manner. In conclusion, LRPPRC exerts critical roles in regulating UCB redox homeostasis and tumorigenesis, and is a prognostic factor for UCB; suggesting that LRPPRC may serve as an exploitable therapeutic target in UCB.

Water deficit is one of the main limiting factors for apple growth and production. Root architecture plays an important role in drought tolerance of plants. However, little is known about the molecular basis of root system in apple trees under drought. In this study, we compared root morphology of two widely used rootstocks of apple (R3 and Malus sieversii) under drought. Our results suggested that M. sieversii is more tolerant to drought than R3, since M. sieversii had a higher ratio of root to shoot as well as root hydraulic conductivity under long-term drought conditions. We then performed whole-genome transcriptomic analysis to figure out the molecular basis of root responses in M. sieversii under drought. It was found that genes involved in transcription regulation, signaling or biosynthesis of hormones, and oxidative stress were differentially expressed under drought. Consistent with the gene expression profile, roots of M. sieversii had higher activities of peroxidase (POD) and superoxide dismutase (SOD) under drought, as well as higher content of abscisic acid (ABA) and lower content of auxin. Taken together, our results revealed the physiological and transcriptomic analyses of M. sieversii roots in response to drought.

Background: Pleural fibrosis is defined as excessive depositions of matrix components that result in pleural tissue architecture destruction and dysfunction. In severe cases, the progression of pleural fibrosis leads to lung entrapment, resulting in dyspnea and respiratory failure. However, the mechanism of pleural fibrosis is poorly understood. Methods: miR-4739 levels were detected by miRNA array and real-time PCR. Real-time PCR, western blotting and immunofluorescence were used to identify the expression profile of indicators related to fibrosis. Target gene of miR-4739 and promoter activity assay was measured by using dual-luciferase reporter assay system. In vivo, pleural fibrosis was evaluated by Masson staining and miR-4739 level was detected by In situ hybridization histochemistry. Findings: We found that bleomycin induced up-regulation of miR-4739 in pleural mesothelial cells (PMCs). Over-regulated miR-4739 mediated mesothelial-mesenchymal transition and increased collagen-I synthesis in PMCs. Investigation on the clinical specimens revealed that high levels of miR-4739 and low levels of bone morphogenetic protein 7 (BMP-7) associated with pleural fibrosis in patients. Then we next identified that miR-4739 targeted and down-regulated BMP-7 which further resulted in unbalance between Smad1/5/9 and Smad2/3 signaling. Lastly, in vivo studies revealed that miR-4739 over-expression induced pleural fibrosis, and exogenous BMP-7 prevented pleural fibrosis in mice. Interpretation: Our data indicated that miR-4739 targets BMP-7 which mediates pleural fibrosis. The miR-4739/BMP-7 axis is a promising therapeutic target for the disease. Fund: The National Natural Science Foundation of China. Keywords: Pleural fibrosis, Pleural mesothelial cells (PMCs), miR-4739, BMP-7, Mesothelial-mesenchymal transition (MMT)

CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR associated nuclease 9) systems have emerged as versatile and convenient (epi) genome editing tools and have become an important player in medical genetic research. CRISPR-Cas9 and its variants such as catalytically inactivated Cas9 (dead Cas9, dCas9) and scaffold-incorporating single guide sgRNA (scRNA) have been applied in various genomic screen studies. CRISPR screens enable high-throughput interrogation of gene functions in health and diseases. Compared with conventional RNAi screens, CRISPR screens incur less off-target effects and are more versatile in that they can be used in multiple formats such as knockout, knockdown and activation screens, and can target coding and non-coding regions throughout the genome. This powerful screen platform holds the potential of revolutionising functional genomic studies in the near future. Herein, we introduce the mechanisms of (epi)genome editing mediated by CRISPR-Cas9 and its variants, introduce the procedures and applications of CRISPR screen in functional genomics, compare it with conventional screen tools and at last discuss current challenges and opportunities and propose future directions. [ABSTRACT FROM AUTHOR]

Abstract The weak decays of a spin-1 / 2 doubly charm baryon ($$\mathcal{B}_{cc}$$ Bcc ) to a spin-1 / 2 singly charm baryon ($$\mathcal{B}_c$$ Bc ) and a light vector meson (V) are studied under a phenomenological scheme. The contributions are classified into different topological diagrams, among which the short distance ones are calculated under the factorization hypothesis, and the long distance contributions are modelled as final-state interactions (FSIs) which are estimated with the one-particle-exchange model. In calculation the topological contributions tend to fall in a hierarchy. The branching fractions or decay widths are estimated, and it indicates that $$\Xi _{cc}^+\rightarrow \Xi _c^+\pi ^+\pi ^-$$ Ξcc+→Ξc+π+π- and $$\Omega _{cc}^{+}\rightarrow \Xi _{c}^{+}K^-\pi ^+$$ Ωcc+→Ξc+K-π+ can be used as candidate decays for searching $$\Xi _{cc}^+$$ Ξcc+ and $$\Omega _{cc}^+$$ Ωcc+ . Some decays that are mainly activated by the long distance effects are found, observation on which in future experiments can help to understand the role of FSIs in charm baryon decays.

AIM:To evaluate the efficacy of phacoemulsification and intraocular lens(IOL)implantation combined with goniosynechialysis in the treatment of primary chronic angle closure glaucoma. METHODS: Eighty patients(96 eyes)with primary chronic angle closure glaucoma were divided into observation group(40 cases, 46 eyes)and control group(40 cases, 50 eyes). The treatment group was treated with phacoemulsification, intraocular lens implantation and goniosynechialysis, while the control group was treated with phacoemulsification and intraocular lens implantation. The best corrected visual acuity, intraocular pressure, visual field mean deviation(MD), mean sensitivity(MS)and the central anterior chamber depth of the two groups before and after the surgery were compared, and the occurrence of complications in patients with postoperative were record. RESULTS:The best corrected visual acuity, visual field, intraocular pressure and central anterior chamber depth of the two groups before operation showed no significant differences(P>0.05). The best corrected visual acuity, visual field, intraocular pressure and central anterior chamber depth between the groups at 6mo postoperatively showed statistically significant(Pχ2=0.351, P=2.095). CONCLUSION:The application of the phacoemulsification and intraocular lens implantation combined with goniosynechialysis in the treatment of primary chronic angle closure glaucoma is more effective than the simple use of phacoemulsification and intraocular lens implantation.

Cytokine-induced killer (CIK) cells that are stimulated using mature dendritic cells (DCs), referred to as (DC-CIK cells) exhibit superior anti-tumor potency. Anti-programmed death-1 (PD-1) antibodies reinvigorate T cell-mediated antitumor immunity. This phase I study aimed to assess the safety and clinical activity of immunotherapy with PD-1 blockade (pembrolizumab)-activated autologous DC-CIK cells in patients with advanced solid tumors. Patients with selected types of advanced solid tumors received a single intravenous infusion of activated autologous DC-CIK cells weekly for the first month and every 2 weeks thereafter. The primary end points were safety and adverse event (AE) profiles. Antitumor responses, overall survival (OS), progression-free survival (PFS) and cytolytic activity were secondary end points. Treatment-related AEs occurred in 20/31 patients. Grade 3 or 4 toxicities, including fever and chills, were observed in two patients. All treatment-related AEs were reversible or controllable. The cytotoxicity of DC-CIK cells induced up-regulation of PD-L1 expression on autologous tumor cells. When activated using pembrolizumab ex vivo, DC-CIK cells exerted superior antitumor properties and elevated IFN-γ secretion. Objective responses (complete or partial responses) were observed in 7 of the 31patients.These responses were durable, with 6 of 7 responses lasting more than 5 months. The overall disease control rate in the patients was 64.5%. At the time of this report, the median OS and PFS were 270 and 162 days, respectively. In conclusions, treatment with pembrolizumab-activated autologous DC-CIK cells was safe and exerted encouraging antitumor activity in advanced solid tumors. A larger phase II trial is warranted.

AIM:To compare the clinical efficacy of TransPRK and LASEK.METHODS:This study included 120 patients(240 eyes)with high myopic, which were divided into TransPRK(60 patients with 120 eyes)group and LASEK group(60 patients with 120 eyes)randomly. Recovery status, visual acuity, haze condition and refractions of the two groups were compared respectively at 1, 2wk, 3mo and 1a.RESULTS:The clinical results were very good for both groups. But at 1d post-operative, 86 eyes(71.7%)in TransPRK group felt no discomfort and had clear vision while there were 81 eyes(67.5%)in LASEK group having the same condition. One hundred and nine eyes(90.8%)had better UCVA than their BCVA pre-operative in TransPRK group compared to 87 eyes(72.5%)in LASEK group at 2wk post-operative. At 3mo post-operative, 113 eyes in TransPRK group had no haze(grade 0), compared to the 109 eyes in LASEK group.CONCLUSION:TransPRK had faster recovery of visual acuity and less discomfort than LASEK. And rate of haze was statistically lower in TransPRK group(PP>0.05). Finally, there was no significant difference on the efficiency, safety and predictability of high myopia treatments between the two methods.

AIM:To evaluate the efficiency and safety of high myopia treatments using AMARIS trans-epithelial photorefractive keratectomy(PRK).METHODS:One hundred and thirty six eyes in 68 patients with high myopic were treated using Amaris trans-epithelial PRK during December 2012～December 2013. Post-operative pain, haze, visual acuity, refraction and intraocular pressure(IOP)were analyzed during 12mo follow-up post-operatively.RESULTS:One hundred and eight eyes in 54 patients felt no discomfort at all, while 28 eyes in 14 patients reported dry eye, slight pain and foreign body sensation. UCVA between the two groups showed statistically different at 3, 6mo and 1a(t=2.04, P=0.047). UCVA at 3mo was the best compared with those at other time pionts, and became stable at 6mo. UCVA of all patients were above 0.8 at 12mo,and had no difference with that before operations(t=1.508, P=0.1670). Haze were hardly seen, and most of them were between grade 0～1. The patients' satisfaction was over 85% according to the survey about night vision, dry eye and asthenopia.CONCLUSION:Because of the great advantages of no-touch, fast recovery and less side effects, trans-epithelial PRK has great efficiency, safety and satisfaction. It now is the most ideal method of surface ablation for high myopia treatments.

The article presents the authors' response to the study "Comparative Effectiveness of Neoadjuvant Therapy for HER2-Positive Breast Cancer: A Network Meta-Analysis," by A. Nagayama and colleagues, published in a 2014 issue. The authors discuss the efficacy of neoadjuvant therapy in human epidermal growth factor receptor 2 (HER2)-positive breast cancer.