The RNA ligase RNA terminal phosphate cyclase B regulates mRNA alternative splicing and is required for mouse oocyte development and maintenance.

Recent large-scale mRNA sequencing has shown that introns are retained in 5-10% of mRNA, and these events are named intron retention (IR). IR has been recognized as a key mechanism in the regulation of gene expression. However, the role of this mechanism in female reproduction in mammals remains unclear. RNA terminal phosphate cyclase B (RTCB) is a RNA ligase; we found that RTCB conditional knockout mice have premature ovarian failure and that RTCB plays a crucial role in follicular development. RTCB regulated the splicing of transcripts related to DNA methylation and DNA damage repair. In addition, it regulated the resumption of oocyte meiosis by affecting CDK1 activation. Moreover, the loss of RTCB suppressed zygotic genome activation (ZGA) and decreased translation at the global level. In addition, Rtcb deletion resulted in the accumulation of maternal mRNAs containing unspliced introns and in a decline in the overall level of transcripts. As a result, the Rtcb-/- females were sterile. Our study highlights the important role of RTCB-regulated noncanonical alternative splicing in female reproduction.

Mechanical study of alisol B 23-acetate on methionine and choline deficient diet-induced nonalcoholic steatohepatitis based on untargeted metabolomics.

Alisol B 23-acetate (AB23A) has been demonstrated to have beneficial effects on nonalcoholic steatohepatitis (NASH). However, the mechanisms of AB23A on NASH remain unclear. This study aimed to investigate the mechanisms underlying the metabolic regulatory effects of AB23A on NASH. We used AB23A to treat mice with NASH, which was induced by a methionine and choline deficient (MCD) diet. We initially investigated therapeutic effect and resistance to oxidation and inflammation of AB23A on NASH. Subsequently, we performed untargeted metabolomic analyses and relative validation assessments to evaluate the metabolic regulatory effects of AB23A. AB23A reduced lipid accumulation, ameliorated oxidative stress and decreased pro-inflammatory cytokines in the liver. Untargeted metabolomic analysis found that AB23A altered the metabolites of liver. A total of 55 differential metabolites and three common changed pathways were screened among the control, model and AB23A treatment groups. Further tests validated the effects of AB23A on modulating common changed pathway-involved factors. AB23A treatment can ameliorate NASH by inhibiting oxidative stress and inflammation. The mechanism of AB23A on NASH may be related to the regulation of alanine, aspartate and glutamate metabolism, d-glutamine and d-glutamate metabolism, and arginine biosynthesis pathways.

Hygroscopic Solutes Enable Non-van der Waals Electrolytes for Fire-Tolerant Dual-Air Batteries.

Thermal safety issues of batteries have hindered their large-scale applications. Nonflammable electrolytes improved safety but solvent evaporation above 100 °C limited thermal tolerance, lacking reliability. Herein, fire-tolerant metal-air batteries were realized by introducing solute-in-air electrolytes whose hygroscopic solutes could spontaneously reabsorb the evaporated water solvent. Using Zn/CaCl2 -in-air/carbon batteries as a proof-of-concept, they failed upon burning at 631.8 °C but self-recovered then by reabsorbing water from the air at room temperature. Different from conventional aqueous electrolytes whose irreversible thermal transformation is determined by the boiling points of solvents, solute-in-air electrolytes make this transformation determined by the much higher decomposition temperature of solutes. It was found that stronger intramolecular bonds instead of intermolecular (van der Waals) interactions were strongly correlated to ultra-high tolerance temperatures of our solute-in-air electrolytes, inspiring a concept of non-van der Waals electrolytes. Our study would improve the understanding of the thermal properties of electrolytes, guide the design of solute-in-air electrolytes, and enhance battery safety.

Insights into Interfacial Mechanism of CeO2/Silicon and Atomic-Scale Removal Process during Chemo-Mechanical Grinding of Silicon.

Chemo-mechanical grinding (CMG) is a valid processing method to achieve a low-damage surface of silicon. However, the atomic interfacial mechanism during the CMG is still unclear. Herein, the CMG process of silicon was investigated using first principles and frictional wear tests in which the effects of pressure and speed on the interfacial reaction were comprehensively analyzed. Simulations showed that the formation and breakage of chemical bonds occurred at the CeO2/silicon interface during CMG, and the newly formed chemical bonds were stronger than those on the silicon surface. Also, it was found that the pressure and speed improved the materials removal rate by means of accelerating the interfacial chemical reactions, which is also verified by frictional wear tests. This study provides new insights into the atomic interfacial mechanism during silicon CMG.

JP1, a polypeptide specifically targeting integrin αVß3, ameliorates choroidal neovascularization and diabetic retinopathy in mice.

Anti-vascular endothelial growth factor (VEGF) drugs have revolutionized the treatment of neovascular eye diseases, but responses are incomplete in some patients. Recent evidence shows that integrins are involved in the pathogenesis of neovascular age-related macular degeneration and diabetic retinopathy. JP1, derived from an optimized seven-amino-acid fragment of JWA protein, is a polypeptide specifically targeting integrin αVß3. In this study we evaluated the efficacy of JP1 on laser-induced choroidal neovascularization (CNV) and retinal vascular leakage. CNV mice received a single intravitreal (IVT) injection of JP1 (10, 20, 40 µg) or ranibizumab (RBZ, 10 µg). We showed that JP1 injection dose-dependently inhibited laser-induced CNV; the effect of RBZ was comparable to that of 20 µg JP1; a combined IVT injection of JP1 (20 µg) and RBZ (5 µg) exerted a synergistic effect on CNV. In the 3rd month after streptozotocin injection, diabetic mice receiving IVT injection of JP1 (40 µg) or RBZ (10 µg) once a week for 4 weeks showed significantly suppressed retinal vascular leakage. In both in vivo and in vitro experiments, JP1 counteracted oxidative stress and inflammation via inhibiting ROS/NF-κB signaling in microglial cells, and angiogenesis via modulating MEK1/2-SP1-integrin αVß3 and TRIM25-SP1-MMP2 axes in vascular endothelial cells. In addition, intraperitoneal injection of JP1 (1, 5 or 10 mg) once every other day for 3 times also dose-dependently inhibited CNV. After intraperitoneal injection of FITC-labeled JP1 (FITC-JP1) or FITC in laser-induced CNV mice, the fluorescence intensity in the CNV lesion was markedly increased in FITC-JP1 group, compared with that in FITC group, confirming that JP1 could penetrate the blood-retinal barrier to target CNV lesion. We conclude that JP1 can be used to design novel CNV-targeting therapeutic agents that may replace current invasive intraocular injections.

Rapid Detection of Estrogens in Cosmetics by Chemical Derivatization and Paper-Spray Ionization Mass-Spectrometry.

Estrogens in personal care products are harmful to customers. Conventional methods such as HPLC and LC-MS require tedious sample pretreatment and long analytical time. Paper-spray ionization mass spectrometry (PSI-MS) is a powerful tool for the determination of compounds with little time and minimal pretreatment procedures. Since most estrogens show poor responses in PSI-MS, we developed a chemical derivatization and PSI-MS method to determinate three estrogens: estradiol, estriol and ethinyloestradiol with estradiol valerate as the internal standard (I.S.). After derivatization with 2-fluoro-1-methyl-pyridinium-p-toluene-sulfonate, the three estrogens could be quantified in seconds. This method showed good linearity in the range of 0.1~30 µg·mL-1, with R2 > 0.999. Their recovery results were all between 85%~115%. The limits of detection (LOD) were 0.04 µg·mL-1, 0.02 µg·mL-1 and 0.02 µg·mL-1 for estradiol, estriol and ethinyloestradiol respectively, which improved around 200, 2000, and 900 times compared to non-derivative PSI-MS. The method could quantitatively determine estrogens in cosmetics.

The Link Between Victimization and Misconduct in Prison Inmates: The Influence of Importation, Deprivation, and Low Self-Control Factors.

There has been limited study of the link between victimization and the criminal offense in the correctional context, despite the extensive literature supporting the overlap of victims and offenders in the general population. In this study, 2,880 inmates in 12 institutional correction facilities in Taiwan were examined to explore the common factors of the victim-offender overlap, guided by the importation, deprivation, and low self-control theories. The results of bivariate probit regression analysis revealed the presence of the victim-offender phenomenon in Taiwanese inmates. Specifically, the inmates who had experienced violent victimization in childhood and those who held negative perceptions of corrections staff and management tended to be both victims and offenders as measured by various types of prison misconduct and victimization. The results also showed that importation and deprivation factors have similar explanatory power for both misconduct and victimization, and low self-control has greater explanatory power for misconduct than for victimization.

Impact of negative pressure wound treatment on incidence of surgical site infection in varied orthopedic surgeries: A systematic review and meta-analysis.

Negative pressure wound therapy (NPWT) is a popular treatment to heal infected wounds. This meta-analysis aimed to determine if NPWT was more effective than conventional wound dressings for surgical site infections (SSI) in varied orthopaedic surgeries. Literature was retrieved from seven electronic databases (Medline, Web of Science, PubMed, Embase, Google Scholar, Cochrane Library, and CNKI). Randomised control trials (RCT) and retrospective cohort studies (RS) involving arthroplasty, fracture, and spinal surgery were extracted. SSI was our primary outcome, while total complications and length of hospital stay were secondary outcomes. We carried out the risk of bias assessment and meta-analysis using the Cochrane Risk of Bias 2.0 tool and Stata 17.0. Among the 798 studies retrieved, 18 of them met our inclusion criteria. We identified 13 RCTs and 5 RSs. The results of meta-analysis showed that the incidence of SSI in the NPWT group was significantly lower relative to the control group (OR = 0.60, 95% CI 0.47 to 0.77, P < 0.001). Subgroup analyses revealed that the incidences of SSI involving arthroplasty, fracture, and spinal surgery in the NPWT group accounted for 46%, 69%, and 37% relative to the control group, respectively. The incidence of SSI in RS (OR = 0.27, 95% CI 0.13 to 0.56) was significantly lower than that in RCT (OR = 0.69, 95% CI 0.54 to 0.90) (P = 0.02). Moreover, patients in the NPWT group had a lower total complication rate (OR = 0.51, 95% CI 0.34 to 0.76) and shorter hospital stays (SMD = -0.42, 95% CI -0.83 to -0.02), although high heterogeneity existed. NPWT may be an efficient alternative to help prevent the incidence of SSI and total complications as well as achieved shorten hospital stay in varied orthopaedic surgeries. The rational use of NPWT should be based on the presence of patients' clinical conditions and relevant risk factors.

NaCdSb: An Orthorhombic Zintl Phase with Exceptional Intrinsic Thermoelectric Performance.

Many Zintl phases are promising thermoelectric materials owning to their features like narrow band gaps, multiband behaviors, ideal charge transport tunnels, and loosely bound cations. Herein we show a new Zintl phase NaCdSb with exceptional intrinsic thermoelectric performance. Pristine NaCdSb exhibits semiconductor behaviors with an experimental hole concentration of 2.9×1018  cm-3 and a calculated band gap of 0.5 eV. As the temperature increases, the hole concentration rises gradually and approaches its optimal one, leading to a high power factor of 11.56 µW cm-1 K-2 at 673 K. The ultralow thermal conductivity is derived from the small phonon group velocity and short phonon lifetime, ascribed to the structural anharmonicity of Cd-Sb bonds. As a consequence, a maximum zT of 1.3 at 673 K has been achieved without any doping optimization or structural modification, demonstrating that NaCdSb is a remarkable thermoelectric compound with great potential for performance improvement.

Comparision of biological and genomic characteristics of five virulent bacteriophages against Enterobacter hormaechei.

Enterobacter hormaechei is a zoonotic bacteria that may cause respiratory diseases in animals and neonatal sepsis in humans. Bacteriophages are increasingly considered as potential biocontrol agents to control pathogens in the food industry. In this study, five E. hormaechei virulent phages, named as Ehp-YZU08, Ehp-YZU10, Ehp-YZU9-1, Ehp-YZU9-2 and Ehp-YZU9-3, were isolated from sewage in China and analyzed for their biological and whole-genome characteristics, and a comparative genomic analysis was performed to study the functional genes and phylogenetic evolution of phages. The results showed that four of the phage strains belong to the Podoviridae family and one belongs to the Myoviridae family. The burst sizes were 70-283 PFU/cell after a latent period of 5-40 min. Phages were able to survive in a pH range of 5-10 and resist temperatures up to 60 °C for 60 min. The sequencing results showed that the full length of the genomes of the five phages ranged from 39,502 to 173,418 bp. Each phage contained multiple genes related to phage replication, and genes related to bacterial virulence or drug resistance were not found. The five phages belonged to three different groups by a construction of a phylogenetic tree, and the significant genetic evolutionary distance from each E. hormaechei phage was observed. The inhibition assay showed that all five phages could completely inhibit the growth of E. hormaechei at 37 °C within 8 h, suggesting that the phages in this study have great potential for the development of biocontrol agents against E. hormaechei in the food industry.

Bacteriophages: A weapon against mixed-species biofilms in the food processing environment.

Mixed-species biofilms represent the most frequent actual lifestyles of microorganisms in food processing environments, and they are usually more resistant to control methods than single-species biofilms. The persistence of biofilms formed by foodborne pathogens is believed to cause serious human diseases. These challenges have encouraged researchers to search for novel, natural methods that are more effective towards mixed-species biofilms. Recently, the use of bacteriophages to control mixed-species biofilms have grown significantly in the food industry as an alternative to conventional methods. This review highlights a comprehensive introduction of mixed-species biofilms formed by foodborne pathogens and their enhanced resistance to anti-biofilm removal strategies. Additionally, several methods for controlling mixed-species biofilms briefly focused on applying bacteriophages in the food industry have also been discussed. This article concludes by suggesting that using bacteriophage, combined with other 'green' methods, could effectively control mixed-species biofilms in the food industry.

The AP2 Transcription Factor BrSHINE3 Regulates Wax Accumulation in Nonheading Chinese Cabbage.

Wax is an acellular structural substance attached to the surface of plant tissues. It forms a protective barrier on the epidermis of plants and plays an important role in resisting abiotic and biotic stresses. In this paper, nonheading Chinese cabbage varieties with and without wax powder were observed using scanning electron microscopy, and the surface of waxy plants was covered with a layer of densely arranged waxy crystals, thus differentiating them from the surface of waxless plants. A genetic analysis showed that wax powder formation in nonheading Chinese cabbage was controlled by a pair of dominant genes. A preliminary bulked segregant analysis sequencing (BSA-seq) assay showed that one gene was located at the end of chromosome A09. Within this interval, we identified BraA09000626, encoding an AP2 transcription factor homologous to Arabidopsis AtSHINE3, and we named it BrSHINE3. By comparing the CDS of the gene in the two parental plants, a 35 bp deletion in the BrSHINE3 gene of waxless plants resulted in a frameshift mutation. Tissue analysis showed that BrSHINE3 was expressed at significantly higher levels in waxy plant rosette stage petioles and bolting stage stems than in the tissues of waxless plants. We speculate that this deletion in BrSHINE3 bases in the waxless material may inhibit wax synthesis. The overexpression of BrSHINE3 in Arabidopsis induced the accumulation of wax on the stem surface, indicating that BrSHINE3 is a key gene that regulates the formation of wax powder in nonheading Chinese cabbage. The analysis of the subcellular localization showed that BrSHINE3 is mainly located in the nucleus and chloroplast of tobacco leaves, suggesting that the gene may function as a transcription factor. Subsequent transcriptome analysis of the homology of BrSHINE3 downstream genes in nonheading Chinese cabbage showed that these genes were downregulated in waxless materials. These findings provide a basis for a better understanding of the nonheading Chinese cabbage epidermal wax synthesis pathway and provide important information for the molecular-assisted breeding of nonheading Chinese cabbage.

Isolation and genomic characterization of P.A-5, a novel virulent bacteriophage against Enterobacter hormaechei.

Enterobacter hormaechei is a foodborne pathogen responsible for neonatal sepsis in humans and respiratory disease in animals. In this work, a new virulent phage (P.A-5) infecting E. hormaechei was isolated from domestic sewage samples and characterized. Transmission electron microscopy revealed that P.A-5 belonged to the family Myoviridae having a head size of 77.53 nm and a tail length of 72.24 nm. The burst size was 262 PFU/cell after a latent period of 20 min. Phage P.A-5 was able to survive in a pH range of 4-9 and resist temperatures up to 55 °C for 60 min. The genome sequence of P.A-5 had homology most similar to that of Shigellae phage MK-13 (GenBank: MK509462.1). Pork artificially contaminated with E. hormaechei was used as a model to evaluate the potential of P.A-5. The results clearly showed that P.A-5 treatment can completely inhibit E. hormaechei growth in pork within 8 h, indicating the potential use of P.A-5 as a biocontrol agent for E. hormaechei.

A Clinical Risk Score to Predict In-hospital Mortality from COVID-19 in South Korea.

BACKGROUND: Early identification of patients with coronavirus disease 2019 (COVID-19) who are at high risk of mortality is of vital importance for appropriate clinical decision making and delivering optimal treatment. We aimed to develop and validate a clinical risk score for predicting mortality at the time of admission of patients hospitalized with COVID-19. METHODS: Collaborating with the Korea Centers for Disease Control and Prevention (KCDC), we established a prospective consecutive cohort of 5,628 patients with confirmed COVID-19 infection who were admitted to 120 hospitals in Korea between January 20, 2020, and April 30, 2020. The cohort was randomly divided using a 7:3 ratio into a development (n = 3,940) and validation (n = 1,688) set. Clinical information and complete blood count (CBC) detected at admission were investigated using Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression to construct a predictive risk score (COVID-Mortality Score). The discriminative power of the risk model was assessed by calculating the area under the curve (AUC) of the receiver operating characteristic curves. RESULTS: The incidence of mortality was 4.3% in both the development and validation set. A COVID-Mortality Score consisting of age, sex, body mass index, combined comorbidity, clinical symptoms, and CBC was developed. AUCs of the scoring system were 0.96 (95% confidence interval [CI], 0.85-0.91) and 0.97 (95% CI, 0.84-0.93) in the development and validation set, respectively. If the model was optimized for > 90% sensitivity, accuracies were 81.0% and 80.2% with sensitivities of 91.7% and 86.1% in the development and validation set, respectively. The optimized scoring system has been applied to the public online risk calculator (https://www.diseaseriskscore.com). CONCLUSION: This clinically developed and validated COVID-Mortality Score, using clinical data available at the time of admission, will aid clinicians in predicting in-hospital mortality.

Characterization of Pingliang xiaoheidou (ZDD 11047), a soybean variety with resistance to soybean cyst nematode Heterodera glycines.

KEY MESSAGE: A novel QTL (qSCN-PL10) for SCN resistance and related candidate genes were identified in the soybean variety Pingliang xiaoheidou, and plant basal immunity seems to contribute to the SCN resistance. Soybean cyst nematode (SCN, Heterodera glycines Ichinohe) is one of the most devastating soybean pests worldwide. The development of host plant resistance represents an effective strategy to control SCN. However, owing to the lack of diversity of resistance genes in soybean varieties, further investigation is necessary to identify new SCN resistance genes. By analyzing the resistance phenotypes of soybean variety Pingliang xiaoheidou (Pingliang, ZDD 11047), we found that it exhibited the different resistance phenotypes from PI 88788 and Peking varieties. Because Pingliang variety contains the Rhg1-a (low copy) haplotype and lacks the resistant Rhg4 haplotype, novel quantitative trait locus might account for their SCN resistance. After sequencing parental lines (Magellan and Pingliang) and 200 F2:3 progenies, a high-density genetic map was constructed using the specific length amplified fragment sequencing method and qSCN-PL10 was identified as a novel locus for SCN resistance. Candidate genes were predicted by RNA sequencing (RNA-seq) in the qSCN-PL10 locus region. The RNA-seq analysis performed also indicated that plant basal immunity plays an important role in the resistance of Pingliang to SCN. These results lay a foundation for the use of marker-assisted breeding to enhance the resistance to SCN.

Overexpression of PpSnRK1α in tomato enhanced salt tolerance by regulating ABA signaling pathway and reactive oxygen metabolism.

BACKGROUND: SNF-related Kinase 1 (SnRK1) is a key component of the cell signaling network. SnRK1 is known to respond to a wide variety of stresses, but its exact role in salt stress response and tolerance is still largely unknown. RESULTS: In this study, we reported that overexpression of the gene encoding the α subunit of Prunus persica SnRK1 (PpSnRK1α) in tomato could improve salt stress tolerance. The increase in salt stress tolerance in PpSnRK1α-overexpressing plants was found to correlate with increased PpSnRK1α expression level and SnRK1 kinase activity. And PpSnRK1α overexpression lines exhibited a lower level of leaf damage as well as increased proline content and reduced malondialdehyde (MDA) compared with wild-type (WT) lines under salt stress. Furthermore, PpSnRK1α enhanced reactive oxygen species (ROS) metabolism by increasing the expression level of antioxidase genes and antioxidant enzyme activities. We further sequenced the transcriptomes of the WT and three PpSnRK1α overexpression lines using RNA-seq and identified about 1000 PpSnRK1α-regulated genes, including many antioxidant enzymes, and these genes were clearly enriched in the MAPK signaling pathway (plant), plant-pathogen interactions and plant hormone signaling transduction and can respond to stimuli, metabolic processes, and biological regulation. Furthermore, we identified the transcriptional levels of several salt stress-responsive genes, SlPP2C37, SlPYL4, SlPYL8, SlNAC022, SlNAC042, and SlSnRK2 family were altered significantly by PpSnRK1α, signifying that SnRK1α may be involved in the ABA signaling pathway to improve tomato salt tolerance. Overall, these findings provided new evidence for the underlying mechanism of SnRK1α conferment in plant salt tolerance phenotypes. CONCLUSIONS: Our findings demonstrated that plant salt stress resistance can be affected by the regulation of the SnRK1α. Further molecular and genetic approaches will accelerate our knowledge of PpSnRK1α functions, and inform the genetic improvement of salt tolerance in tomato through genetic engineering and other related strategies.

[Production and quality control of original herbal materials of Danhong Injection].

Cardiovascular and cerebrovascular diseases are the leading cause of death for residents in China. Danhong Injection(DHI) decoction piece is prepared from Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos, with the function of promoting the blood circulation, removing the blood stasis, relaxing the sinews and dredging the collaterals. In recent years, about 100 million bottles of DHI have been sold. Consequently, its safety and effectiveness are very important to a large number of patients. Raw materials are the source and foundation for production of traditional Chinese medicine injections. In this article, we reviewed the identification of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos, resource distribution, cultivation, quality control, and detection of xenobiotic pollutants, in order to guide the production of high-quality, stable, and pollution-free raw materials. This will be a benefit in ensuring the safety and effectiveness of DHI and reducing the incidence of adverse reactions from the raw materials. By comparing the similarities and differences between the quality standards of Salviae Miltiorrhizae Radix et Rhizoma, Carthami Flos and DHI, we provided some comments for improving the quality standards and post-marketing reevaluation of DHI, and provided some theoretical supports for the production of high-quality herbal raw materials.

High Intensity Exercise for Walking Competency in Individuals with Stroke: A Systematic Review and Meta-Analysis.

OBJECTIVE: To assess the effects of high intensity exercise on walking competency in individuals with stroke. DATA SOURCES: A systematic electronic searching of the PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL (EBSCOhost), and SPORTSDiscus (EBSCOhost) was initially performed up to June 25, 2019. STUDY SELECTION: Randomized controlled trials or clinical controlled trials comparing any walking or gait parameters of the high intensity exercise to lower intensity exercise or usual physical activities were included. The risk of bias of included studies was assessed by the Cochrane risk of bias tool. The quality of evidence was assessed using GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system. DATA EXTRACTION: Data were extracted by 2 independent coders. The mean and standard deviation of the baseline and endpoint scores after training for walking distance, comfortable gait speed, gait analysis (cadence, stride length, and the gait symmetry), cost of walking, Berg Balance Scale , Time Up&Go (TUG) Test and adverse events were extracted. DATA SYNTHESIS: A total of 22 (n = 952) studies were included. Standardized mean difference (SMD), weighted mean difference (WMD), and odds ratios (ORs) were used to compute effect size and subgroup analysis was conducted to test the consistency of results with different characteristics of exercise and time since stroke. Sensitivity analysis was used to assess the robustness of the results, which revealed significant differences on walking distance (SMD = .32, 95% CI, .17-.46, P < .01, I2 = 39%; WMD = 21.76 m), comfortable gait speed (SMD = .28, 95% CI, .06-.49, P = .01, I2 = 47%; WMD = .04 m/s), stride length (SMD = .51, 95% CI, .13-.88, P < .01, I2 = 0%; WMD = .12 m) and TUG (SMD = -.36, 95% CI, -.72 to .01, P = .05, I2 = 9%; WMD = -1.89 s) in favor of high intensity exercise versus control group. No significant differences were found between the high intensity exercise and control group in adverse events, including falls (OR = 1.40, 95% CI, .69-2.85, P = .35, I2 = 11%), pain (OR = 3.34, 95% CI, .82-13.51, P = .09, I2 = 0%), and skin injuries (OR = 1.08, 95% CI, .30-3.90, P = .90, I2 = 0%). CONCLUSIONS: This systematic review suggests that high intensity exercise could be safe and more potent stimulus in enhancing walking competency in stroke survivors, with a capacity to improve walking distance, comfortable gait speed, stride length, and TUG compared with low to moderate intensity exercise or usual physical activities.

Quercetin reversed MDR in breast cancer cells through down-regulating P-gp expression and eliminating cancer stem cells mediated by YB-1 nuclear translocation.

Overexpression of P-glycoprotein (P-gp) plays an important role in mediating multidrug resistance (MDR), resulting in chemotherapy failure of tumor patients and enhancement of cancer stem cell characteristics. By preparing doxorubicin (Dox) resistant human breast cancer MCF-7 cells, here, we wanted to evaluate the effects of quercetin (Que) on MDR reversal activity and investigate its possible mechanism. MCF-7 and MCF-7/dox cells were respectively treated by Dox, paclitaxel (Pac), or vincristine (Vcr) with or without Que intervention for 24 hr. Cell viability, cell apoptosis, cell cycle, intracellular drug accumulation, the expression of P-gp and Y-box binding protein 1 (YB-1), and breast cancer stem cells (BCSCs) were then assessed. The results showed that Que significantly enhanced the antitumor activities of Dox, Pac, and Vcr in breast cancer cells. In addition, combined treatment of Dox, Pac, or Vcr with Que significantly downregulated P-gp expression and eliminated BCSCs. Furthermore, combined treatment of Dox, Pac, or Vcr with Que significantly inhibited nuclear translocation of YB-1. Thus, we speculated that Que reversed MDR in breast cancer cells through downregulating P-gp expression and eliminating cancer stem cells mediated by YB-1 nuclear translocation.

[Establishment of a penile transplantation model in beagle dogs].

OBJECTIVE: To investigate the feasibility of establishing a model of allograft penile transplantation in adult beagle dogs and explore the conditions for constructing a stable animal model of penis transplant. METHODS: Following the principles of similarity, repeatability, feasibility, applicability, and controllability in the construction of experimental animal models, we compared the major anatomic features of the penis of 20 adult beagle dogs with those of 10 adult men. Using microsurgical techniques, we performed cross-transplantation of the penis in the 20 (10 pairs) beagle dogs and observed the survival rate of the transplanted penises by FK506+MMF+MP immune induction. We compared the relevant indexes with those of the 10 cases of microsurgical replantation of the amputated penis. RESULTS: High similarities but no statistically significant differences were observed in penile anatomic features between the 20 beagle dogs and 10 men. All the 10 cases of cross-transplantation of the penis were successfully completed in the 20 beagle dogs, of which the transplanted glans survived with normal micturition in 12 but developed necrosis in the other 8; the success rate of one-time venous anastomosis was 95.0% (38/40) and that of one-time arterial anastomosis was 87.5% (35/40), with an average vascular anastomosis time of (71.0±9.0) minutes, a mean operation time of (133.0±10.3) minutes, and a mean blood loss of (135.8±41.4) ml. In the 10 cases of penile replantation, the success rate of one-time venous anastomosis was 100% (20/20) and that of one-time arterial anastomosis was 90.0% (18/20), with an average vascular anastomosis time of (65.0±7.9) minutes, a mean operation time of (117.4±10.0) minutes, and a mean blood loss of (85.0±10.8) ml. In the 12 cases of replantation of the amputated penis, the success rate of one-time venous anastomosis was 100% (24/24) and that of one-time arterial anastomosis was 95.8% (23/24), with an average vascular anastomosis time of (79.0±17.6) minutes, a mean operation time of (125.0±20.6) minutes, and a mean blood loss of (140.0±44.3) ml. No statistically significant differences were found in the relevant indexes among the three groups. CONCLUSIONS: The anatomic structure of the corpus cavernosum penis of beagle dogs is highly similar to that of men, almost the same in cross-section anatomy. Microsurgical replantation and allograft transplantation of the penis were both successfully performed in beagle dogs, which showed similar operative indexes to those of human penile replantation. The construction of the allograft penile transplantation model in adult beagle dogs is feasible clinically, with the advantages of operability and repeatability.