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Abstract Proinsulin translation and folding is crucial for glucose homeostasis. However, islet β-cell control of Proinsulin translation remains incompletely understood. Here, we identify OSGEP, an enzyme responsible for t6A37 modification of tRNANNU that tunes glucose metabolism in β-cells. Global Osgep deletion causes glucose intolerance, while β-cell-specific deletion induces hyperglycemia and glucose intolerance due to impaired insulin activity. Transcriptomics and proteomics reveal activation of the unfolded protein response (UPR) and apoptosis signaling pathways in Osgep-deficient islets, linked to an increase in misfolded Proinsulin from reduced t6A37 modification. Osgep overexpression in pancreas rescues insulin secretion and mitigates diabetes in high-fat diet mice. Osgep enhances translational fidelity and alleviates UPR signaling, highlighting its potential as a therapeutic target for diabetes. Individuals carrying the C allele at rs74512655, which promotes OSGEP transcription, may show reduced susceptibility to T2DM. These findings show OSGEP is essential for islet β-cells and a potential diabetes therapy target.

Abstract Type I CRISPR-Cas systems employ multi-subunit effector Cascade and helicase-nuclease Cas3 to target and degrade foreign nucleic acids, representing the most abundant RNA-guided adaptive immune systems in prokaryotes. Their ability to cause long fragment deletions have led to increasing interests in eukaryotic genome editing. While the Cascade structures of all other six type I systems have been determined, the structure of the most evolutionarily conserved type I-B Cascade is still missing. Here, we present two cryo-EM structures of the Synechocystis sp. PCC 6714 (Syn) type I-B Cascade, revealing the molecular mechanisms that underlie RNA-directed Cascade assembly, target DNA recognition, and local conformational changes of the effector complex upon R-loop formation. Remarkably, a loop of Cas5 directly intercalated into the major groove of the PAM and facilitated PAM recognition. We further characterized the genome editing profiles of this I-B Cascade-Cas3 in human CD3+ T cells using mRNA-mediated delivery, which led to unidirectional 4.5 kb deletion in TRAC locus and achieved an editing efficiency up to 41.2%. Our study provides the structural basis for understanding target DNA recognition by type I-B Cascade and lays foundation for harnessing this system for long range genome editing in human T cells.

Flavobacterium davisii is one of the causative agents of columnaris disease, significantly impacting Nile tilapia aquaculture. This study examines the invasion and immune evasion mechanisms of a highly virulent F. davisii strain through transcriptomic profiling of tilapia gills following acute immersion. We identified 8192 differentially expressed genes (DEGs) at 2 h, 6 h, and 12 h post-infection. They are enriched in pathways related to oxidative stress, immune suppression, tissue necrosis, and bacterial infection. Notably, early overexpression of rhamnose-binding lectin and mucin genes facilitated bacterial adhesion. Key immune genes, including those encoding major histocompatibility complex (MHC), immunoglobulins (Ig), Toll-like receptors (TLRs), and chemokines, were downregulated, indicating immune suppression. Conversely, immune evasion genes such as Fc receptor-like (FcRL) and programmed death-ligand 1 (PDL1) were upregulated, along with genes associated with reactive oxygen species (ROS) production, leading to increased tissue damage. Additionally, the upregulation of fibroblast growth factor and collagen genes suggested active tissue repair. In conclusion, F. davisii rapidly invades its host by enhancing adhesion to gill tissues, suppressing immune function, and inducing tissue damage. These findings enhance our understanding of F. davisii infection mechanisms and support the future breeding of disease-resistant tilapia and the development of sustainable control strategies.

Abstract Amyotrophic lateral sclerosis (ALS) is a devastating fatal neurodegenerative disease with no cure. Receptor-interacting protein kinase 1 (RIPK1) has been proposed to mediate pathogenesis of ALS. Primidone has been identified as an old drug that can also inhibit RIPK1 kinase. We conducted a drug-repurposing biomarker study of primidone as a RIPK1 inhibitor using SOD1G93A mice and ALS patients. SOD1G93A mice treated with primidone showed significant delay of symptomatic onset and improved motor performance. One-hundred-sixty-two ALS participants dosed daily with primidone (62.5 mg) completed 24-week follow-up. A significant reduction was showed in serum levels of RIPK1 and IL-8, which were significantly higher in ALS patients than that of healthy controls (P

Abstract Background Hemorrhage has always been the focus of battlefield and pre-hospitalization treatment. With the increasing fatality rates associated with junctional bleeding, treatment of bleeding at junctional sites has gradually gained attention in battlefield trauma emergency care. We designed a modified chain-based sponge dressing with a medical polyvinyl alcohol sponge that can be used to treat junctional hemorrhage and tested its hemostatic efficacy and biocompatibility. Methods Twenty adult Bama miniature pigs were randomly divided into the modified chain-based sponge dressing (MCSD) and standard gauze (SG) groups. The right femoral artery of the pigs was shot at after anesthesia. The Bama miniature pigs were moved to the safety zone immediately to assess the condition according to the MARCH strategy, which evaluates massive hemorrhaging, airway obstruction, respiratory status, circulatory status, head injury & hypothermia. Hemoglobin and coagulation status were checked during the experiment.Among the pigs in which the inguinal hemorrhagic model based on bullet penetrating wounds was successfully established, those in the MCSD group received a disinfected MCSD for hemostasis, while those in the SG group received standard gauze in an imbricate manner to pack the bullet exit and entrance wounds to stop bleeding until the wound was filled, followed by compression for 3 min at sufficient pressure. CT scanning, transmission electron microscopy, and HE staining were conducted after experiment. Results The MCSD group showed lower hemostasis time and blood loss than the gauze group. The MCSD group also showed a higher success rate of treatment,more stable vital signs and hemoglobin level. The CT scanning results showed tighter packing without large gaps in the MCSD group. The histopathological assessments and the transmission electron microscopy and HE staining findings indicated good biocompatibility of the polyvinyl alcohol sponge. Conclusion The MCSD met the battlefield’s requirements of speedy hemostasis and biosafety for junctional hemorrhage in Bama miniature pigs. Moreover, in comparison with the conventional approach for hemostasis, it showed more stable performance for deep wound hemostasis. These findings provide the theoretical and experimental basis for the application of MCSD in the treatment of hemorrhage in the battlefield in the future.

The confinement of transgenic fish is essential to prevent their escape and reproduction in natural ecosystems. Reversible transgenic sterilization is a promising approach to control the reproduction of transgenic fish. Therefore, the present study was conducted to develop a reversibly sterile channel catfish (Ictalurus punctatus) via the transgenic overexpression of the goldfish (Carassius auratus) glutamic acid decarboxylase (GAD) gene driven by the common carp (Cyprinus carpio) β-actin promoter to disrupt normal gamma-aminobutyric acid (GABA) regulation. Three generations of GAD-transgenic fish were produced. All studied generations showed repressed reproductive performance; however, this was not always statistically significant. In F1, 5.4% of the transgenic fish showed a sexual maturity score ≥ 4 (maximum = 5) at five years of age, which was lower (p = 0.07) than that of the control group (16.8%). In the spawning experiments conducted on F1 transgenic fish at six and nine years of age, 45.5% and 20.0% of fish spawned naturally, representing lower values (p = 0.09 and 0.12, respectively) than the percentages in the sibling control fish of the same age (83.3% and 66.7%, respectively). Four of six pairs of the putative infertile six-year-old fish spawned successfully after luteinizing hormone-releasing hormone analog (LHRHa) therapy. Similar outcomes were noted in the three-year-old F2 fish, with a lower spawning percentage in transgenic fish (20.0%) than in the control (66.7%). In one-year-old F2-generation transgenic fish, the observed mean serum gonadotropin-releasing hormone (GnRH) levels were 9.23 ± 2.49 and 8.14 ± 2.21 ng/mL for the females and males, respectively. In the control fish, the mean levels of GnRH were 11.04 ± 4.06 and 9.03 ± 2.36 ng/mL for the females and males, respectively, which did not differ significantly from the control (p = 0.15 and 0.27 for females and males, respectively). There was no significant difference in the estradiol levels of the female transgenic and non-transgenic fish in the one- and four-year-old F2-generation fish. The four-year-old F2-generation male transgenic fish exhibited significantly (p < 0.05) lower levels of GnRH and testosterone than the control fish. In conclusion, while overexpressing GAD repressed the reproductive abilities of channel catfish, it did not completely sterilize transgenic fish. The sterilization rate might be improved through selection in future generations.

Fish exhibit a broad spectrum of colors and patterns facilitated by specialized cells known as chromatophores. The vibrant coloration of fish, controlled by complex genetic and environmental interactions, serves critical roles in ecological functions such as mating, predation, and camouflage. This diversity not only makes fish an invaluable model for exploring the molecular mechanisms of pigmentation but also significantly impacts their economic value within the aquaculture industry, where color traits can drive marketability and breeding choices. This review delves into the sophisticated biological processes governing fish pigmentation and discusses their applications in enhancing aquaculture practices. By exploring the intersection of genetic regulation, environmental influences, and advanced breeding techniques, this review highlights both the scientific understanding and practical applications of fish coloration, providing a bridge between basic biological research and its application in commercial aquaculture.

Abstract Clostridioides difficile spores are considered as the major source responsible for the development of C. difficile infection (CDI), which is associated with an increased risk of death in patients and has become an important issue in infection control of nosocomial infections. Current treatment against CDI still relies on antibiotics, which also damage normal flora and increase the risk of CDI recurrence. Therefore, alternative therapies that are more effective against C. difficile bacteria and spores are urgently needed. Here, we designed an oxidation process using H2O2 containing PBS solution to generate Cl− and peroxide molecules that further process Ag and Au ions to form nanoboxes with Ag–Au peroxide coat covering Au shell and AgCl core (AgAu‐based nanoboxes). The AgAu‐based nanoboxes efficiently disrupted the membrane structure of bacteria/spores of C. difficile after 30–45 min exposure to the highly reactive Ag/Au peroxide surface of the nano structures. The Au‐enclosed AgCl provided sustained suppression of the growth of 2 × 107 pathogenic Escherichia coli for up to 19 days. In a fecal bench ex vivo test and in vivo CDI murine model, biocompatibility and therapeutic efficacy of the AuAg nanoboxes to attenuate CDI was demonstrated by restoring the gut microbiota and colon mucosal structure. The treatment successfully rescued the CDI mice from death and prevented their recurrence mediated by vancomycin treatment. The significant outcomes indicated that the new peroxide‐derived AgAu‐based nanoboxes possess great potential for future translation into clinical application as a new alternative therapeutic strategy against CDI.

The hybrid between the female channel catfish (Ictalurus punctatus) and the male blue catfish (I. furcatus) is the best genetic type currently available for commercial catfish farming due to their superior traits. However, further genetic improvements can be achieved by selecting parents with increased combining abilities. Twenty female channel catfish and twelve male blue catfish were crossed in a partial factorial mating design, resulting in forty hybrid families. These families were evaluated for early growth in three different rearing systems, including ponds and aquaria. The early growth performance of hybrid catfish was significantly (p < 0.05) affected by the additive gene action of the female parent and the male parent. There were genotype–environment or genotype–age interactions affecting the combining abilities, both the amount and the type of genetic variation. Dam GCA was significant in all environments/ages; however, sire GCA was variable, and SCA was not significant. These findings suggest that reciprocal recurrent selection for growth could potentially improve the performance of F1 hybrid catfish.

Abstract Background Aortic aneurysm (AA) is a global public health concern. However, little is known about the disease burden of AA in China. Methods Following the general analytic strategy used in the Global Burden of Disease Study (GBD) 2019, we analyzed the mortality and years of life lost (YLLs) due to AA, stratified by sex, age, and province-level region in China from 1990 to 2019. The temporal trend of AA burden in China was analyzed and the main attributable risk factors for AA in China were also explored. Results In China, the total AA deaths were 17,038 (95% UI: 14,392-19,980) in 2019, an increase of 136.1% compared with that in 1990, with an age-standardized death rate (ASDR) of 0.93 (95% UI: 0.79-1.08) per 100,000 person-years in 2019, a decrease of 6.8%. Meanwhile AA caused 378,578 (95% UI: 315,980-450,479) YLLs in 2019, an increase of 102.6% compared with that in 1990, with a crude YLL rate of 26.6 (95% UI: 22.2-31.7) per 100,000 person-years, an increase of 68.6%. The AA mortality and YLLs were higher in males than in females. AA caused most YLLs in the 65- to 75-year-old age group. The AA mortality and YLLs varied significantly among provinces in China, and the change in ASDR showed a negative correlation with the sociodemographic index of different provinces, namely, more decline of ASDR in developed provinces. High systolic blood pressure was shown to be the most significant attributable risk factor for AA burden in both males and females, and smoking was another major attributable risk factor, especially in males. Conclusions The disease burden of AA increased significantly from 1990 to 2019 in China, with higher mortality and YLLs in males, senior populations, and among residents of most western provinces in China. High systolic blood pressure and smoking were two major attributable risk factors for AA mortality in China.

BackgroundBenign prostatic diseases (BPDs), such as benign prostate hyperplasia (BPH) and prostatitis, harm the quality of life of affected patients. However, observational studies exploring the association between thyroid function and BPDs have hitherto yielded inconsistent results. In this study, we explored whether there is a causal genetic association between them using Mendelian randomization (MR) analysis.MethodsWe used publicly available summary statistics from the Thyroidomics Consortium and 23andMe on thyrotropin (TSH; 54,288 participants), thyroxine [free tetraiodothyronine (FT4); 49,269 participants], subclinical hypothyroidism (3,440 cases and 49,983 controls), overt hypothyroidism (8,000 cases and 117,000 controls), and subclinical hyperthyroidism (1,840 cases and 49,983 controls) to screen for instrumental variables of thyroid function. Results for BPD such as prostatic hyperplasia (13,118 cases and 72,799 controls) and prostatitis (1,859 cases and 72,799 controls) were obtained from the FinnGen study. The causal relationship between thyroid function and BPD was primarily assessed using MR with an inverse variance weighted approach. In addition, sensitivity analyses were performed to test the robustness of the results.ResultsWe found that TSH [OR (95% CI) = 0.912(0.845-0.984), p =1.8 x 10-2], subclinical hypothyroidism [OR (95% CI) = 0.864(0.810-0.922), p =1.04 x 10-5], and overt hypothyroidism [OR (95% CI) = 0.885 (0.831-0. 944), p =2 x 10-4] had a significant effect on genetic susceptibility to BPH, unlike hyperthyroidism [OR (95% CI) = 1.049(0.990-1.111), p =1.05 x 10-1] and FT4 [OR (95% CI) = 0.979(0.857-1.119), p = 7.59 x 10-1] had no effect. We also found that TSH [OR (95% CI) =0.823(0.700-0.967), p = 1.8 x 10-2] and overt hypothyroidism [OR (95% CI) = 0.853(0.730-0.997), p = 4.6 x 10-2] significantly influenced the prostatitis, whereas FT4 levels [OR (95% CI) = 1.141(0.901-1.444), p = 2.75 x 10-1], subclinical hypothyroidism [OR (95% CI) =0. 897(0.784- 1.026), p = 1.12 x 10-1], and hyperthyroidism [OR (95% CI) = 1.069(0.947-1.206), p = 2.79 x 10-1] did not have a significant effect.ConclusionOverall, our study results suggest that hypothyroidism and TSH levels influence the risk of genetically predicted BPH and prostatitis, providing new insights into the causal relationship between thyroid function and BPD.

The theory of oxygen vacancy related deep energy defects and valence band offset (VBO) between gate insulator and channel codetermining the threshold voltage shift $(\Delta {V}_{\mathbf {\mathrm {TH}}})$ of ZnO thin film transistor under negative gate bias and illumination stress (NBIS) is proposed and investigated systematically. Two kinds of ZnO thin film transistors are fabricated by atomic layer deposition with different gate oxide structures, a control sample with Al2O3 gate oxide and an improved sample with SiO2/Al2 ${\text{O}}_{3 }$ gate oxide structures. Among two kinds of devices, the device with SiO2/Al2 ${\text{O}}_{3 }$ gate oxide achieves a smaller $\mathbf {\mathrm {\Delta }}{V}_{\mathbf {\mathrm {TH}}}$ under the NBIS with SiO2 thin film acting as a holes-blocking layer, despite the existence of more defects than control device. The improvement in stability is attributed to large VBO up to 3.08 eV. Moreover, the device with SiO2/Al2 ${\text{O}}_{3 }$ gate oxide is evaluated on a 500-nit LCD back light to simulate the practical working environment in displays, which exhibits good stability of ${\mathbf {\Delta }{V}}_{\mathbf {\mathrm {TH}}}\,\,=\,\,-0.3$ V for 3600 seconds.

Abstract Fish is an essential source of high-quality protein for people worldwide. The present study was designed to compare the growth performance among the channel-blue hybrid catfish, channel catfish transgenic for the channel catfish growth hormone (ccGH) cDNA driven by the antifreeze protein promoter from an ocean pout Zoarces americanus (opAFP-ccGH), and non-transgenic channel catfish control. Mean body weight of channel-blue hybrid catfish was 15.80 and 24.06% larger than non-transgenic channel catfish control at 4 and 18 months of age, respectively. However, transgenic opAFP-ccGH channel catfish were 5.52 and 43.41% larger than channel-blue hybrid catfish and 22.19 and 77.91% larger than their controls at 4 and 18 months of age, respectively. Significant differences in mean body weight between the sexes within all genetic types were found. Males were larger than females (P

The transparent floating gate memory based on zinc oxide (ZnO) thin film transistors (TFTs) was fabricated by using one-step atom layer deposition of aluminia tunneling and ZnO charge-trap layers. Free electrons trapping mechanism of this memory device is proposed after systematical investigation of gate voltage scanning and thickness of the trapping layer. Furthermore, the relationship between the geometrical size of the charge-trapping layer and the memory window is explored. The devices with different memory windows can be controlled simply by designing the area of their trapping layer without any external process, which is much beneficial to the low cost process fabrication of the memory array and driving circuits, since the memory and switch/digital transistors can be fabricated at the same time. Finally, the presented TFT memory exhibits a maximum memory window of 15 V, excellent fatigue and retention properties more than 30,000 s without any charge loss. The transparent floating gate memory with the ZnO charge-trap layer has great potential for application of 3D, transparent or multi-value memory.

Gas drilling technology is an effective method to protect low permeability tight sandstone reservoirs from damage. However, using this technology to drill high-pressure fractured reservoirs, the fluid flow characteristics are extremely complex, leading to drilling safety challenges. Therefore, based on the conservation equations of mass, momentum, and energy, a new transient coupled flow model in matrix-fracture is established for high-pressure gas reservoirs opened by gas drilling, considering convection term and energy equation, to research the pressure and flow velocity transient behaviors. This model is solved by Shaher Momani’s algorithm and CyabJiBe format, and the type curves of the pressure and flow velocity are plotted. The three flow stages are developed, and the impact of parameters and equation terms on the transient flow behavior is analyzed and discussed, such as the energy equation, the matrix permeability (k), the fracture aperture (Lf), and the fracture outlet pressure. It is found that the energy equation term of the model has a great influence on the transient characteristics such as velocity and pressure, which cannot be ignored. In the first flow stage, the flow velocity characteristics are not affected by the matrix parameters being extremely unstable, but in the second and third stages, the influence of the gas supplied to fracture cannot be ignored. The proposed transient coupled flow model provides a new understanding of the transient flow behavior in matrix-fracture for high-pressure reservoirs during gas drilling, which can be used to interpret the characteristics of pressure and velocity more realistically, to provide support for safe drilling of gas drilling.

IntroductionThe high incidence of online fraud in China poses a great threat to the social stability and property security of society. Victimity is the state or mindset of victims, referring to the various conditions related to being victims of crimes. Examining the association between the inherent and extrinsic factors of victimity and victimization of online fraud is of great importance for revealing the psychological mechanism of victimization and drawing up preventative measures.MethodsThrough the questionnaire survey of 504 online fraud victims and 523 non-victims, univariate analysis and logistic regression analysis were used to investigate the risk factors correlated with victimization.ResultsAge, education, and social support are positively correlated with fraud victimization, while impulsiveness, trust tendency, smartphone usage, and negative life experiences are negatively correlated with fraud victimization. Subsequent regression analyses showed that all the factors above, except for smartphone usage, are significant predictors for online fraud victimization.DiscussionOur conceptual model and empirical results demonstrate the important role of victimity in making an individual become a victim and help clarify the mixed findings of previous studies on the risk factors for online fraud.

Open thoracoabdominal aortic aneurysm (TAAA) repair is a complex and challenging operation with a high incidence of serious complications, and high perioperative mortality and morbidity. Left heart bypass (LHB) is a circulatory support system used to perfuse the distal aorta during TAAA operation, and the advantages of LHB include guaranteeing distal perfusion, reducing the use of heparin, and diminishing the risk of bleeding and postoperative neurological deficits. In China, the circuit for TAAA repair is deficient, and far from the perfusion requirements. We designed a modular multifunctional LHB circuit for TAAA repair. The modular circuit consisted of cannulation pipelines, functional consumables connection pipelines, and accessory pipelines. The accessory pipelines make up lines for selective visceral perfusion and kidney perfusion, suckers and rapid infusion. The circuit can be assembled according to surgical requirements. The ultrafilter and heat exchanger are integrated into the circuit to fulfill the basic demands of LHB. The LHB circuit also has pipelines for selective visceral perfusion to the celiac artery and superior mesenteric artery and renal perfusion pipelines. Meanwhile, the reserved pipelines facilitate the quick switch from LHB to conventional cardiopulmonary bypass (CPB). The reserved pipelines reduce the time of reassembling the CPB circuit. Moreover, the rapid infusion was integrated into the LHB circuit, which can rapid infusion when massive hemorrhage during the open procedures such as exposure and reconstruction of the aorta. The ultrafiltration can diminish the consequent hemodilution of hemorrhage and rapid infusion. A hemoperfusion cartridge also can be added to reduce the systemic inflammatory during operation. The circuit can meet the needs of LHB and quickly switch to conventional CPB. No oxygenator was required during LHB, which reduce the use of heparin and reduce the risk of bleeding. The heat exchanger contributes to temperature regulation; ultrafiltration, arterial filter, and rapid-infusion facilitated the blood volume management and are useful to maintain hemodynamic stability. This circuit made the assembly of the LHB circuit more easily, and more efficient, which may contribute to the TAAA repair operation performed in lower volume centers easily. 26 patients who received TAAA repair under the modular multifunctional LHB from January 2018-March 2022 were analyzed, and we achieved acceptable clinical outcomes. The in-hospital mortality and 30-day postoperative mortality were 15.4%, and the postoperative incidences of paraparesis (4%), stroke (4%), and AKI need hemodialysis (12%) were not particularly high, based on the limited patients sample size in short research period duration.

Follicle-stimulating hormone (fsh) plays an important role in sexual maturation in catfish. Knocking out the fsh gene in the fish zygote should suppress the reproduction of channel catfish (Ictalurus punctatus). In this study, transcription activator-like effector nuclease (TALEN) plasmids targeting the fsh gene were electroporated into fertilized eggs with the standard double electroporation technique. Targeted fsh cleavage efficiency was 63.2% in P1fsh-knockout catfish. Ten of fifteen (66.7%) control pairs spawned, and their eggs had 32.3–74.3% average hatch rates in 2016 and 2017. Without hormone therapy, the spawning rates of P1 mutants ranged from 33.3 to 40.0%, with an average egg hatching rate of 0.75%. After confirmation of the low fertility of P1 mutants in 2016, human chorionic gonadotropin (HCG) hormone therapy improved the spawning rates by 80% for female mutants and 88.9% for male mutants, and the mean hatch rate was 35.0% for F1 embryos, similar to that of the controls (p > 0.05). Polymerase chain reaction (PCR) identification showed no potential TALEN plasmid integration into the P1 channel catfish genome. Neither the P1 nor the F1 mutant fish showed any noticeable changes in in body weight, survival rate, and hatching rate when the reproductive gene was knocked out. F1 families had a mean inheritance rate of 50.3%. The results brought us one step closer to allowing implementation of certain genetic techniques to aquaculture and fisheries management, while essentially eliminating the potential environment risk posed by transgenic, hybrid, and exotic fish as well as domestic fish.

The melanocortin-4 receptor (MC4R) plays a critical role in homeostasis and the regulation of body weight. Polymorphisms in the mc4r gene have been discovered and linked to growth, carcass composition, and meat quality traits. Therefore, we used the CRISPR-Cas9 system to target the mc4r gene in the most important freshwater aquaculture species in the USA, channel catfish, Ictalurus punctatus. Guide RNAs were designed to direct the Cas9 to the coding sequence of the channel catfish mc4r gene. gRNA(s)-Cas9 mixtures were delivered into one-cell embryos using electroporation and microinjection. For each treatment, the nature and rate of mutations were analyzed. Hatching and survival rates were calculated. The overall mutation rates were 30.6% and 66.7–90.6% for electroporation and microinjection, respectively. Mutated fish generated via electroporation or microinjection exhibited 38% and 20% improvement in body weight, respectively, when compared with the full-sib control. The mean feed conversion ratio of the mutants was 1.18 compared with 1.57 in the control fish. The improved growth and feed conversion indicate that the generation of mc4r-edited fish could economically benefit aquaculture production.

This study examined the dimensionality, reliability, and validity of a Chinese version of the 5-C Model of positive youth development (PYD), originally developed in the U.S., with a sample of rural and urban young adolescents in China. The Cs represent five youth strengths: competence, confidence, character, caring, and connection. The results of the exploratory factor analyses showed a reasonable data fit with the 5-C Model. The total and subscale scores evinced good internal reliability (α = .7 to .9) and the confirmatory factor analyses confirmed the convergence of the five Cs on a second-order latent factor of PYD, showing adequate goodness of fit (CFI = 0.94; TLI = 0.93; RMSEA = 0.04). Metric and scalar invariance were found across gender. Metric and partial scalar invariance were found for rural-urban groups. Supportive evidence on convergent and discriminatory validity was also found. We conclude that the Chinese version of the 5-C PYD Scale is a reliable and valid instrument, with good construct validity for Chinese young adolescents.

Disease vectors such as mosquitoes and ticks play a major role in the emergence and re-emergence of human and animal viral pathogens. Compared to mosquitoes, however, much less is known about the antiviral responses of ticks. Here we showed that Asian longhorned ticks (Haemaphysalis longicornis) produced predominantly 22-nucleotide virus-derived siRNAs (vsiRNAs) in response to severe fever with thrombocytopenia syndrome virus (SFTSV, an emerging tick-borne virus), Nodamura virus (NoV), or Sindbis virus (SINV) acquired by blood feeding. Notably, experimental acquisition of NoV and SINV by intrathoracic injection also initiated viral replication and triggered the production of vsiRNAs in H. longicornis. We demonstrated that a mutant NoV deficient in expressing its viral suppressor of RNAi (VSR) replicated to significantly lower levels than wildtype NoV in H. longicornis, but accumulated to higher levels after knockdown of the tick Dicer2-like protein identified by phylogeny comparison. Moreover, the expression of a panel of known animal VSRs in cis from the genome of SINV drastically enhanced the accumulation of the recombinant viruses. This study establishes a novel model for virus-vector-mouse experiments with longhorned ticks and provides the first in vivo evidence for an antiviral function of the RNAi response in ticks. Interestingly, comparing the accumulation levels of SINV recombinants expressing green fluorescent protein or SFTSV proteins identified the viral non-structural protein as a putative VSR. Elucidating the function of ticks' antiviral RNAi pathway in vivo is critical to understand the virus-host interaction and the control of tick-borne viral pathogens.

Lenvatinib is the latest and promising agent that has demonstrated a significant improvement of progression-free survival in advanced hepatocellular carcinoma (HCC). However, resistance emerges soon after initial treatment, limiting the clinical benefits of lenvatinib. Therefore, understanding the mechanism of resistance is necessary for improving lenvatinib efficacy. YRDC promotes the proliferation of hepatocarcinoma cells via regulating the activity of the RAS/RAF/MEK/ERK pathway, which was the primary pathway of the anticancer effect of lenvatinib. The purpose of this study is to investigate whether YRDC modulates the sensitivity of lenvatinib in hepatocarcinoma cells. Using the CCK-8 cell viability assay, wound-healing assay and clone formation assay in cell models, and xenograft assay in null mouse, we demonstrated that Huh7 cells with YRDC knockdown showed decreased susceptibility to lenvatinib than their control cells. Furthermore, we found that lenvatinib inhibited the expression of YRDC in a time-dependent manner. This effect may aggravate resistance to lenvatinib in hepatocarcinoma cells and may be an underlying cause of resistance, which emerges soon after lenvatinib initial treatment. To investigate how YRDC modulates the sensitivity of lenvatinib, we assessed the effect of tRNA with different t6A levels on the translation of the KRAS gene by in vitro rabbit reticulocyte translation system and measured the expression levels of the KRAS gene by western blot together with qPCR. We found that YRDC regulates the protein translation of KRAS in cell models, and the tRNA with low t6A modification level reduces the translation of the KRAS in the in vitro translation system. These results suggested that YRDC mediates the resistance of lenvatinib in hepatocarcinoma cells via modulating the translation of the KRAS. In this study, YRDC was confirmed to be a potential novel predictive biomarker of lenvatinib sensitivity in HCC.

Considering the pivotal role of students' academic engagement in their success, discovering the intrinsic and extrinsic factors that inspire students to engage in class activities seems crucial. Notwithstanding, only a few empirical studies have been devoted to teachers' personal factors such as emotion regulation and their predictive function. Further, to our knowledge, no theoretical or systematic review study has been conducted on the association between teacher emotion regulation and student academic engagement. The current review study seeks to fill these lacunas by illustrating English as a foreign language (EFL) or English as a second language (ESL) teachers' emotion regulation and its' capability to enhance students' academic engagement. Using the existing evidence, the power of ESL/EFL teachers' emotion regulation in predicting their pupils' academic engagement was proved. The findings' educational implications are further discussed.

Individuals with diabetes are exposed to a higher risk of perioperative stroke than non-diabetics mainly due to persistent hyperglycemia. LncRNA Meg3 has been considered as an important mediator in regulating ischemic stroke. However, the functional and regulatory roles of Meg3 in diabetic brain ischemic injury remain unclear. In this study, rat brain microvascular endothelial cells (RBMVECs) were exposed to 6 h of oxygen and glucose deprivation (OGD), and subsequent reperfusion via incubating cells with glucose of various high concentrations for 24 h to imitate in vitro diabetic brain ischemic injury. It was shown that the marker events of ferroptosis and increased Meg3 expression occurred after the injury induced by OGD combined with hyperglycemia. However, all ferroptotic events were reversed with the treatment of Meg3-siRNA. Moreover, in this in vitro model, p53 was also characterized as a downstream target of Meg3. Furthermore, p53 knockdown protected RBMVECs against OGD + hyperglycemic reperfusion-induced ferroptosis, while the overexpression of p53 exerted opposite effects, implying that p53 served as a positive regulator of ferroptosis. Additionally, the overexpression or knockdown of p53 significantly modulated GPX4 expression in RBMVECs exposed to the injury induced by OGD combined with hyperglycemic treatment. Furthermore, GPX4 expression was suppressed again after the reintroduction of p53 into cells silenced by Meg3. Finally, chromatin immunoprecipitation assay uncovered that p53 was bound to GPX4 promoter. Altogether, these data revealed that, by modulating GPX4 transcription and expression, the Meg3-p53 signaling pathway mediated the ferroptosis of RBMVECs upon injury induced by OGD combined with hyperglycemic reperfusion.

The interferon-regulated antiviral responses are essential for the induction of both innate and adaptive immunity in mammals. Production of virus-derived small-interfering RNAs (vsiRNAs) to restrict virus infection by RNA interference (RNAi) is a recently identified mammalian immune response to several RNA viruses, which cause important human diseases such as influenza and Zika virus. However, little is known about Dicer processing of viral double-stranded RNA replicative intermediates (dsRNA-vRIs) in mammalian somatic cells. Here we show that infected somatic cells produced more influenza vsiRNAs than cellular microRNAs when both were produced by human Dicer expressed de novo, indicating that dsRNA-vRIs are not poor Dicer substrates as previously proposed according to in vitro Dicer processing of synthetic long dsRNA. We report the first evidence both for canonical vsiRNA production during wild-type Nodamura virus infection and direct vsiRNA sequestration by its RNAi suppressor protein B2 in two strains of suckling mice. Moreover, Sindbis virus (SINV) accumulation in vivo was decreased by prior production of SINV-targeting vsiRNAs triggered by infection and increased by heterologous expression of B2 in cis from SINV genome, indicating an antiviral function for the induced RNAi response. These findings reveal that unlike artificial long dsRNA, dsRNA-vRIs made during authentic infection of mature somatic cells are efficiently processed by Dicer into vsiRNAs to direct antiviral RNAi. Interestingly, Dicer processing of dsRNA-vRIs into vsiRNAs was inhibited by LGP2 (laboratory of genetics and physiology 2), which was encoded by an interferon-stimulated gene (ISG) shown recently to inhibit Dicer processing of artificial long dsRNA in cell culture. Our work thus further suggests negative modulation of antiviral RNAi by a known ISG from the interferon response.

ABSTRACTThe RNA interference (RNAi) pathway directs an important antiviral immunity mechanism in plants and invertebrates. Recently, we and others have demonstrated that the antiviral RNAi response is also conserved in mammals, at least to five distinct RNA viruses, including Zika virus (ZIKV). ZIKV may preferentially infect neuronal progenitor cells (NPCs) in the developing foetal brain. Ex vivo ZIKV infection induces RNAi-mediated antiviral response in human NPCs, but not in the more differentiated NPCs or somatic cells. However, litter is known about the in vivo property or function of the virus-derived small-interfering RNAs (vsiRNAs) targeting ZIKV. Here we report a surprising observation: different from ex vivo observations, viral small RNAs (vsRNAs) targeting ZIKV were produced in vivo upon infection in both central neuron system (CNS) and muscle tissues. In addition, our findings demonstrate the production of canonical vsiRNAs in murine CNS upon antiviral RNAi activation by Sindbis virus (SINV), suggesting the possibility of antiviral immune strategy applied by mammals in the CNS.

Certain microRNAs (miRNAs) can function as neuroprotective factors after reperfusion/ischemia brain injury. miRNA-142-3p can participate in the occurrence and development of tumors and myocardial ischemic injury by negatively regulating the activity of Rac1, but it remains unclear whether miRNA-142-3p also participates in cerebral ischemia/reperfusion injury. In this study, a model of oxygen-glucose deprivation/re-oxygenation in primary cortical neurons was established and the neurons were transfected with miR-142-3p agomirs or miR-142-3p antagomirs. miR-142-3p expression was down-regulated in neurons when exposed to oxygen-glucose deprivation/re-oxygenation. Over-expression of miR-142-3p using its agomir remarkably promoted cell death and apoptosis induced by oxygen-glucose deprivation/re-oxygenation and improved mitochondrial biogenesis and function, including the expression of peroxisome proliferator-activated receptor-γ coactivator-1α, mitochondrial transcription factor A, and nuclear respiratory factor 1. However, the opposite effects were produced if miR-142-3p was inhibited. Luciferase reporter assays verified that Rac Family Small GTPase 1 (Rac1) was a target gene of miR-142-3p. Over-expressed miR-142-3p inhibited NOX2 activity and expression of Rac1 and Rac1-GTPase (its activated form). miR-142-3p antagomirs had opposite effects after oxygen-glucose deprivation/re-oxygenation. Our results indicate that miR-142-3p down-regulates the expression and activation of Rac1, regulates mitochondrial biogenesis and function, and inhibits oxygen-glucose deprivation damage, thus exerting a neuroprotective effect. The experiments were approved by the Committee of Experimental Animal Use and Care of Central South University, China (approval No. 201703346) on March 7, 2017.

Previous studies have suggested that pyrrolidine dithiocarbamate (PDTC), a nuclear factor κB (NF-κB) inhibitor, play a role in deterring nerve injury-induced neuropathic pain (NP) The activation of NF-κB pathway may contribute to spinal microglial activation, CX3CR1 and tumor necrosis factor-alpha (TNF-a) up-regulation. The aim of this study was to clarify whether PDTC could inhibit the development of neuropathic pain via decreasing TNF-a-induced CX3CR1 up-regulation. Sprague-Dawley rats were randomly divided into sham group and NP group. Rats in each group were treated with intrathecal infusion of PDTC (100 or 1000 pmol/d) or saline. The sciatic nerve chronic constriction injury (CCI) model was used to induce NP in rats. Mechanical stimuli and radiant heat were used to evaluate mechanical allodynia and thermal hyperalgesia. Spinal microglial marker OX42 and TNF-a were detected by immunohistochemistry. In vitro BV-2 microglia activation was induced by TNF-a incubation, and the levels of CX3CR1 were assessed by Western blot and reverse transcription-polymerase chain reaction. Pain behavior and immunohistochemistry results showed that intrathecal infusion of PDTC at 100 or 1000 pmol/d prevented the development of mechanical and thermal hyperalgesia, spinal microglial activation and TNF-a expression induced by sciatic nerve CCI in rats. In vitro experiment results showed that PDTC inhibited the TNF-a-induced CX3CR1 up-regulation in BV-2 microglial cells. In conclusion, intrathecal infusion of PDTC could attenuate the pain-related behaviors induced by sciatic nerve CCI through suppressing the spinal microglia activation and TNF-a up-regulation in rats. The NF-κB activation might be responsible for TNF-a-induced CX3CR1 up-regulation in microglia.

BackgroundPrevious studies have proved that peripheral nerve injury is involved in the pathogenesis of neuropathic pain (NP). The peripheral nerve injury primes spinal M1 microglia phenotype and produces pro-inflammatory cytokines, which are responsible for neurotoxic and neuronal hyper-excitable outcomes. Spinal peroxisome proliferator-activated receptor gamma (PPAR γ) has been shown to play an anti-inflammatory role in the development of NP. However, the role of PPAR γ in attenuating the pathological pathway of spinal microgliosis is still unknown.MethodsSprague-Dawley rats (male, aged 8–10 weeks) were randomly divided into three groups, i.e., a control group, a NP group, and a NP + lentivirus encoding PPAR γ (LV-PPAR γ) group. The sciatic chronic constriction injury (CCI) model was used to induce NP in rats. Pain behavior was assessed by monitoring the rat hind-paw withdrawal threshold to mechanical stimuli and withdrawal latency to radiant heat. The LV-PPAR γ was intrathecally infused 1 day before CCI. Western blot analysis and real-time qPCR were used to detect the microglia phenotypic molecules and CX3CR1 expression in the spinal cord. In vitro, BV-2 microglia cells were transfected with LV-PPAR γ and incubated with lipopolysaccharides (LPS), and the levels of M1 microglia phenotypic molecules and CX3CR1 in BV-2 microglia cells were assessed by western blot analysis, real-time qPCR, and enzyme-linked immunosorbent assay.ResultsPreoperative intrathecal infusion of LV-PPAR γ attenuated pain in rats 7 days post-CCI. The M1-microglia marker, CX3CR1, and pro-inflammatory signaling factors were increased in the spinal cord of CCI rats, while the preoperative intrathecal infusion of LV-PPAR γ attenuated these changes and increased the expression of IL-10. In vitro, the overexpression of PPAR γ in BV-2 cells reduced LPS-induced M1 microglia polarization and the levels of CX3CR1 and pro-inflammatory cytokines.ConclusionIntrathecal infusion of LV-PPAR γ exerts a protective effect on the development of NP induced by CCI in rats. The overexpression of PPAR γ may produce both analgesic and anti-inflammatory effects due to inhibition of the M1 phenotype and CX3CR1 signaling pathway in spinal microglia.

Transcription activator-like effector nuclease (TALEN) plasmids targeting the channel catfish gonadotropin-releasing hormone (cfGnRH) gene were delivered into fertilized eggs with double electroporation to sterilize channel catfish (Ictalurus punctatus). Targeted cfGnRH fish were sequenced and base deletion, substitution, and insertion were detected. The gene mutagenesis was achieved in 52.9% of P1 fish. P1 mutants (individuals with human-induced sequence changes at the cfGnRH locus) had lower spawning rates (20.0–50.0%) when there was no hormone therapy compared to the control pairs (66.7%) as well as having lower average egg hatch rates (2.0% versus 32.3–74.3%) except for one cfGnRH mutated female that had a 66.0% hatch rate. After low fertility was observed in 2016, application of luteinizing hormone-releasing hormone analog (LHRHa) hormone therapy resulted in good spawning and hatch rates for mutants in 2017, which were not significantly different from the controls (p > 0.05). No exogenous DNA fragments were detected in the genome of mutant P1 fish, indicating no integration of the plasmids. No obvious effects on other economically important traits were observed after the knockout of the reproductive gene in the P1 fish. Growth rates, survival, and appearance between mutant and control individuals were not different. While complete knock-out of reproductive output was not achieved, as these were mosaic P1 brood stock, gene editing of channel catfish for the reproductive confinement of gene-engineered, domestic, and invasive fish to prevent gene flow into the natural environment appears promising.

Abstract Background To explore long non-coding RNA (lncRNA), mRNA and circular RNA (circRNA) expression profiles and their biological functions in the pathogenesis of kidney stones in ethylene glycol-induced urolithiasis rats. Results The expression of 1440 lncRNAs, 2455 mRNAs and 145 circRNAs was altered in the kidneys of urolithiasis rats. GO and KEGG biological pathway analysis were performed to predict the functions of differentially expressed lncRNAs, circRNAs and co-expressed potential targeting genes. Co-expression networks of lncRNA-mRNA and circRNA-miRNA were constructed based on correlation analysis between differentially expressed RNAs. mRNAs coexpressed with lncRNAs were involved in many kidney diseases, e.g., Ephb6 was associated with the reabsorption ability of the kidney. Arl5b was associated with the dynamic changes in the podocyte foot process in podocyte injury. miRNAs co-expressed with circRNAs, such as rno-miR-138-5p and rno-miR-672-5p, have been proven to be functional in hypercalciuria urolithiasis. Conclusion The expression profile provided a systematic perspective on the potential functions of lncRNAs and circRNAs in the pathogenesis of kidney stones. Differentially expressed lncRNAs and circRNAs might serve as treatment targets for kidney stones.

Background/Aims: Recent researches highlighted the protective potential of pioglitazone, a PPAR-γ agonist, in the progression of cerebral ischemia-reperfusion injury. However, there has been no study on the application of pioglitazone in treating ischemic stroke through mechanisms involving pyroptosis. Methods: The cerebral injury was established by middle cerebral artery occlusion (MCAO). in vitro ischemia in primary cultured astrocytes was induced by the oxygen-glucose deprivation (OGD). ELISA and Western Blot analysis were employed to the levels of PPAR-γ, pyroptosis-related biomarkers and cytoplasmic translocation of HMGB-1 and RAGE expression as well as Rac1 activity, respectively. Results: We demonstrated that repeated intraperitoneal administration of pioglitazone remarkably reduced the infarct volume, improved neurological deficits and suppressed the Rac1 activity with significant reduction of excessive ROS in rat model of middle cerebral artery occlusion (MCAO). Moreover, pioglitazone alleviated the up-regulation of pyroptosis-related biomarkers and the increased cytoplasmic translocation of HMGB-1 and RAGE expression in cerebral penumbra cortex. Similarly, the protective effects of pioglitazone on cultured astrocytes were characterized by reduced Rac1 activity, pyroptosis related protein expressions and lactate dehydrogenase (LDH) release. However, these protective effects of pioglitazone were neutralized with the use of GW9662, a PPAR-γ inhibitor. Interestingly, Rac1 knockdown in lentivirus with the Rac1 small hair RNA (shRNA) could inhibit the OGD-induced pyroptosis of primary cultured astrocytes. Furthermore, the combination of Rac1-shRNA and pioglitazone can further strengthen the inhibitory effects on pyroptosis induced by OGD. Conclusion: The neuroprotection of pioglitazone was attributable to the alleviated ischemia/hypoxia-induced pyroptosis and was also associated with the PPARγ-mediated suppression of HGMB-1/RAGE signaling pathway. Moreover, the inhibition of Rac1 promoted this function.

The O/W isocyanate emulsion can be used as a sizing agent to improve the waterproof performance of paper. However, the -NCO content in the emulsion diminishes with the prolongation of standing time. What is happening to this seemingly stable emulsion, especially concerning its microstructure evolution? We propose to monitor the emulsions deteriorative process by combining freeze-drying technique and SEM. Thus, the emulsion containing -NCO active group was obtained by the synthetic polymer emulsification of HDI trimers. The results of SEM demonstrate that the emulsion deteriorative process actually represents the collapsing and fusion of stable honeycomb structure with the prolongation of standing time and increasing temperature. This is possibly due to the fact that the inner aggregative HDI trimers are reacting with outside water to form urethane macromolecules, and this results in the collapsing and fusion of the honeycomb structure, as observed in SEM images. Moreover, the measurement results of -NCO content and FT-IR spectroscopy present the -NCO content as reducing with increasing standing time and temperature. This conclusion further proves our hypotheses. Additionally, the emulsions are used to treat the paper by site-directed reaction. The results show that the with the increase of the standing time and temperature, the contact angles and surface free energy show a decrease and an increase, respectively, whereas surface free energy appeared at a minimum of 29.19 mJ·m−2 when the standing time and temperature was 1 h and 25 °C.

Abstract The myostatin (MSTN) gene is important because of its role in regulation of skeletal muscle growth in all vertebrates. In this study, CRISPR/Cas9 was utilized to successfully target the channel catfish, Ictalurus punctatus, muscle suppressor gene MSTN. CRISPR/Cas9 induced high rates (88–100%) of mutagenesis in the target protein-encoding sites of MSTN. MSTN-edited fry had more muscle cells (p

To investigate the feasibility analysis of ultrasonic detection methods applied in the fatigue crack characteristics of steel structures, the double-probe ultrasonic detection method was applied to the prefabricated crack specimens fabricated from of flat steel plate. The test features including length, width, depth, angle, and crack location were considered. Based on the calculation of geometric relationship and experimental results, a method for judging the crack tip position was developed. The formulae for determining the depth and angle of crack were not only established but also analyzed the detection accuracy of the double-probe penetration method. The feasibility of this method in weld crack detection was verified by a combination of the finite-element simulation and actual experiment. The results showed that the ratio of crack tip wave height to crack free wave height ωK is related to the K value (K value is one of the parameters of the angle probe, which is defined as the tangent value of angle β between the incident wave and an interface normal line), but the influence of crack depth and width can be ignored. Due to higher detection accuracy for crack depth and angle, a double-probe penetrating method could improve the detection accuracy for crack angle by nearly 5% more than the single probe pulse reflection method. Therefore, application of the double-probe penetrating method had a significant impact on accurate crack detection of rib-to-deck weld in the practical issue.

The traumatic experience of contracting and living with HIV/AIDS may produce a myriad of mental health problems, especially posttraumatic stress disorder (PTSD) symptoms, and conversely, bring posttraumatic growth (PTG), that is, positive changes resulting from a struggle with trauma. The growing body of research into the relationship between PTSD symptoms and PTG has produced mixed results. In addition, some research has suggested that psychosocial and cognitive factors may mediate the development of PTG after trauma exposure. Specifically, individuals experience fewer psychological symptoms and better mental health when adaptive coping strategies align with stressors; however, little research is available on the relationship and the mediating effect of coping strategies on the link of PTSD symptoms and PTG among HIV-infected men who have sex with men (MSM) in China. The aims of the current study were to investigate the relationship between PTSD symptoms and PTG as well as the potential mediating effects of coping strategies through which PTSD symptoms contributes to PTG among this vulnerable population. One hundred and forty HIV-positive MSM were recruited from the Beijing Center for Disease Prevention and Control and were asked to complete a battery of self-administered questionnaires, covering sociodemographic and HIV-related characteristics, coping strategies (i.e., problem-solving, seeking social support, self-blame, and wishful thinking), PTSD symptoms, and PTG. Results showed that, after controlling for sociodemographic and HIV-related variables, a negative linear relationship was found between PTSD symptoms and PTG. In addition, problem-solving and self-blame played significant mediating roles in the association between PTSD symptoms and PTG. The mediating effects of seeking social support and engaging in wishful thinking on the PTSD symptoms and PTD link were, however, non-significant. The present study contributes to an understanding of the association between PTSD symptoms and PTG and underscores the mediators through which individuals gain growth from traumatic experience in the context of HIV infection in Beijing, China. Given these findings, the future efforts at psychological intervention should differentiate and target various types of coping strategies, especially focusing on enhancing problem-solving skills and decreasing self-blame, in response to the promotion of positive growth among HIV-infected MSM.

Crack-closure treatment through repeated impact is supposed to be an effective, economical way to extend the fatigue remaining life for fatigue-affected structures with less damage. The material plastic behavior under repeated impact between chisel and material bodies was investigated, for the purpose of describing the crack-closure effect. A numerical model was established associating the impact depth with the number of impact times and device parameters, which is also proved by experiments. The material properties, after repeated impact, was determined via metallographic analysis and microhardness tests, indicating that the material will be hardened within a small affected zone due to the grain refinement caused by repeated impact. The finite-element method was used, as a supplementary approach, to investigate the relationship between impact depth and horizontal deformation on the cracked surface. A one-to-one linear relation was obtained, even under the different chisel tip parameters. Therefore, the contact of fracture surface, i.e. crack closure, can be predicted with the help of this numerical model and the aforementioned relationship.

Traditional annular laminar flow analysis method applied in drilling engineering has poor accuracy and does not apply to complicated rheological models. A general method of calculating annular laminar pressure drop of drilling fluids with different rheological models was proposed, compared with traditional method, and verified using experiment data in published articles. Based on annular slot flow model, the pipe flow equation was popularized in annular and an annular flow equation was established, and the relationship between annular flow and shear stress at pipe wall was established by combining annular flow equation and fluid's rheological equation. If annular flow is given, shear stress at pipe wall can be got, and then the annular pressure drop is also available. Compared with traditional methods, the general method is adapt to any rheological model of annular laminar flow, and has good universality, simple modeling process and high accuracy. The calculation results based on experiment data in published articles show: no matter the flow rate is high or low, the results of the general method match the measured results well, which makes up the error of traditional method. Key words: annular laminar pressure drop, annular flow equation, non-newtonian fluid, rheological equation, traditional method, general method, drilling fluids

Water inrush from the excavation face often occurs in the current shield construction of metro tunnels. In this study, the discontinuity of shield tunnel lining and the interaction between the tunnel segments, the grouting layer, and the surrounding rock are considered. Based on the 3D nonlinear contact theory, a hybrid model of the shield tunnel is constructed. Considering the fluid-solid coupling effect of water and soil, the influences of different water head differences on the mechanical performance and deformation of segments and joints in the shield tunnel are studied. The water gushing from the excavation face leads to vertical convergence of the cross-sectional area of the shield tunnel, and joint opening and dislocation result in sharp decrease of the waterproof capacity of joints. Meanwhile, the stress in the vicinity of segment joints increases sharply, and local cracks occur in the segment lining. The axial force, shear force, and bending moment in the joint bolt are also significantly increased. Based on the current metro standard and the computational results in this study, an emergency control criterion is put forward by means of controlling the discharge of water: the water head difference over the excavation face is required less than 4.6 M.

The purpose of this current study is to evaluate whether improvement of mitochondrial dysfunction was involved in the therapeutic effect of sevoflurane postconditioning in global cerebral ischemia after cardiac arrest (CA) via the PI3K/Akt pathway. In the first experiment, animals were randomly divided into three groups: a sham group, a CA group, a CA+sevoflurane postconditioning group (CA+SE). Sevoflurane postconditioning was achieved by administration of 2.5% sevoflurane for 30 min after resuscitation. Sevoflurane postcontioning has a significant neuroprotective effect by increasing survival rates and reducing neuronal apoptosis. Additionally, the gene and protein expression of PGC-1α, NRF-1 and TFAM, the master regulators of mitochondrial biogenesis, were up-regulated in the CA+SE group, when compared to the CA group. Similarly, in contrast to the CA group, mitochondria-specific antioxidant enzymes, including heat-shock protein 60 (HSP60), peroxiredoxin 3 (Prx3) and thioredoxin 2 (Trx2)were also increased in the CA+SE group. Finally, administration of sevoflurane ameliorated mitochondrial reactive oxygen species (ROS) formation and maintained mitochondrial integrity. In the second experiment, we investigated the relationship between the PI3K/Akt pathway and mitochondrial biogenesis and mitochondria-specific antioxidant enzymes in sevoflurane-induced neuroprotection. The selective PI3K inhibitor wortmannin not only eliminated the beneficial biochemical processes of sevoflurane by reducing the level of mitochondrial biogenesis-related proteins and aggravating mitochondrial integrity, but also reversed the elevation of mitochondria-specific antioxidant enzymes induced by sevoflurane. Therefore, our data suggested that sevoflurane postconditioning provides neuroprotection via improving mitochondrial biogenesis and integrity, as well as increasing mitochondria-specific antioxidant enzymes by a mechanism involving the PI3K/Akt pathway.

Peer victimization can have a profound effect on children’s wellbeing and is a known risk factor for depression in childhood. Migrant children experience peer victimization at higher rates than non-migrant peers; however, limited research has examined psychological factors that may serve to reduce depression risk for this group. In particular, no studies have yet investigated whether resilience, including personal characteristics and a strong social support network, may moderate the relationship between peer victimization and depressive symptoms for migrant children. This study utilized a latent interaction model to examine the effect of resilience on the relationship between peer victimization and depressive symptoms among 721 rural-to-urban migrant children in Beijing, China. Results indicated that peer victimization was positively associated with depressive symptoms. Resilience was found to be a protective factor for depressive symptoms and also mitigated the effects of peer victimization on depressive symptoms. Exploratory analyses suggest that enrollment in private migrant schools may be linked with poorer psychosocial outcomes for Chinese migrant children. Strengthening the internal resilience and social supports for all migrant children may be an effective strategy to lower their risk for depression. Implications for intervention are discussed.

BACKGROUND:The effects of low concentration of sevoflurane on right ventricular (RV) function and intracellular calcium in the setting of pulmonary arterial hypertension (PAH) have not been investigated clearly. We aim to study these effects and associated signaling pathways in rats with PAH. METHODS:Hemodynamics were assessed with or without sevoflurane inhalation in established PAH rats. We analysis the classic RV function parameters and RV-PA coupling efficiency using steady-state PV loop recordings. The protein levels of SERCA2, PLB and p-PLB expression was analyzed by western blot to assess their relevance in PAH. RESULTS:Rats with PAH presented with RV hypertrophy and increased pulmonary arterial pressure. The values of Ea, R/L ratio, ESP, SW, PRSW, +dP/dtmax and the slope of the dP/dtmax-EDV relationship increased significantly in PAH rats (P

Repressible knockdown approaches were investigated for transgenic sterilization in channel catfish, Ictalurus punctatus. Two primordial germ cell (PGC) marker genes, nanos and dead end, were targeted for knockdown, and an off-target gene, vasa, was monitored. Two potentially salt sensitive repressible promoters, zebrafish adenylosuccinate synthase 2 (ADSS) and zebrafish racemase (Rm), were each coupled with four knockdown strategies: ds-sh RNA targeting the 5′ end (N1) or 3′ end (N2) of channel catfish nanos, full-length cDNA sequence of channel catfish nanos for overexpression (cDNA) and ds-sh RNA targeting channel catfish dead end (DND). Each construct had an untreated group and treated group with sodium chloride as the repressor compound. Spawning rates of full-sibling P1 fish exposed or not exposed to the constructs as treated and untreated embryos were 93% and 59%, respectively, indicating potential sterilization of fish and repression of the constructs. Although the mRNA expression data of PGC marker genes were inconsistent in P1 fish, most F1 individuals were able to downregulate the target genes in untreated groups and repress the knockdown process in treated groups. The results indicate that repressible transgenic sterilization is feasible for reproductive control of fish, but more data from F2 or F3 are needed for evaluation.