PRL1 and PRL3 promote macropinocytosis via its lipid phosphatase activity.

PRL1 and PRL3, members of the protein tyrosine phosphatase family, have been associated with cancer metastasis and poor prognosis. Despite extensive research on their protein phosphatase activity, their potential role as lipid phosphatases remains elusive. Methods: We conducted comprehensive investigations to elucidate the lipid phosphatase activity of PRL1 and PRL3 using a combination of cellular assays, biochemical analyses, and protein interactome profiling. Functional studies were performed to delineate the impact of PRL1/3 on macropinocytosis and its implications in cancer biology. Results: Our study has identified PRL1 and PRL3 as lipid phosphatases that interact with phosphoinositide (PIP) lipids, converting PI(3,4)P2 and PI(3,5)P2 into PI(3)P on the cellular membranes. These enzymatic activities of PRLs promote the formation of membrane ruffles, membrane blebbing and subsequent macropinocytosis, facilitating nutrient extraction, cell migration, and invasion, thereby contributing to tumor development. These enzymatic activities of PRLs promote the formation of membrane ruffles, membrane blebbing and subsequent macropinocytosis. Additionally, we found a correlation between PRL1/3 expression and glioma development, suggesting their involvement in glioma progression. Conclusions: Combining with the knowledge that PRLs have been identified to be involved in mTOR, EGFR and autophagy, here we concluded the physiological role of PRL1/3 in orchestrating the nutrient sensing, absorbing and recycling via regulating macropinocytosis through its lipid phosphatase activity. This mechanism could be exploited by tumor cells facing a nutrient-depleted microenvironment, highlighting the potential therapeutic significance of targeting PRL1/3-mediated macropinocytosis in cancer treatment.

Identification of tyrphostin AG879 and A9 inhibiting replication of chikungunya virus by screening of a kinase inhibitor library.

Chikungunya virus (CHIKV) is a globally public health threat. There are currently no medications available to treat CHIKV infection. High-throughput screening of 419 kinase inhibitors was performed based on the cytopathic effect method, and six kinase inhibitors with reduced cytopathic effects, including tyrphostin AG879 (AG879), tyrphostin 9 (A9), sorafenib, sorafenib tosylate, regorafenib, and TAK-632, were identified. The anti-CHIKV activities of two receptor tyrosine kinase inhibitors, AG879 and A9, that have not been previously reported, were selected for further evaluation. The results indicated that 50% cytotoxic concentration (CC50) of AG879 and A9 in Vero cells were greater than 30 µM and 6.50 µM, respectively and 50% effective concentration (EC50) were 0.84 µM and 0.36 µM, respectively. The time-of-addition and time-of-removal assays illustrated that both AG879 and A9 function in the middle stage of CHIKV life cycle. Further, AG879 and A9 do not affect viral attachment; however, they inhibit viral RNA replication, and exhibit antiviral activity against CHIKV Eastern/Central/South African and Asian strains, Ross River virus and Sindbis virus in vitro.

Long-term divergent selection for residual feed intake in Chinese broiler chickens.

This study aimed to assess the effect of inbreeding on production traits using a long-term closed-line population recorded for residual feed intake (RFI). The study first used data from a previously reported population to determine the appropriate period of divergent selection for RFI. The results showed that RFI had similar moderate heritability estimates (0.28-0.34) during the fast-growing period (7-12 wk), and RFI at 7 to 10 wk had the highest heritability (0.34). Therefore, divergent selection was performed in a Chinese broiler population for RFI at 7 to 10 wk; the total sample size from generations zero (G0) to 13 was 9050. The divergence between the 2 lines increased steadily throughout generations, resulting in G13 with average RFI values of 304.55 in high RFI (HRFI) males, -160.31 in low RFI (LRFI) males, 296.30 in HRFI females and -157.55 in LRFI females. The feed intake (FI) and feed conversion ratio were almost higher in HRFI broilers than in LRFI broilers, and the magnitude of the difference in FI increased from approximately 4% for both sexes in G1 to approximately 33% in G13. Body weight gain was irregular from G1 to G13 and higher in LRFI broilers than in HRFI broilers after G10. Indeed, the HRFI broilers consumed more food, but they were lighter than LRFI broilers. In G13, LRFI males had heavier slaughter weight, longer cecum length, more white blood cells (WBC), red blood cells (RBC) and hemoglobin (HGB), but triglycerides, lower dressed percentage, percentage of half eviscerated yield, and eviscerated yield than HRFI males. LRFI females had a higher percentage of breast muscle and gizzard yield, longer cecum length, and more WBCs, RBCs and HGB but less abdominal fat and serum total cholesterol than HRFI females. This study was the first to verify that long-term divergent selection for RFI in Chinese broiler chickens is positive and beneficial.

PDCA nursing in improving quality management efficacy in endoscopic submucosal dissection.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a common surgical strategy for the treatment of early gastrointestinal tumors and precancerous lesions. PDCA nursing can effectively prevent potential risks in the nursing process, protect patient privacy, and improve patient satisfaction, nursing integrity, and service quality. AIM: To explore the effects of PDCA nursing model on the quality management of gastrointestinal ESD, the 36-item Shot-Form Health Survey (SF-36) score, and negative emotions. METHODS: A total of 178 patients who underwent ESD between January 2020 and January 2021 were divided into two groups. The usual care mode was the control group, with 80 cases from January to July 2020; from July 2020 to January 2021, 98 patients were enrolled in the PDCA care mode as the research group. The length of hospital stay and the costs of the two groups were statistically analyzed. The visual analog scale (VAS), SF-36 score, Zung self-rating scale for anxiety and depression, and postoperative complications were also assessed. RESULTS: The length of hospitalization and cost in the research group were lower than in the control group (P < 0.05), and the VAS scores were lower than those before care (P < 0.05). Moreover, the VAS score of the research group was lower than that of the control group (P < 0.05). The SF-36 scores for physical function, role status, social function, pain, mental health, and physical strength were higher in the research group than in the control group (P < 0.05). Depression and anxiety scores of the research group were lower than those of the control group (P < 0.05). The postoperative complication rate in the research group (6.12%) was lower than in the control group (32.50%) (P < 0.05). CONCLUSION: PDCA nursing can improve the quality of management of ESD surgery, shorten the length of hospital stay and cost, reduce the VAS and Zung scale scores to alleviate adverse emotions, improve the SF-36 score, and reduce postoperative complications.

Multiomics approach reveals the ubiquitination-specific processes hijacked by SARS-CoV-2.

The Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a global pandemic that seriously threatens health and socioeconomic development, but the existed antiviral drugs and vaccines still cannot yet halt the spread of the epidemic. Therefore, a comprehensive and profound understanding of the pathogenesis of SARS-CoV-2 is urgently needed to explore effective therapeutic targets. Here, we conducted a multiomics study of SARS-CoV-2-infected lung epithelial cells, including transcriptomic, proteomic, and ubiquitinomic. Multiomics analysis showed that SARS-CoV-2-infected lung epithelial cells activated strong innate immune response, including interferon and inflammatory responses. Ubiquitinomic further reveals the underlying mechanism of SARS-CoV-2 disrupting the host innate immune response. In addition, SARS-CoV-2 proteins were found to be ubiquitinated during infection despite the fact that SARS-CoV-2 itself didn't code any E3 ligase, and that ubiquitination at three sites on the Spike protein could significantly enhance viral infection. Further screening of the E3 ubiquitin ligases and deubiquitinating enzymes (DUBs) library revealed four E3 ligases influencing SARS-CoV-2 infection, thus providing several new antiviral targets. This multiomics combined with high-throughput screening study reveals that SARS-CoV-2 not only modulates innate immunity, but also promotes viral infection, by hijacking ubiquitination-specific processes, highlighting potential antiviral and anti-inflammation targets.

School EFL Teachers' Research Identity Construction in the Chinese University-School Community.

Despite a relatively large number of studies on teachers' identity development in the University-School community, few studies have explicitly focused on school EFL teachers' research identity construction. This study adopts the Activity Theory and examines three English as a foreign language (EFL) teachers from three middle schools in a University-School community in China. It investigates how three teachers constructed their research identity and what factors influenced the construction of their identities within the University-School activity system from the dual perspectives of the school and university teachers. Data are collected through semi-structured narrative interviews, triangulated by documents such as meeting minutes, and then analyzed by NVivo 12. The findings of this study show that (1) the University-School collaborative program helps form a University-School community of both teaching and research; (2) in this community, school EFL teachers continuously construct their identities in a spiral process of "practitioner" and "researcher"; (3) it highlights the internal factors containing the research experience and the stage of career and the external factors including the curriculum reform context and the communication in the community. The findings carry important implications for school EFL teachers' research identity construction and professional development in the University-School cooperation.

High-Throughput Screening of FDA-Approved Drug Library Reveals Ixazomib Is a Broad-Spectrum Antiviral Agent against Arboviruses.

The emergence of significant arboviruses and their spillover transmission to humans represent a major threat to global public health. No approved drugs are available for the treatment of significant arboviruses in circulation today. The repurposing of clinically approved drugs is one of the most rapid and promising strategies in the identification of effective treatments for diseases caused by arboviruses. Here, we screened small-molecule compounds with anti-tick-borne encephalitis virus, West Nile virus, yellow fever virus and chikungunya virus activity from 2580 FDA-approved drugs. In total, 60 compounds showed antiviral efficacy against all four of the arboviruses in Huh7 cells. Among these compounds, ixazomib and ixazomib citrate (inhibitors of 20S proteasome ß5) exerted antiviral effects at a low-micromolar concentration. The time-of-drug-addition assay suggested that ixazomib and ixazomib citrate disturbed multiple processes in viruses' life cycles. Furthermore, ixazomib and ixazomib citrate potently inhibited chikungunya virus replication and relieved virus-induced footpad swelling in a mouse model. These results offer critical information which supports the role of ixazomib as a broad-spectrum agent against arboviruses.

Identification of clinical candidates against West Nile virus by activity screening in vitro and effect evaluation in vivo.

The West Nile virus (WNV) is a member of the flavivirus and is known to cause encephalitis. There is currently no specific treatment for WNV infection. Repurposing of clinically approved drugs appeared promising for rapidly identifying effective, safe, and readily available candidates for antiviral drugs. Here, we screened the small-molecule compounds with anti-WNV activity from 978 Food Drug Administration-approved drugs. Four compounds, including cilnidipine, mycophenolate mofetil, nitazoxanide, and teriflunomide, were found to efficiently abrogate WNV infection in Vero cells and human neuroblastoma SH-SY5Y cells. The four compounds also exert broad-spectrum antiviral activity against the Zika virus, Japanese encephalitis virus, yellow fever virus, tick-borne encephalitis virus, and chikungunya virus. Furthermore, nitazoxanide (a synthetic benzamide) and teriflunomide (an inhibitor of dihydroorotate dehydrogenase, DHODH) protected 20% and 40% of mice from lethal WNV challenge, respectively. Both drugs, which are orally bioavailable and have been approved clinically for many years, may be promising therapeutics for WNV infection. Moreover, the other two DHODH inhibitors, ML390 and vidofludimus, also displayed potent activity against WNV infection in vitro and in vivo.

Antiviral efficacy of selective estrogen receptor modulators against SARS-CoV-2 infection in vitro and in vivo reveals bazedoxifene acetate as an entry inhibitor.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the seventh member of the coronavirus family that can infect humans. Recently, more contagious and pathogenic variants of SARS-CoV-2 have been continuously emerging. Clinical candidates with high efficacy and ready availability are still in urgent need. To identify potent anti-SARS-CoV-2 repurposing drugs, we evaluated the antiviral efficacy of 18 selective estrogen receptor modulators (SERMs) against SARS-CoV-2 infection. Six SERMs exhibited excellent anti-SARS-CoV-2 effects in Vero E6 cells and three human cell lines. Clomifene citrate, tamoxifen, toremifene citrate, and bazedoxifene acetate reduced the weight loss of hamsters challenged with SARS-CoV-2, and reduced hamster pulmonary viral load and interleukin-6 expression when assayed at 4 days postinfection. In particular, bazedoxifene acetate was identified to act on the penetration stage of the postattachment step via altering cholesterol distribution and endosome acidification. And, bazedoxifene acetate inhibited pseudoviruses infection of original SARS-CoV-2, Delta variant, Omicron variant, and SARS-CoV. These results offer critical information supporting bazedoxifene acetate as a promising agent against coronaviruses.

A design of red emission CDs-based aptasensor for sensitive detection of insulin via fluorescence resonance energy transfer.

We successfully designed an aptasensor based on the red emission carbon dots (R-CDs) and effectively detected insulin (INS) via fluorescence resonance energy transfer (FRET). In the process, the aptamer (apt) labeled with R-CDs (R-CDs@apt) was used as fluorescence donor and graphene oxide (GO) was used as fluorescence receptor. The successful detection due to the aptamer sequence has a certain affinity for Go and INS, while the affinity for INS is stronger than that of GO. When INS is not added to the detection system, the aptamer is adsorbed onto the surface of GO, shortening the distance between R-CDs@apt and GO, resulting in FRET and the quenching of fluorescence of R-CDs@apt. When INS was added to the detection system, the aptamer selectively bound INS and separated from the adsorption of GO, FRET gradually disappeared and the fluorescence of R-CDs@apt/GO/INS system was restored. By comparing the changes of fluorescence intensity before and after adding INS, the detection of INS was implemented. The aptasensor has a good linear curve with the detection limit of as low as 1.1 nM when the concentration of INS reached 1.3-150 nM. This method has excellent selectivity and anti-interference. Therefore, it is a potential method for detecting substances in biological fluids.

Elements of chronic disease management service system: an empirical study from large hospitals in China.

At present, more patients suffer from multiple chronic diseases. However, the hospital's existing chronic disease management is carried out according to the department. This means that a patient needs to go to more than one department for a chronic disease treatment. Therefore, this study proposes 6 dimensions (organizational management, medical service support, medical service, community alliance, self-management support, management information system) and 36 questions, to help evaluate the current chronic disease management system in China's large third-class hospitals. In this study, 143 survey samples from doctors and nurses were collected. A principal component analysis was used to extract three key elements of chronic disease management service delivery system (service management organization, management information system, medical core service). Then, multiple regression was used to establish the relationship model between the overall performance of the system and the main elements. Three key service nodes of the system (medical specialist support, patient tracking management and personalized intervention) were determined according to the weight of the regression model. The regression coefficients of the above three main elements show a similar impact on the overall performance of the system, but the key service nodes under each major element have relative differences, including medical specialist support, patient tracking management and personalized intervention. Finally, to establish a chronic disease management system with multiple departmental continuous care for chronic diseases, it is necessary to improve the chronic disease management system from three aspects of medical specialty support, patient tracking management and personalized intervention. This paper proposes corresponding improvement strategies.

Discovery of potential anti-SARS-CoV-2 drugs based on large-scale screening in vitro and effect evaluation in vivo.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global crisis. Clinical candidates with high efficacy, ready availability, and that do not develop resistance are in urgent need. Despite that screening to repurpose clinically approved drugs has provided a variety of hits shown to be effective against SARS-CoV-2 infection in cell culture, there are few confirmed antiviral candidates in vivo. In this study, 94 compounds showing high antiviral activity against SARS-CoV-2 in Vero E6 cells were identified from 2,580 FDA-approved small-molecule drugs. Among them, 24 compounds with low cytotoxicity were selected, and of these, 17 compounds also effectively suppressed SARS-CoV-2 infection in HeLa cells transduced with human ACE2. Six compounds disturb multiple processes of the SARS-CoV-2 life cycle. Their prophylactic efficacies were determined in vivo using Syrian hamsters challenged with SARS-CoV-2 infection. Seven compounds reduced weight loss and promoted weight regain of hamsters infected not only with the original strain but also the D614G variant. Except for cisatracurium, six compounds reduced hamster pulmonary viral load, and IL-6 and TNF-α mRNA when assayed at 4 d postinfection. In particular, sertraline, salinomycin, and gilteritinib showed similar protective effects as remdesivir in vivo and did not induce antiviral drug resistance after 10 serial passages of SARS-CoV-2 in vitro, suggesting promising application for COVID-19 treatment.

miR-200c-141 Enhances Sheep Kidney Cell Reprogramming into Pluripotent Cells by Targeting ZEB1.

BACKGROUND AND OBJECTIVES: Sheep-induced pluripotent stem cells (siPSCs) have low reprogramming efficiency, thereby hampering their use in biotechnology and agriculture. Several studies have shown that some microRNAs play an important role in promoting somatic reprogramming in mouse and human. In this study, we investigated the effect of miR-200c-141 on somatic reprogramming in sheep and explored the mechanism of promoting the reprogramming. METHODS AND RESULTS: The lentivirus system driven by tetracycline (TET)-on carrying Oct4, Sox2, c-Myc, Klf4, Nanog, Lin28, hTERT, and SV40LT (OSKMNLST) could reprogram sheep kidney cells into pluripotent cells. Overexpression of miR-200c-141 in combination with OSKMNLST could significantly improve the efficiency of sheep iPSC generation (p<0.01). Sheep iPSCs derived from miR-200c-141 showed embryonic stem cell (ESC)-like pluripotent properties, were positive for alkaline phosphatase and some pluripotent markers by quantitative real-time PCR (qRT-PCR) and immunofluorescence, and were able to differentiate into three germ layers in vitro. Oar-miR-200c was transfected into HEK293FT cells and was able to target the zinc finger E-box-binding homeobox 1 (ZEB1) 3'UTR using dual luciferase reporting analysis. Overexpression of oar-miR-200c in SKCs significantly reduced the expression of ZEB1, but increased the expression of E-cadherin by qRT-PCR and western blotting analysis. CONCLUSIONS: These results suggest that miR-200c-141 can promote the reprogramming of sheep somatic cells to iPSCs, and oar-miR-200c targeted ZEB1 3'UTR, significantly decreased expression of ZEB1, and increased expression of E-cadherin. Oar-miR-200c may improve the MET process by affecting the TGF-ß signaling pathway, thus improving the efficiency of somatic cell reprogramming in sheep.

CRISPR-Cas13a-Based Detection for Bovine Viral Diarrhea Virus.

Bovine Viral Diarrhea Virus (BVDV) is the main pathogen of bovine viral diarrhea disease (BVD), which leads to enormous economic losses in the cattle industry. A sensitive and specific detection for BVDV is advantageous to the control of BVDV. Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems have been used for detecting virus RNA. In this study, the expression and purification of LwCas13a protein was optimized and the RNase activity of LwCas13a in vitro was verified. CRISPR-LwCas13a system could detect BVDV virus and BVDV RNA with high specificity and simplicity. The detection limit of the LwCas13a system was 103 pM, and there were no cross-reactions with HEK293T and MDBK. In summary, a sensitive, specific, and simple nucleic acid detection method based on CRISPR-Cas13a was developed for BVDV. This method provides a new detection strategy for early diagnosis of BVDV.

Effect of a medicinal and edible decoction YH0618 on chemotherapy-induced dermatologic toxicity: a randomized controlled trial.

BACKGROUND: Dermatologic toxicities are the common adverse events (AE) with several chemotherapy agents, but they are usually neglected in the research literature and clinical practice, and there are no clinically safe and effective methods to solve the problem. This study was to determine whether a medicinal and edible decoction YH0618 is effective in accelerating reducing chemotherapy-induced dermatologic toxicity in cancer patients who have completed chemotherapy. METHODS: This was a prospective randomized controlled trial conducted between 2015 and 2017. Cancer patients who have completed chemotherapy (received taxanes or anthracyclines or fluoropyrimidine) within two weeks were enrolled and then they were randomly divided into YH0618 decoction group (n=104) and wait-list control (n=110). The primary end points were the incidence of protocol-specified grade ≥2 dermatologic toxicities after 6-week intervention assessed using the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Chinese version 4.0, and changes of fingernails color and skin color evaluated by L*a*b after 6 weeks of intervention. Secondary end points included assessment of quality of life (QOL) and fatigue, and some clinical objective indicators associated with myelosuppression, hepatotoxicity and nephrotoxicity. RESULTS: The study included 214 participants [mean (SD) age, 52.49 (9.08) years in YH0618 group and 50.44 (9.71) years in wait-list group]. At 6-week, YH0618 significantly reduced the incidence of grade ≥2 in nail discoloration [odds ratio (OR), 0.653; 95% CI, 0.5-0.9; P=0.005] and alopecia (OR, 0.776; 95% CI, 0.6-1.0; P=0.048) compared with control group. Besides, YH0618 increased the L* value and reduced the a* and b* values compared with control group, indicating that YH0618 increased the brightness and reduced hyperpigmentation. YH0618 also significantly reduced chemotherapy-induced fatigue (95% CI, 0.2-4.8; P=0.033). CONCLUSIONS: YH0618 may be a safe method in ameliorating chemotherapy-induced dermatologic toxicity especially nail discoloration, alopecia and skin hyperpigmentation, and on improving fatigue. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trials Registry, ChiCTR-IOR-15006486.

Layered double hydroxide nanoparticles as an adjuvant for inactivated foot-and-mouth disease vaccine in pigs.

BACKGROUND: Foot-and-mouth disease (FMD) is a highly transmissible disease that leads to vast economic losses in many countries. Prevention using inactivated vaccines is one effective measure used to control FMD. Unfortunately, inactivated FMD vaccines provide only short-term protection and require a cold-chain system. In recent years, many studies have shown that layered double metal hydroxides (LDHs) carrying antigens can be used to strongly induce immune responses. In this study, LDH nanoparticles (NPs) were prepared by hydrothermal synthesis. LDH particle size, electric potential, and morphology were measured and observed. The adsorption capacity of LDH NPs to FMDV was tested. The effects of LDH as an adjuvant on inactivated FMDV vaccines were further evaluated and compared with commercial FMDV Montanide ISA-206 in BALB/C female mice and Yorkshire pigs. RESULTS: LDH NPs were successfully prepared with a uniform particle size of ~ 87.21 nm, regular edges, a loose hexagonal shape and positive zeta charge of 32 mV. The maximum absorption concentration was 0.16-0.31 µg FMDV/µg LDH. In the mouse experiment, antibody levels in group LDH + FMDV were significantly higher compared to group saline + FMDV (P < 0.01) from days 42-98 and were significantly higher to group ISA-206 + FMDV on day 56 post-immunization (P < 0.05). After day 14 post-immunization, IFN-γ content was significantly increased (P < 0.05). In the pig experiment, antibody levels in both the ISA-206 + FMDV and LDH + FMDV were positive and were significantly higher compared with the PBS group on day 7 (P < 0.005). Antibody levels in 90% pigs were positive on day 56 in the LDH group. The neutralizing antibody levels in the LDH and ISA-206 groups were significantly higher from days 7-28 compared to the PBS control group (P < 0.05). Thus, LDH NPs were effective at inducing an immune response against FMDV. CONCLUSIONS: LDHs with a loose hexagonal shape and a positive charge were prepared and evaluated as adjuvant for FMD vaccine. It was demonstrated that LDHs can induce immune responses in mice and pigs. In addition, the LDHs produced antibodies continuously which may indicate a slow-release effect. The study shows that LDHs may act as a potentially useful FMDV adjuvant.

Effects of the DMRT1 genotype on the body weight and gut microbiota in the broiler chicken.

Intestinal microbiota is a critical determinant of growth and risk of metabolic diseases. Our previous studies showed that the locus rs16775833 within the DMRT1 gene is significantly associated with variation in the population structure of the gut microbiota, which is involved in determining the BW of the chicken. To assess the accuracy of correlation of rs16775833 located in the DMRT1 gene on microbial population and BW in birds, 2 genotypes GG and TT in the rs16775833 were identified in Chinese Yellow broiler breeders. We found that BW in the TT genotype group was significantly higher than in the GG genotype group at 7 and 13 wk of age in 777 female chickens. A full-length 16S rRNA sequencing approach was used to further evaluate the fecal bacterial composition of female broilers in 11 TT genotype chickens with high weight (HW-TT) and 11 GG genotype chickens with low weight (LW-GG) at 91 D of age. Partial least squares discriminant analysis revealed that the microbiota of the HW-TT and LW-GG females were clearly separated into 2 clusters. Furthermore, we identified 13 significantly different (P < 0.05) microbes at the genus level and 17 significantly different (P < 0.05) species between the HW-TT and LW-GG groups. Our data show that rs16775833 can modulate the microbial community structure and is associated with the BW of birds. To our knowledge, this is the first time that DMRT1 has been identified as a specific host factor, which is not only involved in sex determination but also has an effect on microbial function that might regulate animal growth.

A quencher-free 2-aminopurine modified hairpin aptasensor for ultrasensitive detection of Ochratoxin A.

A sensitive, efficient and quencher-free fluorescence aptasensor to detect Ochratoxin A (OTA) based on aptamer, 2-aminopurine (2AP) labeled Oligonucleotide sequence, as well as exonuclease I (Exo I) activity was developed. In which the aptamer specific to OTA was modified into a hairpin structure, and 8 bases at the 3' ends are exposed (H); also, 2AP is embedded in the oligonucleotide complementary to the 8 bases (2AP-probe).The detection principle based on 2AP-probe could be bonded to its complementary sequence and quenches the fluorescence of 2AP; The aptamer has a stronger affinity for the target than its complementary sequence; Exo I can dissociate single-stranded DNA and has little effect on double-stranded DNA as well as folded DNA. In the absence of OTA, the fluorescence of 2AP is quenched due to the complementary pairing of H and 2AP-probe; in the presence of OTA, H selective binding target is detached from 2AP-probe, and the fluorescence of 2AP is slightly restored. Moreover, when the Exo I is added to the detection system, 2AP-probe is dissociated by the Exo I to release the free 2AP, and the fluorescence of the system is further enhanced thereby realizing the detection of OTA. The detection limit of the aptasensor was low as 0.03 nM with a linear range of 0.5-100 nM. Moreover, the aptasensor has good selectivity and practicability and also has good potential in realizing the detection of toxic and harmful substances in food complex matrices.

Incomplete fluid-air exchange technique for idiopathic macular hole surgery.

AIM: To explore an improved procedure involving incomplete fluid-air exchange for idiopathic macular hole (IMH), and the closure rate, visual function, and the visual field of macular holes (MHs) were evaluated. METHODS: This prospective randomized controlled study, included 40 eyes of 40 patients with IMH who were treated with pars plana vitrectomy and peeling of the internal limiting membrane. They were grouped by random digital table. Twenty-one eyes underwent incomplete fluid-air exchange (IFA) and 19 eyes underwent traditional complete fluid-air exchange (CFA) as the control group. Outcomes included best-corrected visual acuity (BCVA), intraocular pressure, and optical coherence tomography, light adaptive electroretinography, and visual field evaluations. RESULTS: All MHs <400 µm were successfully closed. BCVAs before and 6mo after surgery were 0.82±0.41 logMAR and 0.28±0.17 logMAR in IFA group and 0.86±0.34 logMAR and 0.34±0.23 logMAR in CFA group, respectively. The electroretinogram analysis of patients in IFA group revealed increases in b-wave amplitudes at 1, 3, and 6mo after surgery. Additionally, patients in IFA group showed an amplitude increase of 28.6% from baseline at 6mo (P<0.05), while no obvious improvements were noted in CFA group. Although there were no statistically significant improvements in either group, the IFA group showed a slight increase in mean sensitivity (P>0.05). CONCLUSION: IFA is a reliable method that offers comparable closure rate to CFA and facilitates improvements in visual function.