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In recent years, universities in northeastern China have been losing teachers. This paper uses the survey results of university teachers in Northeastern China to analyze the factors that cause the loss of teachers in universities in Northeastern China. Based on the findings of this study, the factors that affect the flow tendency of teachers at worklife include promotion and development, university management, working conditions, salary and interpersonal relationship, of which promotion and development has the greatest impact. The factors that affect the flow tendency of teachers in the external environment include family responsibility, organizational prestige, conditions for talent acquisition and urban living environment, of which organizational prestige has the greatest impact. To alleviate the loss of teachers in universities from northeastern China, universities can improve the promotion and development channels of teachers, perfect their working conditions and management level, raise the basic salary standard of teachers and establish a remuneration system for distribution according to performance. For good measure, they can also stabilize the current teachers while attracting more outstanding talents by exploiting the advantages of location, making more efforts to build high-level disciplines, and offering more favorable conditions for talent introduction.

Purpose: To investigate the effect of Jinlida granule on glycolipid metabolism, oxidative stress, and inflammatory factors in type 2 diabetes mellitus (T2DM) patients with non-alcoholic fatty liver disease (NAFLD). Methods: A total of 132 T2DM patients with NAFLD were equally and randomly divided into study and control groups. Patients in the control group were treated with non-drug therapy including routine diet control, exercise, alcohol avoidance, and drug therapy (using blood glucose and lipid lowering drugs). The study group was treated with Jinlida granule in addition to other measures used in the control group. Blood glucose, blood lipid, and liver function parameters were compared after treatment. Nesfatin-1, oxidative stress, inflammatory factors, liver fat content, and degree of fibrosis were assessed. The efficacy and potential mechanism of Jinlida granule in the patients were assessed. Results: Blood glucose, lipid, and liver function parameters in the study group were lower than in the control group following treatment. Nesfatin-1, GSH-Px, and adiponectin levels were higher, while MDA, TNF-α, liver fat, LSM and CAP levels were lower than in the control group (p < 0.05). The response rate of the study group was 96.97 %, which was higher than the 87.88 % in the control group (p < 0.05). The incidence of adverse drug reactions in the two groups during treatment was comparable (p > 0.05). Conclusion: Jinlida granule exerts positive effect on T2DM patients with NAFLD. Thus, Jinlida granule has potentials for application as an adjuvant in the treatment of T2DM with NAFLD.

After a failed in vitro fertilization (IVF) procedure in which no transferable embryo was obtained, the possibility of a subsequent pregnancy for the patient is unknown. We conducted a cohort retrospective study evaluating the live birth rate in the subsequent cycles of the patients with no embryo for transfer in their first IVF attempt between 2017and 2020. The first cycle variables of patients who conceived in subsequent cycles were compared to those who did not. Additionally, for patients who conceived at last, variables related to ovarian stimulation were compared between the first cycle and the conceiving cycle. In accordance with the inclusion criteria, 529 were enrolled during the study period, of which 230 had successful pregnancies and 192 gave birth to a live infant. Cumulative live birth rates (CLBR) per cycle and patient were 26% and 36% respectively. Moreover, 99% of the live births were obtained within the first three attempts, beyond six cycles, there was no pregnancy. Stimulating variables in the first cycle were not effective in predicting the likelihood of a patient's subsequent pregnancy. Overall, patients who did not have embryos available for transfer in the first cycle had a 36% chance of getting a live birth in subsequent attempts, and the cause of failure should be considered.

To clarify the effect of particle gradation of filling soil on the dewatering and consolidation performance of geotubes, the content of four-particle size classes (powder, fine, medium, and coarse) which are commonly used in engineering as the research object was taken. The dewatering rate, soil infiltration and solid-liquid mixing pressure in the bag with time when filling soil with different particles were studied, and the soil loss of the hanging bag was analyzed from the perspective of seepage soil gradation. The research results show that the dewatering process could be divided into the quick dewatering stage, silting stage, and stable stage according to the dewatering rate. According to the performance of soil conservation, it could be divided into the loss stage and reverse filtration stage. Further, based on the effects of powder content, non-uniformity coefficient, and curvature coefficient of soil on the dewatering rate of the hanging bag, a formula for calculating the dewatering rate of geotubes is summarized.

Because of climate change, the McMurdo Dry Valleys of Antarctica (MCM) have experienced an increase in the frequency and magnitude of summer pulse warming and surface ice and snow melting events. In response to these environmental changes, some nematode species in the MCM have experienced steady population declines over the last three decades, but Plectus murrayi, a mesophilic nematode species, has responded with a steady increase in range and abundance. To determine how P. murrayi responds to increasing temperatures, we measured metabolic heat and CO2 production rates and calculated O2 consumption rates as a function of temperature at 5 °C intervals from 5 to 50 °C. Heat, CO2 production, and O2 consumption rates increase approximately exponentially up to 40 °C, a temperature never experienced in their polar habitat. Metabolic rates decline rapidly above 40 °C and are irreversibly lost at 50 °C due to thermal stress and mortality. Caenorhabditis elegans, a much more widespread nematode that is found in more temperate environments reaches peak metabolic heat rate at just 27 °C, above which it experiences high mortality due to thermal stress. At temperatures from 10 to 40 °C, P. murrayi produces about 6 times more CO2 than the O2 it consumes, a respiratory quotient indicative of either acetogenesis or de novo lipogenesis. No potential acetogenic microbes were identified in the P. murrayi microbiome, suggesting that P. murrayi is producing increased CO2 as a byproduct of de novo lipogenesis. This phenomenon, in conjunction with increased summer temperatures in their polar habitat, will likely lead to increased demand for carbon and subsequent increases in CO2 production, population abundance, and range expansion. If such changes are not concomitant with increased carbon inputs, we predict the MCM soil ecosystems will experience dramatic declines in functional and taxonomic diversity.

BackgroundDay 5 (D5) blastocysts are generally given priority to transfer than day 6 (D6) blastocysts; however, which one should be prioritized to transfer when only low-grade D5 and high-grade D6 blastocysts are available?MethodsA large retrospective cohort study was carried out to evaluate the live birth rate (LBR) following D5 and D6 blastocysts in single frozen-thawed blastocyst transfer (FBT) during January 2014 and December 2018. A multivariate logistic regression was conducted to evaluate the combined impact of expansion day (D5 and D6) and blastocyst quality (high grade/low grade) on LBR, accounting for the potential confounding factors. The biopsied blastocysts from a consecutive PGT-A case series during February 2013 to December 2021 were analyzed in a supplementary study.ResultsThe LBR achieved in high-grade D6 blastocyst transfer was significantly higher than that in low-grade D5 blastocyst transfer (50.43% vs. 40.70%, aOR 1.54, 95% CI 1.05–2.26, p = 0.027). There were no significant differences in preterm birth rate, very preterm birth rate, mean live birth weight, and birth weight 4,000 g between the two cohorts. As for aneuploidy analysis in PGT, there were 54.55% of euploid blastocysts (30/55) among high-grade D6 blastocysts, significantly higher than the 41.39% of euploid blastocysts (565/1,365) among low-grade D5 blastocysts (p < 0.001).ConclusionsOur data suggest that D6 blastocysts with high morphology grading are preferred than D5 blastocysts with low morphology grading when selecting blastocyst transfer to shorten the time of conception.

Objective To investigate the potential effect of repeated intravitreal injection of anti-Vascular Endothelial Growth factor(anti-VEGF)drugs on corneal endothelium in patients with macular edema. Methods This is a prospective study in which a total of 64 patients (64 eyes) were treated with intravitreal injection of anti-VEGF. There were 19 cases of neovascular Age-Related Macular Degeneration (nAMD), 20 cases of Diabetic Macular Edema (DME)and 25 cases of Retinal Vein Occlusion (RVO). 29 cases were treated with Aflibercept (2mg/0.05ml) and 35 cases with Ranibizumab (0.5mg /0.05ml). 3 + PRN therapy was used. Corneal endothelial microscopy was used to measure the corneal thickness and corneal endothelium. The various changes in corneal thickness, corneal endothelial cell density, average cell area, coefficient of variation, and proportion of hexagonal cells were compared between one month after each injection and before injection. Results The proportion of corneal endothelial hexagonal cells (Hex%) in the operative eyes after the 2nd and 3rd injection was found to be significantly lower than that of baseline. Hex% in the operative eyes after the 4th injection was lower than that of baseline, 2nd as well 3rd injection and the difference was statistically significant (P

We aimed to evaluate the pregnancy outcomes of cleavage-stage embryo transfers (ETs) for the first time and explore optimal number of high-quality cleavage-stage embryos for extended culture to blastocyst-stage in women of advanced maternal age (AMA). We retrospectively identified 1646 AMA women ≥ age 38 years for the first fresh ETs between January 2014 and December 2020 at our hospital. Double ETs were divided into three groups as follows: DET-HH (two high-quality embryos), DET-HL (one high-quality and one low-quality embryo), and DET-LL (two low-quality embryos) groups. We mainly analyzed the pregnancy outcomes of double cleavage-stage ETs with different embryo grades and blastocyst-stage ETs with different number of high-quality cleavage-stage embryos on day 3. Our data indicated that the DET-HH group had significantly higher clinical pregnancy, ongoing pregnancy, and live birth rates than DET-HL and DET-LL groups (p < .05). For extended culture to blastocyst-stage with 2 (D3-2H), 3 (D3-3H), and 4 (D3-≥4H) high-quality cleavage-stage embryos, the D3-≥ 4H group had significantly higher ongoing pregnancy and live birth rates than D3-2H and D3-3H groups (p < .05). We observed that the number of high-quality embryos on day 3 was independently associated with live birth rate for blastocyst transfers (OR: 1.133, 95% CI 1.023–1.256, p = .017). There were no significant differences in the clinical pregnancy, ongoing pregnancy and live birth rates among DET-HH, D3-2H and D3-3H groups (p > .05). Extended culture to blastocyst-stage for transfer was safe and recommended for AMA women with ≥ 4 high-quality embryos on day 3.

Sequential models that encode user activity for next action prediction have become a popular design choice for building web-scale personalized recommendation systems. Traditional methods of sequential recommendation either utilize end-to-end learning on realtime user actions, or learn user representations separately in an offline batch-generated manner. This paper (1) presents Pinterest's ranking architecture for Homefeed, our personalized recommendation product and the largest engagement surface; (2) proposes TransAct, a sequential model that extracts users' short-term preferences from their realtime activities; (3) describes our hybrid approach to ranking, which combines end-to-end sequential modeling via TransAct with batch-generated user embeddings. The hybrid approach allows us to combine the advantages of responsiveness from learning directly on realtime user activity with the cost-effectiveness of batch user representations learned over a longer time period. We describe the results of ablation studies, the challenges we faced during productionization, and the outcome of an online A/B experiment, which validates the effectiveness of our hybrid ranking model. We further demonstrate the effectiveness of TransAct on other surfaces such as contextual recommendations and search. Our model has been deployed to production in Homefeed, Related Pins, Notifications, and Search at Pinterest., Comment: \c{opyright} {ACM} {2023}. This is the author's version of the work. It is posted here for your personal use. Not for redistribution. The definitive Version of Record was published in KDD'23, http://dx.doi.org/10.1145/3580305.3599918

Objectives To find out the association between the sensorineural hearing loss and coronavirus disease 2019 (COVID-19), the expression of ACE2 and TMPRSS2 in hamsters and mice was detected. Design Using the public data from the National Center for Biotechnology Information and the Global Initiative on Sharing All Influenza Data, the expression of ACE2 and TMPRSS2 at the transcriptomic, DNA, and protein levels of ACE2 in the brain, inner ear, and muscle from the golden Syrian hamsters (Mesocricetus auratus) and mice (Mus musculus) was assessed. Results We identified ACE2 and TMPRSS2 expressed at different levels in the inner ear and brain at DNA and transcriptomic levels of both mice and hamsters. The protein expression from the brain and inner ear showed a similar pattern, while the expression of ACE2 from the inner ear was relatively higher than that from the muscle. Conclusion Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shows genetic potential to infect the hearing system of rodents and lead to sudden sensorineural hearing loss that can be used as a characteristic to detect asymptomatic patients of COVID-19.

STUDY QUESTION Are mutations in MOS (MOS proto-oncogene, serine/threonine kinase) involved in early embryonic arrest in infertile women? SUMMARY ANSWER We identified mutations in MOS that may cause human female infertility characterized by preimplantation embryonic arrest (PREMBA), and the effects of the mutations in human embryonic kidney 293T (HEK293T cells) and mouse oocytes provided evidence for a causal relation between MOS and female infertility. WHAT IS KNOWN ALREADY MOS, an activator of mitogen-activated protein kinase, mediates germinal vesicle breakdown and metaphase II arrest. Female MOS knockout mice are viable but sterile. Thus, MOS seems to be an important part of the mammalian cell cycle mechanism that regulates female meiosis. STUDY DESIGN, SIZE, DURATION Whole-exome sequencing, bioinformatics filtering analysis and genetic analysis were performed to identify two different biallelic mutations in MOS in two independent families. The infertile patients presenting with early embryonic arrest were recruited from October 2018 to June 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS The female patients diagnosed with primary infertility were recruited from the reproduction centres of local hospitals. Genomic DNA from the affected individuals, their family members and healthy controls was extracted from peripheral blood. We performed whole-exome sequencing in patients diagnosed with PREMBA. Functional effects of the mutations were investigated in HEK293T cells by western blotting and in mouse oocytes by microinjection and immunofluorescence. MAIN RESULTS AND THE ROLE OF CHANCE We identified the homozygous missense mutation c.285C>A (p.(Asn95Lys)) and the compound heterozygous mutations c.467delG (p.(Gly156Alafs*18)) and c.956G>A (p.(Arg319His)) in MOS in two independent patients. The mutations c.285C>A (p.(Asn95Lys)) and c.467delG (p.(Gly156Alafs*18)) reduced the protein level of MOS, and all mutations reduced the ability of MOS to phosphorylate its downstream target, extracellular signal-regulated kinase1/2. In addition, the identified mutations reduced the capacity of exogenous human MOS to rescue the metaphase II exit phenotype, and the F-actin cytoskeleton of mouse oocytes was affected by the patient-derived mutations. LIMITATIONS, REASONS FOR CAUTION Owing to the lack of in vivo data from patient oocytes, the exact molecular mechanism affected by MOS mutations and leading to PREMBA is still unknown and should be further investigated using knock-out or knock-in mice. WIDER IMPLICATIONS OF THE FINDINGS We identified recessive mutations in MOS in two independent patients with the PREMBA phenotype. Our findings reveal the important role of MOS during human oocyte meiosis and embryonic development and suggest that mutations in MOS may be precise diagnostic markers for clinical genetic counselling. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the National Natural Science Foundation of China (81725006, 81822019, 81771581, 81971450, 81971382,82001538 and 82071642), the project supported by the Shanghai Municipal Science and Technology Major Project (2017SHZDZX01), the Project of the Shanghai Municipal Science and Technology Commission (19JC1411001), the Natural Science Foundation of Shanghai (19ZR1444500 and 21ZR1404800), the Shuguang Program of the Shanghai Education Development Foundation and the Shanghai Municipal Education Commission (18SG03), the Foundation of the Shanghai Health and Family Planning Commission (20154Y0162), the Capacity Building Planning Program for Shanghai Women and Children’s Health Service and the collaborative innovation centre project construction for Shanghai Women and Children’s Health. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A.

Biochanin A (Bioch A) is a natural plant estrogen, with various biological activities such as anti-apoptosis, anti-oxidation, and suppression of inflammation. In this study, we investigated the protective effects of Bioch A on angiotensin II (AngII) – induced dopaminergic (DA) neuron damage in vivo and on molecular mechanisms. Spontaneous activity and motor ability of mice among groups was detected by open-field test and swim-test. The expression of TH, microtubule-associated proteins light chain 3B II (LC3BII)/LC3BI, beclin-1, P62, forkhead box class O3 (FoxO3), phosphorylated (p) FoxO3a/FoxO3a, FoxO3, and endophilin A2 were determined by Western blot and immunohistochemistry or immunofluorescence staining. Our results showed that AngII treatment significantly increased the behavioral dysfunction of mice and DA neuron damage. Meanwhile, AngII treatment increased the expression of LC3BII/LC3BI, beclin-1, P62, and FoxO3a and decreased the expression of endophilin A2 and p-FoxO3a/FoxO3a, however, Bioch A treatment alleviate these changes. In summary, these results suggest that Bioch A exerts protective effects on AngII-induced mouse model may be related to regulating endophilin A2, FoxO3a, and autophagy-related proteins; however, the specific mechanism is not yet clear and needs further study.

In this work, non-isocyanate poly(hydroxyl)urethane (NIPHU) was prepared. The chemical structures of the cyclic carbonated polypropylene glycol diglycidyl ether and NIPHU were confirmed. The thermoresponsive behavior of NIPHU was researched by Rayleigh light scattering, dynamic light scattering, and scanning electron microscopy upon heating and cooling. A reversible thermoresponsive behavior from micelles to aggregated structures was discovered above the critical micelle concentration (CMC). Thermoresponsive behavior processes, including a micelle stage, aggregation upon heating, disaggregation, a fusion stage, further disaggregate stage, and an additional micelle stage upon cooling, were revealed when the concentration was equal to or below the CMC. Furthermore, the hemocompatibility and biocompatibility of NIPHU were good, as confirmed by a low toxicity by hemolysis, a low cytotoxicity toward L929 cells, and the observed confocal laser scanning microscopy images of the live/dead-stained cells. The potential application of NIPHU should therefore be explored as the component of biomedical composite materials. Reversible thermoresponsive behavior of non-isocyanate poly(hydroxyl)urethane were investigated

Solar thermochemical CO2-splitting (STCS) is a promising solution for solar energy harvesting and storage. However, practical solar fuel production by utilizing earth-abundant iron/iron oxides remains a great challenge because of the formation of passivation layers, resulting in slow reaction kinetics and limited CO2 conversion. Here, we report a novel material consisting of an iron-nickel alloy embedded in a perovskite substrate for intensified CO production via a two-step STCS process. The novel material achieved an unprecedented CO production rate of 381 mL g−1 min−1 with 99% CO2 conversion at 850 °C, outperforming state-of-the-art materials. In situ structural analyses and density functional theory calculations show that the alloy/substrate interface is the main active site for CO2 splitting. Preferential oxidation of the FeNi alloy at the interface (as opposed to forming an FeOx passivation shell encapsulating bare metallic iron) and rapid stabilization of the iron oxide species by the robust perovskite matrix significantly promoted the conversion of CO2 to CO. Facile regeneration of the alloy/perovskite interfaces was realized by isothermal methane reduction with simultaneous production of syngas (H2/CO = 2, syngas yield > 96%). Overall, the novel perovskite-mediated dealloying-exsolution redox system facilitates highly efficient solar fuel production, with a theoretical solar-to-fuel efficiency of up to 58%, in the absence of any heat integration.

Turnover prediction has an important impact on alleviating the brain drain, which can help organizations reduce costs and enhance competitiveness. Existing studies on turnover are mainly based on analyzing the turnover correlation, using different models to predict various employee turnover scenarios, and only predicting turnover category, while the class imbalance and turnover possibility have been ignored. To this end, in this paper, we propose a novel fine-grained adaptation-based turnover prediction neural network (FATPNN) model. Specifically, we first employ a GRU to learn profile-aware features representations of the personnel samples. Then, to evaluate the contribution of various turnover factors, we further exploit an attention mechanism to model the profile information. Finally, we creatively design a weighted-based probability loss function suitable for our turnover prediction tasks. Experimental results show the effectiveness and universality of the FATPNN model in terms of turnover prediction.

ObjectiveTo explore the association between endometrial thickness (EMT) and adverse neonatal outcomes in frozen in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) cycles.MethodsThis retrospective study involved a total of 8,235 women under the age of 35 years who underwent IVF/ICSI cycles and received frozen embryo transfer (FET) at a tertiary-care academic medical from January 2015 to December 2019, resulting in a live singleton newborn. Patients were categorized into three groups depending on EMT: ≤7.5 mm, 7.5-12 mm and >12 mm. The primary outcome was low birthweight (LBW). The secondary outcomes were preterm birth (PTB), small-for-gestational age (SGA), large-for-gestational age (LGA) and high birthweight (HBW).Result(s)Compared with EMT >7.5–12 mm group, the risk of being born LBW was statistically significantly increased in the EMT ≤7.5 mm group (adjusted odds ratio [aOR] 2.179; 95% confidence interval [CI], 1.305–3.640; P=.003), while dramatically decreased in the EMT >12 mm group (aOR 0.584; 95% CI, 0.403-0.844; P=.004). Moreover, newborn gender and pregnancy complications were all independent predictors for LBW. Furthermore, a significant decrease in birthweight was found in the EMT ≤7.5 mm group as compared with EMT >7.5–12 mm group and EMT >12 mm group (3,239 ± 612 vs. 3,357 ± 512 and 3,374 ± 479 g, respectively), and similar result was found in term of gestational age (38.41 ± 2.19 vs. 39.01 ± 1.68 and 39.09 ± 1.5 weeks, respectively).Conclusion(s)After frozen IVF/ICSI-ET, EMT ≤7.5 mm is independently associated with increased risk of LBW among women with singleton newborns. Therefore, we suggest that women with EMT ≤7.5 mm after achieving pregnancy by IVF/ICSI-ET treatment should warrant more attention to reduce the risk of delivering a LBW newborn.

ImportanceThere is a lack of information regarding the need to postpone conception after COVID-19 vaccination.ObjectiveTo investigate the time interval between the first dose of inactivated COVID-19 vaccine and in vitro fertilization (IVF) treatment as well as the rate of pregnancy after a fresh embryo transfer.Design, Setting, and ParticipantsThis cohort study was conducted at a single public IVF center in China. Female patients aged 20 to 47 years and undergoing IVF treatment were consecutively registered from May 1 to December 22, 2021, with follow-up until March 31, 2022. Patients with SARS-CoV-2 infection before or during IVF treatment and those who underwent 2 or more IVF treatments, received the noninactivated or unknown COVID-19 vaccine, or did not have a fresh embryo transfer were excluded from this study.ExposuresThe vaccinated group (subdivided into 4 subgroups of time interval from first vaccination to fertilization treatment: ≤30 days, 31-60 days, 61-90 days, and ≥91 days) and nonvaccinated group.Main Outcomes and MeasuresRisk ratios (RRs) for the association between the time interval and ongoing pregnancy (pregnancy continued at least 12 weeks).ResultsA total of 3052 female patients (mean [SD] age, 31.45 [3.96] years) undergoing IVF treatment were analyzed in this study. There were 667 vaccinated patients receiving IVF (35 were vaccinated ≤30 days, 58 were vaccinated 31-60 days, 105 were vaccinated 61-90 days, and 469 were vaccinated ≥91 days before fertilization treatment), and 2385 unvaccinated patients receiving treatment. The ovarian stimulation and laboratory parameters were similar among all groups. Ongoing pregnancy was significantly lower in the 30 days or less subgroup (34.3% [12 of 35]; adjusted RR [aRR], 0.61; 95% CI, 0.33-0.91) and the 31 to 60 days’ subgroup (36.2% [21 of 58]; aRR, 0.63; 95% CI, 0.42-0.85). A slightly but not statistically lower rate was found in the 61 to 90 days’ subgroup, and no reduced risk for ongoing pregnancy in the 91 days or more subgroup was observed (56.3% [264 of 469]; aRR, 0.96; 95% CI, 0.88-1.04) compared with the unvaccinated group (60.3% [1439 of 2385], as reference).Conclusions and RelevanceFindings of this study suggest that receipt of the first inactivated COVID-19 vaccine dose 60 days or less before fertilization treatment is associated with a reduced rate of pregnancy. In patients undergoing IVF treatment with a fresh embryo transfer, the procedure may need to be delayed until at least 61 days after COVID-19 vaccination.

Zika virus (ZIKV), a mosquito-borne flavivirus, is a global health concern because of its association with severe neurological disorders such as neonatal microcephaly and adult Guillain-Barre syndrome. Although many efforts have been made to combat ZIKV infection, there is currently no approved vaccines or antiviral drugs available and there is an urgent need to develop effective anti-ZIKV agents. In this study, 26 acetylarylamine-S-DACOs derivatives were prepared, and eight of them were found to have inhibitory activity against Zika virus. Among these substances, 2-[(4-cyclohexyl-5-ethyl-6-oxo-1,6-dihydropyrimidin-2-yl)thio]-N-(3,5-difluorophenyl)acetamide (4w) with the best anti-ZIKV activity was selected for in-depth study of antiviral activity and mechanism of action. Here, we discovered 4w targeted on the ZIKV NS5 RNA -dependent RNA polymerase (RdRp), which exhibited good in vitro antiviral activity without cell species specificity, both at the protein level and at the RNA level can significantly inhibit ZIKV replication. Preliminary molecular docking studies showed that 4w preferentially binds to the palm region of NS5A RdRp through hydrogen bonding with residues such as LYS468, PHE466, GLU465, and GLY467. ZIKV NS5 RdRp enzyme activity experiment showed that 4w could directly inhibit ZIKV RdRp activity with EC50 = 11.38 ± 0.51 μM. In antiviral activity studies, 4w was found to inhibit ZIKV RNA replication with EC50 = 6.87 ± 1.21 μM. ZIKV-induced plaque formation was inhibited with EC50 = 7.65 ± 0.31 μM. In conclusion, our study disclosed that acetylarylamine-S-DACOs is a new active scaffolds against ZIKV, among which compound 4w was proved to be a potent novel anti-ZIKV compound target ZIKV RdRp protein. These promising results provide a future prospective for the development of ZIKV RdRp inhibitors.

Herein, a novel series of dual histone deacetylase (HDAC) and vascular endothelial growth factor receptor (VEGFR) inhibitors were designed, synthesized and biologically evaluated based on previously reported pazopanib-based HDAC and VEGFR dual inhibitors. Most target compounds showed significant HDAC1, HDAC6 and VEGFR2 inhibition, which contributed to their potent antiproliferative activities against multiple cancer cell lines and significant antiangiogenic potencies in both human umbilical vein endothelial cell (HUVEC) tube formation assays and rat thoracic aorta ring assays. Further HDAC selectivity evaluations indicated that hydroxamic acids 5 and 9e possessed HDAC isoform selectivity profiles similar to that of the approved HDAC inhibitor suberoylanilide hydroxamic acid(SAHA), while hydrazide12 presented an HDAC isoform selectivity profilesimilar to that of the clinical HDAC inhibitor MS-275. The VEGFR inhibition profiles of 5, 9e and 12 were similar to that of the approved VEGFR inhibitor pazopanib. The intracellular target engagements of Compounds 5 and 12 were confirmed by western blot analysis. The metabolic stabilities of 5, 9e and 12 in mouse liver microsomes were inferior to that of pazopanib. These dual HDAC and VEGFR inhibitors provide lead compounds for further structural optimization to obtainpolypharmacological anticancer agents.

In in vitro fertilization (IVF), the patient's probability of subsequent pregnancy after a failed procedure with no transferable embryo is unknown. We conducted a cohort retrospective study evaluating the live birth rate in the subsequent cycles of the patients with no embryo transfer in their first IVF attempt between 2017and 2020. The variables in the first cycle were compared between the patients who conceived in subsequent cycles and who did not. Additionally, for patients who conceived at last, variables related to ovarian stimulation were compared between the first cycle and the pregnancy cycle. According to the inclusion criteria, 529 were enrolled during the study period, of which 230 had successful pregnancies and 192 gave birth to a live infant. Cumulative live birth rates (CPR) per cycle and per patient were 26%, 36% respectively. 99% of the live births were obtained within the first 3 attempts, no pregnancy was achieved beyond 6 cycles. Stimulating variables in the first cycle were not effective in predicting the likelihood of a patient's subsequent pregnancy. Overall, patients who did not have embryos available for transfer in the first cycle had a 36% chance of having a live birth in subsequent attempts, and more than three attempts were not recommended.

Zika virus (ZIKV), a mosquito-borne flavivirus, is a global health concern because of its association with severe neurological disorders such as neonatal microcephaly and adult Guillain-Barre syndrome. Although many efforts have been made to combat ZIKV infection, there is currently no approved vaccines or antiviral drugs available and there is an urgent need to develop effective anti-ZIKV agents. In this study, 26 acetylarylamine

Because of climate change, the McMurdo Dry Valleys of Antarctica (MCM) have experienced increased summer temperatures and surface ice and snow melting events. In response to these environmental changes, some nematode species in the MCM have experienced steady population declines over the last three decades, but Plectus murrayi, a mesophilic nematode species, has responded with a steady increase in range and abundance. To determine how P. murrayi responds to increasing temperatures we measured metabolic heat and CO2 production rates and calculated O2 consumption rates as a function of temperature at 5°C intervals from 5 to 50°C. Heat, CO2 production, and O2 consumption rates increase approximately exponentially up to 40°C, a temperature never experienced in their polar habitat. Metabolic rates decline rapidly above 40°C and are irreversibly lost at 50°C due to thermal stress and mortality. Caenorhabditis elegans, a much more widespread nematode that is found in more temperate environments reaches peak metabolic heat rate at just 27°C, above which it experiences high mortality due to thermal stress. At temperatures from 10 to 40°C, P. murrayi produces about 6 times more CO2 than the O2 it consumes, a respiratory quotient indicative of either acetogenesis or de novo lipogenesis. No potential acetogenic microbes were identified in the P. murrayi microbiome. We, therefore, conclude that P. murrayi is producing increased CO2 as a byproduct of de novo lipogenesis. This phenomenon, in conjunction with increased summer temperatures in their polar habitat, will likely lead to increased CO2 production, population abundance, and range expansion.

Background Phosphate-solubilizing bacteria (PSB) can enhance plant growth and phosphorus (P) solubilization, it also has been reported to reduce the negative effects of overused agricultural fertilizer in farmland and protect the soil environment. However, the mechanism behind this interaction has not been fully elucidated. Results In this study, we screened out Pseudomonas moraviensis, Bacillus safensis, and Falsibacillus pallidus which can both solubilize P efficiently and produce indole-3-acetic acid (IAA) from sandy fluvo-aquic soils. The yield of wheat (Triticum aestivum) under PSB inoculation significantly increased up to 14.42% (P P P Conclusion PSB from sandy fluvo-aquic soil improve wheat growth and crop productivity by increasing the labile P fraction and IAA content in the greenhouse and wheat field. Our work provides an environment and economy-friendly bacterial resource that potentially promotes sustainable agricultural development in the long term.

Esophageal cancer (EC) represents a human malignancy, diagnosed often at the advanced stage of cancer and resulting in high morbidity and mortality. The development of precision medicine allows for the identification of more personalized therapeutic strategies to improve cancer treatment. By implanting primary cancer tissues into immunodeficient mice for expansion, patient-derived xenograft (PDX) models largely maintain similar histological and genetic representations naturally found in patients' tumor cells. PDX models of EC (EC-PDX) provide fine platforms to investigate the tumor microenvironment, tumor genomic heterogeneity, and tumor response to chemoradiotherapy, which are necessary for new drug discovery to combat EC in addition to optimization of current therapeutic strategies for EC. In this review, we summarize the methods used for establishing EC-PDX models and investigate the utilities of EC-PDX in screening predictive biomarkers and potential therapeutic targets. The challenge of this promising research tool is also discussed.

A novel coordination polymer containing Mn(II) ions as nodes was prepared by the hydrothermal method, and its chemical formula is {[Mn2(L)(hfpd)(H2O)]·1.75H2O}n (1) (L = 4,4′-bis(imidazol-1-yl)-biphenyl and H4hfpd = 4,4′-(hexafluoroisopropylidene)diphthalic acid). It was then used for evaluation the relationship with the Endometriosis (EMs). The activation for the estrogen receptor relative expression on the surface of endometrial cell was detected through the real time RT-PCR, and the results showed that complex 1 could obviously decreased the estrogen receptor over expression on the endometrial cell surface dose dependently. The immune function of the macrophages under the endometrial cells were determined by Western blot, the data indicated that complex 1 exerts the excellent treatment activity via activating the autophagy in macrophages. Molecular docking simulations reveal that the origin of the biological activity is from the carboxyl functional groups on the complex.

Monkeypox is a zoonotic disease. Since the first human monkeypox case was detected in 1970, it has been prevalent in some countries in central and western Africa. Since May 2022, monkeypox cases have been reported in more than 96 non-endemic countries and regions worldwide. As of September 14, 2022, there have been more than 58,200 human monkeypox cases, and there is community transmission. The cessation of smallpox vaccination in 1980, which had some cross-protection with monkeypox, resulted in a general lack of immunity to monkeypox, which caused global concern and vigilance. As of September 14, 2022, there are four monkeypox cases in China, including three in Taiwan province and one in Hong Kong city. Previous foreign studies have shown that children are vulnerable to monkeypox and are also at high risk for severe disease or complications. In order to improve pediatricians' understanding of monkeypox and achieve early detection, early diagnosis, early treatment, and early disposal, we have organized national authoritative experts in pediatric infection, respiratory, dermatology, critical care medicine, infectious diseases, and public health and others to formulate this expert consensus, on the basis of the latest "Clinical management and infection prevention and control for monkeypox" released by The World Health Organization, the "guidelines for diagnosis and treatment of monkeypox (version 2022)" issued by National Health Commission of the People's Republic of China and other relevant documents. During the development of this consensus, multidisciplinary experts have repeatedly demonstrated the etiology, epidemiology, transmission, clinical manifestations, laboratory examinations, diagnosis, differential diagnosis, treatment, discharge criteria, prevention, disposal process, and key points of prevention and control of suspected and confirmed cases.

This files are supplementary files for "Rop plays conserved roles in the reproductive and digestive processes of spider mites"

N-Linked glycoproteins are rich in seminal plasma, playing various essential roles in supporting sperm function and the fertilization process. However, the detailed information on these glycoproteins, particularly site-specific glycan structures, is still limited. In this study, a precision site-specific

The dissemination of antibiotic resistance genes (ARGs) in aquaculture systems is a potential threat to environmental safety and human health. However, the spatiotemporal distribution pattern of ARGs and key factors associated with their dissemination in aquaculture sediments remain unclear. In this study, ARGs, mobile genetic elements, microbial community composition, heavy metal contents, and nutrient contents of samples collected from a whole culture cycle of fish in a representative aquaculture farm were characterized. The distribution patterns of nine subtypes of ARGs (tetW, tetM, tetA, ermC, ermB, sul1, sul2, floR, and qnrS) showed clear spatiotemporal differences. The absolute abundance of ARGs in aquaculture sediments was higher in winter and in rivers of the aquaculture farm. Proteobacteria was the dominant phylum in all sediment samples. The results of network and redundancy analyses confirmed that the Dechloromonas, Candidatus Accumulibacter, Smithella, Geobacter, and Anaeromyxobacter belonging to Proteobacteria were positively correlated with ARGs, suggesting that these microbial species are potential hosts of corresponding ARGs. Our study highlights that the microbial community is the determining factor for ARG dissemination. Strategies for inhibiting these potential hosts of ARGs should be developed based on controllable factors.

The automatic recognition of personality traits from texts has attracted significant attention. Existing studies typically combine linguistic feature engineering with traditional models, use five various neural networks to predict personality traits with multiple labels, and fail to achieve the best performance on each label. To this end, in this paper, we propose a novel semantic-enhanced personality recognition neural network (SEPRNN) model, which has a goal of avoiding dependence on feature engineering, allowing the same model to adapt to detecting five various personality traits with no modification to the model itself, and employing deep learning based methods and atomic features of texts to build vectorial word-level representation for personality trait recognition. Specifically, to precisely recognize multi-labeled personality traits, we first propose a word-level semantic representation for texts based on context learning. Then, a fully connected layer is used to obtain higher-level semantics of texts. Finally, the experimental results demonstrate that the proposed approach achieves significant performance improvement for multi-labeled personality traits compared with several baselines.

Background Primary hyperoxaluria(PH)is a rare autosomal recessive genetic disease that contains three subtypes (PH1, PH2 and PH3). Approximately 80% of PH patients has been reported as subtype PH1, this subtype of PH has been related to a higher risk of renal failure at any age. Several genetic studies indicate that the variants in gene AGXT are responsible for the occurrence of PH1. However, the population heterogeneity of the variants in AGXT makes the genetic diagnosis of PH1 more challenging as it is hard to locate each specific variant. It is valuable to have a complete spectrum of AGXT variants from different population for early diagnosis and clinical treatments of PH1. Case presentation In this study, We performed high-throughput sequencing and genetic analysis of a 6-year-old male PH1 patient from a Chinese family. Two variants (c.346G > A: p.Gly116Arg; c.864G > A: p.Trp288X) of the gene AGXT were identified. We found a nonsense variant (c.864G > A: p.Trp288X) that comes from the proband’s mother and has never been reported previously. The other missense variant (c.346G > A: p.Gly116Arg) was inherited from his father and has been found previously in a domain of aminotransferase, which plays an important role in the function of AGT protein. Furthermore, we searched 110 pathogenic variants of AGXT that have been reported worldwide in healthy local Chinese population, none of these pathogenic variants was detected in the local genomes. Conclusions Our research provides an important diagnosis basis for PH1 on the genetic level by updating the genotype of PH1 and also develops a better understanding of the variants in AGXT by broadening the variation database of AGXT according to the Chinese reference genome.

Background Our previous study have shown that the PSMD11 protein was an important survival factor for cancer cells except for its key role in regulation of assembly and activity of the 26S proteasome. To further investigate the role of PSMD11 in carcinogenesis, we constructed a conditional exon 5 floxed allele of PSMD11 (PSMD11flx) in mice. Results It was found that homozygous PSMD11 flx/flx mice showed normal and exhibited a normal life span and fertility, and showed roughly equivalent expression of PSMD11 in various tissues, suggesting that the floxed allele maintained the wild-type function. Cre recombinase could induce efficient knockout of the floxed PSMD11 allele both in vitro and in vivo. Mice with constitutive single allele deletion of PSMD11 derived from intercrossing between PSMD11flx/flx and CMV-Cre mice were all viable and fertile, and showed apparent growth retardation, suggesting that PSMD11 played a significant role in the development of mice pre- or postnatally. No whole-body PSMD11 deficient embryos (PSMD11−/−) were identified in E7.5–8.5 embryos in uteros, indicating that double allele knockout of PSMD11 leads to early embryonic lethality. To avoid embryonic lethality produced by whole-body PSMD11 deletion, we further developed conditional PSMD11 global knockout mice with genotype Flp;FSF-R26CAG − CreERT2/+; PSMD11flx/flx, and demonstrated that PSMD11 could be depleted in a temporal and tissue-specific manner. Meanwhile, it was found that depletion of PSMD11 could induce massive apoptosis in MEFs. Conclusions In summary, our data demonstrated that we have successfully generated a conditional knockout allele of PSMD11 in mice, and found that PSMD11 played a key role in early and postnatal development in mice, the PSMD11 flx/flx mice will be an invaluable tool to explore the functions of PSMD11 in development and diseases.

Personnel performance is a key factor to maintain core competitive advantages. Thus, predicting personnel future performance is a significant research domain in human resource management (HRM). In this paper, to improve the performance, we propose a novel method for personnel performance prediction which helps decision-makers select high-potential talents. Specifically, for modeling the personnel performance, we first devise a GRU model to learn sequential information from personnel performance data without any expertise. Then, to better cluster the features, we exploit capsule network. Finally, to precisely make predictions, we further design one strategy, i.e., an improved loss function, and embed it into the capsule network. In addition, by introducing this strategy, our proposed model can well deal with the imbalanced data problem. Extensive experiments on real-world data clearly demonstrate the effectiveness of the proposed approach.