Protein features fusion using attributed network embedding for predicting protein-protein interaction.

BACKGROUND: Protein-protein interactions (PPIs) hold significant importance in biology, with precise PPI prediction as a pivotal factor in comprehending cellular processes and facilitating drug design. However, experimental determination of PPIs is laborious, time-consuming, and often constrained by technical limitations. METHODS: We introduce a new node representation method based on initial information fusion, called FFANE, which amalgamates PPI networks and protein sequence data to enhance the precision of PPIs' prediction. A Gaussian kernel similarity matrix is initially established by leveraging protein structural resemblances. Concurrently, protein sequence similarities are gauged using the Levenshtein distance, enabling the capture of diverse protein attributes. Subsequently, to construct an initial information matrix, these two feature matrices are merged by employing weighted fusion to achieve an organic amalgamation of structural and sequence details. To gain a more profound understanding of the amalgamated features, a Stacked Autoencoder (SAE) is employed for encoding learning, thereby yielding more representative feature representations. Ultimately, classification models are trained to predict PPIs by using the well-learned fusion feature. RESULTS: When employing 5-fold cross-validation experiments on SVM, our proposed method achieved average accuracies of 94.28%, 97.69%, and 84.05% in terms of Saccharomyces cerevisiae, Homo sapiens, and Helicobacter pylori datasets, respectively. CONCLUSION: Experimental findings across various authentic datasets validate the efficacy and superiority of this fusion feature representation approach, underscoring its potential value in bioinformatics.

Dual-Responsive Near-Infrared BODIPY-Based Fluorescent Probe for the Detection of F- and HClO in Organisms.

Fluoride anions (F-) play a crucial role in human physiological processes. However, excessive intake of F- would affect oxygen metabolism and promote the generation of oxygen-free radicals. Hence, it is essential to develop a precise and efficient fluorescent probe for visualizing F--induced oxidative stress. In this work, we developed the first bifunctional BODIPY-based fluorescent probe dfBDP with p-tert-butyldimethylsilanolate benzyl thioether as the sensing site for the detection of F- and HClO via two distinct reactions, the self-immolative removal and the thioether oxidation, which generate the sensing products with two nonoverlap fluorescence bands: 800-1200 and 500-750 nm, respectively. The probe dfBDP displays rapid response, high specificity, and sensitivity for the detection of F- (LOD, 316.2 nM) and HClO (LOD, 33.9 nM) in vitro. Cellular imaging reveals a correlation between F--induced oxidative stress and the upregulation of HClO. Finally, probe dfBDP was employed to detect F- and HClO in mice under the stimulation of F-. The experimental results display that the level of HClO elevates in the liver of mice.

Clinical effectiveness of nirmatrelvir plus ritonavir on the short- and long-term outcome in high-risk children with COVID-19.

This study investigated the clinical effectiveness of nirmatrelvir plus ritonavir (NMV-r) on short-term outcome and the risk of postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) among pediatric patients with coronavirus disease 2019 (COVID-19). This retrospective cohort study used the TriNetX research network to identify pediatric patients between 12 and 18 years with COVID-19 between January 1, 2022 and August 31, 2023. The propensity score matching (PSM) method was used to match patients receiving NMV-r (NMV-r group) with those who did not receive NMV-r (control group). Two cohorts comprising 633 patients each (NMV-r and control groups), with balanced baseline characteristics, were identified using the PSM method. During the initial 30 days, the NMV-r group showed a lower incidence of all-cause hospitalization, mortality, or ED visits (hazard ratio [HR] = 0.546, 95% confidence interval [CI]: 0.372-0.799, p = 0.002). Additionally, the NMV-r group had a significantly lower risk of all-cause hospitalization compared with the control group (HR = 0.463, 95% CI: 0.269-0.798), with no deaths occurring in either group. In the 30-180-day follow-up period, the NMV-r group exhibited a non-significantly lower incidence of post-acute sequelae of SARS-CoV-2 infection (PASC), encompassing symptoms such as fatigue, cardiopulmonary symptoms, pain, cognitive impairments, headache, dizziness, sleep disorders, anxiety, and depression, compared to the control group. This study underscores the potential effectiveness of NMV-r in treating high-risk pediatric patients with COVID-19, demonstrating significant reductions in short-term adverse outcomes such as emergency department visits, hospitalization, or mortality within the initial 30-day period. Additionally, NMV-r shows promise in potentially preventing the development of PASC.

Detrimental Role of CXCR3 in α-Naphthylisothiocyanate- and Triptolide-Induced Cholestatic Liver Injury.

The chemokine receptor CXCR3 is functionally pleiotropic, not only recruiting immune cells to the inflamed liver but also mediating the pathological process of cholestatic liver injury (CLI). However, the mechanism of its involvement in the CLI remains unclear. Both alpha-naphthylisothiocyanate (ANIT) and triptolide are hepatotoxicants that induce CLI by bile acid (BA) dysregulation, inflammation, and endoplasmic reticulum (ER)/oxidative stress. Through molecular docking, CXCR3 is a potential target of ANIT and triptolide. Therefore, this study aimed to investigate the role of CXCR3 in ANIT- and triptolide-induced CLI and to explore the underlying mechanisms. Wild-type mice and CXCR3-deficient mice were administered with ANIT or triptolide to compare CLI, BA profile, hepatic recruitment of IFN-γ/IL-4/IL-17+CD4+T cells, IFN-γ/IL-4/IL-17+iNKT cells and IFN-γ/IL-4+NK cells, and the expression of ER/oxidative stress pathway. The results showed that CXCR3 deficiency ameliorated ANIT- and triptolide-induced CLI. CXCR3 deficiency alleviated ANIT-induced dysregulated BA metabolism, which decreased the recruitment of IFN-γ+NK cells and IL-4+NK cells to the liver and inhibited ER stress. After triptolide administration, CXCR3 deficiency ameliorated dysregulation of BA metabolism, which reduced the migration of IL-4+iNKT cells and IL-17+iNKT cells and reduced oxidative stress through inhibition of Egr1 expression and AKT phosphorylation. Our findings suggest a detrimental role of CXCR3 in ANIT- and triptolide-induced CLI, providing a promising therapeutic target and introducing novel mechanisms for understanding cholestatic liver diseases.

Association between vitamin D deficiency and post-acute outcomes of SARS-CoV-2 infection.

OBJECTIVES: This study aimed to investigate the association between vitamin D deficiency (VDD) and post-acute outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: This retrospective study used the TriNetX research network to identify COVID-19 patients between January 1 and November 30, 2022. Patients were matched using propensity score matching (PSM) and divided into VDD (< 20 ng/mL) and control (≥ 20 ng/mL) groups. The primary outcome was a composite of post-COVID-19 condition (identified by ICD-10 code), all-cause emergency department (ED) visits, hospitalization, and death during the follow-up period (90-180 days) after the diagnosis of COVID-19. RESULTS: From an initial recruitment of 42,674 non-hospitalized patients with COVID-19 and known 25(OH)D status, a VDD group of 8300 was identified and propensity matched with 8300 controls. During the follow-up period, the VDD group had a higher risk of the primary outcome than did the control group [hazard ratio (HR) = 1.122; 95% confidence interval (CI) = 1.041-1.210]. The VDD group also had a higher risk of all-cause ED visits (HR = 1.114; 95% CI = 1.012-1.226), all-cause hospitalization (HR = 1.230; 95% CI = 1.105-1.369), and all-cause death (HR = 1.748; 95% CI = 1.047-2.290) but not post-COVID-19 condition (HR = 0.980; 95% CI = 0.630-1.523), individually. CONCLUSION: Among the COVID-19 patients, VDD might be associated with a higher risk of all-cause ED visits, hospitalization, and death during the post-acute phase.

Early cumulus cell removal increases cumulative live birth rate while having no negative effect on the malformation rate in in vitro fertilization: a propensity score-matched cohort study.

PURPOSE: The aim of this study was to investigate the efficacy and safety of early cumulus cell removal (ECCR) during human in vitro fertilization (IVF). METHODS: A retrospective analysis was performed between January 2011 and December 2019. The study enrolled 1131 couples who underwent IVF treatment with ECCR. After propensity score matching at a 1:1 ratio, 1131 couples who underwent overnight coincubation of gametes were selected. The main outcome measure was the cumulative live birth rate. Secondary outcome measures included the cumulative pregnancy rate, polyspermy rate, available embryo rate, miscarriage rate, malformation rate, time to live birth, and oocyte-to-baby rate. RESULTS: There were no significant differences found between the two groups in the polyspermy rate, available embryo rate, miscarriage rate, time to live birth, oocyte-to-baby rate, and neonatal congenital anomalies rate. The results of the study showed that ECCR was associated with a significantly higher cumulative live birth rate and cumulative pregnancy rate, along with a significantly lower fertilization rate. CONCLUSIONS: ECCR tended to confer increased cumulative live birth rate and had no negative effect on the neonatal malformation rate.

GKLOMLI: a link prediction model for inferring miRNA-lncRNA interactions by using Gaussian kernel-based method on network profile and linear optimization algorithm.

BACKGROUND: The limited knowledge of miRNA-lncRNA interactions is considered as an obstruction of revealing the regulatory mechanism. Accumulating evidence on Human diseases indicates that the modulation of gene expression has a great relationship with the interactions between miRNAs and lncRNAs. However, such interaction validation via crosslinking-immunoprecipitation and high-throughput sequencing (CLIP-seq) experiments that inevitably costs too much money and time but with unsatisfactory results. Therefore, more and more computational prediction tools have been developed to offer many reliable candidates for a better design of further bio-experiments. METHODS: In this work, we proposed a novel link prediction model based on Gaussian kernel-based method and linear optimization algorithm for inferring miRNA-lncRNA interactions (GKLOMLI). Given an observed miRNA-lncRNA interaction network, the Gaussian kernel-based method was employed to output two similarity matrixes of miRNAs and lncRNAs. Based on the integrated matrix combined with similarity matrixes and the observed interaction network, a linear optimization-based link prediction model was trained for inferring miRNA-lncRNA interactions. RESULTS: To evaluate the performance of our proposed method, k-fold cross-validation (CV) and leave-one-out CV were implemented, in which each CV experiment was carried out 100 times on a training set generated randomly. The high area under the curves (AUCs) at 0.8623 ± 0.0027 (2-fold CV), 0.9053 ± 0.0017 (5-fold CV), 0.9151 ± 0.0013 (10-fold CV), and 0.9236 (LOO-CV), illustrated the precision and reliability of our proposed method. CONCLUSION: GKLOMLI with high performance is anticipated to be used to reveal underlying interactions between miRNA and their target lncRNAs, and deciphers the potential mechanisms of the complex diseases.

Insight into the evolutionary and domesticated history of the most widely cultivated mushroom Agaricus bisporus via mitogenome sequences of 361 global strains.

Agaricus bisporus is the most widely cultivated edible mushroom in the world with a only around three hundred years known history of cultivation. Therefore, it represents an ideal organism not only to investigate the natural evolutionary history but also the understanding on the evolution going back to the early era of domestication. In this study, we generated the mitochondrial genome sequences of 352 A. bisporus strains and 9 strains from 4 closely related species around the world. The population mitogenomic study revealed all A. bisporus strains can be divided into seven clades, and all domesticated cultivars present only in two of those clades. The molecular dating analysis showed this species origin in Europe on 4.6 Ma and we proposed the main dispersal routes. The detailed mitogenome structure studies showed that the insertion of the plasmid-derived dpo gene caused a long fragment (MIR) inversion, and the distributions of the fragments of dpo gene were strictly in correspondence with these seven clades. Our studies also showed A. bisporus population contains 30 intron distribution patterns (IDPs), while all cultivars contain only two IDPs, which clearly exhibit intron loss compared to the others. Either the loss occurred before or after domestication, that could suggest that the change facilitates their adaptation to the cultivated environment.

CD200 in dentate gyrus improves depressive-like behaviors of mice through enhancing hippocampal neurogenesis via alleviation of microglia hyperactivation.

BACKGROUND: Neuroinflammation and microglia play critical roles in the development of depression. Cluster of differentiation 200 (CD200) is an anti-inflammatory glycoprotein that is mainly expressed in neurons, and its receptor CD200R1 is primarily in microglia. Although the CD200-CD200R1 pathway is necessary for microglial activation, its role in the pathophysiology of depression remains unknown. METHODS: The chronic social defeat stress (CSDS) with behavioral tests were performed to investigate the effect of CD200 on the depressive-like behaviors. Viral vectors were used to overexpress or knockdown of CD200. The levels of CD200 and inflammatory cytokines were tested with molecular biological techniques. The status of microglia, the expression of BDNF and neurogenesis were detected with immunofluorescence imaging. RESULTS: We found that the expression of CD200 was decreased in the dentate gyrus (DG) region of mice experienced CSDS. Overexpression of CD200 alleviated the depressive-like behaviors of stressed mice and inhibition of CD200 facilitated the susceptibility to stress. When CD200R1 receptors on microglia were knocked down, CD200 was unable to exert its role in alleviating depressive-like behavior. Microglia in the DG brain region were morphologically activated after exposure to CSDS. In contrast, exogenous administration of CD200 inhibited microglia hyperactivation, alleviated neuroinflammatory response in hippocampus, and increased the expression of BDNF, which in turn ameliorated adult hippocampal neurogenesis impairment in the DG induced by CSDS. CONCLUSIONS: Taken together, these results suggest that CD200-mediated alleviation of microglia hyperactivation contributes to the antidepressant effect of neurogenesis in dentate gyrus in mice.

Clinical efficacy of nirmatrelvir and ritonavir combination for treating diabetic patients with COVID-19.

The aim of this study was to investigate the clinical efficacy of a combination of nirmatrelvir and ritonavir (NMV-r) for treating COVID-19 in patients with diabetes mellitus (DM). This retrospective cohort study used the TriNetX research network to identify adult diabetic patients with COVID-19 between January 1, 2020, and December 31, 2022. Propensity score matching was used to match patients who received NMV-r (NMV-r group) with those who did not receive NMV-r (control group). The primary outcome was all-cause hospitalization or death during the 30-day follow-up period. Two cohorts comprising 13 822 patients with balanced baseline characteristics were created using propensity score matching. During the follow-up period, the NMV-r group had a lower risk of all-cause hospitalization or death than the control group (1.4% [n = 193] vs. 3.1% [n = 434]; hazard ratio [HR], 0.497; 95% confidence interval [CI], 0.420-0.589). Compared with the control group, the NMV-r group also had a lower risk of all-cause hospitalization (HR, 0.606; 95% CI, 0.508-0.723) and all-cause mortality (HR, 0.076; 95% CI, 0.033-0.175). This lower risk was consistently observed in almost all subgroup analyses, which examined sex (male: 0.520 [0.401-0.675]; female: 0.586 [0.465-0.739]), age (age 18-64 years: 0.767 [0.601-0.980]; ≥65 years: 0.394 [0.308-0.505]), level of HbA1c (<7.5%: 0.490 [0.401-0.599]; ≥7.5%: 0.655 [0.441-0.972]), unvaccinated (0.466 [0.362-0.599]), type 1 DM (0.453 [0.286-0.718]) and type 2 DM (0.430 [0.361-0.511]). NMV-r can help reduce the risk of all-cause hospitalization or death in nonhospitalized patients with DM and COVID-19.

Nutritional deficiency anemia and post-acute sequelae in patients with severe acute respiratory syndrome coronavirus 2 infection: A six-month retrospective cohort analysis of 30 892 patients.

The effect of anemia on the post-acute outcome of patients with severe acute respiratory syndrome coronavirus 2 infection was unclear. This study aimed to investigate the potential association between nutritional deficiency anemia (NDA) status and post-acute sequelae of patients with SARS-CoV-2 infection. This retrospective cohort study included patients with coronavirus disease (COVID-19) from January 1, 2022 to November 30, 2022 using the TriNetX research network. The patients were grouped into the NDA group comprising patients diagnosed with NDA and the control group comprising patients without NDA, and propensity score matching (PSM) was performed to balance the two groups. The primary outcome was a composite of post-COVID-19 condition, all-cause hospitalization, and all-cause death. The secondary outcomes were any individual outcomes of the primary composite. The follow-up period was set at 90-180 days after COVID-19 diagnosis. Two cohorts comprising 15 446 nonhospitalized patients with COVID-19 in each group with balanced baseline characteristics were created using PSM. During the follow-up period, the NDA group demonstrated a higher risk of the composite primary outcome, including post-COVID-19 condition, all-cause hospitalization, or all-cause death (hazard ratio [HR], 1.896; 95% confidence interval [CI] = 1.757-2.045). Regarding secondary outcomes, the NDA group was associated with worse outcomes, including post-COVID-19 condition (HR, 1.992; 95% CI = 1.403-2.828), all-cause hospitalization (HR, 1.856; 95% CI = 1.714-2.009), and all-cause death (HR, 3.922; 95% CI = 2.910-5.285) compared to the control group. Among nonhospitalized patients with COVID-19, NDA was associated with a higher risk of post-COVID-19 condition, all-cause hospitalization, and all-cause death during the 90-180-day follow-up period.

Efficacy and safety of adjunctive corticosteroids in the treatment of severe community-acquired pneumonia: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: This systematic review and meta-analysis aimed to investigate the clinical efficacy and safety of systemic corticosteroids in the treatment of patients with severe community-acquired pneumonia (sCAP). METHODS: A comprehensive search was conducted using the Medline, Embase, ClinicalTrials.gov, and Scopus databases for articles published until April 24, 2023. Only randomized controlled trials (RCTs) that assessed the clinical efficacy and safety of adjunctive corticosteroids for treating sCAP were included. The primary outcome was the 30-day all-cause mortality. RESULTS: A total of severe RCTs involving 1689 patients were included in this study. Overall, the study group had a lower mortality rate at day 30 than the control group (risk ratio [RR], 0.61; 95% CI 0.44 to 0.85; p < 0.01) with low heterogeneity (I2 = 0%, p = 0.42). Compared to the control group, the study group had a lower risk of the requirement of mechanical ventilation (RR 0.57; 95% CI 0.45 to 0.73; p < 0.001), shorter length of intensive care unit (MD - 0.8; 95% CI - 1.4 to - 0.1; p = 0.02), and hospital stay (MD - 1.1; 95% CI - 2.0 to - 0.1; p = 0.04). Finally, no significant difference was observed between the study and the control groups in terms of gastrointestinal tract bleeding (RR 1.03; 95% CI 0.49 to 2.18; p = 0.93), healthcare-associated infection (RR 0.89; 95% CI 0.60 to 1.32; p = 0.56), and acute kidney injury (RR 0.68; 95% CI 0.21 to 2.26; p = 0.53). CONCLUSIONS: In patients with sCAP, adjunctive corticosteroids can provide survival benefits and improve clinical outcomes without increasing adverse events. However, because the pooled evidence remains inconclusive, further studies are required.

Development and Application of a Multi-Component Exercise Training Program for Elderly COPD Patients with Skeletal Muscle Dysfunction.

Objective: To develop a multi-component exercise training program for elderly patients with chronic obstructive pulmonary disease (COPD) and skeletal muscle dysfunction (SMD), and to explore its application value. Methods: This study involved 68 elderly patients with both COPD and SMD who were hospitalized at The First Affiliated Hospital of Hainan Medical College from September 2019 to August 2021. They were randomly divided into an intervention group and a control group. The intervention group received a 12-month multi-component exercise training program, while the control group received routine intervention. We compared skeletal muscle function, strength, lung function, and oxygen saturation between the groups before and at 3, 6, and 12 months after the intervention. The patient's daily living activities and dyspnea severity were assessed using the Modified Barthel Index (MBI) and the modified British Medical Research Council (mMRC) dyspnea scale. Flow cytometry was used to determine changes in the proportion of CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells, and the CD3+CD4+/CD3+CD8+ ratio in the patients' lymphocytes before and after the intervention. Results: The six-minute walk distance of the intervention group at 6 and 12 months after the intervention was longer than that of the control group. The peak torque of elbow flexion and extension and knee flexion and extension muscles of the intervention group at 12 months after intervention was higher than that of the control group (P < .05). The forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC of the intervention group at 6 and 12 months after intervention were higher than those of the control group. The oxygen saturation (SaO2) and partial pressure of oxygen (PaO2) of the intervention group at 6 and 12 months after the intervention were higher than those of the control group (P < .05). The MBI and mMRC scores of the intervention group at 6 and 12 months after intervention were higher than those of the control group (P < .05). The indexes of T lymphocyte immune function, CD3+T cells, CD3+CD4+T cells, and the ratio of CD3+CD4+/CD3+CD8+ in the intervention group were also higher than those in the control group at 3, 6, and 12 months (P < .05). Conclusion: Multi-component exercise training program intervention can effectively improve skeletal muscle function and lung function in elderly COPD patients with SMD, reduce the degree of hypoxia and dyspnea, and improve patients' daily living activities and immune function recovery.

Epidemiololgical and etiological analysis of two clusters of severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease, caused by severe fever with thrombocytopenia syndrome virus (SFTSV), which is primarily transmitted via tick bites. Clusters of SFTS caused by human-to-human transmission have been reported both at home and abroad, mainly focused on the transmission or exposure modes. However, the correlation between SFTS clusters and viral genotypes has not been investigated. This study mainly reported two clusters of SFTS in Xinyang City, Henan Province, from 2022 to 2023, discussed the possible route of person-to-person transmission of SFTSV infection and analyzed the association between SFTS clusters and virus genotypes. We found that two groups of SFTSV in two clusters were clustered separately into different genotypes through viral sequence analysis of 4 confirmed patients. We also performed phylogenetic analysis, after including SFTSV sequences obtained from SFTS clusters deposited in the GenBank. Three SFTSV genotypes have been reported among cases of human-to-human transmission, suggesting that the occurrence of SFTS clusters may not be related to SFTSV genotypes. This study provided genetic evidence for revealing the chain of human-to-human transmission of SFTS clusters, indicating that contact with patients' blood is an important transmission route of SFTSV. The findings laid the foundation for preventing and controlling human-to-human transmission of SFTS.

[Advancements in virtual screening techniques for study of enzyme inhibitor compounds].

Enzymes are closely associated with the onset and progression of numerous diseases, making enzymes a primary target in innovative drug development. However, the challenge remains in identifying compounds that exhibit potent inhibitory effects on the target enzymes. With the continuous expansion of the total number of natural products and increasing difficulty in isolating and enriching new compounds, traditional high-throughput screening methods are finding it increasingly challenging to meet the demands of new drug development. Virtual screening, characterized by its high efficiency and low cost, has gradually become an indispensable technology in drug development. It represents a prominent example of the integration of artificial intelligence with biopharmaceuticals and is an inevitable trend in the rapid development of innovative drug screening in the future. Therefore, this article primarily focused on systematically reviewing the recent applications of virtual screening technology in the development of enzyme inhibitors and explored the prospects and advantages of using this technology in developing new drugs, aiming to provide essential theoretical insights and references for the application of related technologies in the field of new drug development.

Adult restoration of Shank3 expression rescues selective autistic-like phenotypes.

Because autism spectrum disorders are neurodevelopmental disorders and patients typically display symptoms before the age of three, one of the key questions in autism research is whether the pathology is reversible in adults. Here we investigate the developmental requirement of Shank3 in mice, a prominent monogenic autism gene that is estimated to contribute to approximately 1% of all autism spectrum disorder cases. SHANK3 is a postsynaptic scaffold protein that regulates synaptic development, function and plasticity by orchestrating the assembly of postsynaptic density macromolecular signalling complex. Disruptions of the Shank3 gene in mouse models have resulted in synaptic defects and autistic-like behaviours including anxiety, social interaction deficits, and repetitive behaviour. We generated a novel Shank3 conditional knock-in mouse model, and show that re-expression of the Shank3 gene in adult mice led to improvements in synaptic protein composition, spine density and neural function in the striatum. We also provide behavioural evidence that certain behavioural abnormalities including social interaction deficit and repetitive grooming behaviour could be rescued, while anxiety and motor coordination deficit could not be recovered in adulthood. Together, these results reveal the profound effect of post-developmental activation of Shank3 expression on neural function, and demonstrate a certain degree of continued plasticity in the adult diseased brain.

Obstetric and neonatal outcomes after frozen-thawed embryos transfer with laser-assisted hatching: a retrospective cohort study.

PURPOSE: To ascertain if assisted hatching (AH) increases the risk of placenta-associated diseases and perinatal outcomes after frozen-thawed cleavage-stage embryo transfer. METHODS: We retrospectively evaluated 924 women who conceived with frozen-thawed cleavage-stage embryos transfer with (n = 390) or without (n = 534) laser-AH between 2013 and 2015. Data were obtained from the database on in vitro fertilization (IVF) patients in Shanghai First Maternity and Infant Hospital. We assessed neonatal (preterm birth, low birthweight, fetal macrosomia, stillbirth) and obstetric (miscarriage, ectopic pregnancy, post-term pregnancy, gestational diabetes (GDM), preeclampsia, intrahepatic cholestasis (ICP), placenta previa, placental abruption, premature rupture of membranes) outcomes. RESULTS: In twins, the median birthweight was lower in the AH group than that in the control group, and the prevalence of low birthweight (< 2500 g) was significantly higher in the AH group; after adjusting for maternal age, body mass index, mode of fertilization, and parity, no significant difference was found. In twins, no significant difference was detected in the prevalence of stillbirth or preterm pregnancy. In singleton births, there was no significant difference in the prevalence of low birthweight, macrosomia, preterm pregnancy or post-term pregnancy between the two groups. In singletons and twins, there were no significant differences in the prevalence of miscarriage, ectopic pregnancy, preeclampsia, GDM, ICP, or placenta abruption between the two groups. CONCLUSIONS: AH is a relatively safe method and our study provides important information for using this method in carefully selected patients.

Deficit irrigation and leaf removal modulate anthocyanin and proanthocyanidin repartitioning of Cabernet Sauvignon (Vitis vinifera L.) grape and resulting wine profile.

BACKGROUND: In monsoonal climates, grape anthocyanin and proanthocyanidin (PA) accumulations are unsatisfactory for producing optimal wine. Agronomical practices are often considered to be effective means for regulating fruit components. However, there is a lack of quantitative information on the effects of deficit irrigation (DI), basal leaf removal (LR) or their combination of deficit irrigation and leaf removal (DILR) on the characteristics of anthocyanin and PA compositions and their implications on the resulting wine quality. In this study, the dynamics of grape anthocyanin and PA accumulation were investigated in DI, LR and DILR during grape ripening, and the resulting wine profile was assessed. RESULTS: The contents of reducing sugar and total anthocyanins in Cabernet Sauvignon berries were significantly increased by DI, LR and DILR, while titratable acidity, total flavan-3-ols and tannins levels were generally decreased. Notably, the levels of 3'5'-substituted anthocyanins, such as malvidin and its derivatives significantly increased, and 3'-substituted anthocyanins decreased in both grape and wine under DI and DILR strategies. Skin PAs were sensitive to water deficits, whereas they were insensitive to LR. In resulting wine, PAs content and the proportion of 3'-hydroxylated PAs, such as (+)-catechin, (-)-epicatechin and (-)-epicatechin-3-O-gallate units were significantly decreased under DI and DILR, while molecular mass and the proportion of 3'5'-hydroxylated units of PAs were increased in response to DILR. CONCLUSION: The DILR was the most favorable for the repartitioning of anthocyanin and PA metabolites, and promoted the accumulation of tri-substituted forms contributing a higher color intensity, mouthfeel persistence, structure, and astringency of wine. This information provides an important strategy for modulating the anthocyanin and PA compositions by agricultural practices and achieving the desired quality of grapes and wines in monsoonal climates. © 2021 Society of Chemical Industry.

LNRLMI: Linear neighbour representation for predicting lncRNA-miRNA interactions.

LncRNA and miRNA are key molecules in mechanism of competing endogenous RNAs(ceRNA), and their interactions have been discovered with important roles in gene regulation. As supplementary to the identification of lncRNA-miRNA interactions from CLIP-seq experiments, in silico prediction can select the most potential candidates for experimental validation. Although developing computational tool for predicting lncRNA-miRNA interaction is of great importance for deciphering the ceRNA mechanism, little effort has been made towards this direction. In this paper, we propose an approach based on linear neighbour representation to predict lncRNA-miRNA interactions (LNRLMI). Specifically, we first constructed a bipartite network by combining the known interaction network and similarities based on expression profiles of lncRNAs and miRNAs. Based on such a data integration, linear neighbour representation method was introduced to construct a prediction model. To evaluate the prediction performance of the proposed model, k-fold cross validations were implemented. As a result, LNRLMI yielded the average AUCs of 0.8475 ± 0.0032, 0.8960 ± 0.0015 and 0.9069 ± 0.0014 on 2-fold, 5-fold and 10-fold cross validation, respectively. A series of comparison experiments with other methods were also conducted, and the results showed that our method was feasible and effective to predict lncRNA-miRNA interactions via a combination of different types of useful side information. It is anticipated that LNRLMI could be a useful tool for predicting non-coding RNA regulation network that lncRNA and miRNA are involved in.

Direct Dehydrative Glycosylation Catalyzed by Diphenylammonium Triflate.

Methods for direct dehydrative glycosylations of carbohydrate hemiacetals catalyzed by diphenylammonium triflate under microwave irradiation are described. Both armed and disarmed glycosyl-C1-hemiacetal donors were efficiently glycosylated in moderate to excellent yields without the need for any drying agents and stoichiometric additives. This method has been successfully applied to a solid-phase glycosylation.