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During mammalian preimplantation development, a totipotent zygote undergoes several cell cleavages and two rounds of cell fate determination, ultimately forming a mature blastocyst. Along with compaction, the establishment of apicobasal cell polarity breaks the symmetry of an embryo and guides subsequent cell fate choice. Although the lineage segregation of the inner cell mass (ICM) and trophectoderm (TE) is the first symbol of cell differentiation, several molecules have been shown to bias the early cell fate through their inter-cellular variations at much earlier stages, including the 2- and 4-cell stages. The underlying mechanisms of early cell fate determination have long been an important research topic. In this review, we summarize the molecular events that occur during early embryogenesis, as well as the current understanding of their regulatory roles in cell fate decisions. Moreover, as powerful tools for early embryogenesis research, single-cell omics techniques have been applied to both mouse and human preimplantation embryos and have contributed to the discovery of cell fate regulators. Here, we summarize their applications in the research of preimplantation embryos, and provide new insights and perspectives on cell fate regulation.

Background: The gut microbiota is believed to influence neurodevelopment through the gut–brain axis, but prior studies have shown inconsistent results regarding early childhood antibiotic exposure and subsequent risk of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). The purpose of this study was to evaluate the hypothesis that exposure to antibacterial agents in the first 2 years of life increases the risk of ASD and/or ADHD. Methods: This was a retrospective cohort study using 2003–2019 data from the National Health Insurance Research Database in Taiwan. Livebirths born between 2004 and 2016 were identified and separated into singleton, full sibling, and exposure-discordant sibling pair cohorts. The exposure group included children who filled at least one prescription for antibacterial agents between 0 and 2 years old in outpatient settings. The outcome, ASD and/or ADHD, was defined by at least one inpatient or outpatient diagnosis. The maximum follow-up age was 15 years in this study. Potential neonatal, maternal and paternal confounders were adjusted for. Cox proportional hazards models were used to estimate the relative event risk. Results: The final sample contained 946,581 children in the singleton cohort, 1,142,693 children in the full sibling cohort, and 352,612 children in the exposure-discordant sibling pair cohort. Antibiotic exposure marginally increased the risk of ASD and/or ADHD in the singleton cohort (adjusted hazard ratio [aHR]: 1.06, 95% confidence interval [CI]: 1.04–1.07) and in the full sibling cohort (aHR: 1.03, 95% CI: 1.01–1.04). A slight decrease in the risk of ASD and/or ADHD was observed in the exposure-discordant sibling pair cohort (aHR: 0.92, 95% CI: 0.90–0.94). Conclusions: The results suggest that early life antibiotic exposure has minimal impact on the risk of ASD and/or ADHD. Given that the estimated effects are marginal and close to null, concerns about ASD and/or ADHD risk increase should not postpone or deter timely and reasonable antibiotic use. [ABSTRACT FROM AUTHOR]

Organic small molecular materials with coplanar π-conjugated system as HTMs in perovskite solar cells (PSCs) have attracted considerable attention due to their high charge transport capability and thermal stability. Herein, three novel pentafulvalene-fused derivatives with or without fluorine atoms incorporated (YSH-oF and YSH-mF and YSH-H, respectively) are designed, synthesized, and applied as hole-transporting materials (HTMs) in PSCs fabrication. The fluorinated HTMs, YSH-oF and YSH-mF, exhibited higher hole mobility and better charge extraction at the perovskite/HTM interface than non-fluorinated one do, presumably due to the closer intermolecular π-π packing interactions. As a result, small-area (0.09 cm2) PSCs made with YSH-oF and YSH-mF achieved an impressive power conversion efficiency (PCE) of 23.59% and 22.76% respectively, with negligible hysteresis, in contrast with the 20.57% for the YSH-H-based devices. Furthermore, for large-area (1.00 cm2) devices, the PSCs employing YSH-oF exhibited a PCE of 21.92%. Moreover, excellent long-term device stability is demonstrated for PSCs with F-substituted HTMs (YSH-oF and YSH-mF), presumably due to the higher hydrophobicity. This study shows the great potential of fluorinated pentafulvalene-fused materials as low-cost HTM for efficient and stable PSCs. [ABSTRACT FROM AUTHOR]

Background and Aims: This study aimed to update the epidemiology, clinical, and economic outcomes of patients diagnosed with chronic hepatitis B (CHB) infection in Taiwan. Methods: This is a retrospective observational study using claims data from the National Health Insurance Research Database. Cases were identified between 2010 and 2019 using CHB diagnosis codes and claims for alanine aminotransferase laboratory tests or CHB treatment within one year of the first CHB diagnosis. Patient characteristics, epidemiology, clinical, and economic outcomes were described. Results: A total of 730 154 CHB‐diagnosed cases were identified. The prevalence of diagnosed CHB increased from 1.13% in 2010 to 2.43% in 2019, with the highest occurring among those aged 55–64 years (4.76%) and 45–54 years (4.37%) and being higher in men (2.98%) than in women (2.21%). The majority of newly diagnosed CHB patients were 35 years of age or older (86.6%), with a median age of 49 years. After a median follow‐up period of 6.42 years, 12.5%, 7.9%, 2.8%, and 0.35% were diagnosed with cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and liver transplantation respectively. Among 456 706 incident CHB‐diagnosed patients, 17.4% had received at least one CHB medication, with the majority taking entecavir (67.9%). Patients with increasing disease severity had higher healthcare resource utilization, and inpatient costs accounted for 48.9%–65.5% of the overall medical cost in different health states. Conclusion: Despite the decreasing incidence of newly diagnosed CHB, the prevalence of diagnosed CHB remains high and poses a significant healthcare challenge owing to the high economic burden associated with the complications of CHB. [ABSTRACT FROM AUTHOR]

As a kind of refractory glaucoma, the neovascular glaucoma causes severe pain and is extremely destructive with very high rate of blindness. Though there were a variety of clinical treatments to the neovascular glaucoma, their effects are very limited. With the application of new technology in recent years, many new kinds of treatment methods and strategies are applied in the clinic, such as anti-VEGF agents and glaucoma drainage devices, and the therapeutic effect is thus improved to some extent. Combined treatments can improve the efficacy from improving the blood supply for retina, anti-angiogenesis and anti-glaucoma. A more appropriate treatment coming with the individual situation of patients' visual acuity may help keep the remaining vision at the greatest extent, relieve the pain. Based on the literatures published at home and abroad during recent years, this paper gives a brief review on the advances in treatment of neovascular glaucoma.

Background: Researchers have yet to obtain conclusive evidence differentiating among fixed-dose combinations (FDCs) of long-acting muscarinic antagonists (LAMAs) and long-acting beta-agonists (LABAs) for chronic obstructive pulmonary disease (COPD) in terms of real-world clinical outcomes.Research Question: What are the differences between available LAMA/LABA FDCs on the risk of acute exacerbation and cardiovascular events?Study Design and Methods: This retrospective cohort study based on a national insurance claims database included COPD patients aged 40 and older who were newly prescribed glycopyrronium/indacaterol (GLY/IND), umeclidinium/vilanterol (UMEC/VI), or tiotropium/olodaterol (TIO/OLO) FDC between January 1, 2015, and June 30, 2019. Propensity score matching and Cox regression models were used to compare outcomes of acute exacerbation (AE) and cardiovascular events associated with LAMA/LABA FDC treatment.Results: Among the 44,498 patients identified and included, 15,586 received GLY/IND, 20,460 received UMEC/VI, and 8,452 received TIO/OLO. Baseline characteristics were well balanced after 1:1 matching of UMEC/VI and GLY/IND, 2:1 matching of UMEC/VI and TIO/OLO, and 2:1 matching of GLY/IND and TIO/OLO. Risk of severe AE was lower among patients treated with UMEC/VI or GLY/IND than among those who received TIO/OLO (UMEC/VI vs. TIO/OLO: 17.85 vs. 29.32 per 100 person-years; hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.68-0.84; GLY/IND vs. TIO/OLO: 15.54 vs. 25.53 per 100 person-years; HR 0.77, 95% CI 0.67-0.88). In addition, GLY/IND users tended to have a lower risk of cardiovascular events than TIO/OLO users, but the difference dissipated when restricting follow-up to a shorter duration.Interpretation: Our results revealed that the risk of severe AE was lower among COPD patients receiving UMEC/VI or GLY/IND than among those receiving TIO/OLO, while the incidence of cardiovascular events was similar across groups but was slightly lower in GLY/IND users when compared with TIO/OLO users. Further research will be required to confirm these findings. [ABSTRACT FROM AUTHOR]

Beta-blockers are widely used, but the benefit is now challenged in patients at risk of atherosclerotic cardiovascular disease (ASCVD) in the present coronary reperfusion era. We aimed to identify the risk factors of a major adverse cardiac event (MACE) and the long-term effect of beta-blockers in two large cohorts in Taiwan. Two prospective observational cohorts, including patients with known atherosclerosis cardiovascular disease (T-SPARCLE) and patients with at least one risk factor of ASCVD but without clinically evident ASCVD (T-PPARCLE), were conducted in Taiwan. The primary endpoint is the time of first occurrence of a MACE (cardiovascular death, nonfatal stroke, nonfatal myocardial infarction, and cardiac arrest with resuscitation). Between December 2009 and November 2014, with a median 2.4 years follow-up, 11,747 eligible patients (6921 and 4826 in T-SPARCLE and T-PPARCLE, respectively) were enrolled. Among them, 273 patients (2.3%) met the primary endpoint. With multivariate Cox PH model analysis, usage of beta-blocker was lower in patients with MACE (42.9% vs. 52.4%, p < 0.01). In patients with ASCVD, beta-blocker usage was associated with lower MACEs (hazard ratio 0.72; p < 0.001), but not in patients without ASCVD. The event-free survival of beta-blocker users remained higher during the follow-up period (p < 0.005) of ASCVD patients. In conclusion, in ASCVD patients, reduced MACE was associated with beta-blocker usage, and the effect was maintained during a six-year follow-up. Prescribing beta-blockers as secondary prevention is reasonable in the Taiwanese population. [ABSTRACT FROM AUTHOR]