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The current study examined early grammatical marking in a relatively understudied language, Mandarin, by using the Mandarin version of MacArthur-Bates Communicative Development Inventory. Two waves of data collection included 338 monolingual children (17-36 months; 143 female) at Time 1 and 308 children (32-55 months; 139 female) at Time 2 and their caregivers, whose education ranged from third grade (elementary school) or below to postgraduate with a median of high school. Our data showed a clear order of grammatical marking acquisition among these children and supported findings on the linguistic specificity of morphological development such that early- and late-acquired markers in Mandarin are not acquired in the same order as English or other languages. Negative "mei2," "bu4," possessive "-de," classifiers, and the aspect marker "le" were the earliest-acquired markers, followed by modals, negative "bie2," adverbs, sentence final particles, resultative verb compounds, and aspect markers "guo4" and "yao4." Complex clauses and the aspect marker "zheng4" were acquired the latest. Furthermore, consistent with previous cross-linguistic studies, the development patterns of a wide range of Mandarin grammatical markers indicate that markers that are more perceptually salient and obligatory, have clear form-meaning mappings, and often appear in isolation or utterance-final position were acquired earlier than others.

Diester diterpenoid alkaloids (DDAs) are the main active ingredients of herbaceous perennial plants Aconitum. DDAs possess cardiotoxic and neurotoxic properties. Although most deaths caused by DDA poisoning are accidental, a few instances of suicide and homicide have been reported. Presented is a case of an acute aconitine (AC) poisoning following the ingestion of approximately 50 mL of homemade medicinal liquor. We described the clinical manifestations after poisoning and detailed postmortem changes, and detected the concentrations of AC and hypaconitine (HA) by liquid chromatography–tandem mass spectrometry (LC–MS/MS). The decedent experienced a burning sensation in the gastrointestinal tract after poisoning, followed by flushing and paralysis of the face and limbs, and severe cardiac arrhythmia. An autopsy revealed cyanosis of the lips and nail beds; conjunctival hemorrhage in both eyes; pulmonary edema; tissue hemorrhage and congestion in multiple organs; and inflammatory cell infiltration in the stomach, duodenum, pancreas, and cardiac muscle. The concentrations of AC and HA were as follows: cardiac blood, 38.4 ng/mL and 7.1 ng/mL; pericardial fluid, 7.3 ng/mL and 41 ng/mL; urine, 28.1 ng/mL and 574 ng/mL; bile, 38.5 ng/mL and 108 ng/mL; gastric contents, 0.06 mg and 0.56 mg; liver tissue, 10.7 ng/g and 109.6 ng/g; and medicinal liquor, 0.568 mg/mL and 0.664 mg/mL, respectively. The clinical manifestations, anatomy findings, and quantitative data on the concentrations of AC and HA in body fluids and tissues will aid forensic investigations of deaths caused by acute AC poisoning. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B (CHB) virus infection, which can be divided into immune‐tolerant (IT), immune‐active (IA), inactive carrier (IC) phases, and HBeAg‐negative hepatitis (ENEG), can induce liver cirrhosis and eventually hepatocellular carcinoma (HCC). CD3+CD56+ NKT‐like cells play an important role in antiviral immune response. However, the mechanism of NKT‐like cells to mediate immune tolerance remains largely elusive. In this study, we observed circulating NKT‐like cells from IC and IT CHB patients were phenotypically and functionally impaired, manifested by increased expression of inhibitory receptor TIGIT and decreased capacity of secreting antiviral cytokines. Besides, TIGIT+ NKT‐like cells of IC and IT CHB patients expressed lower levels of cytotoxic cytokines than the TIGIT− subset. Furthermore, increased expression of CD155, the ligand of TIGIT, on plasmacytoid dendritic cells (pDCs) was detected in IC and IT CHB patients. Importantly, the co‐culture of NKT‐like cells and pDCs showed that NKT‐like cells restored their antiviral ability after TIGIT blockade upon HBV peptide stimulation in IC and IT CHB patients. In conclusion, our findings suggest that the TIGIT pathway may mediate immune tolerance in IT CHB patients and lead to functional impairment in IC patients, indicating that TIGIT may be a potential therapeutic checkpoint for immunotherapy of CHB patients. [ABSTRACT FROM AUTHOR]

BackgroundPreterm-associated complications remain the main cause of neonatal death. Survivors face the challenges of short- and long-term complications. Among all complications, bronchopulmonary dysplasia (BPD) remains the first important cause of neonatal mortality and morbidity. Current treatment does not address this main preterm complication. Cord blood is regarded as a convenient source of stem cells. The paracrine bioactive factors of stem cells contribute to tissue repair and immune modulation. Our clinical studies and those of others have shown that cord blood cell infusion is both safe and possibly effective in the prevention and treatment of BPD. The therapeutic use of cord blood has emerged as a promising therapy. However, the genetic heterogeneity between control and intervention groups may reduce the comparability especially among small sample trials. The purpose of this study protocol is to investigate the effects of autologous cord blood mononuclear cell (ACBMNC) infusion on the prevention of BPD in very preterm monozygotic twins of less than 32 gestation weeks.MethodsIn this prospective, randomized, placebo-controlled, double-blinded multicenter clinical trial, 60 pairs of monozygotic twin preterm neonates of less than 32 weeks admitted to the Neonatal Intensive Care Unit are randomly assigned to receive intravenous ACBMNC infusion (targeted at 5 × 107 cells/kg) or placebo (normal saline) within 24 h after birth in a 1:1 ratio. The primary outcome will be survival without BPD at 36 weeks of postmenstrual age. The secondary outcomes will include the mortality rate, BPD severity, other common preterm complication rates, respiratory support duration, length and cost of hospitalization, and long-term respiratory and neurodevelopmental outcomes during a 2-year follow-up. Furthermore, we will perform single-cell RNA sequencing for cord blood cells and blood cells 3–10 days after intervention and detect whether reactive oxygen species and inflammatory cytokines are present.ConclusionThis will be the first randomized, placebo-controlled, double-blinded trial to evaluate the efficacy of ACBMNC infusion to prevent BPD in monozygotic twin premature infants and investigate the underlying protective mechanisms. The results of this trial will provide valuable clinical evidence for translational application of cord blood cell therapy in very preterm infants.Trial registration: ClinicalTrials.gov, NCT05087498, registered 10/09/2021, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000BAD7&selectaction=Edit&uid=U0002PLA&ts=2&cx=qvyylv.

Transition metal-based pre-catalysts undergo drastic reconstruction to form active catalysts during the alkaline oxygen evolution reaction. However, little is known about how pre-catalysts affect the activity of the in situ generated active species. Herein, the reconstruction degree is modulated by varying hydrate/anhydrous molybdate pre-catalysts, which will reveal the effects of pre-catalysts in the OER activity. The hydrate molybdate not only presents a faster reconstruction rate but also outstanding OER activity and stability, and exhibits a low overpotential of only 206 mV at 10 mA cm−2 in an alkaline solution. Experimental investigations reveal that the oxide hydroxides/hydroxyls derived from hydrates exhibit a larger surface area, and a higher concentration of OH− on the surface, which accelerates the OER kinetics rate. Furthermore, the lattice oxygen was triggered and therefore able to react via a faster lattice-oxygen-mediated mechanism (LOM) pathway, which presents lower thermodynamic barriers compared to catalysts derived from anhydrous pre-catalysts. This work may provide new insight into elucidating the OER activity enhancement mechanism. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to investigate the role of plasmacytoma variant translocation 1 (PVT1), a long non‐coding RNA, in glioblastoma multiforme (GBM) and its impact on the tumor microenvironment (TME). Methods: We assessed aberrant PVT1 expression in glioma tissues and its impact on GBM cell growth in vitro and in vivo. Additionally, we investigated PVT1's role in influencing glioma‐associated macrophages. To understand PVT1's role in cell growth and the immunosuppressive TME, we performed a series of comprehensive experiments. Results: PVT1 was overexpressed in GBM due to copy number amplification, correlating with poor prognosis. Elevated PVT1 promoted GBM cell proliferation, while its downregulation inhibited growth in vitro and in vivo. PVT1 inhibited type I interferon‐stimulated genes (ISGs), with STAT1 as the central hub. PVT1 correlated with macrophage enrichment and regulated CX3CL1 expression, promoting recruitment and M2 phenotype polarization of macrophages. PVT1 localized to the cell nucleus and bound to DHX9, enriching at the promoter regions of STAT1 and CX3CL1, modulating ISGs and CX3CL1 expression. Conclusion: PVT1 plays a significant role in GBM, correlating with poor prognosis, promoting cell growth, and shaping an immunosuppressive TME via STAT1 and CX3CL1 regulation. Targeting PVT1 may hold therapeutic promise for GBM patients. [ABSTRACT FROM AUTHOR]

Developing excellent electrocatalysts is a significant step in accelerating the widespread implementation of the electrochemical hydrogen evolution reaction (HER). MoS2 is one of the promising alternatives to platinum-based catalysts, while its HER activity is far from Pt due to the lack of active sites. It is urgent to develop a novel strategy to activate the basal planes of MoS2 for enhancing the HER activity. Herein, a facile hydrothermal method with a low-temperature H2O2 etching method is developed to fabricate MoS2 with O-doped and S-vacancy dual defects. The dual defects MoS2 nanosheet demonstrates remarkable hydrogen evolution reaction (HER) activity, achieving 10 mA cm−2 with a small overpotential of around 143 mV in 0.5 M H2SO4. Construct dual-defect MoS2 via a facile hydrothermal method and mild H2O2 etching process. [ABSTRACT FROM AUTHOR]