Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery.

JOURNAL/nrgr/04.03/01300535-202501000-00030/figure1/v/2024-05-14T021156Z/r/image-tiff Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery. Our previous in vitro study demonstrated that exosomes/small extracellular vesicles (sEVs) isolated from cerebral endothelial cells (CEC-sEVs) of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a (miR-27a) is an elevated miRNA in ischemic CEC-sEVs. In the present study, we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a (27a-sEVs) further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs. 27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector. Small EVs isolated from CECs transfected with a scramble vector (Scra-sEVs) were used as a control. Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs. An array of behavior assays was used to measure neurological function. Compared with treatment of ischemic stroke with Scra-sEVs, treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side, and significantly improved neurological outcomes. In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth. Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone, while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a, and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone. Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs. Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes. Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.

Causal relationships between serum albumin, neuroticism and suicidal ideation in depressed patients: A Mendelian randomization study.

Although serum albumin and neuroticism have revealed a strong association with suicidal ideation in individuals with depression, the causal relationship between them is uncertain. This study analyzed the causal association of serum albumin, neuroticism and suicidal ideation using large-scale GWAS data and Univariable Mendelian Randomization (UVMR) methods. The Multivariable MR (MVMR) analysis was used to explore the causal pathways. UVMR analysis revealed that genetically determined serum albumin is causally associated with neuroticism (ß = -0.006 S.D.; 95 % CI: 0.009, -0.002; p = 0.003) and suicidal ideation (ß = 0.009 S.D.; 95 % CI: 0.001, 0.016; p = 0.037); and that neuroticism mediates 100 % of the causal association between serum albumin and suicidal ideation in individuals with depression. These findings suggest genetic evidence for the causal effect of serum albumin on suicidal ideation in depressed patients and the significant mediation effect of neuroticism on this causal association. This study proves the protective role of serum albumin for neuroticism and the riskiness of personality traits for suicidal ideation in individuals with depression.

PAM-1: an antimicrobial peptide with promise against ceftazidime-avibactam resistant Escherichia coli infection.

Introduction: Antibiotic misuse and overuse have led to the emergence of carbapenem-resistant bacteria. The global spread of resistance to the novel antibiotic combination ceftazidime-avibactam (CZA) is becoming a severe problem. Antimicrobial peptide PAM-1 offers a novel approach for treating infections caused by antibiotic-resistant bacteria. This study explores its antibacterial and anti-biofilm activities and mechanisms against CZA-resistant Escherichia. Coli (E. coli), evaluating its stability and biosafety as well. Methods: The broth microdilution method, growth curve analysis, crystal violet staining, scanning electron microscopy, and propidium iodide staining/N-phenyl-1-naphthylamine uptake experiments were performed to explore the antibacterial action and potential mechanism of PAM-1 against CZA-resistant E. coli. The biosafety in diverse environments of PAM-1 was evaluated by red blood cell hemolysis, and cytotoxicity tests. Its stability was further assessed under different temperatures, serum concentrations, and ionic conditions using the broth microdilution method to determine its minimum inhibitory concentration (MIC). Galleria mellonella infection model and RT-qPCR were used to investigate the in vivo antibacterial and anti-inflammatory effects. Results and discussion: In vitro antibacterial experiments demonstrated that the MICs of PAM-1 ranged from 2 to 8 µg/mL, with its effectiveness sustained for a duration of 24 h. PAM-1 exhibited significant antibiofilm activities against CZA-resistant E. coli (p < 0.05). Furthermore, Membrane permeability test revealed that PAM-1 may exert its antibacterial effect by disrupting membrane integrity by forming transmembrane pores (p < 0.05). Red blood cell hemolysis and cytotoxicity tests revealed that PAM-1 exerts no adverse effects at experimental concentrations (p < 0.05). Moreover, stability tests revealed its effectiveness in serum and at room temperature. The Galleria mellonella infection model revealed that PAM-1 can significantly improve the survival rate of Galleria mellonella (>50%)for in vivo treatment. Lastly, RT-qPCR revealed that PAM-1 downregulates the expression of inflammatory cytokines (p < 0.05). Overall, our study findings highlight the potential of PAM-1 as a therapeutic agent for CZA-resistant E. coli infections, offering new avenues for research and alternative antimicrobial therapy strategies.

The Chinese customers and service staff interactive affective system (CCSIAS): introduction to a multimodal stimulus dataset.

To research the emotional interaction between customers and service staff, single-modal stimuli are being used to activate subjects' emotions while multimodal emotion stimuli with better efficiency are often neglected. This study aims to construct a multimodal emotion stimuli database (CCSIAS) with video records of real work status of 29 service staff and audio clips of interactions between customers and service staff by setting up wide-angle cameras and searching in company's Ocean Engine for 15 consecutive days. First, we developed a tool to assess the emotional statuses of customers and service staff in Study 1. Second, 40 Masters and PhD students were invited to assess the audio and video data to evaluate the emotional states of customers and service staff in Study 2, using the tools developed in Study 1. Third, 118 participants were recruited to test the results from Study 2 to ensure the stability of the derived data. The results showed that 139 sets of stable emotional audio & video data were constructed (26 sets were high, 59 sets were medium and 54 sets were low). The amount of emotional information is important for the effective activation of participants' emotional states, and the degree of emotional activation of video data is significantly higher than that of the audio data. Overall, it was shown that the study of emotional interaction phenomena requires a multimodal dataset. The CCSIAS (https://osf.io/muc86/) can extend the depth and breadth of emotional interaction research and can be applied to different emotional states between customers and service staff activation in the fields of organizational behavior and psychology.

Trends and drivers of anthropogenic NOx emissions in China since 2020.

Nitrogen oxides (NOx), significant contributors to air pollution and climate change, form aerosols and ozone in the atmosphere. Accurate, timely, and transparent information on NOx emissions is essential for decision-making to mitigate both haze and ozone pollution. However, a comprehensive understanding of the trends and drivers behind anthropogenic NOx emissions from China-the world's largest emitter-has been lacking since 2020 due to delays in emissions reporting. Here we show a consistent decline in China's NOx emissions from 2020 to 2022, despite increased fossil fuel consumption, utilizing satellite observations as constraints for NOx emission estimates through atmospheric inversion. This reduction is corroborated by data from two independent spaceborne instruments: the TROPOspheric Monitoring Instrument (TROPOMI) and the Ozone Monitoring Instrument (OMI). Notably, a reduction in transport emissions, largely due to the COVID-19 lockdowns, slightly decreased China's NOx emissions in 2020. In subsequent years, 2021 and 2022, reductions in NOx emissions were driven by the industry and transport sectors, influenced by stringent air pollution controls. The satellite-based inversion system developed in this study represents a significant advancement in the real-time monitoring of regional air pollution emissions from space.

Adherence and recommended optimal treatment to Azvudine application for the treatment of outpatient COVID-19 patients: A real-world retrospective study.

Background: Azvudine was approved for the treatment of coronavirus disease 2019 (COVID-19) in China and has been widely used since the outbreak in December 2022. However, real-world research on the adherence of Azvudine is lacking. Additionally, limited research exists on determining the optimal duration for Azvudine treatment. Methods: We studied adult patients with COVID-19 who got Azvudine or supportive treatment at an outpatient department between December 19, 2022 and January 5, 2023. The enrolled patients were divided into two groups: the Azvudine group, which received Azvudine, and the control group, which only received supportive care. We recorded their information and analyzed it using descriptive statistics. The primary outcome of this study was the compliance of outpatients with Azvudine, and the secondary outcome of this study was the optimal duration of Azvudine. Inverse probability weighting (IPW) was used to address the imbalance between groups when comparing the optimal duration of Azvudine, and Cox regression to evaluate the effect of Azvudine on the 28-day disease progression rate. Results: We enrolled a total of 882 patients, of which 382 received Azvudine. Among the patients, 94.0 % (359) had good compliance, and non-compliance was primarily attributed to dosage errors. Azvudine appeared to have a beneficial therapeutic effect when administered for at least 7 days. Conclusions: Outpatients have relatively good compliance with Azvudine, and optimal therapeutic effects were observed with the recommended duration of at least 7 days.

Successful In Situ Growth of Conductive MOFs on 2D Cobalt-Based Compounds and Their Electrochemical Performance.

Conductive metal-organic frameworks (cMOFs), as a kind of porous material, are considered to be highly promising materials in the field of electrochemistry due to their excellent conductivity. However, due to the low specific capacitance of pure cMOFs, their application in supercapacitors is limited. By virtue of the high theoretical capacity and excellent chemical stability of Co-based compounds, in this work, cMOFs' M-HHTP (M = Ni, Co, NiCo, HHTP = 2,3,6,7,10,11-hexahydroxytriphenylene) are grown in situ on Co(OH)2, CoP, and Co3O4 nanosheets, resulting in a series of electroactive compounds as electrode materials used in supercapacitors. Among all of the compounds, Ni-HHTP@Co(OH)2 shows the most excellent energy storage performance and outstanding cyclic stability in the application of aqueous asymmetric supercapacitors.

Insights into Euphorbia diversity: Probing the contrasts between Euphorbia fischeriana Steud and Euphorbia ebracteolata Hayata.

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Predicting tall-cell subtype of papillary thyroid carcinomas independently with preoperative multimodal ultrasound.

OBJECTIVES: This study aimed to explore the differences between tall-cell subtype of papillary thyroid carcinoma (TCPTC) and classical papillary thyroid carcinoma (cPTC) using multimodal ultrasound, and identify independent risk factors for TCPTC to compensate the deficiency of preoperative cytological and molecular diagnosis on PTC subtypes. METHODS: 46 TCPTC patients and 92 cPTC patients were included. Each patient received grey-scale ultrasound, color Dopplor flow imaging (CDFI) and shear-wave elastography (SWE) preoperatively. Clinicopathologic information, grey-scale ultrasound features, CDFI features and SWE features of 98 lesion were compared using univariate analysis to find out predictors of TCPTC, based on which, a predictive model was built to differentiate TCPTC from cPTC and validated with 40 patients. RESULTS: Univariate and multivariate analysis identified that extrathyroidal extension (OR, 15.12; 95% CI, 2.26-115.44), aspect ratio (≥0.91) (OR, 29.34; 95% CI, 1.29-26.23), and maximum diameter ≥ 14.6 mm (OR, 20.79; 95% CI, 3.87-111.47) were the independent risk factors for TCPTC. Logistic regression equation: p = 1/1+ExpΣ[-5.099 + 3.004 × (if size ≥14.6 mm)+2.957 × (if aspect ratio≥0.91)+2.819 × (if extra-thyroidal extension)]. The prediction model had a good discrimination performance for TCPTC: the AUC, sensitivity and specificity were 0.928, 0.848 and 0.954 in cohort 1, and the corresponding values in cohort 2 were 0.943, 0.923 and 0.926. CONCLUSION: Ultrasound has potential for differential diagnosis of TCPTC from cPTC. A prediction model based on ultrasound characteristics (extrathyroidal extension, aspect ratio ≥0.91, and maximum diameter ≥14.6 mm) was useful to predict TCPTC. ADVANCES IN KNOWLEDGE: Multimodal ultrasound prediction of TCPTC were supplements to preoperative cytological diagnosis and molecular diagnosis on PTC subtypes.

Growth Evaluation After Costochondral Graft Combined With Functional Appliance in Children With Temporomandibular Joint Ankylosis.

The treatment of temporomandibular joint (TMJ) ankylosis in children is a great challenge for surgeons. Costochondral graft (CCG) is a common method of reconstructing the TMJ in children. However, the growth pattern of CCG is unpredictable. In this study, we introduced a surgical-orthodontic approach and evaluated the growth results of the mandible and maxilla in children with TMJ ankylosis through 3-dimensional computed tomography measurements. A prospective cohort study was conducted on child patients diagnosed as having TMJ ankylosis between September 1, 2018 and June 1, 2020. Computer-aided virtual mandibular position guided the CCG, and removable functional appliance was used after surgery. The maximal incisal opening (MIO), the maxilla height, and the length of mandibular ramus were determined. Paired t test was performed to analyze the differences among various stages. Six patients (3 females, 3 males; aged 6-9 y) were included in this study. MIO was 12.4 mm before surgery and improved to 36.8 mm after 42.8 months' follow-up. Mandible length increased by 5.1 mm in the affected side and by 5.3 mm in the unaffected side, without significant difference. The affected maxilla height increased by 6.7 mm, which was more than 5.0 mm in the unaffected side. In conclusion, continued growth of mandible and maxilla can be achieved through CCG combined with functional appliance treatment for children TMJ ankylosis.

Identification and coregulation pattern analysis of long noncoding RNAs in the mouse brain after Angiostrongylus cantonensis infection.

BACKGROUND: Angiostrongyliasis is a highly dangerous infectious disease. Angiostrongylus cantonensis larvae migrate to the mouse brain and cause symptoms, such as brain swelling and bleeding. Noncoding RNAs (ncRNAs) are novel targets for the control of parasitic infections. However, the role of these molecules in A. cantonensis infection has not been fully clarified. METHODS: In total, 32 BALB/c mice were randomly divided into four groups, and the infection groups were inoculated with 40 A. cantonensis larvae by gavage. Hematoxylin and eosin (H&E) staining and RNA library construction were performed on brain tissues from infected mice. Differential expression of long noncoding RNAs (lncRNAs) and mRNAs in brain tissues was identified by high-throughput sequencing. The pathways and functions of the differentially expressed lncRNAs were determined by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. The functions of the differentially expressed lncRNAs were further characterized by lncRNA‒microRNA (miRNA) target interactions. The potential host lncRNAs involved in larval infection of the brain were validated by quantitative real-time polymerase chain reaction (qRT‒PCR). RESULTS: The pathological results showed that the degree of brain tissue damage increased with the duration of infection. The transcriptome results showed that 859 lncRNAs and 1895 mRNAs were differentially expressed compared with those in the control group, and several lncRNAs were highly expressed in the middle-late stages of mouse infection. GO and KEGG pathway analyses revealed that the differentially expressed target genes were enriched mainly in immune system processes and inflammatory response, among others, and several potential regulatory networks were constructed. CONCLUSIONS: This study revealed the expression profiles of lncRNAs in the brains of mice after infection with A. cantonensis. The lncRNAs H19, F630028O10Rik, Lockd, AI662270, AU020206, and Mexis were shown to play important roles in the infection of mice with A. cantonensis infection.

Disruption of maternal vascular remodeling by a fetal endoretrovirus-derived gene in preeclampsia.

BACKGROUND: Preeclampsia, one of the most lethal pregnancy-related diseases, is associated with the disruption of uterine spiral artery remodeling during placentation. However, the early molecular events leading to preeclampsia remain unknown. RESULTS: By analyzing placentas from preeclampsia, non-preeclampsia, and twin pregnancies with selective intrauterine growth restriction, we show that the pathogenesis of preeclampsia is attributed to immature trophoblast and maldeveloped endothelial cells. Delayed epigenetic reprogramming during early extraembryonic tissue development leads to generation of excessive immature trophoblast cells. We find reduction of de novo DNA methylation in these trophoblast cells results in selective overexpression of maternally imprinted genes, including the endoretrovirus-derived gene PEG10 (paternally expressed gene 10). PEG10 forms virus-like particles, which are transferred from the trophoblast to the closely proximate endothelial cells. In normal pregnancy, only a low amount of PEG10 is transferred to maternal cells; however, in preeclampsia, excessive PEG10 disrupts maternal vascular development by inhibiting TGF-beta signaling. CONCLUSIONS: Our study reveals the intricate epigenetic mechanisms that regulate trans-generational genetic conflict and ultimately ensure proper maternal-fetal interface formation.

Predictive value of the domain specific PLA2R antibodies for clinical remission in patients with primary membranous nephropathy: A retrospective study.

BACKGROUND: M-type phospholipase A2 receptor (PLA2R) is a major auto-antigen of primary membranous nephropathy(PMN). Anti-PLA2R antibody levels are closely associated with disease severity and therapeutic effectiveness. Analysis of PLA2R antigen epitope reactivity may have a greater predictive value for remission compared with total PLA2R-antibody level. This study aims to elucidate the relationship between domain-specific antibody levels and clinical outcomes of PMN. METHODS: This retrospective analysis included 87 patients with PLA2R-associated PMN. Among them, 40 and 47 were treated with rituximab (RTX) and cyclophosphamide (CTX) regimen, respectively. The quantitative detection of -immunoglobulin G (IgG)/-IgG4 targeting PLA2R and its epitope levels in the serum of patients with PMN were obtained through time-resolved fluorescence immunoassays and served as biomarkers in evaluating the treatment effectiveness. A predictive PMN remission possibility nomogram was developed using multivariate logistic regression analysis. Discrimination in the prediction model was assessed using the area under the receiver operating characteristic curve (AUC-ROC).Bootstrap ROC was used to evaluate the performance of the prediction model. RESULTS: After a 6-month treatment period, the remission rates of proteinuria, including complete remission and partial remission in the RTX and CTX groups, were 70% and 70.21% (P = 0.983), respectively. However, there was a significant difference in immunological remission in the PLA2R-IgG4 between the RTX and CTX groups (21.43% vs. 61.90%, P = 0.019). Furthermore, we found differences in PLA2R-CysR-IgG4(P = 0.030), PLA2R-CTLD1-IgG4(P = 0.005), PLA2R-CTLD678-IgG4(P = 0.003), and epitope spreading (P = 0.023) between responders and non-responders in the CTX group. Multivariate logistic analysis showed that higher levels of urinary protein (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.26-0.95; P = 0.035) and higher levels of PLA2R-CTLD1-IgG4 (OR, 0.79; 95%CI,0.62-0.99; P = 0.041) were independent risk factors for early remission. A multivariate model for estimating the possibility of early remission in patients with PMN is presented as a nomogram. The AUC-ROC of our model was 0.721 (95%CI, 0.601-0.840), in consistency with the results obtained with internal validation, for which the AUC-ROC was 0.711 (95%CI, 0.587-0.824), thus, demonstrating robustness. CONCLUSIONS: Cyclophosphamide can induce immunological remission earlier than rituximab at the span of 6 months. The PLA2R-CTLD1-IgG4 has a better predict value than total PLA2R-IgG for remission of proteinuria at the 6th month.

Phase 1 study of safety and preliminary efficacy of intranasal transplantation of human neural stem cells (ANGE-S003) in Parkinson's disease.

BACKGROUND: Intranasal transplantation of ANGE-S003 human neural stem cells showed therapeutic effects and were safe in preclinical models of Parkinson's disease (PD). We investigated the safety and tolerability of this treatment in patients with PD and whether these effects would be apparent in a clinical trial. METHODS: This was a 12-month, single-centre, open-label, dose-escalation phase 1 study of 18 patients with advanced PD assigned to four-time intranasal transplantation of 1 of 3 doses: 1.5 million, 5 million or 15 million of ANGE-S003 human neural stem cells to evaluate their safety and efficacy. RESULTS: 7 patients experienced a total of 14 adverse events in the 12 months of follow-up after treatment. There were no serious adverse events related to ANGE-S003. Safety testing disclosed no safety concerns. Brain MRI revealed no mass formation. In 16 patients who had 12-month Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) data, significant improvement of MDS-UPDRS total score was observed at all time points (p<0.001), starting with month 3 and sustained till month 12. The most substantial improvement was seen at month 6 with a mean reduction of 19.9 points (95% CI, 9.6 to 30.3; p<0.001). There was no association between improvement in clinical outcome measures and cell dose levels. CONCLUSIONS: Treatment with ANGE-S003 is feasible, generally safe and well tolerated, associated with functional improvement in clinical outcomes with peak efficacy achieved at month 6. Intranasal transplantation of neural stem cells represents a new avenue for the treatment of PD, and a larger, longer-term, randomised, controlled phase 2 trial is warranted for further investigation.

Tracking single-cell evolution using clock-like chromatin accessibility loci.

Single-cell chromatin accessibility sequencing (scATAC-seq) reconstructs developmental trajectory by phenotypic similarity. However, inferring the exact developmental trajectory is challenging. Previous studies showed age-associated DNA methylation (DNAm) changes in specific genomic regions, termed clock-like differential methylation loci (ClockDML). Age-associated DNAm could either result from or result in chromatin accessibility changes at ClockDML. As cells undergo mitosis, the heterogeneity of chromatin accessibility on clock-like loci is reduced, providing a measure of mitotic age. In this study, we developed a method, called EpiTrace, that counts the fraction of opened clock-like loci from scATAC-seq data to determine cell age and perform lineage tracing in various cell lineages and animal species. It shows concordance with known developmental hierarchies, correlates well with DNAm-based clocks and is complementary with mutation-based lineage tracing, RNA velocity and stemness predictions. Applying EpiTrace to scATAC-seq data reveals biological insights with clinically relevant implications, ranging from hematopoiesis, organ development, tumor biology and immunity to cortical gyrification.

Hinokione: an abietene diterpene with pancreatic ß cells regeneration and hypoglycemic activity, and other derivatives with novel structures from the woods of Agathis dammara.

In this study, 14 abietene and pimarene diterpenoids were isolated from the woods of Agathis dammara. Among them, 4 new compounds, dammarone A-C and dammaric acid A (1-4), were firstly reported, respectively. The structure of the new compounds was determined by HR ESI-MS and 1D/2D NMR spectroscopy, and their absolute configuration was determined by electronic circular dichroism (ECD) exciton chirality method. The hypoglycemic effect of all compounds was evaluated by transgenic zebrafish model, and the structure-activity relationship was discussed. Hinokione (7, HO) has low toxicity and significant hypoglycemic effects on zebrafish, the mechanism is mainly by promoting the differentiation of zebrafish pancreatic endocrine precursor cells (PEP cells) into ß cells, thereby promoting the regeneration of pancreatic ß cells.

Palmitic acid impairs human and mouse placental function by inhibiting trophoblast autophagy through induction of acyl-coenzyme A-binding protein (ACBP) upregulation.

STUDY QUESTION: Can exposure to palmitic acid (PA), a common saturated fatty acid, modulate autophagy in both human and mouse trophoblast cells through the regulation of acyl-coenzyme A-binding protein (ACBP)? SUMMARY ANSWER: PA exposure before and during pregnancy impairs placental development through mechanisms involving placental autophagy and ACBP expression. WHAT IS KNOWN ALREADY: High-fat diets, including PA, have been implicated in adverse effects on human placental and fetal development. Despite this recognition, the precise molecular mechanisms underlying these effects are not fully understood. STUDY DESIGN, SIZE, DURATION: Extravillous trophoblast (EVT) cell line HTR-8/SVneo and human trophoblast stem cell (hTSC)-derived EVT (hTSCs-EVT) were exposed to PA or vehicle control for 24 h. Female wild-type C57BL/6 mice were divided into PA and control groups (n = 10 per group) and subjected to a 12-week dietary intervention. Afterward, they were mated with male wild-type C57BL/6 mice and euthanized on Day 14 of gestation. Female ACBPflox/flox mice were also randomly assigned to control and PA-exposed groups (each with 10 mice), undergoing the same dietary intervention and mating with ACBPflox/floxELF5-Cre male mice, followed by euthanasia on Day 14 of gestation. The study assessed the effects of PA on mouse embryonic development and placental autophagy. Additionally, the role of ACBP in the pathogenesis of PA-induced placental toxicity was investigated. PARTICIPANTS/MATERIALS, SETTING, METHODS: The findings were validated using real-time PCR, Western blot, immunofluorescence, transmission electron microscopy, and shRNA knockdown approaches. MAIN RESULTS AND THE ROLE OF CHANCE: Exposure to PA-upregulated ACBP expression in both human HTR-8/SVneo cells and hTSCs-EVT, as well as in mouse placenta. PA exposure also induced autophagic dysfunction in HTR-8/SVneo cells, hTSCs-EVT, and mouse placenta. Through studies on ACBP placental conditional knockout mice and ACBP knockdown human trophoblast cells, it was revealed that reduced ACBP expression led to trophoblast malfunction and affected the expression of autophagy-related proteins LC3B-II and P62, thereby impacting embryonic development. Conversely, ACBP knockdown partially mitigated PA-induced impairment of placental trophoblast autophagy, observed both in vitro in human trophoblast cells and in vivo in mice. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Primary EVT cells from early pregnancy are fragile, limiting research use. Maintaining their viability is tough, affecting data reliability. The study lacks depth to explore PA diet cessation effects after 12 weeks. Without follow-up, understanding postdiet impacts on pregnancy stages is incomplete. Placental abnormalities linked to elevated PA diet in embryos lack confirmation due to absence of control groups. Clarifying if issues stem solely from PA exposure is difficult without proper controls. WIDER IMPLICATIONS OF THE FINDINGS: Consuming a high-fat diet before and during pregnancy may result in complications or challenges in successfully carrying the pregnancy to term. It suggests that such dietary habits can have detrimental effects on the health of both the mother and the developing fetus. STUDY FUNDING/COMPETING INTEREST(S): This work was supported in part by the National Natural Science Foundation of China (82171664, 82301909) and the Natural Science Foundation of Chongqing Municipality of China (CSTB2022NS·CQ-LZX0062, cstc2019jcyj-msxmX0749, and cstc2021jcyj-msxmX0236). The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Chlorine-Rich Na6-xPS5-xCl1+x: A Promising Sodium Solid Electrolyte for All-Solid-State Sodium Batteries.

Developing argyrodite-type, chlorine-rich, sodium-ion, solid-state electrolytes with high conductivity is a long-term challenge that is crucial for the advancement of all-solid-state batteries (ASSBs). In this study, chlorine-rich, argyrodite-type Na6-xPS5-xCl1+x solid solutions were successfully developed with a solid solution formation range of 0 ≤ x ≤ 0.5. Na5.5PS4.5Cl1.5 (x = 0.5), displaying a highest ionic conductivity of 1.2 × 10-3 S/cm at 25 °C, which is more than a hundred times higher than that of Na6PS5Cl. Cyclic voltammetry and electrochemical impedance spectroscopy results demonstrated that the rich chlorine significantly enhanced the ionic conductivity and electrochemical stability, in addition to causing a reduction in activation energy. The Na5.5PS4.5Cl1.5 composite also showed the characteristics of a pure ionic conductor without electronic conductivity. Finally, the viability of Na5.5PS4.5Cl1.5 as a sodium electrolyte for all-solid-state sodium batteries was checked in a lab-scale ASSB, showing stable battery performance. This study not only demonstrates new composites of sodium-ionic, solid-state electrolytes with relatively high conductivity but also provides an anion-modulation strategy to enhance the ionic conductivity of argyrodite-type sodium solid-state ionic conductors.

Magnetic Ion-Imprinted Materials for Selective Adsorption of Cr(VI): Adsorption Behavior and Mechanism Study.

With the increase of hexavalent Cr(VI) wastewater discharged from industrial production, it seriously pollutes water bodies and poses a risk to human health. Adsorption is used as an effective means to treat Cr(VI), but its effectiveness is affected by pH, and the adsorption performance decreases when acidity is strong. Furthermore, research on the mechanism of Cr(VI) adsorption using DFT calculations needs to be developed. This study focuses on the development of magnetically responsive core-shell nano-ion imprinted materials (Fe3O4@GO@IIP) through magnetic separation and surface imprinting techniques. Characterization techniques including FT-IR, XRD, and EDS confirmed the core-shell nanostructure of Fe3O4@GO@IIP. Batch adsorption experiments and model simulations demonstrated the exceptional adsorption capacity of Fe3O4@GO@IIP for Cr(VI) in strongly acidic solutions (pH = 1), reaching a maximum of 89.18 mg/g. The adsorption mechanism was elucidated through XPS and DFT calculations, revealing that Fe3O4@GO@IIP operates through electrostatic interactions and chemical adsorption, with charge transfer dynamics quantified during the process. This research provides new insights for addressing Cr(VI) treatment in highly acidic environments.

Ensemble-Based Virtual Screening Led to the Discovery of Novel Lead Molecules as Potential NMBAs.

Neuromuscular blocking agents (NMBAs) are routinely used during anesthesia to relax skeletal muscle. Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels; NMBAs can induce muscle paralysis by preventing the neurotransmitter acetylcholine (ACh) from binding to nAChRs situated on the postsynaptic membranes. Despite widespread efforts, it is still a great challenge to find new NMBAs since the introduction of cisatracurium in 1995. In this work, an effective ensemble-based virtual screening method, including molecular property filters, 3D pharmacophore model, and molecular docking, was applied to discover potential NMBAs from the ZINC15 database. The results showed that screened hit compounds had better docking scores than the reference compound d-tubocurarine. In order to further investigate the binding modes between the hit compounds and nAChRs at simulated physiological conditions, the molecular dynamics simulation was performed. Deep analysis of the simulation results revealed that ZINC257459695 can stably bind to nAChRs' active sites and interact with the key residue Asp165. The binding free energies were also calculated for the obtained hits using the MM/GBSA method. In silico ADMET calculations were performed to assess the pharmacokinetic properties of hit compounds in the human body. Overall, the identified ZINC257459695 may be a promising lead compound for developing new NMBAs as an adjunct to general anesthesia, necessitating further investigations.