The influence of electrode types to the visually induced gamma oscillations in mouse primary visual cortex.

The local field potential (LFP) is an extracellular electrical signal associated with neural ensemble input and dendritic signaling. Previous studies have linked gamma band oscillations of the LFP in cortical circuits to sensory stimuli encoding, attention, memory, and perception. Inconsistent results regarding gamma tuning for visual features were reported, but it remains unclear whether these discrepancies are due to variations in electrode properties. Specifically, the surface area and impedance of the electrode are important characteristics in LFP recording. To comprehensively address these issues, we conducted an electrophysiological study in the V1 region of lightly anesthetized mice using two types of electrodes: one with higher impedance (1 MΩ) and a sharp tip (10 µm), while the other had lower impedance (100 KΩ) but a thicker tip (200 µm). Our findings demonstrate that gamma oscillations acquired by sharp-tip electrodes were significantly stronger than those obtained from thick-tip electrodes. Regarding size tuning, most gamma power exhibited surround suppression at larger gratings when recorded from sharp-tip electrodes. However, the majority showed enhanced gamma power at larger gratings when recorded from thick-tip electrodes. Therefore, our study suggests that microelectrode parameters play a significant role in accurately recording gamma oscillations and responsive tuning to sensory stimuli.

Methanetriol─Formation of an Impossible Molecule.

Orthocarboxylic acids─organic molecules carrying three hydroxyl groups at the same carbon atom─have been distinguished as vital reactive intermediates by the atmospheric science and physical (organic) chemistry communities as transients in the atmospheric aerosol cycle. Predicted short lifetimes and their tendency to dehydrate to a carboxylic acid, free orthocarboxylic acids, signify one of the most elusive classes of organic reactive intermediates, with even the simplest representative methanetriol (CH(OH)3)─historically known as orthoformic acid─not previously been detected experimentally. Here, we report the first synthesis of the previously elusive methanetriol molecule in low-temperature mixed methanol (CH3OH) and molecular oxygen (O2) ices subjected to energetic irradiation. Supported by electronic structure calculations, methanetriol was identified in the gas phase upon sublimation via isomer-selective photoionization reflectron time-of-flight mass spectrometry combined with isotopic substitution studies and the detection of photoionization fragments. The first synthesis and detection of methanetriol (CH(OH)3) reveals its gas-phase stability as supported by a significant barrier hindering unimolecular decomposition. These findings progress our fundamental understanding of the chemistry and chemical bonding of methanetriol, hydroxyperoxymethane (CH3OOOH), and hydroxyperoxymethanol (CH2(OH)OOH), which are all prototype molecules in the oxidation chemistry of the atmosphere.

PARP1 promotes EGFR-TKI drug-resistance via PI3K/AKT pathway in non-small-cell lung cancer.

PURPOSE: Tyrosine kinase inhibitor (TKI) resistance is the main type of drug resistance in lung cancer patients with epidermal growth factor receptor (EGFR) mutations, but its underlying mechanism remains unclear. The purpose of this work was to investigate the mechanism by which PARP1 regulates EGFR-TKI resistance to identify potential targets for combating drug resistance. METHODS: The GEO databases, TCGA databases, western blot and qPCR studies were used to investigate the expression of PARP1 in lung cancer cells and tissues and its correlation with the prognosis of lung cancer. The expression of PARP1 in lung cancer TKI resistant cell PC9-ER and TKI sensitive cell PC9 was analyzed by qPCR and western blot. After knocking down of PARP1, CCK-8 assays, colony formation, flow cytometry were used to investigate its impact on erlotinib sensitivity, cell survival, cell cycle, and apoptosis. RNA-seq was used to investigate the mechanism by which PARP1 participates in EGFR-TKI resistance, and the results were validated in vitro and in vivo studies. RESULTS: PARP1 was highly expressed in both lung cancer tissues and cells. Subsequently, increased PARP1 expression was observed in PC9-ER compared with its parental cell line. Knockdown of PARP1 increased erlotinib sensitivity, promoted cell apoptosis, and suppressed cell growth. RNA-seq and previous studies have shown that the PI3K/AKT/mTOR/P70S6K pathway is involved in PARP1-mediated TKI resistance, and these results were confirmed by Western blot in vitro and in vivo. CONCLUSION: PARP1 may serve as a potential therapeutic target for reversing EGFR-TKI resistance in NSCLC via the PI3K/AKT/mTOR/P70S6K pathway.

Composite interfaces of g-C3N4 fragments loaded on a Cu substrate for CO2 reduction.

Designing an electrocatalyst with high efficiency and product selectivity is always crucial for an electrocatalytic CO2 reduction reaction (CO2RR). Inspired by the great progress of two-dimensional (2D) nanomaterials growing on Cu surfaces and their promising CO2RR catalytic efficiencies at their interfaces, the unique performance of Cu-based 2D materials as high-efficiency and low-cost CO2RR electrocatalysts has attracted extensive attention. Herein, based on density functional theory (DFT) calculations, we proposed a composite structure of graphitic carbon nitride (g-C3N4) fragments loaded on a Cu surface to explore the CO2RR catalytic property of the interface between g-C3N4 and the Cu surface. Three composite interfaces of C3N4/Cu(111), C3N4/Cu(110) and C3N4/Cu(100) have been studied by considering the reaction sites of vertex nitrogen atoms, edge nitrogen atoms and the nearby Cu atoms. It was found that the C3N4/Cu interfaces where nitrogen atoms contact the Cu substrate present competitive CO2RR activity. Among them, C3N4/Cu(111)-N3 exhibited a better activity for CH3OH production, with a low overpotential of 0.38 V. For HCOOH and CH4 production, C3N4/Cu(111)-Cu and C3N4/Cu(100)-N1 have overpotentials of 0.26 V and 0.44 V. The electronic analysis indicates the electron transfer from the Cu substrate to the g-C3N4 fragment and mainly accumulates on the nitrogen atoms of the interface. Such charge accumulation can activate the adsorbed CO bond of CO2 and lead to lower energetic barriers of CO2RR. DFT calculations indicate that the boundary nitrogen sites reduced the energy barrier of *CHO, which is crucial for CO2RR, compared with that of the pristine Cu surface. Our study explores a new Cu-based electrocatalyst and indicates that the C3N4/Cu interface can enhance the activities and selectivity of CO2RR and open a new strategy to design high-efficiency electrocatalysts for CO2RR.

NEAR-INFRARED DYE IR-780 ALLEVIATES HEMATOPOIETIC SYSTEM DAMAGE BY PROMOTING HEMATOPOIETIC STEM CELLS INTO QUIESCENCE.

ABSTRACT: Potential radiation exposure is a general concern, but there still lacks radioprotective countermeasures. Here, we found a small molecular near-infrared dye IR-780, which promoted hematopoietic stem cells (HSCs) into quiescence to resist stress. When mice were treated with IR-780 before stress, increased HSC quiescence and better hematopoietic recovery were observed in mice in stress conditions. However, when given after radiation, IR-780 did not show obvious benefit. Transplantation assay and colony-forming assay were carried out to determine self-renewal ability and repopulation capacity of HSCs. Furthermore, IR-780 pretreatment reduced the generation of reactive oxygen species (ROS) and DNA damage in HSCs after radiation. In homeostasis, the percentage of Lineage - , Sca-1 + , and c-Kit + cells and long-term HSCs (LT-HSCs) were improved, and more HSCs were in G0 state after administration of IR-780. Further investigations showed that IR-780 selectively accumulated in mitochondria membrane potential high LT-HSCs (MMP-high LT-HSCs). Finally, IR-780 promoted human CD34 + HSC reconstruction ability in NOD-Prkdc scid Il2rg null mice after transplantation and improved repopulation capacity in vitro culture. Our research showed that IR-780 selectively entered MMP-high LT-HSCs and promoted them into dormancy, thus reducing hematopoietic injury and improving regeneration capacity. This novel approach might hold promise as a potential countermeasure for radiation injury.

Implication of PD­L1 polymorphisms rs2297136 on clinical outcomes of patients with advanced NSCLC who received PD­1 blockades: A retrospective exploratory study.

Clinically, programmed death-1 (PD-1) blockades have demonstrated promising therapeutic outcomes for patients with advanced non-small cell lung cancer (NSCLC). The present study aimed to examine the impact of programmed death-ligand 1 (PD-L1) polymorphism on clinical outcomes of patients with advanced NSCLC who were treated with PD-1 blockades therapy. The present study was designed as a retrospective analysis, where a consecutive screening of 89 patients with advanced NSCLC who received PD-1 blockades monotherapy were screened. Biological specimens were collected to determine the presence of polymorphism and PD-L1 mRNA expression through genotyping. The analysis focused on examining the relationship between the genotype status of PD-L1 polymorphism and clinical outcomes. Among the 89 patients with advanced NSCLC, the use of PD-1 blockades monotherapy resulted in objective response rate (ORR) of 22.5%, a median progression-free survival (PFS) of 3.4 months [95% Confidence Interval (CI): 1.80-5.00) and a median overall survival (OS) of 11.3 months (95% CI: 7.93-14.67). The analysis of polymorphism indicated that only rs2297136 had clinical significance. Among the 89 patients with NSCLC, the prevalence of rs2297136 was as follows: A total of 58 cases (65.2%) had the AA genotype, 28 cases (31.5%) had the AG genotype and 3 cases (3.4%) had the GG genotype. This resulted in a minor allele frequency of 0.19, which was in consistent with Hardy-Weinberg Equilibrium (P=0.865). The correlation analysis between genotype status of rs2297136 and clinical outcomes indicated that patients with the AA genotype had an ORR of 19.0%, while those with the AG/GG genotype had an ORR of 29.0% (P=0.278). Additionally, the median PFS for the AA genotype was 2.95 months, compared with 5.30 months for the AG/GG genotype (P=0.038). Accordingly, median OS of the AA and AG/GG genotypes was 8.8 and 18.4 months, respectively (P=0.011). The mRNA expression of PD-L1 was significantly higher in patients with AG/GG genotype compared with those with AA genotype (P<0.001). In clinical practice, PD-1 blockades demonstrated promising effectiveness in treating patients with advanced NSCLC. The presence of the rs2297136 variant in PD-L1 gene could potentially be used as a biomarker to predict the clinical outcomes of PD-1 blockades.

Refined preferences of prioritizers improve intelligent diagnosis for Mendelian diseases.

Phenotype-guided gene prioritizers have proved a highly efficient approach to identifying causal genes for Mendelian diseases. In our previous study, we preliminarily evaluated the performance of ten prioritizers. However, all the selected software was run based on default settings and singleton mode. With a large-scale family dataset from Deciphering Developmental Disorders (DDD) project (N = 305) and an in-house trio cohort (N = 152), the four optimal performers in our prior study including Exomiser, PhenIX, AMELIE, and LIRCIAL were further assessed through parameter optimization and/or the utilization of trio mode. The in-depth assessment revealed high diagnostic yields of the four prioritizers with refined preferences, each alone or together: (1) 83.3-91.8% of the causal genes were presented among the first ten candidates in the final ranking lists of the four tools; (2) Over 97.7% of the causal genes were successfully captured within the top 50 by either of the four software. Exomiser did best in directly hitting the target (ranking the causal gene at the very top) while LIRICAL displayed a predominant overall detection capability. Besides, cases affected by low-penetrance and high-frequency pathogenic variants were found misjudged during the automated prioritization process. The discovery of the limitations shed light on the specific directions of future enhancement for causal-gene ranking tools.

Newly discovered variants in unexplained neonatal encephalopathy.

BACKGROUND: The genetic background of neonatal encephalopathy (NE) is complicated and early diagnosis is beneficial to optimizing therapeutic strategy for patients. METHODS: NE Patients with unclear etiology received regular clinical tests including ammonia test, metabolic screening test, amplitude-integrated electroencephalographic (aEEG) monitoring, brain Magnetic Resonance Imaging (MRI) scanning, and genetic test. The protein structure change was predicted using Dynamut2 and RoseTTAFold. RESULTS: 15 out of a total of 113 NE Patients were detected with newly reported pathogenic variants. In this sub-cohort, (1) seizure was the primary initial symptoms; (2) four patients had abnormal metabolic screening results, and two of them were also diagnosed with excessive blood ammonia concentration; (3) the brain MRI results were irregular in three infants and the brain waves were of moderate-severe abnormality in about a half of the patients. The novel pathogenic variants discovered in this study belonged to 12 genes, and seven of them were predicted to introduce a premature translation termination. In-silicon predictions showed that four variants were destructive to the protein structure of KCNQ2. CONCLUSION: Our study expands the mutation spectrum of genes associated with NE and introduces new evidence for molecular diagnosis in this newborn illness.

Enhance Hydrogen Evolution Reaction Performance via Double-Stacked Edges of Black Phosphorene.

Based on the density functional theory (DFT) calculations, we explored the structures and HER catalytic properties of reconstructed and double-stacked black phosphorene (BP) edges. Ten bilayer BP edges were constructed by the double stacking of three typical monolayer edges, i.e., zigzag (ZZ) edge, armchair (AC) edge, skewed diagonal (SD) edge, and their reconstructed derivatives with their layer's configurations, edge deformations and thermodynamic stabilities were discussed. Based on these edges, five chemical sites on four bilayer BP edges were selected to be promising candidates for a HER catalyst, which present higher HER activities than that of Pt(111). Besides, among these four edges, two edges have even lower energetic barriers for the Tafel reaction. Compared with the monolayer edges, these selected bilayer BP edges confirm the remarkable enhancement of the HER catalytic properties, which can be attributed to their unique edge structures and the enhanced electronic densities after the hydrogen adsorptions. Finally, the thermostability of these edges at room temperature has also been proved by the DFT-MD simulations. This theoretic study deepens our fundamental understanding of the double-stacked edge structures of the BP and provides a new way for the rational design of highly efficient and noble-metal-free HER catalysts.

Identification and validation of basic fibroblast growth factor as a prognostic biomarker for the response of lung adenocarcinoma patients to bevacizumab treatment.

Basic fibroblast growth factor (bFGF) stimulates angiogenesis, influencing the proliferation, migration, and survival of tumour cells, which have pivotal roles in tumour progression. This study investigated the prognostic significance of bFGF expression in lung adenocarcinoma treated with bevacizumab. The expression levels of bFGF were assessed in bevacizumab-treated patients with lung adenocarcinoma using immunohistochemistry. Propensity score matching (PSM) analysis was performed to evaluate prognostic potential. bFGF expression was also investigated in another independent cohort of patients with lung adenocarcinoma treated with routinechemotherapy. We also compared the PSM value of bFGF expression levels independently and in combination with epidermal growth factor receptor and vascularendothelial growth factor expression levels. A high bFGF expression level was found to be an independent prognostic factor for disease-free survival in patients receiving bevacizumab-based chemotherapy. Similar results were not observed in patients who underwent routinechemotherapy. In conclusion, the bFGF expression level may be a clinically feasible prognostic marker and bFGF is a potential therapeutic target for patients with lung adenocarcinoma receiving routinechemotherapy.

Extracellular polysaccharide of Lactobacillus plantarum enhance immune efficacy of oprH gene recombinant subunit vaccine from Pseudomonas aeruginosa.

To evaluate the immune enhancement effect of the extracellular polysaccharide of Lactobacillus plantarum on oprH recombinant subunit vaccine from Pseudomonas aeruginosa, a recombinant subunit vaccine of oprH (rOprH vaccine) was developed. The EP-rOprH vaccine was prepared with the extracellular polysaccharide of L. plantarum as an adjuvant. Mice were vaccinated with the rOprH and EP-rOprH vaccines, and the outer membrane protein (OMP) and inactivated vaccines were used as controls. The levels of serum antibody, interferon-γ (IFN-γ), interleukin (IL-2), and IL-4 were determined after vaccination. Finally, the protective efficacy of the vaccine was evaluated after challenge with virulent P. aeruginosa. Following vaccination, the serum antibody levels were significantly higher in mice vaccinated with the EP-rOprH vaccine than in those vaccinated with the rOprH vaccine (P<0.05). Moreover, the serum antibody levels detected in the EP-rOprH vaccine group were similar to those detected in the OMP vaccine group when P. aeruginosa suspension was used as the coating antigen. However, the levels in the EP-rOprH vaccine group were higher than those in the OMP vaccine and inactivated vaccine groups when the purified rOprH protein was used as the coating antigen (P<0.05). The level of IFN-γ, IL-2, and IL-4 in mice vaccinated with the EP-rOprH vaccine was significantly higher than that in mice vaccinated with the rOprH vaccine (P<0.05) and comparable to that in mice vaccinated with the OMP vaccine. The protective rates were 65%, 80%, 80%, and 95% with the rOprH, EP-rOprH, OMP, and inactivated vaccines, respectively. Thus, the extracellular polysaccharide of L. plantarum significantly enhanced the immune response and protection provided by the recombinant subunit vaccine of oprH.

Inhibition of CARM1 suppresses proliferation of multiple myeloma cells through activation of p53 signaling pathway.

BACKGROUND: Multiple myeloma (MM) is a malignant proliferative disease of plasma cells, the incidence of which is increasing every year and remains incurable. The enzyme co-activator-associated arginine methyltransferase 1 (CARM1) is highly expressed in a variety of cancers, such as Hodgkin's lymphoma and acute myeloid leukemia, and CARM1 is closely associated with tumor cell proliferation. However, the role of CARM1 in MM has not been elucidated. METHODS AND RESULTS: In this study, we found that CARM1 is overexpressed in MM and closely associated with poor prognosis in MM. CCK-8 and colony formation assays showed that the proliferation of MM cell lines was downregulated when CARM1 expression was knockdown by specific shRNA. Knockdown of CARM1 reduced the proportion of MM cell lines in the S phase and increased the proportion in G0/G1 phase. RNA-seq analysis of the CARM1-KD cell line revealed that it was closely associated with apoptosis and activated the p53 pathway. CCK-8 and apoptosis results showed that CARM1 knockdown made MM cells more sensitive to standard-of-care drugs. CONCLUSION: This study provides an experimental basis for elucidating the pathogenesis of multiple myeloma and searching for potential therapeutic targets.

A novel report of Cys1298Gly mutation in exon 24 of NOTCH3 gene in a Chinese family with CADASIL.

OBJECTIVES: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is the most common monogenic hereditary small cerebral vessel disease, which is caused by mutation of the neurogenic locus notch homolog protein 3 gene (NOTCH3). The exon 24 encodes EGF-like repeats, variants on this exon are rare. Here, we report a novel heterozygous variant c.3892 T >G (p. Cys1298Gly) on exon 24 of NOTCH3 gene in a 57-year-old Chinese woman. MATERIALS AND METHODS: We present a patient with clinical manifestations, laboratory examination and imaging reveal suspicion of CADASIL. The family and genetic test and pathological examination were performed. RESULTS: Magnetic resonance imaging revealed diffuse leukoencephalopathy with hyperintense signals in the bilateral temporal poles, periventricular white matter, centrum semiovale, basal ganglia, frontal and parietal cortex and subcortical areas bilaterally. Molecular Genetic testing identified a heterozygous variant c.3892 T >G (p. Cys1298Gly) on exon 24 of NOTCH3 gene. Her brother and his son were confirmed as subclinical carriers of the variant. The skin biopsy was negative, but the pathologic role of this mutation is predicted by using the DynaMut database and results showed the stability of the NOTCH gene is decreased. CONCLUSIONS: To the best of our knowledge, this is the second case of exon 24 mutations reported from China and the variant of c.3892 T >G (p. Cys1298Gly) on exon 24 of NOTCH3 has not been reported so far. Our report broadens the mutation spectrum of the NOTCH3 gene in CADASIL.

Pediatric paragonimiasis: a retrospective analysis of cases from a county in south-west China.

Introduction: The clinical manifestations of paragonimiasis are diverse and non-specific, and can easily lead to misdiagnosis. We aimed to analyze the clinical manifestations, laboratory features, treatment, and clinical outcome of children with paragonimiasis in order to improve recognition of this disease and avoid misdiagnosis. Methods: Children diagnosed with paragonimiasis from August 2016 to July 2022 were included in the study. Information on population informatics, medical history, and laboratory features was extracted from case data. The clinical features of paragonimiasis were retrospectively analyzed. Results: A total of 45 children were included in this study. All children had, at least, one risk factor. The clinical features mainly included fever, cough, pleural effusion, peritoneal effusion, and subcutaneous nodules. The main imaging findings were alveolar exudation, peritoneal effusion, pleural thickening, and local nodules. The "tunnel sign" finding on computed tomography (CT)/magnetic resonance imaging (MRI) was helpful in establishing the diagnosis of paragonimiasis. After praziquantel treatment, most of the children improved, and one child with cerebral paragonimiasis experienced sequelae. Conclusion: Most children with paragonimiasis have a good prognosis, but few children can experience sequelae. Avoidance of untreated water and raw food is a simple, feasible, and effective preventive measure.

Recent advances and challenges in primary central nervous system lymphoma: a narrative review.

Background and Objective: Primary central nervous system lymphoma (PCNSL) is a rare and highly invasive non-Hodgkin lymphoma that is challenging to diagnose and treat. It is typically confined to the brain, spinal cord, and eyes. The diagnosis of PCNSL lacks specificity, and the misdiagnosis and missed diagnosis rates of PCNSL are high. Traditional treatments for PCNSL, such as surgery, whole-brain radiation therapy, high-dose methotrexate-based chemotherapy, and rituximab (RTX), have been associated with higher initial remission rates. However, the duration of any remission is short, the recurrence rate is high, and treatment-related neurotoxicity is strong, which are challenges for medical researchers. This review provides an overview of and perspectives on the diagnosis, treatment, and evaluation of patients with PCNSL. Methods: The PubMed database was searched to retrieve articles published from January 1, 1991, to June 2, 2022 using the following Medical Subject Headings (MeSH) terms: "Primary central nervous system lymphoma" and "clinical trial". The American Society of Clinical Oncology and the National Comprehensive Cancer Network guidelines were also reviewed to obtain additional information. The search was limited to articles published in English, German, and French. In total, 126 articles were deemed eligible for inclusion in this study. Key Content and Findings: In terms of the diagnosis of PCNSL, a combination of flow cytometry and cytology has been shown to improve the diagnostic accuracy of PCNSL. Additionally, interleukin 10 and chemokine C-X-C motif ligand 13 are promising biomarkers. In terms of the treatment of PCNSL, programmed death-1 (PD-1) blockage and chimeric antigen receptor T cell (CAR-T) therapy treatments have shown prospective efficacy, but more clinical trials need to be conducted to gather further evidence. We also reviewed and summarized prospective clinical trials on PCNSL. Conclusions: PCNSL is a rare and highly aggressive lymphoma. The treatment of PCNSL has progressed significantly, and while the survival of patients has improved, relapse and low long-term survival remain huge challenges. Continuous in-depth research is being conducted on new drug therapies and combination therapies for PCNSL. A combination of targeted drugs (e.g., ibrutinib, lenalidomide, and PD-1 monoclonal antibody) and traditional therapy represents the main research direction for future PCNSL treatments. CAR-T has also shown great potential in the treatment of PCNSL. With the development of these new diagnostic and therapeutic methods and further research into the molecular biology of PCNSL, patients with PCNSL should achieve a better prognosis.

Cold atmospheric plasma alleviates radiation-induced skin injury by suppressing inflammation and promoting repair.

Currently, there is no effective treatment for chronic skin radiation injury, which burdens patients significantly. Previous studies have shown that cold atmospheric plasma has an apparent therapeutic effect on acute and chronic skin injuries in clinical. However, whether CAP is effective for radiation-induced skin injury has not been reported. We created 35Gy X-ray radiation exposure within 3 * 3 cm2 region of the left leg of rats and applied CAP to the wound bed. Wound healing, cell proliferation and apoptosis were examined in vivo or vitro. CAP alleviated radiation-induced skin injury by enhancing proliferation and migration and cellular antioxidant stress and promoting DNA damage repair through regulated nuclear translocation of NRF2. In addition, CAP inhibited the proinflammatory factors' expression of IL-1ß, TNF-α and temporarily increased the pro repair factor's expression of IL-6 in irradiated tissues. At the same time, CAP also changed the polarity of macrophages to a repair-promoting phenotype. Our finding suggested that CAP ameliorated radiation-induced skin injury by activating NRF2 and ameliorating the inflammatory response. Our work provided a preliminary theoretical foundation for the clinical administration of CAP in high-dose irradiated skin injury.

Wuzi Yanzong Pill protects neural tube defects by activating PI3K/Akt signaling pathway.

Neural tube defects (NTDs) are severe congenital malformations that can lead to lifelong disability. Wuzi Yanzong Pill (WYP) is an herbal formula of traditional Chinese medicine (TCM) that has been shown to have a protective effect against NTDs in a rodent model induced by all-trans retinoic acid (atRA), but the mechanism remains unclear. In this study, the neuroprotective effect and mechanism of WYP on NTDs were investigated in vivo using an atRA-induced mouse model and in vitro using cell injury model induced by atRA in Chinese hamster ovary (CHO) cells and Chinese hamster dihydrofolate reductase-deficient (CHO/dhFr) cells. Our findings suggest that WYP has an excellent preventive effect on atRA-induced NTDs in mouse embryos, which may be related to the activation of the PI3K/Akt signaling pathway, improved embryonic antioxidant capacity, and anti-apoptotic effects, and this effect is not dependent on folic acid (FA). Our results demonstrated that WYP significantly reduced the incidence of NTDs induced by atRA; increased the activity of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and content of glutathione (GSH); decreased the apoptosis of neural tube cells; up-regulated the expression of phosphatidylinositol 3 kinase (PI3K), phospho protein kinase B (p-Akt), nuclear factor erythroid-2 related factor (Nrf2), and b-cell lymphoma-2 (Bcl-2); and down-regulated the expression of bcl-2-associated X protein (Bax). Our in vitro studies suggested that the preventive effect of WYP on atRA-treated NTDs was independent of FA, which might be attributed to the herbal ingredients of WYP. The results suggest that WYP had an excellent prevention effect on atRA-induced NTDs mouse embryos, which may be independent of FA but related to the activation of the PI3K/Akt signaling pathway and improvement of embryonic antioxidant capacity and anti-apoptosis.