Efficacy and safety of Ginkgo biloba extract in the treatment of unstable angina pectoris: A systematic review and network meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba is a traditional Chinese medicine extracted from the Ginkgophyta and is commonly used in the treatment of cardiovascular diseases in China. Clinical trials have demonstrated the clinical benefits of Ginkgo biloba extract (GBE) preparations for patients with unstable angina pectoris (UAP). AIM OF THE STUDY: The efficacy of different GBE preparations in treating UAP may vary, leading to a lack of guidance for physicians when choosing GBE preparations. How to make choices among different GBE preparations is a topic worthy of investigation. In order to clarify the efficacy differences among different GBE preparations, provide a reference for their optimal use conditions, this study was conducted. MATERIALS AND METHODS: This study included literature from eight databases from inception to November 2023. It included UAP patients, with the control group receiving conventional treatment and the treatment group receiving different GBE preparations in addition to conventional treatment. Angina efficacy, electrocardiogram (ECG) improvement, and frequency of angina were chosen as outcomes. This study employed a systematic review and Bayesian network meta-analysis, and the surface under the cumulative ranking (SUCRA) curve was used for estimating the efficacy ranking. RESULTS: A total of 98 studies involving 9513 patients and 9 interventions were included. Compared with conventional treatment, GBE preparations combined with conventional treatment had better efficacy in angina symptoms and ECG improvement. According to the SUCRA ranking, Shuxuening injection was most effective in improving angina symptoms and reducing the frequency of angina. Among oral GBE preparations, Ginkgo tablets had the best performance in improving angina symptoms and ECG manifestations, and reducing the frequency of angina. There was no significant difference in the incidence of adverse events between the treatment group and the control group, and all adverse events were mild and self-limiting. Compared with oral preparations, the incidence of adverse events for injections was higher. CONCLUSIONS: GBE preparations may alleviate angina symptoms and myocardial ischemia in the treatment of UAP with favorable safety. Shuxuening injection may be the most effective among all GBE preparations in improving angina symptoms, while Ginkgo tablets may perform best among oral formulations. The optimal use of GBE injection may be for rapidly alleviating angina symptoms and myocardial ischemia in patients with UAP, and oral formulation of GBE may be more suitable for the long-term treatment of patients with milder symptoms. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022361487, ID: CRD42022361487.

Microcephaly Gene Mcph1 Deficiency Induces p19ARF-Dependent Cell Cycle Arrest and Senescence.

MCPH1 has been identified as the causal gene for primary microcephaly type 1, a neurodevelopmental disorder characterized by reduced brain size and delayed growth. As a multifunction protein, MCPH1 has been reported to repress the expression of TERT and interact with transcriptional regulator E2F1. However, it remains unclear whether MCPH1 regulates brain development through its transcriptional regulation function. This study showed that the knockout of Mcph1 in mice leads to delayed growth as early as the embryo stage E11.5. Transcriptome analysis (RNA-seq) revealed that the deletion of Mcph1 resulted in changes in the expression levels of a limited number of genes. Although the expression of some of E2F1 targets, such as Satb2 and Cdkn1c, was affected, the differentially expressed genes (DEGs) were not significantly enriched as E2F1 target genes. Further investigations showed that primary and immortalized Mcph1 knockout mouse embryonic fibroblasts (MEFs) exhibited cell cycle arrest and cellular senescence phenotype. Interestingly, the upregulation of p19ARF was detected in Mcph1 knockout MEFs, and silencing p19Arf restored the cell cycle and growth arrest to wild-type levels. Our findings suggested it is unlikely that MCPH1 regulates neurodevelopment through E2F1-mediated transcriptional regulation, and p19ARF-dependent cell cycle arrest and cellular senescence may contribute to the developmental abnormalities observed in primary microcephaly.

DTDNet: Dynamic Target Driven Network for pedestrian trajectory prediction.

Predicting the trajectories of pedestrians is an important and difficult task for many applications, such as robot navigation and autonomous driving. Most of the existing methods believe that an accurate prediction of the pedestrian intention can improve the prediction quality. These works tend to predict a fixed destination coordinate as the agent intention and predict the future trajectory accordingly. However, in the process of moving, the intention of a pedestrian could be a definite location or a general direction and area, and may change dynamically with the changes of surrounding. Thus, regarding the agent intention as a fixed 2-d coordinate is insufficient to improve the future trajectory prediction. To address this problem, we propose Dynamic Target Driven Network for pedestrian trajectory prediction (DTDNet), which employs a multi-precision pedestrian intention analysis module to capture this dynamic. To ensure that this extracted feature contains comprehensive intention information, we design three sub-tasks: predicting coarse-precision endpoint coordinate, predicting fine-precision endpoint coordinate and scoring scene sub-regions. In addition, we propose a original multi-precision trajectory data extraction method to achieve multi-resolution representation of future intention and make it easier to extract local scene information. We compare our model with previous methods on two publicly available datasets (ETH-UCY and Stanford Drone Dataset). The experimental results show that our DTDNet achieves better trajectory prediction performance, and conducts better pedestrian intention feature representation.

PARP1 UFMylation ensures the stability of stalled replication forks.

The S-phase checkpoint involving CHK1 is essential for fork stability in response to fork stalling. PARP1 acts as a sensor of replication stress and is required for CHK1 activation. However, it is unclear how the activity of PARP1 is regulated. Here, we found that UFMylation is required for the efficient activation of CHK1 by UFMylating PARP1 at K548 during replication stress. Inactivation of UFL1, the E3 enzyme essential for UFMylation, delayed CHK1 activation and inhibits nascent DNA degradation during replication blockage as seen in PARP1-deficient cells. An in vitro study indicated that PARP1 is UFMylated at K548, which enhances its catalytic activity. Correspondingly, a PARP1 UFMylation-deficient mutant (K548R) and pathogenic mutant (F553L) compromised CHK1 activation, the restart of stalled replication forks following replication blockage, and chromosome stability. Defective PARP1 UFMylation also resulted in excessive nascent DNA degradation at stalled replication forks. Finally, we observed that PARP1 UFMylation-deficient knock-in mice exhibited increased sensitivity to replication stress caused by anticancer treatments. Thus, we demonstrate that PARP1 UFMylation promotes CHK1 activation and replication fork stability during replication stress, thus safeguarding genome integrity.

Universal, school-based transdiagnostic interventions to promote mental health and emotional wellbeing: a systematic review.

OBJECTIVE: This systematic review aims to evaluate the effectiveness of universal school-based transdiagnostic interventions in promoting the mental health of children and adolescents. It compares and discusses interventions targeting the prevention of mental disorders versus the promotion of mental health. Additionally, the roles of teachers and psychologists as intervention conductors are examined. METHODS: A comprehensive search of the Psycinfo, Pubmed, and Web of Science databases was conducted without any time restrictions to identify relevant literature on universal school-based transdiagnostic interventions promoting children and adolescents' mental health. RESULTS AND DISCUSSION: The findings reveal that universal school-based transdiagnostic promotion/prevention programs have a small to medium overall effect size. These interventions demonstrate a broad coverage of different aspects of children and adolescents' mental health. However, the relative effectiveness of teacher-led versus psychologist-led interventions remains unclear. Interventions focused on preventing mental disorders exhibit a higher effect size, albeit on a narrower range of mental health aspects for children and adolescents. SIGNIFICANCE: This study enhances our understanding of universal school-based transdiagnostic interventions and their impact on children and adolescents' mental health. Further research is needed to elucidate the comparative efficacy of teacher-led and psychologist-led interventions and to explore the specific dimensions of mental health targeted by these interventions.

Postoperative morbidity and mortality of patients with COVID-19 undergoing cardiovascular surgery: an inverse propensity-weighted study : Postoperative outcomes of patients undergoing cardiovascular surgery during the COVID-19 pandemic.

BACKGROUND: To evaluate the postoperative morbidity and mortality of patients undergoing cardiovascular surgery during the 2022 nationwide Omicron variant infection wave in China. METHODS: This retrospective cohort study included 403 patients who underwent cardiovascular surgery for the first time during the 2022 wave of the pandemic within 1 month. Among them, 328 patients were preoperatively diagnosed with COVID-19 Omicron variant infection during the pandemic, and 75 patients were negative. The association between Omicron variant exposure and postoperative prognosis was explored by comparing patients with and without COVID-19 exposure. The primary outcome was in-hospital death after cardiovascular surgery. The secondary outcomes were major postoperative morbidity, including myocardial infarction (MI), acute kidney injury (AKI), postoperative mechanical ventilation hours, ICU stay hours, and postoperative length of stay. The data were analyzed using inverse probability of treatment weighting (IPTW) to minimize bias. RESULTS: We identified 403 patients who underwent cardiovascular surgery, 328 (81.39%) had Omicron variant infections. In total, 10 patients died in the hospital. Omicron variant infection was associated with a much greater risk of death during cardiovascular surgery after adjustment for IPTW (2.8% vs. 1.3%, adjusted OR 2.185, 95%CI = 1.193 to 10.251, P = 0.041). For major postoperative morbidity, there were no significant differences in terms of myocardial infarction between the two groups (adjusted OR = 0.861, 95%CI = 0.444 to 1.657, P = 0.653), acute kidney injury (adjusted OR = 1.157, 95%CI = 0.287 to 5.155, P = 0.820), postoperative mechanical ventilation hours (B -0.375, 95%CI=-8.438 to 7.808, P = 0.939), ICU stay hours (B 2.452, 95%CI=-13.269 to 8.419, P = 0.660) or postoperative stay (B -1.118, 95%CI=-2.237 to 1.154, P = 0.259) between the two groups. CONCLUSION: Perioperative COVID-19 infection was associated with an increased risk of in-hospital death among patients who underwent cardiovascular surgery during the Omicron variant wave of the pandemic.

JADE1 is dispensable for the brain development in mice.

In mammalian brain development, WNT signaling balances proliferation and differentiation of neural progenitor cells, and is essential for the maintenance of regular brain development. JADE1 is a candidate transcription co-factor essential for DNA replication, cell division, and cell cycle regulation. In 293T cells, JADE1 is stabilized by von Hippel-Lindau protein pVHL, promotes the ß-catenin ubiquitination and thus blunts canonical WNT signaling. Furthermore, JADE1 inhibits ß-catenin-induced ectopic axis formation in Xenopus embryos. However, JADE1's role in mammalian brain development remains unknown. Here, we generated a new Jade1 knockout mouse line using CRISPR-Cas9 technology. We found that JADE1 null resulted in decreased survival rate, reduced body weight and brain weight in mice. However, histological analysis revealed a normal brain development. Furthermore, Jade1 null neural progenitor cells proliferated normally in vivo and in vitro. RNA-seq analysis further showed that JADE1 loss did not affect the cerebral cortex gene expression. Our findings indicate that JADE1 is dispensable for developing the cerebral cortex in mice.

The MRI radiomics signature can predict the pathologic response to neoadjuvant chemotherapy in locally advanced esophageal squamous cell carcinoma.

OBJECTIVES: To investigate the MRI radiomics signatures in predicting pathologic response among patients with locally advanced esophageal squamous cell carcinoma (ESCC), who received neoadjuvant chemotherapy (NACT). METHODS: Patients who underwent NACT from March 2015 to October 2019 were prospectively included. Each patient underwent esophageal MR scanning within one week before NACT and within 2-3 weeks after completion of NACT, prior to surgery. Radiomics features extracted from T2-TSE-BLADE were randomly split into the training and validation sets at a ratio of 7:3. According to the progressive tumor regression grade (TRG), patients were stratified into two groups: good responders (GR, TRG 0 + 1) and poor responders (non-GR, TRG 2 + 3). We constructed the Pre/Post-NACT model (Pre/Post-model) and the Delta-NACT model (Delta-model). Kruskal-Wallis was used to select features, logistic regression was used to develop the final model. RESULTS: A total of 108 ESCC patients were included, and 3/2/4 out of 107 radiomics features were selected for constructing the Pre/Post/Delta-model, respectively. The selected radiomics features were statistically different between GR and non-GR groups. The highest area under the curve (AUC) was for the Delta-model, which reached 0.851 in the training set and 0.831 in the validation set. Among the three models, Pre-model showed the poorest performance in the training and validation sets (AUC, 0.466 and 0.596), and the Post-model showed better performance than the Pre-model in the training and validation sets (AUC, 0.753 and 0.781). CONCLUSIONS: MRI-based radiomics models can predict the pathological response after NACT in ESCC patients, with the Delta-model exhibiting optimal predictive efficacy. CLINICAL RELEVANCE STATEMENT: MRI radiomics features could be used as a useful tool for predicting the efficacy of neoadjuvant chemotherapy in esophageal carcinoma patients, especially in selecting responders among those patients who may be candidates to benefit from neoadjuvant chemotherapy. KEY POINTS: • The MRI radiomics features based on T2WI-TSE-BLADE could potentially predict the pathologic response to NACT among ESCC patients. • The Delta-model exhibited the best predictive ability for pathologic response, followed by the Post-model, which similarly had better predictive ability, while the Pre-model performed less well in predicting TRG.

Disinfection efficiency of chlorine dioxide and peracetic acid against MNV-1 and HAV in simulated soil-rich wash water.

Wash water from fresh vegetables and root vegetables is an important vehicle for foodborne virus transmission. However, there is lack of assessing rapid viral inactivation strategies in wash water characterized by a high soil content at the post-harvest stage. Considering the significance of food safety during the washing stage for fresh and root vegetable produce prior to marketing, we assessed the inactivation efficacy by using chlorine dioxide (ClO2) and peracetic acid (PAA) against a surrogate of human norovirus (murine norovirus 1, MNV-1) and hepatitis A virus (HAV), in wash water containing black soil and clay loam. The results indicated that MNV-1 and HAV were reduced to the process limit of detection (PLOD), with reductions ranging from 4.89 to 6.35 log10 PFU, and 4.63 to 4.96 log10 PFU when treated with ClO2 at 2.5 ppm for 10 mins. Comparatively, when treated with 500 ppm of PAA for 10 mins, MNV-1 and HAV were maximum reduced to 1.75 ± 0.23 log10 PFU (4.50 log10 PFU reduction) and 2.13 ± 0.12 log10 PFU (2.72 log10 PFU reduction). This demonstrated the efficacy of ClO2 in eliminating foodborne viruses in soil-rich wash water. When we validated the recovery of the virus from two types of wash water, the pH (9.24 ± 0.33 and 5.95 ± 0.05) had no impact on the recovery of MNV-1, while the recovery of HAV was less than 1 %. By adjusting the pH to a neutral level, recovery of HAV and its RNA levels was increased to 15.94 and 3.89 %. Thus, this study emphasized the critical role of pH in the recovery of HAV from the complex soil-rich aqueous environment, and the efficacy of ClO2 serving as a pivotal reference for the development of control strategies against foodborne viruses in the supply chain of fresh and root vegetables.

Melatonin protects against myocardial ischemia-reperfusion injury by inhibiting excessive mitophagy through the Apelin/SIRT3 signaling axis.

Excessive or uncontrolled mitophagy may result in a drastic shortage of healthy mitochondrial for ATP supply after reperfusion, leading to irreversible myocardial damage. Melatonin, a hormone produced by the pineal gland, has been proven to ameliorate myocardial ischemia-reperfusion (I/R) injury via regulating mitophagy. However, its underlying mechanism has not been fully elucidated. The present study focused on the role of mitophagy in the cardioprotective effects of melatonin by using the myocardial I/R rat model. The rats were pretreated with or without the apelin inhibitor ML221, the sirtuin 3 (SIRT3) inhibitor 3-TYP and then subjected to I/R injury, with melatonin administrated 10 min before reperfusion. The effects of melatonin on myocardial infarct size, biomarkers of myocardial injury, oxidative stress, and mitochondrial function were detected, and the expression of apelin, SIRT3, and mitophagy-related proteins were also measured. Excessive mitophagy was activated after I/R injury and was correlated with oxidative stress and mitochondrial dysfunction. Melatonin pretreatment ameliorated myocardial injury by decreasing oxidative stress, restoring mitochondrial function, and inhibiting excessive mitophagy. However, ML221 or 3-TYP disrupted these beneficial effects of melatonin on I/R injury. Taken together, these results suggest that melatonin pretreatment ameliorates myocardial I/R injury through regulating the apelin/SIRT3 pathway to inhibit excessive mitophagy.

Comparison of the virucidal efficacy of essential oils (cinnamon, clove, and thyme) against hepatitis A virus in suspension and on food-contact surfaces.

Essential oils (EOs) have been used for centuries as flavor enhancers in foods, and owing to their antimicrobial properties, they have potential as natural food preservatives. However, their effect on food-borne viruses is unknown. Therefore, in this study, the virucidal effects of three EOs (cinnamon, clove, and thyme) on the infectivity of the hepatitis A virus (HAV) were investigated. Different concentrations of each EO (0.05, 0.1, 0.5, and 1%) were mixed with viral suspensions in accordance with ASTM E1052-11:2011 and incubated for 1 h at room temperature. The EOs exhibited a concentration-dependent effect in the suspension tests, and HAV titers decreased by approximately 1.60 log PFU/mL when treated with EOs at the highest concentration of 1%. The antiviral effect of EOs treated at 1% for 1 h was also evidenced in surface disinfection tests according to the OECD:2013, as approximately 2 log PFU/mL reduction on hard food-contact surfaces (stainless steel and polypropylene) and approximately 2 and 1.4 log PFU/mL reduction on low-density polyethylene and kraft (soft food-contact surfaces), respectively. Moreover, RT-qPCR results revealed that HAV genome copies were negligibly reduced until treated with a high concentration (1%) in suspension and carrier tests. Overall, our findings highlighted the potential of cinnamon, clove, and thyme EOs as natural disinfectants capable of limiting HAV (cross-) contamination conveyed by food-contact surfaces. These findings advance our knowledge of EOs as antimicrobials and their potential in the food sector as alternative natural components to reduce viral contamination and improve food safety.

Janus 2H-MXTe (M = Zr, Hf; X = S, Se) monolayers with outstanding thermoelectric properties and low lattice thermal conductivities.

Two-dimensional (2D) materials have been one of the most popular objects in the research field of thermoelectric (TE) materials and have attracted substantial attention in recent years. Inspired by the synthesized 2H-MoSSe and numerous theoretical studies, we systematically investigated the electronic, thermal, and TE properties of Janus 2H-MXTe (M = Zr and Hf; X = S and Se) monolayers by using first-principles calculations. The phonon dispersion curves and AIMD simulations confirm the thermodynamic stabilities. Moreover, Janus 2H-MXTe were evaluated as indirect band-gap semiconductors with band gaps ranging from 0.56 to 0.90 eV using the HSE06 + SOC method. To evaluate the TE performance, firstly, we calculated the temperature-dependent carrier relaxation time with acoustic phonon scattering τac, impurity scattering τimp, and polarized scattering τpol. Secondly, the calculation of lattice thermal conductivity (κl) shows that these monolayers possess relatively poor κl with values of 3.4-5.4 W mK-1 at 300 K, which is caused by the low phonon lifetime and group velocity. After computing the electronic transport properties, we found that the n-type doped Janus 2H-MXTe monolayers exhibit a high Seebeck coefficient exceeding 200 µV K-1 at 300 K, resulting in a high TE power factor. Eventually, combining the electrical and thermal conductivities, the optimal dimensionless figure of merit (zT) at 300 K (900 K) can be obtained, which is 0.94 (3.63), 0.51 (2.57), 0.64 (2.72), and 0.50 (1.98) for n-type doping of ZrSeTe, HfSeTe, ZeSTe, and HfSTe monolayers. Particularly, the ZrSeTe monolayer shows the best TE performance with the maximal zT value. These results indicate the excellent application potential of Janus 2H-MXTe (M = Zr and Hf; X = S and Se) monolayers in TE materials.

Inhibition of herpes simplex virus by wedelolactone via targeting viral envelope and cellular TBK1/IRF3 and SOCS1/STAT3 pathways.

OBJECTIVES: Development of novel antiherpes simplex virus (HSV) agents with active mechanisms different from nucleoside analogues is of high importance. Herein, we investigated the anti-HSV activities and mechanisms of wedelolactone (WDL) both in vitro and in vivo. METHODS: Cytopathic effect (CPE) inhibition assay, plaque assay, and western blot assay were used to evaluate the anti-HSV effects of WDL in vitro. The immunofluorescence assay, RT-PCR assay, plaque reduction assay, sandwich ELISA assay, syncytium formation assay, tanscriptome analysis and western blot assay were used to explore the anti-HSV mechanisms of WDL. The murine encephalitis and vaginal models of HSV infection were performed to evaluate the anti-HSV effects of WDL in vivo. RESULTS: WDL possessed inhibitory effects against both HSV-1 and HSV-2 in different cells with low toxicity, superior to the effects of acyclovir. WDL can directly inactivate the HSV particle via destruction of viral envelope and block HSV replication process after virus adsorption, different from the mechanisms of acyclovir. WDL may influence the host genes and signaling pathways related to HSV infection and immune responses. WDL can mainly interfere with the TBK1/IRF3 and SOCS1/STAT3 pathways to reduce HSV infection and inflammatory responses. Importantly, WDL treatment markedly improved mice survival, attenuated inflammatory symptoms, and reduced the virus titres in both HSV-1 and HSV-2 infected mice. CONCLUSIONS: Thus, the natural compound WDL has the potential to be developed into a novel anti-HSV agent targeting both viral envelope and cellular TBK1/IRF3 and SOCS1/STAT3 pathways.

Two-dimensional Janus pentagonal MSeTe (M = Ni, Pd, Pt): promising water-splitting photocatalysts and optoelectronic materials.

Inspired by the interesting and novel properties exhibited by Janus transition metal dichalcogenides (TMDs) and two-dimensional pentagonal structures, we here investigated the structural stability, mechanical, electronic, photocatalytic, and optical properties for a class of two-dimensional (2D) pentagonal Janus TMDs, namely penta-MSeTe (M = Ni, Pd, Pt) monolayers, by using density functional theory (DFT) combined with Hubbard's correction (U). Our results showed that these monolayers exhibit good structural stability, appropriate band structures for photocatalysts, high visible light absorption, and good photocatalytic applicability. The calculated electronic properties reveal that the penta-MSeTe are semiconductors with a bandgap range of 2.06-2.39 eV, and their band edge positions meet the requirements for water-splitting photocatalysts in various environments (pH = 0-13). We used stress engineering to seek higher solar-to-hydrogen (STH) efficiency in acidic (pH = 0), neutral (pH = 7) and alkaline (pH = 13) environments for penta-MSeTe from 0% to +8% biaxial and uniaxial strains. Our results showed that penta-PdSeTe stretched 8% along the y direction and demonstrates an STH efficiency of up to 29.71% when pH = 0, which breaks the theoretical limit of the conventional photocatalytic model. We also calculated the optical properties and found that they exhibit high absorption (13.11%) in the visible light range and possess a diverse range of hyperbolic regions. Hence, it is anticipated that penta-MSeTe materials hold great promise for applications in photocatalytic water splitting and optoelectronic devices.

The role and advantage of traditional Chinese medicine in the prevention and treatment of COVID-19.

The global coronavirus disease 2019 (COVID-19) pandemic has had a massive impact on global social and economic development and human health. By combining traditional Chinese medicine (TCM) with modern medicine, the Chinese government has protected public health by supporting all phases of COVID-19 prevention and treatment, including community prevention, clinical treatment, control of disease progression, and promotion of recovery. Modern medicine focuses on viruses, while TCM focuses on differential diagnosis of patterns associated with viral infection of the body and recommends the use of TCM decoctions for differential treatment. This differential diagnosis and treatment approach, with its profoundly empirical nature and holistic view, endows TCM with an accessibility advantage and high application value for dealing with COVID-19. Here, we summarize the advantage of and evidence for TCM use in COVID-19 prevention and treatment to draw attention to the scientific value and accessibility advantage of TCM and to promote the use of TCM in response to public health emergencies. Please cite this article as: Huang M, Liu YY, Xiong K, Yang FW, Jin XY, Wang ZQ, Zhang JH, Zhang BL. The role and advantage of traditional Chinese medicine in the prevention and treatment of COVID-19. J Integr Med. 2023; 21(5): 407-412.

Poly(ADP-Ribose) Polymerase-1 Lacking Enzymatic Activity Is Not Compatible with Mouse Development.

Poly(ADP-ribose) polymerase-1 (PARP1) binds DNA lesions to catalyse poly(ADP-ribosyl)ation (PARylation) using NAD+ as a substrate. PARP1 plays multiple roles in cellular activities, including DNA repair, transcription, cell death, and chromatin remodelling. However, whether these functions are governed by the enzymatic activity or scaffolding function of PARP1 remains elusive. In this study, we inactivated in mice the enzymatic activity of PARP1 by truncating its C-terminus that is essential for ART catalysis (PARP1ΔC/ΔC, designated as PARP1-ΔC). The mutation caused embryonic lethality between embryonic day E8.5 and E13.5, in stark contrast to PARP1 complete knockout (PARP1-/-) mice, which are viable. Embryonic stem (ES) cell lines can be derived from PARP1ΔC/ΔC blastocysts, and these mutant ES cells can differentiate into all three germ layers, yet, with a high degree of cystic structures, indicating defects in epithelial cells. Intriguingly, PARP1-ΔC protein is expressed at very low levels compared to its full-length counterpart, suggesting a selective advantage for cell survival. Noticeably, PARP2 is particularly elevated and permanently present at the chromatin in PARP1-ΔC cells, indicating an engagement of PARP2 by non-enzymatic PARP1 protein at the chromatin. Surprisingly, the introduction of PARP1-ΔC mutation in adult mice did not impair their viability; yet, these mutant mice are hypersensitive to alkylating agents, similar to PARP1-/- mutant mice. Our study demonstrates that the catalytically inactive mutant of PARP1 causes the developmental block, plausibly involving PARP2 trapping.

The neurological and non-neurological roles of the primary microcephaly-associated protein ASPM.

Primary microcephaly (MCPH), is a neurological disorder characterized by small brain size that results in numerous developmental problems, including intellectual disability, motor and speech delays, and seizures. Hitherto, over 30 MCPH causing genes (MCPHs) have been identified. Among these MCPHs, MCPH5, which encodes abnormal spindle-like microcephaly-associated protein (ASPM), is the most frequently mutated gene. ASPM regulates mitotic events, cell proliferation, replication stress response, DNA repair, and tumorigenesis. Moreover, using a data mining approach, we have confirmed that high levels of expression of ASPM correlate with poor prognosis in several types of tumors. Here, we summarize the neurological and non-neurological functions of ASPM and provide insight into its implications for the diagnosis and treatment of MCPH and cancer.

Fabrication of Hematite Photoanode Consisting of (110)-Oriented Single Crystals.

In this work, α-Fe2 O3 photoanode consisted of (110)-oriented α-Fe2 O3 single crystals were synthesized by a facile hydrothermal method. By using particular additive (C4 MimBF4 ) and regulation of hydrothermal reaction time, the Fe-25 consisted of a single-layer of highly crystalline (110)-oriented crystals with fewer grain boundaries, which was vertically grown on the substrate. As a result, the charge separation efficiency and photoelectrochemical (PEC) performance of Fe-25A (Fe-25 after dehydration treatment) have been greatly improved. Fe-25A yields a photocurrent of 1.34 mA cm-2 (1.23 V vs RHE) and an incident photon-to-current conversion efficiency (IPCE) of 31.95 % (380 nm). With the assistance of cobalt-phosphate water oxidation catalyst (Co-Pi), the PEC performance could be further improved by enhancing the holes transfer at electrode/electrolyte interface and inhibiting surface recombination. Fe-25A/Co-Pi yields a photocurrent of 2.67 mA cm-2 (1.23 V vs RHE) and IPCE value of 50.8 % (380 nm), which is 3.67 times and 2.39 times as that of Fe-2A/Co-Pi. Our work provides a simple method to fabricate highly efficient Fe2 O3 photoanodes consist of characteristic (110)-oriented single crystals with high crystallinity and high quality interface contact to enhance charge separation efficiencies.

MR imaging characteristics of different pathologic subtypes of esophageal carcinoma.

OBJECTIVES: To describe the specific MRI characteristics of different pathologic subtypes of esophageal carcinoma (EC) METHODS: This prospective study included EC patients who underwent esophageal MRI and esophagectomy between April 2015 and October 2021. Pathomorphological characteristics of EC such as localized type (LT), ulcerative type (UT), protruding type (PT), and infiltrative type (IT) were assessed by two radiologists relying on the imaging characteristics of tumor, especially the specific imaging findings on the continuity of the mucosa overlying the tumor, the opposing mucosa, mucosa linear thickening, and transmural growth pattern. Intraclass correlation coefficients (ICC) were calculated for the consistency between two readers. The associations of imaging characteristics with different pathologic subtypes were assessed using multilogistic regression model (MLR). RESULTS: A total of 201 patients were identified on histopathology with a high inter-reader agreement (ICC = 0.991). LT showed intact mucosa overlying the tumor. IT showed transmural growth pattern extending from the mucosa to the adventitia and a "sandwich" appearance. The remaining normal mucosa on the opposing side was linear and nodular in UT. PT showed correlation with T1 staging and grade 1; IT showed correlation with T3 staging and grades 2-3. Four MLR models showed high predictive performance on the test set with AUCs of 0.94 (LT), 0.87 (PT), 0.96 (IT), and 0.97 (UT), respectively, and the predictors that contributed most to the models matched the four specific characteristics. CONCLUSIONS: Different pathologic subtypes of EC displayed specific MR imaging characteristics, which could help predict T staging and the degree of pathological differentiation. CLINICAL RELEVANCE STATEMENT: Different pathologic subtypes of esophageal carcinoma displayed specific MR imaging characteristics, which correspond to differences in the degree of differentiation, T staging, and sensitivity to radiotherapy, and could also be one of the predictive factors of cause-specific survival and local progression-free rates. KEY POINTS: Different types of EC had different characteristics on MR images. A total of 91/95 (96%) LTEC showed intact mucosa over the tumor, while masses or nodules are specific to PTEC; 21/27 (78%) ITEC showed a "sandwich" sign; and 33/35 (60%) UTEC showed linear and nodular opposing mucosa. In the association of tumor type with degree of differentiation and T staging, PTEC was predominantly associated with T1 and grade 1, and ITEC was associated with T3 and grades 2-3, while LTEC and UECT were likewise primarily linked with T2-3 and grades 2-3.

Simultaneous Nbs1 and p53 inactivation in neural progenitors triggers high-grade gliomas.

AIMS: Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder caused by hypomorphic mutations of NBS1. NBS1 is a member of the MRE11-RAD50-NBS1 (MRN) complex that binds to DNA double-strand breaks and activates the DNA damage response (DDR). Nbs1 inactivation in neural progenitor cells leads to microcephaly and premature death. Interestingly, p53 homozygous deletion rescues the NBS1-deficient phenotype allowing long-term survival. The objective of this work was to determine whether simultaneous inactivation of Nbs1 and p53 in neural progenitors triggered brain tumorigenesis and if so in which category this tumour could be classified. METHODS: We generated a mouse model with simultaneous genetic inactivation of Nbs1 and p53 in embryonic neural stem cells and analysed the arising tumours with in-depth molecular analyses including immunohistochemistry, array comparative genomic hybridisation (aCGH), whole exome-sequencing and RNA-sequencing. RESULTS: NBS1/P53-deficient mice develop high-grade gliomas (HGG) arising in the olfactory bulbs and in the cortex along the rostral migratory stream. In-depth molecular analyses using immunohistochemistry, aCGH, whole exome-sequencing and RNA-sequencing revealed striking similarities to paediatric human HGG with shared features with radiation-induced gliomas (RIGs). CONCLUSIONS: Our findings show that concomitant inactivation of Nbs1 and p53 in mice promotes HGG with RIG features. This model could be useful for preclinical studies to improve the prognosis of these deadly tumours, but it also highlights the singularity of NBS1 among the other DNA damage response proteins in the aetiology of brain tumours.