DKK2 promotes the progression of oral squamous cell carcinoma through the PI3K/AKT signaling pathway.

OBJECTIVE: This study aimed to investigate the impact of Dickkopf 2 (DKK2) on the progression of oral squamous cell carcinoma (OSCC) and explore its role in the PI3K/AKT signaling transduction pathway. MATERIALS AND METHODS: The study initially examined the expression of the DKK2 gene in OSCC tissues and normal tissues. Simultaneously, the expression of DKK2 in HOK cells and OSCC cells was verified, and changes in DKK2 expression under hypoxic conditions were detected. DKK2 overexpression and knockdown were performed in SCC-15 and CAL-27 cells. Subsequently, the effects of DKK2 on the proliferation, migration and invasion of OSCC were detected. Western blotting was employed to detect the expression of key proteins in the DKK2/PI3K/AKT signaling axis before and after transfection, and further explore the relevant molecular mechanisms. RESULTS: Compared to normal tissues, DKK2 expression was elevated in OSCC tissues. The expression of DKK2 in the SCC-15 and CAL-27 cell lines was higher than that in HOK cells, and hypoxic conditions could promote DKK2 expression. DKK2 overexpression promoted cell proliferation, migration, and invasion, while DKK2 knockdown inhibited these processes. DKK2 overexpression activated the PI3K/AKT pathway, while DKK2 knockdown suppressed this pathway. CONCLUSION: This study suggests that hypoxic conditions enhance the expression of DKK2 in OSCC. DKK2 regulates the proliferation, migration, and invasion of OSCC through the PI3K/AKT signaling pathway.

Ab initio determination of melting and sound velocity of neon up to the deep interior of the Earth.

The thermophysical properties and elemental abundances of the noble gases in terrestrial materials can provide unique insights into the Earth's evolution and mantle dynamics. Here, we perform extensive ab initio molecular dynamics simulations to determine the melting temperature and sound velocity of neon up to 370 GPa and 7500 K to constrain its physical state and storage capacity, together with to reveal its implications for the deep interior of the Earth. It is found that solid neon can exist stably under the lower mantle and inner core conditions, and the abnormal melting of neon is not observed under the entire temperature (T) and pressure (P) region inside the Earth owing to its peculiar electronic structure, which is substantially distinct from other heavier noble gases. An inspection of the reduction for sound velocity along the Earth's geotherm evidences that neon can be used as a light element to account for the low-velocity anomaly and density deficit in the deep Earth. A comparison of the pair distribution functions and mean square displacements of MgSiO3-Ne and Fe-Ne alloys further reveals that MgSiO3 has a larger neon storage capacity than the liquid iron under the deep Earth condition, indicating that the lower mantle may be a natural deep noble gas storage reservoir. Our results provide valuable information for studying the fundamental behavior and phase transition of neon in a higher T-P regime, and further enhance our understanding for the interior structure and evolution processes inside the Earth.

Repopulated microglia after pharmacological depletion decrease dendritic spine density in adult mouse brain.

Microglia are innate immune cells in the brain and show exceptional heterogeneity. They are key players in brain physiological development regulating synaptic plasticity and shaping neuronal networks. In pathological disease states, microglia-induced synaptic pruning mediates synaptic loss and targeting microglia was proposed as a promising therapeutic strategy. However, the effect of microglia depletion and subsequent repopulation on dendritic spine density and neuronal function in the adult brain is largely unknown. In this study, we investigated whether pharmacological microglia depletion affects dendritic spine density after long-term permanent microglia depletion and after short-term microglia depletion with subsequent repopulation. Long-term microglia depletion using colony-stimulating-factor-1 receptor (CSF1-R) inhibitor PLX5622 resulted in increased overall spine density, especially of mushroom spines, and increased excitatory postsynaptic current amplitudes. Short-term PLX5622 treatment with subsequent repopulation of microglia had an opposite effect resulting in activated microglia with increased synaptic phagocytosis and consequently decreased spine density and reduced excitatory neurotransmission, while Barnes maze and elevated plus maze testing was unaffected. Moreover, RNA sequencing data of isolated repopulated microglia showed an activated and proinflammatory phenotype. Long-term microglia depletion might be a promising therapeutic strategy in neurological diseases with pathological microglial activation, synaptic pruning, and synapse loss. However, repopulation after depletion induces activated microglia and results in a decrease of dendritic spines possibly limiting the therapeutic application of microglia depletion. Instead, persistent modulation of pathological microglia activity might be beneficial in controlling synaptic damage.

SIRT3 and RORα are two prospective targets against mitophagy during simulated ischemia/reperfusion injury in H9c2 cells.

Autophagy during myocardial ischemia/reperfusion (MI/R) exacerbates cardiomyocyte injury. Melatonin (Mel) alleviates myocardial damage by regulating mitochondrial function and mitophagy, but the role of mitophagy in melatonin-induced cardioprotection remains unclear. This study aimed to explore the roles of sirtuin3 (SIRT3) and retinoid-related orphan nuclear receptor-α (RORα) in mitophagy during simulated ischemia reperfusion (SIR) in H9c2 cells. Our data showed that mitophagy was excessively activated after SIR injury, which was consistent with reduced cell survival, enhanced oxidative responses and mitochondrial dysfunction in H9c2 myocytes. Melatonin greatly enhanced cell viability, reduced oxidative stress and improved mitochondrial function. The effects of melatonin protection were involved in excessive mitophagy inhibition, as demonstrated by the reduced levels of mitophagy-linked proteins, including Parkin, Beclin1, NIX and BNIP3, and the LC3 II/LC3 I ratio and elevations in p62. Additionally, the decreases in SIRT3 and RORα in H9c2 myocytes after SIR were reversed by melatonin, and the above effects of melatonin were eliminated by small interfering RNA (siRNA)-mediated knockdown of SIRT3 and RORα. In brief, SIRT3 and RORα are two prospective targets in the cardioprotection of melatonin against mitophagy during SIR in H9c2 myocytes.

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.

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.

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.

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.

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.

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.

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.

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.

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.