A weapon to fight against pervasive Omicron: systematic actions transiting to pre-COVID normal

The Coronavirus Disease-2019 (COVID-19) pandemic is not just a health crisis but also a social crisis. Confronted with the resurgence of variants with massive infections, the triggered activities from personal needs may promote the spread, which should be considered in risk management. Meanwhile, it is important to ensure that the policy responses on citizen life to a lower level. In the face of Omicron mutations, we need to sum up the control experience accumulated, adapting strategies in the dynamic coevolution process while balancing life resumption and pandemic control, to meet challenges of future crises. We collected 46 cases occurring between 2021 and 2022, mainly from China, but also including five relevant cases from other countries around the world. Based on case studies, we combine micro-view individual needs/behaviors with macro-view management measures linking Maslow’s hierarchy of needs with the transmission chain of Omicron clusters. The proposed loophole chain could help identify both individual and management loopholes in the spread of the virus. The systematic actions that were taken have effectively combated these ubiquitous vulnerabilities at lower costs and lesser time. In the dynamic coevolution process, the Chinese government has made effective and more socially acceptable prevention policies while meeting the divergent needs of the entire society at the minimum costs. Systematic actions do help maintain the balance between individuals’ satisfaction and pandemic containment. This implies that risk management policies should reasonably consider individual needs and improve the cooperation of various stakeholders with targeted flexible measures, securing both public health and life resumption

The histone H3K9M mutation synergizes with H3K14 ubiquitylation to selectively sequester histone H3K9 methyltransferase Clr4 at heterochromatin

International audienceOncogenic histone lysine-to-methionine mutations block the methylation of their corresponding lysine residues on wild-type histones. One attractive model is that these mutations sequester histone methyltransferases, but genome-wide studies show that mutant histones and histone methyltransferases often do not colocalize. Using chromatin immunoprecipitation sequencing (ChIP-seq), here, we show that, in fission yeast, even though H3K9M-containing nucleosomes are broadly distributed across the genome, the histone H3K9 methyltransferase Clr4 is mainly sequestered at pericentric repeats. This selective sequestration of Clr4 depends not only on H3K9M but also on H3K14 ubiquitylation (H3K14ub), a modification deposited by a Clr4-associated E3 ubiquitin ligase complex. In vitro, H3K14ub synergizes with H3K9M to interact with Clr4 and potentiates the inhibitory effects of H3K9M on Clr4 enzymatic activity. Moreover, binding kinetics show that H3K14ub overcomes the Clr4 aversion to H3K9M and reduces its dissociation. The selective sequestration model reconciles previous discrepancies and demonstrates the importance of protein-interaction kinetics in regulating biological processes

PGC-1α Participates in the Protective Effect of Chronic Intermittent Hypobaric Hypoxia on Cardiomyocytes

Background/Aims: Myocardial ischemia/reperfusion (I/R) or hypoxia/reoxygenation (H/R) injury is always characterized by Ca2+ overload, energy metabolism disorder and necrocytosis of cardiomyocytes. We showed previously that chronic intermittent hypobaric hypoxia (CIHH) improves cardiac function during I/R through improving cardiac glucose metabolism. However, the underlying cellular and molecular mechanisms of CIHH treatment improving energy metabolism in cardiomyocytes are still unclear. In this study, we determined whether and how CIHH protects cardiomyocytes from Ca2+ overload and necrocytosis through energy regulating pathway. Methods: Adult male Sprague-Dawley rats were randomly divided into two groups: control (CON) and CIHH group. CIHH rats received a hypobaric hypoxia simulating 5,000-m altitude for 28 days, 6 hours each day, in hypobaric chamber. Rat ventricular myocytes were obtained by enzymatic dissociation. The intracellular calcium concentration ([Ca2+]i) and cTnI protein expression were used to evaluate the degree of cardiomyocytes injury during and after H/R. The mRNA and protein expressions involved in cardiac energy metabolism were determined using quantitative PCR and Western blot techniques. PGC-1α siRNA adenovirus transfection was used to knock down PGC-1α gene expression of cardiomyocytes to determine the effect of PGC-1α in the energy regulating pathway. Results: H/R increased [Ca2+]i and cTnI protein expression in cardiomyocytes. CIHH treatment decreased [Ca2+]i (p< 0.01) and cTnI protein expression (p< 0.01) in cardiomyocytes after H/R. Both mRNA and protein expression of PGC-1α increased after CIHH treatment, which was reversed by PGC-1α siRNA adenovirus transfection. Furthermore, CIHH treatment increased the expression of HIF-1α, AMPK and p-AMPK in cardiomyocytes, and pretreatment with AMPK inhibitor dorsomorphin abolished the enhancement of PGC-1α protein expression in cardiomyocytes by CIHH (p< 0.01). In addition, PGC-1α knock down also abolished the increased protein level of GLUT4 (p< 0.01) and decreased the protein level of CPT-1b (p< 0.05) in cardiomyocytes by CIHH treatment. Conclusion: CIHH treatment could reduce the calcium overload and H/R injury in cardiomyocytes by up-regulating the expression of PGC-1α and regulating the energy metabolism of glucose and lipid. The HIF-1α-AMPK signaling pathway might be involved in the process

OpenLane-V2: A Topology Reasoning Benchmark for Unified 3D HD Mapping

Accurately depicting the complex traffic scene is a vital component for autonomous vehicles to execute correct judgments. However, existing benchmarks tend to oversimplify the scene by solely focusing on lane perception tasks. Observing that human drivers rely on both lanes and traffic signals to operate their vehicles safely, we present OpenLane-V2, the first dataset on topology reasoning for traffic scene structure. The objective of the presented dataset is to advance research in understanding the structure of road scenes by examining the relationship between perceived entities, such as traffic elements and lanes. Leveraging existing datasets, OpenLane-V2 consists of 2,000 annotated road scenes that describe traffic elements and their correlation to the lanes. It comprises three primary sub-tasks, including the 3D lane detection inherited from OpenLane, accompanied by corresponding metrics to evaluate the model's performance. We evaluate various state-of-the-art methods, and present their quantitative and qualitative results on OpenLane-V2 to indicate future avenues for investigating topology reasoning in traffic scenes.Comment: Accepted by NeurIPS 2023 Track on Datasets and Benchmarks | OpenLane-V2 Dataset: https://github.com/OpenDriveLab/OpenLane-V

Schisandrin C enhances type I IFN response activation to reduce tumor growth and sensitize chemotherapy through antitumor immunity

With the advancing comprehension of immunology, an increasing number of immunotherapies are being explored and implemented in the field of cancer treatment. The cGAS-STING pathway, a crucial element of the innate immune response, has been identified as pivotal in cancer immunotherapy. We evaluated the antitumor effects of Schisandra chinensis lignan component Schisandrin C (SC) in 4T1 and MC38 tumor-bearing mice, and studied the enhancing effects of SC on the cGAS-STING pathway and antitumor immunity through RNA sequencing, qRT-PCR, and flow cytometry. Our findings revealed that SC significantly inhibited tumor growth in models of both breast and colon cancer. This suppression of tumor growth was attributed to the activation of type I IFN response and the augmented presence of T cells and NK cells within the tumor. Additionally, SC markedly promoted the cGAS-STING pathway activation induced by cisplatin. In comparison to cisplatin monotherapy, the combined treatment of SC and cisplatin exhibited a greater inhibitory effect on tumor growth. The amplified chemotherapeutic efficacy was associated with an enhanced type I IFN response and strengthened antitumor immunity. SC was shown to reduce tumor growth and increase chemotherapy sensitivity by enhancing the type I IFN response activation and boosting antitumor immunity, which enriched the research into the antitumor immunity of S. chinensis and laid a theoretical basis for its application in combating breast and colon cancer

Prospective memory in non-psychotic first-degree relatives of patients with schizophrenia

Although a number of studies have found prospective memory (PM) impairment in patients with schizophrenia, very little is known about the PM performance in non-psychotic relatives of these patients. The current study aimed to explore the PM performance in non-psychotic first-degree relatives of these patients. Two groups of participants (26 non-psychotic first-degree relatives of schizophrenia patients and 26 healthy comparison participants) were administered three PM tasks (time-, event-, and activity-based) and a set of neurocognitive tests. Results showed that the relatives performed significantly worse than the comparisons on most indices of the PM tasks, with a similar pattern of impairment found in other neurocognitive measures. Together with findings from previous studies, results of the current study suggest that PM may be a potential endophenotype for schizophrenia. (C) 2009 Elsevier Ireland Ltd. All rights reserved.</p

Rabies virus pseudotyped with CVS-N2C glycoprotein as a powerful tool for retrograde neuronal network tracing

Abstract Background: Efficient viral vectors for mapping and manipulating long projection neuronal circuits are crucial in brain structural and functional studies. The glycoprotein gene-deleted SAD strain rabies virus pseudotyped with the N2C glycoprotein (SAD-RV(ΔG)-N2C(G)) shows high neuro-tropism in cell culture, but its in vivo retrograde infection efficiency and neuro-tropism have not been systematically characterized. Methods: SAD-RV(ΔG)-N2C(G) and two other broadly used retrograde tracers, SAD-RV(ΔG)-B19(G) and rAAV2-retro were respectively injected into the VTA or DG in C57BL/6 mice. The neuron numbers labeled across the whole brain regions were counted and analyzed by measuring the retrograde infection efficiencies and tropisms of these viral tools. The labeled neural types were analyzed using fluorescence immunohistochemistry or GAD67-GFP mice. Result: We found that SAD-RV (ΔG)-N2C (G) enhanced the infection efficiency of long-projecting neurons by ~ 10 times but with very similar neuro-tropism, compared with SAD-RV (ΔG)-B19(G). On the other hand, SAD-RV(ΔG)-N2C(G) showed comparable infection efficiency with rAAV2-retro, but had a more restricted diffusion range, and broader tropism to different types and regions of long-projecting neuronal populations. Conclusions: These results demonstrate that SAD-RV(ΔG)-N2C(G) can serve as an effective retrograde vector for studying neuronal circuits. Key words：Viral vector, N2C Glycoprotein, Neuronal circuits, Retrograde tracin

The Impact of Variational Primary Collaterals on Cerebral Autoregulation

The influence of the anterior and posterior communicating artery (ACoA and PCoA) on dynamic cerebral autoregulation (dCA) is largely unknown. In this study, we aimed to test whether substantial differences in collateral anatomy were associated with differences in dCA in two common types of stenosis according to digital subtraction angiography (DSA): either isolated basal artery and/or bilateral vertebral arteries severe stenosis/occlusion (group 1; group 1A: with bilateral PCoAs; and group 1B: without bilateral PCoAs), or isolated unilateral internal carotid artery severe stenosis/occlusion (group 2; group 2A: without ACoA and with PCoA; group 2B: with ACoA and without PCoAs; and group 2C: without both ACoA and PCoA). The dCA was calculated by transfer function analysis (a mathematical model), and was evaluated in middle cerebral artery (MCA) and/or posterior cerebral artery (PCA). Of a total of 231 non-acute phase ischemic stroke patients who received both dCA assessment and DSA in our lab between 2014 and 2017, 51 patients met inclusion criteria based on the presence or absence of ACoA or PCoA, including 21 patients in the group 1, and 30 patients in the group 2. There were no significant differences in gender, age, and mean blood pressure between group 1A and group 1B, and among group 2A, group 2B, and group 2C. In group 1, the PCA phase difference values (autoregulatory parameter) were significantly higher in the subgroup with patent PCoAs, compared to those without. In group 2, the MCA phase difference values were higher in the subgroup with patent ACoA, compared to those without. This pilot study found that the cross-flow of the ACoA/PCoA to the affected area compensates for compromised dCA in the affected area, which suggests an important role of the ACoA/PCoA in stabilizing cerebral blood flow

Effects of Low-Level Autonomic Stimulation on Prevention of Atrial Fibrillation Induced by Acute Electrical Remodeling

Background. Rapid atrial pacing (RAP) can induce electrical and autonomic remodeling and facilitate atrial fibrillation (AF). Recent reports showed that low-level vagosympathetic nerve stimulation (LLVNS) can suppress AF, as an antiarrhythmic effect. We hypothesized that LLVNS can reverse substrate heterogeneity induced by RAP. Methods and Results. Mongrel dogs were divided into (LLVNS+RAP) and RAP groups. Electrode catheters were sutured to multiple atrial sites, and LLVNS was applied to cervical vagosympathetic trunks with voltage 50% below the threshold slowing sinus rate by ⩽30 msec. RAP induced a significant decrease in effective refractory period (ERP) and increase in the window of vulnerability at all sites, characterized by descending and elevated gradient differences towards the ganglionic plexi (GP) sites, respectively. The ERP dispersion was obviously enlarged by RAP and more significant when the ERP of GP-related sites was considered. Recovery time from AF was also prolonged significantly as a result of RAP. LLVNS could reverse all these changes induced by RAP and recover the heterogeneous substrate to baseline. Conclusions. LLVNS can reverse the electrical and autonomic remodeling and abolish the GP-central gradient differences induced by RAP, and thus it can recover the homogeneous substrate, which may be the underlying mechanism of its antiarrhythmic effect