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Since the outbreak of coronavirus disease 2019 (COVID-19), clinicians have tried every effort to understand the disease, and a brief portrait of its clinical features have been identified. In clinical practice, we noticed that many severe or critically ill COVID-19 patients developed typical clinical manifestations of shock, including cold extremities and weak peripheral pulses, even in the absence of overt hypotension. Understanding the mechanism of viral sepsis in COVID-19 is warranted for exploring better clinical care for these patients. With evidence collected from autopsy studies on COVID-19 and basic science research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV, we have put forward several hypotheses about SARS-CoV-2 pathogenesis after multiple rounds of discussion among basic science researchers, pathologists, and clinicians working on COVID-19. We hypothesise that a process called viral sepsis is crucial to the disease mechanism of COVID-19. Although these ideas might be proven imperfect or even wrong later, we believe they can provide inputs and guide directions for basic research at this moment.

HighlightsThe unique 0D-2D ZnS nanodots/Ti3C2Tx MXene hybrids with strong interfacial interaction enable to achieve stable cyclability and excellent rate performance for lithium storage.The lithium storage mechanism of ZnS is clarified and new insights into phase transition mechanism are proposed.The strong interfacial interaction between ZnS nanodots and MXene nanosheets at the ZnS-MXene heterointerface exhibits high lithium adsorption capability, enhanced interfacial electron transfer, and low lithium diffusion energy barrier.ZnS has great potentials as an anode for lithium storage because of its high theoretical capacity and resource abundance; however, the large volume expansion accompanied with structural collapse and low conductivity of ZnS cause severe capacity fading and inferior rate capability during lithium storage. Herein, 0D-2D ZnS nanodots/Ti3C2Tx MXene hybrids are prepared by anchoring ZnS nanodots on Ti3C2Tx MXene nanosheets through coordination modulation between MXene and MOF precursor (ZIF-8) followed with sulfidation. The MXene substrate coupled with the ZnS nanodots can synergistically accommodate volume variation of ZnS over charge–discharge to realize stable cyclability. As revealed by XPS characterizations and DFT calculations, the strong interfacial interaction between ZnS nanodots and MXene nanosheets can boost fast electron/lithium-ion transfer to achieve excellent electrochemical activity and kinetics for lithium storage. Thereby, the as-prepared ZnS nanodots/MXene hybrid exhibits a high capacity of 726.8 mAh g−1 at 30 mA g−1, superior cyclic stability (462.8 mAh g−1 after 1000 cycles at 0.5 A g−1), and excellent rate performance. The present results provide new insights into the understanding of the lithium storage mechanism of ZnS and the revealing of the effects of interfacial interaction on lithium storage performance enhancement.

Ischemic stroke is one of the leading causes of death worldwide and the most common cause of disability in Western countries. Multiple mechanisms contribute to the development and progression of ischemic stroke, and inflammation is one of the most important mechanisms. Ischemia induces the release of adenosine triphosphate/reactive oxygen species, which activates immune cells to produce many proinflammatory cytokines that activate downstream inflammatory cascades to induce fatal immune responses. Research has confirmed that peripheral blood immune cells play a vital role in the immunological cascade after ischemic stroke. The role of monocytes has received much attention among numerous peripheral blood immune cells. Monocytes induce their effects by secreting cytokines or chemokines, including CCL2/CCR2, CCR4, CCR5, CD36, CX3CL1/CX3CR1, CXCL12(SDF-1), LFA-1/ICAM-1, Ly6C, MMP-2/9, NR4A1, P2X4R, P-selectin, CD40L, TLR2/4, and VCAM-1/VLA-4. Those factors play important roles in the process of monocyte recruitment, migration, and differentiation. This review focuses on the function and mechanism of the cytokines secreted by monocytes in the process of ischemic stroke and provides novel targets for treating cerebral ischemic stroke.

Recent magnetospheric observations and three‐dimensional (3D) kinetic simulations have shown that plasma wave activities are significantly enhanced around the reconnection x‐line, implying that the reconnection process is fully 3D. However, how the turbulence affects the local reconnection process has been poorly understood so far. We find by means of large‐scale particle‐in‐cell simulation in 3D system that the local reconnection rate can be significantly enhanced, reaching 0.4, which is much larger than theoretical predictions for two‐dimensional (2D) reconnection. The large reconnection rate is associated with large energy conversion rate and strong electron acceleration. The enhancement of the reconnection rate is caused by local increases of electron momentum transport and pressure gradient force induced by turbulence, which can not occur in 2D system. The result is expected to give better interpretations to in‐situ satellite observations where magnetic reconnection proceeds in 3D system. Plain Language Summary Magnetic reconnection is an important process in space physics to convert the magnetic field energy into particle kinetic energy. In this study, we investigate reconnection rate, a physical quantity that measures the speed of magnetic reconnection by using fully kinetic simulation, in which both electrons and ions are particles. We find very fast local reconnection processes in three‐dimensional system that far exceeds expectation. It indicates that magnetic reconnection is a three‐dimensional process. The high reconnection rate comes from the electrons rather than ions. And the main reason is the increasing of electron momentum transport and pressure gradient caused by strong turbulence, leading to a strong magnetic reconnection process in the current sheet. Key Points Magnetic reconnection can be strongly intensified in turbulent current sheet with the local reconnection rate exceeding 0.4 High reconnection rate is caused by local enhancements of electron momentum transport and pressure gradient force induced by turbulence Reconnection process is essentially 3D, suggesting that local satellite observations may be insufficient in capturing the global process

Investigators in China report the results of an open-label, randomized clinical trial of lopinavir–ritonavir for the treatment of Covid-19 in 199 infected adult patients. The primary end point was the time to clinical improvement.

Reliable projections of permafrost change are crucial for estimating permafrost carbon loss. However, potential model biases in surface air temperature may yield unrealistic projections of future permafrost area. Here, by leveraging the emergent relationship between equilibrium climate sensitivity and projected changes in mean annual air temperature over High Mountain Asia (HMA), we mitigate the overestimated local warming rates and excessive thawing of permafrost associated with the “hot model” problem in models participating in the Coupled Model Intercomparison Project phase 6. After constraint, permafrost area over HMA will reduce by 37%, 64% and 99% in 2081–2100 relative to present‐day under the SSP1‐2.6, SSP2‐4.5 and SSP5‐8.5 scenarios, respectively. In contrast, the unconstrained projections tend to overestimate the loss of permafrost area by nearly 10% under the low and mid‐emission scenarios due to the overestimation of local warming rates. These findings are crucial for policymaking and provide valuable insights into global permafrost projection. Plain Language Summary This study shows a comprehensive picture of permafrost changes over High Mountain Asia (HMA) in the coming future. A subset of the newest generation of climate models participating in Coupled Model Intercomparison Project phase 6 (CMIP6) have a “hot model” problem with high equilibrium climate sensitivity (ECS) exceeding the likely range of 2.5°C–4°C assessed by Intergovernmental Panel on Climate Change Sixth Assessment Report. This indicates that the surface temperature projections in response to changes in atmospheric carbon dioxide concentrations are higher than those expected based on other evidence. Here, taking HMA as a case study, we establish a relationship between ECSs and the future changes in mean annual air temperature over HMA to constrain the future projections of warming rates and permafrost degradation. The constrained projection is 0.2°C, 0.4°C and 0.5°C lower than the unconstrained warming simulated by the CMIP6 ensemble during 2081–2100 under low, intermediate, and very high emission scenarios (SSP1‐2.6, SSP2‐4.5 and SSP5‐8.5). Based on the more reliable projections of future warming, reductions of permafrost area by 37%, 64% and 99% in 2081–2100 under SSP1‐2.6, SSP2‐4.5 and SSP5‐8.5 scenarios, respectively, are expected. The constraining solves the exaggerated projection of permafrost degradation caused by CMIP6 models. Key Points Models that overestimate warming rates tend to also overestimate permafrost degradation over High Mountain Asia An emergent relationship between equilibrium climate sensitivity and surface warming is used to constrain future permafrost projections The permafrost area will reduce by 37%, 64% and 99% in 2081–2100 relative to 2000–2016 under SSP1‐2.6, SSP2‐4.5 and SSP5‐8.5 scenarios

During pregnancy, the appropriate allocation of nutrients between the mother and the fetus is dominated by maternal–fetal interactions, which is primarily governed by the placenta. The syncytiotrophoblast (STB) lining at the outer surface of the placental villi is directly bathed in maternal blood and controls feto–maternal exchange. The STB is the largest multinucleated cell type in the human body, and is formed through syncytialization of the mononucleated cytotrophoblast. However, the physiological advantage of forming such an extensively multinucleated cellular structure remains poorly understood. Here, we discover that the STB uniquely adapts to nutrient stress by inducing the macropinocytosis machinery through repression of mammalian target of rapamycin (mTOR) signaling. In primary human trophoblasts and in trophoblast cell lines, differentiation toward a syncytium triggers macropinocytosis, which is greatly enhanced during amino acid shortage, induced by inhibiting mTOR signaling. Moreover, inhibiting mTOR in pregnant mice markedly stimulates macropinocytosis in the syncytium. Blocking macropinocytosis worsens the phenotypes of fetal growth restriction caused by mTOR-inhibition. Consistently, placentas derived from fetal growth restriction patients display: 1) Repressed mTOR signaling, 2) increased syncytialization, and 3) enhanced macropinocytosis. Together, our findings suggest that the unique ability of STB to undergo macropinocytosis serves as an essential adaptation to the cellular nutrient status, and support fetal survival and growth under nutrient deprivation.

Cardiovascular-kidney-metabolic (CKM) syndrome poses a significant and growing public health challenge. While sleep disturbances are recognized as a risk factor, the role of daytime napping in the progression of CKM syndrome remains unclear. We utilized data from the China Health and Retirement Longitudinal Study (CHARLS), a nationally representative cohort. This study included 9,810 participants for cross-sectional analysis and 4,990 participants free of advanced CKM syndrome at baseline for longitudinal analysis. Nap duration was categorized into four groups: 0, 1–29, 30–89, and ≥ 90 min. Advanced CKM syndrome (stages 3–4) was defined according to the American Heart Association criteria. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). In the longitudinal analysis, a short afternoon nap (1–29 min) was associated with a 35.3% reduction in the risk of incident advanced CKM syndrome compared to non-napping (adjusted OR = 0.647, 95% CI 0.451–0.928). This protective association was particularly significant in males (OR = 0.645, 95% CI 0.432–0.964) and individuals who were married or partnered (OR = 0.734, 95% CI 0.545–0.988). Furthermore, for older adults over 60 years of age, a moderate nap duration (30–89 min) was also linked to a lower risk (OR = 0.664, 95% CI 0.476–0.927). The cross-sectional analysis yielded consistent results. Sensitivity analyses confirmed the robustness of these findings. Short afternoon napping is associated with a reduced risk of developing advanced CKM syndrome in middle-aged and older Chinese adults, highlighting its potential as a target for primary prevention strategies aimed at mitigating CKM syndrome risk in an aging population.