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The omicron variant of SARS-CoV-2 has been spreading rapidly across the globe. The virus-surface spike protein plays a critical role in the cell entry and immune evasion of SARS-CoV-2. Here we determined the 3.0 Å cryo-EM structure of the omicron spike protein ectodomain. In contrast to the original strain of SARS-CoV-2 where the receptor-binding domain (RBD) of the spike protein takes a mixture of open (“standing up”) and closed (“lying down”) conformations, the omicron spike molecules are predominantly in the open conformation, with one upright RBD ready for receptor binding. The open conformation of the omicron spike is stabilized by enhanced inter-domain and inter-subunit packing, which involves new mutations in the omicron strain. Moreover, the omicron spike has undergone extensive mutations in RBD regions where known neutralizing antibodies target, allowing the omicron variant to escape immune surveillance aimed at the original viral strain. The stable open conformation of the omicron spike sheds light on the cell entry and immune evasion mechanisms of the omicron variant. This study determined the structure of the spike protein of the SARS-CoV-2 omicron variant, revealing a predominantly open conformation of the molecule that may help omicron infect cells more efficiently than do previous variants.

A novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) is causing the global coronavirus disease 2019 (COVID-19) pandemic. Understanding how SARS-CoV-2 enters human cells is a high priority for deciphering its mystery and curbing its spread. A virus surface spike protein mediates SARS-CoV-2 entry into cells. To fulfill its function, SARS-CoV-2 spike binds to its receptor human ACE2 (hACE2) through its receptor-binding domain (RBD) and is proteolytically activated by human proteases. Here we investigated receptor binding and protease activation of SARS-CoV-2 spike using biochemical and pseudovirus entry assays. Our findings have identified key cell entry mechanisms of SARS-CoV-2. First, SARS-CoV-2 RBD has higher hACE2 binding affinity than SARS-CoV RBD, supporting efficient cell entry. Second, paradoxically, the hACE2 binding affinity of the entire SARS-CoV-2 spike is comparable to or lower than that of SARS-CoV spike, suggesting that SARS-CoV-2 RBD, albeit more potent, is less exposed than SARS-CoV RBD. Third, unlike SARS-CoV, cell entry of SARS-CoV-2 is preactivated by proprotein convertase furin, reducing its dependence on target cell proteases for entry. The high hACE2 binding affinity of the RBD, furin preactivation of the spike, and hidden RBD in the spike potentially allow SARS-CoV-2 to maintain efficient cell entry while evading immune surveillance. These features may contribute to the wide spread of the virus. Successful intervention strategies must target both the potency of SARS-CoV-2 and its evasiveness.

A novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) recently emerged and is rapidly spreading in humans, causing COVID-19 1 , 2 . A key to tackling this pandemic is to understand the receptor recognition mechanism of the virus, which regulates its infectivity, pathogenesis and host range. SARS-CoV-2 and SARS-CoV recognize the same receptor—angiotensin-converting enzyme 2 (ACE2)—in humans 3 , 4 . Here we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 (engineered to facilitate crystallization) in complex with ACE2. In comparison with the SARS-CoV RBD, an ACE2-binding ridge in SARS-CoV-2 RBD has a more compact conformation; moreover, several residue changes in the SARS-CoV-2 RBD stabilize two virus-binding hotspots at the RBD–ACE2 interface. These structural features of SARS-CoV-2 RBD increase its ACE2-binding affinity. Additionally, we show that RaTG13, a bat coronavirus that is closely related to SARS-CoV-2, also uses human ACE2 as its receptor. The differences among SARS-CoV-2, SARS-CoV and RaTG13 in ACE2 recognition shed light on the potential animal-to-human transmission of SARS-CoV-2. This study provides guidance for intervention strategies that target receptor recognition by SARS-CoV-2. The crystal structure of the receptor-binding domain of the SARS-CoV-2 spike in complex with human ACE2, compared with the receptor-binding domain of SARS-CoV, sheds light on the structural features that increase its binding affinity to ACE2.

The safe and efficient operation of nuclear power systems largely relies on sensor networks that continuously collect and transmit monitoring data. However, due to the high sensitivity of the nuclear power field and strict privacy restrictions, data among different nuclear entities are typically not directly shareable, which poses challenges to constructing a global digital twin with strong generalization capability. Moreover, most existing digital twin approaches tend to treat sensor data as static, overlooking critical temporal patterns that could enhance fault prediction performance. To address these issues, this paper proposes an Edge Temporal Digital Twin Network (ETDTN) for cloud-edge collaborative, sensor-driven fault detection in nuclear power systems. ETDTN introduces a continuous variable temporal representation to fully exploit temporal information from sensors, incorporates a global representation module to alleviate the non-IID characteristics among different subsystems, and integrates a temporal attention mechanism based on graph neural networks in the latent space to strengthen temporal feature learning. Extensive experiments on real nuclear power datasets from 17 independent units demonstrate that ETDTN achieves significantly better fault detection performance than existing methods under non-sharing data scenarios, obtaining the best results in both accuracy and F1 score. The findings indicate that ETDTN not only effectively preserves data privacy through federated parameter aggregation but also captures latent temporal patterns, providing a powerful tool for sensor-driven fault detection and predictive maintenance in nuclear power systems.

Solar‐driven water evaporation and valuable fuel generation is an environmentally friendly and sustainable way for clean water and energy production. However, a few bottlenecks for practical applications are high‐cost, low productivity, and severe sunlight angle dependence. Herein, solar evaporation with enhanced photocatalytic capacity that is light direction insensitive and of efficiency breakthrough by virtue of a three‐dimensional (3D) photothermal catalytic spherical isotopic evaporator is demonstrated. A homogeneous layer of microfluidic blow spun polyamide nanofibers loaded with efficient light absorber of polypyrrole nanoparticles conformally wraps onto a lightweight, thermal insulating plastic sphere, featuring favorable interfacial solar heating and efficient water transportation. The 3D spherical geometry not only guarantees the omnidirectional solar absorbance by the light‐facing hemisphere, but also keeps the other hemisphere under shadow to harvest energy from the warmer environment. As a result, the light‐to‐vapor efficiency exceeds the theoretical limit, reaching 217% and 156% under 1 and 2 sun, respectively. Simultaneously, CO2 photoreduction with generated steam reveals a favorable clean fuels production rate using photocatalytic spherical evaporator by secondary growth of Cu2O nanoparticles. Finally, an outdoor demonstration manifests a high evaporation rate and easy‐to‐perform construction on‐site, providing a promising opportunity for efficient and decentralized water and clean fuel production. A three‐dimensional (3D) photothermal catalytic spherical evaporator with double‐layer structure that enables the theoretical light‐to‐vapor efficiency limits breakthrough and efficient clean fuels production. The isotropy of spherical structure exhibits the omnidirectional light absorption, reducing the influence of natural light incident angle on solar evaporation rate and circumventing the trade‐off between water condensation and photocatalytic reaction, which is significant for practical applications.

Curcumin, the active component of turmeric, has been shown to protect against carcinogenesis and prevent tumor development. However, little is known about its anti-tumor mechanism in small cell lung cancer (SCLC). In this study, we found that curcumin can inhibit SCLC cell proliferation, cell cycle, migration, invasion and angiogenesis through suppression of the STAT3. SCLC cells were treated with curcumin (15 µmol/L) and the results showed that curcumin was effective in inhibiting STAT3 phosphorylation to downregulate of an array of STAT3 downstream targets ,which contributed to suppression of cell proliferation, loss of colony formation, depression of cell migration and invasion. Curcumin also suppressed the expression of proliferative proteins (Survivin, Bcl-X(L) and Cyclin B1), and invasive proteins (VEGF, MMP-2, MMP-7 and ICAM-1). Knockdown of STAT3 expression by siRNA was able to induce anti-invasive effects in vitro. In contrast, activation of STAT3 upstream of interleukin 6 (IL-6) leads to the increased cell proliferation ,cell survival, angiogenesis, invasion, migration and tumor growth. Our findings illustrate the biologic significance of IL-6/JAK/STAT3 signaling in SCLC progression and provide novel evidence that the pathway may be a new potential target for therapy of SCLC. It was concluded that curcumin is a potent agent in the inhibition of STAT3 with favorable pharmacological activity,and curcumin may have translational potential as an effective cancer therapeutic or preventive agent for SCLC.

Developing supramolecular porous crystalline frameworks with tailor-made architectures from advanced secondary building units (SBUs) remains a pivotal challenge in reticular chemistry. Particularly for hydrogen-bonded organic frameworks (HOFs), construction of geometrical cavities through secondary units has been rarely achieved. Herein, a body-centered cubic HOF (TCA_NH 4 ) with octahedral cages was constructed by a C 3 -symmetric building block and NH 4 + node-assembled cluster (NH 4 ) 4 (COOH) 8 (H 2 O) 2 that served as supramolecular secondary building units (SSBUs), akin to the polynuclear SBUs in reticular chemistry. Specifically, the octahedral cages could encapsulate four homogenous haloforms including CHCl 3 , CHBr 3 , and CHI 3 with truncated octahedron configuration. Crystallographic evidence revealed the cages served as spatially-confined nanoreactors, enabling fast, broadband photochromic effect associated with the reversible photo/thermal transformation between encapsulated CHI 3 and I 2 . Overall, this work provides a strategy by shaping SSBUs to expand the framework topology of HOFs and a prototype of hydrogen-bonded nanoreactors to accommodate reversible photochromic reactions. The development of supramolecular porous crystalline frameworks with architectures from secondary building units remains challenging. Here, the authors report ammonium node-assembled clusters as supramolecular secondary building units to sustain a body centered cubic hydrogenbonded framework with octahedral cages for haloform encapsulation and reversible photochromism.

This study aimed to evaluate the adverse event profile of remimazolam, a novel ultra-short-acting benzodiazepine, with a focus on its safety in the respiratory, cardiovascular, and immune systems across diverse patient populations. We analyzed adverse event reports from the FAERS database over a defined period, performing signal detection using the proportional reporting ratio (PRR) and the reporting odds ratio (ROR), and contextualized the findings with a concurrent literature review. Remimazolam demonstrated a strong signal for hypoventilation. In the cardiovascular system, it was associated with serious adverse events, including cardiac and cardiorespiratory arrest, particularly in high-risk patients. Furthermore, we detected significant signals for severe hypersensitivity reactions, such as anaphylactic shock and laryngeal edema, while signals in other systems were less pronounced but remained clinically significant. Given that the study population was predominantly elderly, and considering the serious nature of the identified signals, its potential for adverse events necessitates vigilant monitoring. Future research should focus on clarifying risks within specific high-risk groups to establish optimized safety protocols.

Lymphocyte subsets are the most intuitive expression of the body’s immune ability, and the lymphocyte-to-monocyte ratio (LMR) also clearly reflect the degree of chronic inflammation activity. The purpose of this study is to investigate their predictive value of lymphocyte subsets and LMR to neoadjuvant therapy (NAT) efficacy in breast cancer patients. In this study, lymphocyte subsets and LMR were compared between breast cancer patients (n = 70) and benign breast tumor female populations (n = 48). Breast cancer patients were treated with NAT, and the chemotherapy response of the breast was evaluated using established criteria. The differences in lymphocyte subsets and LMR were also compared between pathological complete response (pCR) and non-pCR patients before and after NAT. Finally, data were analyzed using SPSS. The analytical results demonstrated that breast cancer patients showed significantly lower levels of CD3 + T cells, CD4 + T cells, CD4 + /CD8 + ratio, NK cells, and LMR compared to benign breast tumor women ( P  < 0.05). Among breast cancer patients, those who achieved pCR had higher levels of CD4 + T cells, NK cells, and LMR before NAT ( P  < 0.05). NAT increased CD4 + /CD8 + ratio and decreased CD8 + T cells in pCR patients ( P  < 0.05). Additionally, both pCR and non-pCR patients exhibited an increase in CD3 + T cells and CD4 + T cells after treatment, but the increase was significantly higher in pCR patients ( P  < 0.05). Conversely, both pCR and non-pCR patients experienced a decrease in LMR after treatment. However, this decrease was significantly lower in pCR patients ( P  < 0.05). These indicators demonstrated their predictive value for therapeutic efficacy. In conclusion, breast cancer patients experience tumor-related immunosuppression and high chronic inflammation response. But this phenomenon can be reversed to varying degrees by NAT. It has been found that lymphocyte subsets and LMR have good predictive value for pCR. Therefore, these markers can be utilized to identify individuals who are insensitive to NAT early on, enabling the adjustment of treatment plans and achieving precise breast cancer treatment.

By integrating multi-scale computational simulation with photo-regulated macromolecular synthesis, this study presents a new paradigm for smart design while customizing polymeric adsorbents for uranium harvesting from seawater. A dissipative particle dynamics (DPD) approach, combined with a molecular dynamics (MD) study, is performed to simulate the conformational dynamics and adsorption process of a model uranium grabber, i.e., PAO m - b -PPEGMA n , suggesting that the maximum adsorption capacity with atomic economy can be achieved with a preferred block ratio of 0.18. The designed polymers are synthesized using the PET-RAFT polymerization in a microfluidic platform, exhibiting a record high adsorption capacity of uranium (11.4 ± 1.2 mg/g) in real seawater within 28 days. This study offers an integrated perspective to quantitatively assess adsorption phenomena of polymers, bridging metal-ligand interactions at the molecular level with their spatial conformations at the mesoscopic level. The established protocol is generally adaptable for target-oriented development of more advanced polymers for broadened applications. Developing materials for uranium harvesting from seawater with high adsorption capacity remains challenging. Here, the authors develop a new protocol, by combining multi-scale computational simulations with the PET-RAFT polymerization, for rational design and precise synthesis of block copolymers with optimal architectures and atomic economy, achieving a capacity of 11.4 mg/g within 28 days.