TMPRSS2 and glycan receptors synergistically facilitate coronavirus entry.

The entry of coronaviruses is initiated by spike recognition of host cellular receptors, involving proteinaceous and/or glycan receptors. Recently, TMPRSS2 was identified as the proteinaceous receptor for HCoV-HKU1 alongside sialoglycan as a glycan receptor. However, the underlying mechanisms for viral entry remain unknown.

CA-based urban growth model considering the temporal dynamic adjustment of local spatial driving factors: An application in Wuhan City.

Cellular Automaton (CA) is widely used because of its ability to simulate complex spatiotemporal dynamic processes through applying simple rules. The basis of the CA model is the definition of transformation rules. During a simulation process, the rules determine the change of the cell state.

CircRNA (circ)_0007823 Contributes to Triple-Negative Breast Cancer Progression and Cisplatin Resistance via the miR-182-5p/FOXO1 Pathway.

Cisplatin (DDP) is used for the clinical management of triple-negative breast cancer (TNBC). However, the development of drug resistance limits its therapeutic efficacy. Circular RNAs (circRNAs) are known to be involved in tumor DDP resistance.

Effect of Thyroid Function on Offspring Neurodevelopment in People Receiving ART Therapy: A Prospective Cohort Study.

Context: Adequate maternal thyroid hormone is vital for fetal neurodevelopment. Abnormal thyroid function can cause developmental defects in offspring from spontaneous pregnancies; however, research in assisted reproduction is lacking.

Objectives: This work aimed to investigate the association between thyroid disorders and offspring neurodevelopment from assisted reproduction.

The ratio of lymphocyte/red blood cells and platelets/lymphocytes are predictive biomarkers for lymph node metastasis in patients with breast cancer.

Background: Axillary lymph node metastasis (LNM) affects the progression of breast cancer. However, it is difficult to preoperatively diagnose axillary lymph node status with high sensitivity. Therefore, we hypothesized that platelets/lymphocytes ratio (PLR) and lymphocytes/ red blood cells ratio (LRR) might help in the prognosis of lymph node metastasis in T1-T2 breast cancer.

Temperature impacts on the growth of hydrogen bubbles during ultrasonic vibration-enhanced hydrogen generation.

To improve the hydrogen precipitation performance on the surface of the catalytic layer of the proton exchange membrane (PEM) hydrogen cathode, ultrasonic vibration was employed to accelerate the detachment of hydrogen bubbles on the surface of the catalytic layer. Based on the energy and mechanical analyses of nano and microbubbles, the hydrogen bubble generation mechanism and the effect of temperature on bubble parameters during the evolution process when the ultrasonic field is coupled with the electric field are investigated. The nucleation frequency of the hydrogen bubbles, the relationship between the pressure and temperature and the operating temperature during the generation and detachment of bubbles as well as the detachment radius of bubbles under the action of the ultrasonic field are obtained.

Radon exhalation behavior and determination of diffusion migration parameters in spherical porous emanation media.

There is a significant impact of the radon diffusion coefficient and the free radon production rate on the exhalation of radon from porous materials that can be regarded as spheres, hexahedrons, or cylinders. To understand this effect, the radon exhalation rules of spherical porous media with different radii were studied according to the radon diffusion migration theory. A specialized method for simultaneous determination of the radon diffusion coefficient and the free radon production rate of the spherical porous media was proposed, and applied to determine the above two parameters for two hemispherical test blocks with different radii.

Structure-based discovery of dual pathway inhibitors for SARS-CoV-2 entry.

Since 2019, SARS-CoV-2 has evolved rapidly and gained resistance to multiple therapeutics targeting the virus. Development of host-directed antivirals offers broad-spectrum intervention against different variants of concern. Host proteases, TMPRSS2 and CTSL/CTSB cleave the SARS-CoV-2 spike to play a crucial role in the two alternative pathways of viral entry and are characterized as promising pharmacological targets.

Hsa_circ_0007823 Overexpression Suppresses the Progression of Triple-Negative Breast Cancer via Regulating miR-182-5p-FOXO1 Axis.

Background: This study aimed to analyze the specific expression of hsa_circ_0007823 in triple-negative breast cancer (TNBC) and explore the roles and related molecular mechanisms of hsa_circ_0007823 in TNBC.

Materials And Methods: Relative hsa_circ_0007823 levels in TNBC tissues and cell lines were examined by reverse transcription-quantitative polymerase chain reaction. The value of hsa_circ_0007823 levels was evaluated in patients' clinicopathological characteristics and prognostic prediction.

Crystal structure of mRNA cap (guanine-N7) methyltransferase E12 subunit from monkeypox virus and discovery of its inhibitors.

In July 2022, the World Health Organization announced monkeypox as a public health emergency of international concern (PHEIC), and over 85,000 global cases have been reported currently. However, preventive and therapeutic treatments for the monkeypox virus (MPXV) remain limited. MPXV mRNA cap N7 methyltransferase (MTase) is composed of two subunits (E1 C-terminal domain (E1) and E12) which are essential for the replication of MPXV.

Molecular mechanisms of SARS-CoV-2 resistance to nirmatrelvir.

Nirmatrelvir is a specific antiviral drug that targets the main protease (M) of SARS-CoV-2 and has been approved to treat COVID-19. As an RNA virus characterized by high mutation rates, whether SARS-CoV-2 will develop resistance to nirmatrelvir is a question of concern. Our previous studies have shown that several mutational pathways confer resistance to nirmatrelvir, but some result in a loss of viral replicative fitness, which is then compensated for by additional alterations.

Structural biology of SARS-CoV-2 M and drug discovery.

Since its outbreak in late 2019, the COVID-19 pandemic has drawn enormous attention worldwide as a consequence of being the most disastrous infectious disease in the past century. As one of the most immediately druggable targets of SARS-CoV-2, the main protease (M) has been studied thoroughly. In this review, we provide a comprehensive summary of recent advances in structural studies of M, which provide new knowledge about M in terms of its biological function, structural characteristics, substrate specificity, and autocleavage process.

Application effect of low-dose spiral CT on pulmonary nodules and its diagnostic value for benign and malignant nodules.

Objective: This study was designed to determine the application effect of low-dose computed tomography (LDCT) on detecting pulmonary nodules (PNs) and its diagnostic value for benign and malignant pulmonary nodules.

Methods: Data of 432 patients with PNs admitted to Julu County Hospital between March 2018 and June 2021 in were collected and analysed retrospectively. All patients underwent LDCT and conventional-dose spiral computed tomography (CT).

Structure-based design of anti-mycobacterial drug leads that target the mycolic acid transporter MmpL3.

New anti-tubercular agents are urgently needed to address the emerging threat of drug resistance to human tuberculosis. Here, we have used structure-assisted methods to develop compounds that target mycobacterial membrane protein large 3 (MmpL3). MmpL3 is essential for the transport of mycolic acids, an important cell-wall component of mycobacteria.

Dynamic modeling and simulation of rigid-flexible coupling cable system by absolute nodal coordinate formulation.

The rigid-flexible coupling cable system under large deformation is studied, and the beam element from absolute node coordinate formulation is used to establish flexible cable body of the system. Different numerical integral algorithms are discussed for solving the rigid-flexible cable system and an integration strategy which combines Implicit Euler with Minimum Residual Method (MINRES) is proposed. The influence of the position and number of rigid components and different the lengths of the flexible elements on the system dynamics are analyzed.

Crystal Structures of Wolbachia CidA and CidB Reveal Determinants of Bacteria-induced Cytoplasmic Incompatibility and Rescue.

Cytoplasmic incompatibility (CI) results when Wolbachia bacteria-infected male insects mate with uninfected females, leading to embryonic lethality. "Rescue" of viability occurs if the female harbors the same Wolbachia strain. CI is caused by linked pairs of Wolbachia genes called CI factors (CifA and CifB).

Remdesivir overcomes the S861 roadblock in SARS-CoV-2 polymerase elongation complex.

Remdesivir (RDV), a nucleotide analog with broad-spectrum features, has exhibited effectiveness in COVID-19 treatment. However, the precise working mechanism of RDV when targeting the viral RNA-dependent RNA polymerase (RdRP) has not been fully elucidated. Here, we solve a 3.

Structural and mechanistic insights into the complexes formed by cytoplasmic incompatibility factors.

bacteria, inherited through the female germ line, infect a large fraction of arthropod species. Many strains manipulate host reproduction, most commonly through cytoplasmic incompatibility (CI). CI, a conditional male sterility, results when -infected male insects mate with uninfected females; viability is restored if the female is similarly infected (called "rescue").

The main protease and RNA-dependent RNA polymerase are two prime targets for SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses an unprecedented global health crisis. It is particularly urgent to develop clinically effective therapies to contain the pandemic. The main protease (M) and the RNA-dependent RNA polymerase (RdRP), which are responsible for the viral polyprotein proteolytic process and viral genome replication and transcription, respectively, are two attractive drug targets for SARS-CoV-2.

Cryo-EM Structure of an Extended SARS-CoV-2 Replication and Transcription Complex Reveals an Intermediate State in Cap Synthesis.

Transcription of SARS-CoV-2 mRNA requires sequential reactions facilitated by the replication and transcription complex (RTC). Here, we present a structural snapshot of SARS-CoV-2 RTC as it transitions toward cap structure synthesis. We determine the atomic cryo-EM structure of an extended RTC assembled by nsp7-nsp8-nsp12-nsp13-RNA and a single RNA-binding protein, nsp9.

Architecture of a SARS-CoV-2 mini replication and transcription complex.

Non-structural proteins (nsp) constitute the SARS-CoV-2 replication and transcription complex (RTC) to play a pivotal role in the virus life cycle. Here we determine the atomic structure of a SARS-CoV-2 mini RTC, assembled by viral RNA-dependent RNA polymerase (RdRp, nsp12) with a template-primer RNA, nsp7 and nsp8, and two helicase molecules (nsp13-1 and nsp13-2), by cryo-electron microscopy. Two groups of mini RTCs with different conformations of nsp13-1 are identified.

One-Pot Synthesis of Benzimidazo[2,1-]thiazoline Derivatives through an Addition/Cyclization/Oxidative Coupling Reaction.

A novel and efficient approach to the synthesis of benzimidazo[2,1-]thiazoline derivatives has been developed through an addition/cyclization/intramolecular oxidative C-H functionalization process. A variety of alkylene benzimidazo[2,1-] thiazolines were conveniently assembled from the reaction of aryl isothiocyanate and propargylic amine in the presence of Cu(OAc) and PIFA at room temperature. The product could be further converted to substituted benzimidazo[2,1-]thiazole derivatives.