Structural basis of main proteases of coronavirus bound to Bofutrelvir.

Globally, the continuous spread and evolution of SARS-CoV-2, along with its variants, profoundly impact human well-being, health, security, and the growth of socio-economic. In the field of development of drugs against COVID-19, the main protease (Mpro) is a critical target as it plays a core role in the lifecycle of SARS-CoV-2. Bofutrelvir acts as a potent inhibitor of SARS-CoV-2 Mpro, demonstrating high efficacy and broad-spectrum antiviral activity. Compared to therapies that require pharmacokinetic boosters, such as ritonavir, the monotherapy approach of Bofutrelvir reduces the risk of potential drug interactions, making it suitable for a wider patient population. However, further studies on the potency and mechanism of inhibition of Bofutrelvir against the Mpro of COVID-19 and its variants, together with other coronaviruses, are needed to prepare for the possibility of a possible re-emerging threat from an analogous virus in the future. Here, we reveal the effective inhibition of Bofutrelvir against the Mpro of SARS-CoV-2, SARS-CoV, and HCoV-229E through FRET and crystallographic analysis. Furthermore, the inhibitory mechanisms of Bofutrelvir against two SARS-CoV-2 Mpro mutants (G15S and K90R) were also elucidated through FRET and crystallographic studies. Through detailed analysis and comparison of these crystal structures, we identified crucial structural determinants of inhibition and elucidated the binding mode of Bofutrelvir to Mpros from different coronaviruses. These findings are hopeful to accelerate the development of safer and more potent inhibitors against the Mpro of coronavirus, and to provide important references for the prevention and treatment of similar viruses that may emerge in the future.

Structural basis of main proteases of MERS-CoV bound to antineoplastic drug carmofur.

Recurrent epidemics of coronaviruses have posed significant threats to human life and health. The mortality rate of patients infected with the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is 35 %. The main protease (Mpro) plays a crucial role in the MERS-CoV life cycle, and Mpro exhibited a high degree of conservation among different coronaviruses. Therefore inhibition of Mpro has become an effective strategy for the development of broad-spectrum anti-coronaviral drugs. The inhibition of SARS-CoV-2 Mpro by the anti-tumor drug carmofur has been revealed, but structural studies of carmofur in complex with Mpro from other types of coronavirus have not been reported. Hence, we revealed the structure of the MERS-CoV Mpro-carmofur complex, analysed the structural basis for the binding of carmofur to MERS-CoV Mpro in detail, and compared the binding patterns of carmofur to Mpros of two different coronaviruses, MERS-CoV and SARS-CoV-2. Considering the importance of Mpros for coronavirus therapy, structural understanding of Mpro inhibition by carmofur could contribute to the design and development of novel antiviral drugs with safe and broad-spectrum efficacy.

Structural basis for the inhibition of coronaviral main proteases by PF-00835231.

The main protease (M pro) of coronaviruses plays a key role in viral replication, thus serving as a hot target for drug design. PF-00835231 is a promising inhibitor of SARS-CoV-2 M pro. Here, we report the inhibitory potency of PF-00835231 against SARS-CoV-2 M pro and seven M pro mutants (G15S, M49I, Y54C, K90R, P132H, S46F, and V186F) from SARS-CoV-2 variants. The results confirm that PF-00835231 has broad-spectrum inhibition against various coronaviral M pros. In addition, the crystal structures of SARS-CoV-2 M pro, SARS-CoV M pro, MERS-CoV M pro, and seven SARS-CoV-2 M pro mutants (G15S, M49I, Y54C, K90R, P132H, S46F, and V186F) in complex with PF-00835231 are solved. A detailed analysis of these structures reveals key determinants essential for inhibition and elucidates the binding modes of different coronaviral M pros. Given the importance of the main protease for the treatment of coronaviral infection, structural insights into M pro inhibition by PF-00835231 can accelerate the design of novel antivirals with broad-spectrum efficacy against different human coronaviruses.

A spermine-responsive supramolecular chemotherapy system constructed from a water-soluble pillar[5]arene and a diphenylanthracene-containing amphiphile for precise chemotherapy.

Stimuli-responsive supramolecular chemotherapy, particularly in response to cancer biomarkers, has emerged as a promising strategy to overcome the limitations associated with traditional chemotherapy. Spermine (SPM) is known to be overexpressed in certain cancers. In this study, we introduced a novel supramolecular chemotherapy system triggered by SPM. The system featured pyridine salts of a diphenylanthracene derivative (PyEn) and a complementary water-soluble pillar[5]arene (WP5C5) with long alkyl chains. The diphenylanthracene unit of PyEn is effectively encapsulated within the long alkyl chains of WP5C5, resulting in a substantial reduction in the cytotoxicity of PyEn towards normal cells. The therapeutic effect of PyEn is selectively triggered intracellularly through SPM, leading to the endosomal release of PyEn and concurrent in situ cytotoxicity. This supramolecular chemotherapy system exhibits notable tumor inhibition against SPM-overexpressed cancers with reduced side effects on normal tissues. The supramolecular strategy for intracellular activation provides a novel tool with potential applications in chemotherapeutic interventions, offering enhanced selectivity and reduced cytotoxicity to normal cells.

High-performance, large-area flexible SERS substrates prepared by reactive ion etching for molecular detection.

In the realm of molecular detection, the surface-enhanced Raman scattering (SERS) technique has garnered increasing attention due to its rapid detection, high sensitivity, and non-destructive characteristics. However, conventional rigid SERS substrates are either costly to fabricate and challenging to prepare over a large area, or they exhibit poor uniformity and repeatability, making them unsuitable for inspecting curved object surfaces. In this work, we present a flexible SERS substrate with high sensitivity as well as good uniformity and repeatability. First, the flexible polydimethylsiloxane (PDMS) substrate is manually formulated and cured. SiO2/Ag layer on the substrate can be obtained in a single process by using ion beam sputtering. Then, reactive ion etching is used to etch the upper SiO2layer of the film, which directly leads to the desired densely packed nanostructure. Finally, a layer of precious metal is deposited on the densely packed nanostructure by thermal evaporation. In our proposed system, the densely packed nanostructure obtained by etching the SiO2layer directly determines the SERS ability of the substrate. The bottom layer of silver mirror can reflect the penetrative incident light, the spacer layer of SiO2and the top layer of silver thin film can further localize the light in the system, which can realize the excellent absorption of Raman laser light, thus enhancing SERS ability. In the tests, the prepared substrates show excellent SERS performance in detecting crystalline violet with a detection limit of 10-11M. The development of this SERS substrate is anticipated to offer a highly effective and convenient method for molecular substance detection.

Structural Basis for Coronaviral Main Proteases Inhibition by the 3CLpro Inhibitor GC376.

The main protease (Mpro) of coronaviruses participates in viral replication, serving as a hot target for drug design. GC376 is able to effectively inhibit the activity of Mpro, which is due to nucleophilic addition of GC376 by binding covalently with Cys145 in Mpro active site. Here, we used fluorescence resonance energy transfer (FRET) assay to analyze the IC50 values of GC376 against Mpros from six different coronaviruses (SARS-CoV-2, HCoV-229E, HCoV-HUK1, MERS-CoV, SARS-CoV, HCoV-NL63) and five Mpro mutants (G15S, M49I, K90R, P132H, S46F) from SARS-CoV-2 variants. The results showed that GC376 displays effective inhibition to various coronaviral Mpros and SARS-CoV-2 Mpro mutants. In addition, the crystal structures of SARS-CoV-2 Mpro (wide type)-GC376, SARS-CoV Mpro-GC376, MERS-CoV Mpro-GC376, and SARS-CoV-2 Mpro mutants (G15S, M49I, S46F, K90R, and P132H)-GC376 complexes were solved. We found that GC376 is able to fit into the active site of Mpros from different coronaviruses and different SARS-CoV-2 variants properly. Detailed structural analysis revealed key molecular determinants necessary for inhibition and illustrated the binding patterns of GC376 to these different Mpros. In conclusion, we not only proved the inhibitory activity of GC376 against different Mpros including SARS-CoV-2 Mpro mutants, but also revealed the molecular mechanism of inhibition by GC376, which will provide scientific guidance for the development of broad-spectrum drugs against SARS-CoV-2 as well as other coronaviruses.

Amorphous Albumin Gadolinium-Based Nanoparticles for Ultrahigh-Resolution Magnetic Resonance Angiography.

Magnetic resonance angiography (MRA) contrast agents are extensively utilized in clinical practice due to their capability of improving the image resolution and sensitivity. However, the clinically approved MRA contrast agents have the disadvantages of a limited acquisition time window and high dose administration for effective imaging. Herein, albumin-coated gadolinium-based nanoparticles (BSA-Gd) were meticulously developed for in vivo ultrahigh-resolution MRA. Compared to Gd-DTPA, BSA-Gd exhibits a significantly higher longitudinal relaxivity (r1 = 76.7 mM-1 s-1), nearly 16-fold greater than that of Gd-DTPA, and an extended blood circulation time (t1/2 = 40 min), enabling a dramatically enhanced high-resolution imaging of microvessels (sub-200 µm) and low dose imaging (about 1/16 that of Gd-DTPA). Furthermore, the clinically significant fine vessels were successfully mapped in large mammals, including a circle of Willis, kidney and liver vascular branches, tumor vessels, and differentiated arteries from veins using dynamic contrast-enhanced MRA BSA-Gd, and have superior imaging capability and biocompatibility, and their clinical applications hold substantial promise.

Highly sensitive detection of tryptophan based on Schiff base reaction and surface-enhanced Raman spectroscopy.

In this study, a simple, rapid and sensitive method combining surface-enhanced Raman spectroscopy and Schiff base reaction was developed for the detection of tryptophan. This method does not require product separation to obtain a significant Raman signal of the derivatized product, and the derivatization reaction can be controlled by experimental parameters such as reaction temperature, time, concentration of derivatization reagent and concentration of sodium nitrite. The characteristic peak of the derivative of tryptophan (1620 cm-1) was selected for quantitative analysis, and the intensity of the characteristic Raman spectrum peak showed a linear relationship with the concentration of tryptophan (10-8-10-4 mol/L) in the range of with a correlation coefficient R2 of 0.9922. This assay combines surface-enhanced Raman spectroscopy and Schiff base reaction, which is characterized by high sensitivity and easy operation, and has good application prospects in the detection of tryptophan in food.

In Situ Mitochondrial Biomineralization for Drug-Free Cancer Therapy.

The common clinical chemotherapy often brings serious side effects to patients, mainly due to the off-target and leakage of toxic drugs. However, this is fatal for some specific clinical tumors, such as brain tumors and neuroma. This study performs a drug-free approach by encapsulating black phosphorus (BP) and calcium peroxide (CaO2) in liposomes with surface-modified triphenylphosphonium (BCLT) to develop mitochondria targeting calcification for cancer therapy without damaging normal cells. BCLT preferentially accumulates inside tumor mitochondria and then is activated by near-infrared (NIR) laser irradiation to produce abundant PO4 3- and Ca2+ to accelerate in situ mitochondrial mineralization, leading to mitochondrial dysfunction and cancer cell death. More importantly, both PO4 3- and Ca2+ are essential components of metabolism in the body, and random gradient diffusion or premature leakage does not cause damage to adjacent normal cells. This achievement promises to be an alternative to conventional chemotherapy in clinical practice for many specific tumor types.

SERS detection of foodborne pathogens in beverage with Au nanostars.

The aim of this study is to develop a simple but rapid method for the determination of foodborne pathogens in complex matrices (beverages) by surface enhanced Raman spectroscopy (SERS) combined with Au nanostar solid-phase substrates. The star-shaped singlet Au nanostructure was formed on the surface of a stainless steel sheet by chemical replacement reaction. Rhodamine 6G verified the sensitivity and reproducibility of this substrate, and the relative standard deviations of the SERS intensity at 1312 cm-1, 1364 cm-1, and 1510 cm-1 displacements were 3.40%, 5.64%, and 3.48%, respectively. By detecting four pathogens in beverage samples on Au nanostar substrates, the utility of the SERS assay was demonstrated, while the combination of principal component analysis (PCA) and hierarchical cluster analysis (HCA) further enabled the isolation and identification of pathogens. The results of spiked beverages were validated in conventional culture identification and Vitek 2 Compact biochemical identification system experiments. Thus, this research demonstrated that Au nanostar substrates can be effectively utilized for the recognition of pathogenic bacteria and have immense promise to advance the progress of quick detection of foodborne pathogens and food safety.

Constructing a 3D interconnected network of Ag nanostructures for high-performance SERS detection of food coloring agents.

The design and preparation of various effective three-dimensional (3D) silver nanostructures is a frontier area of research in the field of surface-enhanced Raman scattering (SERS). This paper demonstrates a simple and novel method for the preparation of a substrate, whose surface was covered by a 3D interconnected network of Ag nanostructures, and the resulting network structure surface is free of organic contaminants. The EDS measurements confirm the metallic nature of the formed 3D Ag nanonetwork substrate. Additionally, the influence of experimental parameters on the morphology of the 3D Ag nanonetwork was also investigated, such as reaction time, hydrofluoric acid concentration, silver nitrate concentration and sodium citrate concentration. The 3D Ag nanonetwork has good uniformity. Importantly, the 3D Ag nanonetwork substrate was used to accurately and reliably detect amaranth (AR) and sunset yellow (SY) in beverages, with the lowest detection limit of 3 and 0.1 µg L-1, respectively. Therefore, this substrate is expected to be a promising candidate for SERS detection and offers attractive potential for a wider range of applications.

Markers of insulin resistance associated with non-alcoholic fatty liver disease in non-diabetic population.

Insulin resistance (IR) plays an important role in the development of non-alcoholic fatty liver disease (NAFLD). IR markers are divided into two types: (1) insulin-based IR marker, homeostatic model assessment of IR (HOMA-IR); and (2) non-insulin-based IR markers, such as triglyceride-glucose (TyG) index, TyG index with body mass index (TyG-BMI), triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-c), and metabolic score for IR (METS-IR). The non-insulin-based IR markers are often associated with lipids. The aim of this study was to analyse the association between IR markers and NAFLD in non-diabetic population. Baseline data of NAFLD and non-NAFLD groups were compared. Logistic regression was used to evaluate the relationship between five IR markers and NAFLD risk. The odds ratios (ORs) and 95% confidence intervals (CIs) of IR markers were calculated. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were used to evaluate the ability of different IR markers to detect NAFLD. Subgroup analyses were performed in obese and non-obese subgroups. This study found a positive correlation between NAFLD risk and elevation in five IR markers (HOMA-IR, TyG, TyG-BMI, TG/HDL-c, and METS-IR). In non-obese subjects, the AUC of TyG-BMI was larger than that of the other four IR markers to detect NAFLD. The AUC of HOMA-IR was larger than that of the other four IR markers to detect NAFLD in obese subjects. In non-diabetic population, the five IR markers are associated with the risk of NAFLD, including non-obese and obese NAFLD. TyG-BMI and HOMA-IR can be used to detect non-obese and obese NAFLD, respectively, with better detection ability compared with the other IR markers.

Quantum Complementarity Approach to Device-Independent Security.

Complementarity is an essential feature of quantum mechanics. The preparation of an eigenstate of one observable implies complete randomness in its complementary observable. In quantum cryptography, complementarity allows us to formulate security analyses in terms of phase-error correction. However, the concept becomes much subtler in the device-independent regime that offers security without device characterization. Security proofs of device-independent quantum cryptography tasks are often complex and quite different from those of their more standard device-dependent cousins. The existing proofs pose huge challenges to experiments, among which large data-size requirement is a crux. Here, we show the complementarity security origin of the device-independent tasks. By linking complementarity with quantum nonlocality, we recast the device-independent scheme into a quantum error correction protocol. Going beyond the identical-and-independent-distribution case, we consider the most general attack. We generalize the sample entropy in classical Shannon theory for the finite-size analysis. Our method exhibits good finite-size performance and brings the device-independent scheme to a more practical regime. Applying it to the data in a recent ion-trap-based device-independent quantum key distribution experiment, one could reduce the requirement on data size to less than a third. Furthermore, the operational meaning of complementarity naturally extends device-independent scenarios to advantage key distillation, easing experiments by tolerating higher loss and lower transmittance.

HOMA-IR is an effective biomarker of non-alcoholic fatty liver disease in non-diabetic population.

OBJECTIVES: This study aimed to investigate the correlation between homeostasis model assessment of insulin resistance (HOMA-IR) and non-alcoholic fatty liver disease (NAFLD) in the non-diabetic population and establish its diagnostic efficacy. METHODS: This observational study involved participants divided into NAFLD and non-NAFLD groups, and baseline data were analyzed. Univariate and multivariate logistic regression analyses were used to correlate HOMA-IR with the risk of NAFLD. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficacy of HOMA-IR for NAFLD. Subgroup analyses of non-obese individuals were performed. RESULTS: Overall, 2234 non-diabetic participants were included. The HOMA-IR was significantly higher in the NAFLD group than in the non-NAFLD group. Multivariate logistic regression analysis showed that HOMA-IR was a strong and independent risk factor for NAFLD after correcting for confounding factors. The area under the ROC curve (AUC) value of HOMA-IR for predicting NAFLD was 0.792. In the non-obese non-diabetic population, HOMA-IR was an independent risk factor for increased risk of lean NAFLD after correcting for confounding factors. The AUC value of HOMA-IR for predicting lean NAFLD was 0.770. CONCLUSIONS: HOMA-IR is independently associated with the risk of NAFLD in the non-diabetic and non-obese non-diabetic populations and has good diagnostic value.

Serum neurofilament light chain predicts spinal cord atrophy in neuromyelitis optica spectrum disorder.

Levels of serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) are useful biomarkers of disease activity and disability in neuromyelitis optica spectrum disorder (NMOSD). Here we investigated the association of sNfL and sGFAP levels with brain and spinal cord volumes in patients with NMOSD. Fifteen patients with NMOSD were enrolled in this prospective study. The median baseline level of sNfL was 42.2 (IQR, 16.1-72.6) pg/mL and decreased to 8.5 (IQR, 7.4-16.6) pg/mL at the end of the study. The reduction in sNfL was associated with a 7.5% loss of cervical spinal cord volume (CSCV) (p = 0.001). The levels of sGFAP reduced from 239.2 (IQR, 139.0-3393.3) pg/mL at baseline to 108.5 (IQR, 74.2-154.6) pg/mL. However, there was no strong correlation between sGFAP levels and CSCV changes during the follow-up period. Our data suggested that sNfL level is a useful biomarker for predicting spinal cord atrophy in patients with NMOSD.

Cause of Death in Patients with Oropharyngeal Carcinoma by Human Papillomavirus Status: Comparative Data Analysis.

BACKGROUND: The incidence of oropharyngeal squamous cell carcinomas (OPSCC) has increased in recent decades, and human papillomavirus (HPV) infection is the main cause of OPSCC. The data regarding causes of death (CODs) are vitally important in informing follow-up strategies and revising treatment strategies to deal with any possible preventable treatment-related COD. However, limited studies have assessed the competing COD by HPV status in patients with OPSCC. OBJECTIVE: We aimed to analyze the distribution of the competing COD according to HPV status in OPSCC. METHODS: We retrospectively included stage I-IVB patients with OPSCC from the Surveillance, Epidemiology, and End Results database between 2010 and 2015. The association between HPV status and head and neck cancer-specific mortality (HNCSM), second primary cancer mortality (SPCM), and noncancer-caused mortality (NCCM) were analyzed. The chi-square test, Kaplan-Meier analysis, and Fine and Gray model were used for statistical analysis. RESULTS: We included 5852 patients in this study and 73.2% (n=4283) of them had HPV-related tumors. A total of 1537 (26.3%) patients died, including 789 (51.3%), 333 (21.7%), and 415 (27%) patients who died from head and neck cancer, second cancer, and noncancer causes, respectively. The 5-year HNCSM, SPCM, NCCM, and overall mortality were 14.7%, 6.5%, 7.7%, and 26.4%, respectively. Those with HPV-positive disease had a lower cumulative incidence of HNCSM (subdistribution hazard ratio [sHR] 0.362, 95% CI 0.315-0.417; P<.001), SPCM (sHR 0.400, 95% CI 0.321-0.496; P<.001), and NCCM (sHR 0.460, 95% CI 0.378-0.560; P<.001) than those with HPV-negative disease. The 5-year risk of HNCSM was 26.9% and 10.7% in those with HPV-negative and HPV-positive disease, respectively (P<.001). The 5-year risk of SPCM was 12.4% and 4.6% in those with HPV-negative and HPV-positive disease, respectively (P<.001). The 5-year risk of NCCM of death was 13.7% and 5.8% in those with HPV-negative and HPV-positive disease, respectively (P<.001). Using the Fine and Gray competing-risks model, our results show that those with HPV-negative tumors had a significantly higher risk of HNCSM (P<.001), SPCM (P<.001), and NCCM (P<.001) than those with HPV-negative tumors. CONCLUSIONS: HPV-positive OPSCC has a lower NCSM, SPCM, and NCCM as compared to those with HPV-negative OPSCC. HPV positivity is a favorable prognostic factor in the context of overcoming cancer as well as in terms of reducing the risk of other CODs in OPSCC. Our finding supports the need to tailor patient follow-up based on the HPV status of patients with OPSCC.

Crystal structures of main protease (Mpro) mutants of SARS-CoV-2 variants bound to PF-07304814.

There is an urgent need to develop effective antiviral drugs to prevent the viral infection caused by constantly circulating SARS-CoV-2 as well as its variants. The main protease (Mpro) of SARS-CoV-2 is a salient enzyme that plays a vital role in viral replication and serves as a fascinating therapeutic target. PF-07304814 is a covalent inhibitor targeting SARS-CoV-2 Mpro with favorable inhibition potency and drug-like properties, thus making it a promising drug candidate for the treatment of COVID-19. We previously solved the structure of PF-07304814 in complex with SARS-CoV-2 Mpro. However, the binding modes of PF-07304814 with Mpros from evolving SARS-CoV-2 variants is under-determined. In the current study, we expressed six Mpro mutants (G15S, K90R, M49I, S46F, V186F, and Y54C) that have been identified in Omicron variants including the recently emerged XBB.1.16 subvariant and solved the crystal structures of PF-07304814 bound to Mpro mutants. Structural analysis provided insight into the key molecular determinants responsible for the interaction between PF-07304814 and these mutant Mpros. Patterns for PF-07304814 to bind with these investigated Mpro mutants and the wild-type Mpro are generally similar but with some differences as revealed by detailed structural comparison. Structural insights presented in this study will inform the development of novel drugs against SARS-CoV-2 and the possible conformation changes of Mpro mutants when bound to an inhibitor.

Prevalence and related factors of epilepsy in children and adolescents with cerebral palsy: a systematic review and meta-analysis.

Objective: To study the worldwide prevalence and associated factors of epilepsy in children and adolescents with Cerebral Palsy (CP) and to analyze the differences between various subgroups. Method: We identified all potential studies on the prevalence of epilepsy in children and adolescents with CP from PubMed, Web of Science, and Embase. The search time was from the establishment of the database to November 2022. Randomized effects meta-analysis models were used to calculate the prevalence of epilepsy in CP. Subgroup analysis and meta-regression were utilized to further explore heterogeneity between articles and prevalence disparities between subgroups. The funnel plot and Egger's test were used to investigate potential publication bias. Results: Seventy-two articles, comprising 53,969 children and adolescents with CP, were included in this study. The results indicated a total epilepsy prevalence of 38.0% (95% CI: 34.8%-41.2%) in CP. The prevalence of epilepsy was 46.4% (95% CI: 41.4%-51.5%) in clinical sample-based studies and 31.6% (95% CI: 28.7%-34.5%) in population-based studies. Meta-regression demonstrated that the sample source, neonatal seizure, family history of epilepsy, EEG or cranial imaging abnormalities, intellectual/cognitive impairment, and topographical types of CP were heterogeneous contributors to the epilepsy prevalence in CP. Conclusion: Approximately one-third of children and adolescents with CP have epilepsy, and the sample source can significantly impact the total prevalence of epilepsy. Neonatal seizures, family history of epilepsy, EEG abnormalities, cranial imaging abnormalities, severe intellectual disability, and quadriplegia may be contributing factors to epilepsy comorbid in CP. Further study is required to verify the strength of these associations with epilepsy. This study aids in identifying the clinical characteristics of young people with CP at risk of developing epilepsy, which may assist clinicians in the early prevention and diagnosis of epilepsy within this population.Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=367766, identifier CRD42022367766.

Personal Microenvironment Management by Smart Textiles with Negative Oxygen Ions Releasing and Radiative Cooling Performance.

In recent years, significant strides have been made in the development of smart clothing, which combines traditional apparel with advanced technology. As our climate and environment undergo continuous changes, it has become critically important to invent and refine sophisticated textiles that enhance thermal comfort and human health. In this study, we present a "wearable forest-like textile". This textile is based on helical lignocellulose-tourmaline composite fibers, boasting mechanical strength that outperforms that of cellulose-based and natural macrofibers. This wearable microenvironment does more than generate approximately 18625 ions/cm3 of negative oxygen ions; it also effectively purifies particulate matter. Furthermore, our experiments demonstrate that the negative oxygen ion environment can slow fruit decay by neutralizing free radicals, suggesting promising implications for aging retardation. In addition, this wearable microenvironment reflects solar irradiation and selectively transmits human body thermal radiation, enabling effective radiative cooling of approximately 8.2 °C compared with conventional textiles. This sustainable and efficient wearable microenvironment provides a compelling textile choice that can enhance personal heat management and human health.

Structural basis for the inhibition of coronaviral main proteases by ensitrelvir.

Main protease (Mpro) is a highly conserved cysteine protease that plays a vital role in the replication of coronaviruses, making it an attractive pan-coronaviral therapeutic target. Ensitrelvir (S-217622), developed by Shionogi, is the first orally active non-covalent, non-peptidic SARS-CoV-2 Mpro inhibitor, which also displays antiviral efficacy against other human coronaviruses as well as SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs). Here, we report the crystal structures of the main proteases from SARS-CoV-2, SARS-CoV-2 VOC/VOIs, SARS-CoV, MERS-CoV, and HCoV-NL63 bound to the inhibitor S-217622. A detailed analysis of these structures illuminates key structural determinants essential for inhibition and elucidates the binding modes of the main proteases from different coronaviruses. Given the importance of the main protease for the treatment of coronaviral infection, structural insights obtained from this study could accelerate the design of novel antivirals with broad-spectrum efficacy against different human coronaviruses.