Substantial viral diversity in bats and rodents from East Africa: insights into evolution, recombination, and cocirculation.

BACKGROUND: Zoonotic viruses cause substantial public health and socioeconomic problems worldwide. Understanding how viruses evolve and spread within and among wildlife species is a critical step when aiming for proactive identification of viral threats to prevent future pandemics. Despite the many proposed factors influencing viral diversity, the genomic diversity and structure of viral communities in East Africa are largely unknown. RESULTS: Using 38.3 Tb of metatranscriptomic data obtained via ultradeep sequencing, we screened vertebrate-associated viromes from 844 bats and 250 rodents from Kenya and Uganda collected from the wild. The 251 vertebrate-associated viral genomes of bats (212) and rodents (39) revealed the vast diversity, host-related variability, and high geographic specificity of viruses in East Africa. Among the surveyed viral families, Coronaviridae and Circoviridae showed low host specificity, high conservation of replication-associated proteins, high divergence among viral entry proteins, and frequent recombination. Despite major dispersal limitations, recurrent mutations, cocirculation, and occasional gene flow contribute to the high local diversity of viral genomes. CONCLUSIONS: The present study not only shows the landscape of bat and rodent viromes in this zoonotic hotspot but also reveals genomic signatures driven by the evolution and dispersal of the viral community, laying solid groundwork for future proactive surveillance of emerging zoonotic pathogens in wildlife. Video Abstract.

Emergence of SARS and COVID-19 and preparedness for the next emerging disease X.

Severe acute respiratory syndrome (SARS) and Coronavirus disease 2019 (COVID-19) are two human Coronavirus diseases emerging in this century, posing tremendous threats to public health and causing great loss to lives and economy. In this review, we retrospect the studies tracing the molecular evolution of SARS-CoV, and we sort out current research findings about the potential ancestor of SARS-CoV-2. Updated knowledge about SARS-CoV-2-like viruses found in wildlife, the animal susceptibility to SARS-CoV-2, as well as the interspecies transmission risk of SARS-related coronaviruses (SARSr-CoVs) are gathered here. Finally, we discuss the strategies of how to be prepared against future outbreaks of emerging or re-emerging coronaviruses.

The association between flavonoids intake and hypertension in U.S. adults: A cross-sectional study from The National Health and Nutrition Examination Survey.

Although in vitro experiments have demonstrated the potential of flavonoid compounds in regulating blood pressure, there is still a lack of evidence from large population studies. We conducted a cross-sectional study using the National Health and Nutrition Examination Survey to investigate the relationship between flavonoid intake levels (natural log transformation) and hypertension events. A total of 15 752 participants aged over 20 years were included, and a weighted multivariable logistic regression analysis was performed to explore the relationship between total flavonoids, five sub types intake, and hypertension events. Smooth curve fitting was used to explore potential nonlinear relationships. Higher total flavonoids intake was associated with a lower risk of hypertension than the lowest group. The adjusted odds ratios (95% CIs) were 0.79 (0.70-0.88) for total flavonoids intake. Elevated total flavonoids intake levels were significantly and linearly associated with a lower risk of hypertension. For each unit increase in the total flavonoids intake level, the adjusted ORs for risk of hypertension decrease by 5% (OR 0.95; 95% CI, 0.92-0.98). In addition, in restricted cubic spline regression, we found that flavan-3-ols, anthocyanidins, and flavonols intake were linearly and negatively related to prevalence of hypertension. Flavones intake showed nonlinear associations with prevalence of hypertension with inflection points of -1.90. Within a certain range, a negative correlation exists between flavonoids intake and hypertension events. This finding provides insights into dietary modifications in the prevention of hypertension.

Global, regional and national temporal trends in prevalence for cardiovascular diseases in women of childbearing age, from 1990 to 2019: An age-period-cohort analysis.

Background: Epidemiological studies on cardiovascular diseases (CVD) among women of childbearing age (WCBA) remain scarce. Our research aims to delineate the prevalence trends of CVD within this population over the past three decades, considering age, period, and birth cohort dynamics. Methods: Estimates of CVD prevalence for WCBA, along with their 95% uncertainty intervals (UI), were extracted from the Global Burden of Diseases 2019 (GBD2019). An age-period-cohort (APC) model was utilized to assess the annual percentage change (net drifts) in overall prevalence, annual percentage changes in prevalence for individual age groups (local drifts), and fitted longitudinal age-specific rates adjusted for age effects and period/cohort relative risks (period/cohort effect). Results: In 2019, the global prevalence of CVD among WCBA was 53.42 million (95% UI: 47.77 to 60.18). Eight countries recorded a prevalence exceeding one million, accounting for 54.17% of the global CVD prevalence in WCBA. Over the past 30 years, the annual net drift in CVD prevalence among the global WCBA was 0.27% (95% CI: 0.25 to 0.29). This value was 0.01% (95% CI: 0.04 to 0.06) in regions with a high sociodemographic index (SDI) and 0.21% (95% CI: 0.19 to 0.22) in those with a low SDI. Seventy-seven countries demonstrated an increasing trend in CVD prevalence, while 53 showed a decrease, and 74 remained relatively stable. Notably, as shown in local drift, there was a rise in CVD prevalence among adolescents aged 15-19 and adults aged 40-49 in regions categorized by five distinct SDI levels. This drift varied by SDI regions. Regions with a high SDI consistently had elevated period risks throughout the study duration, while other regions had lower period risks until 2000-2004 and displayed increased adverse period risks. The prevalence in low-middle and low SDI regions manifested detrimental trends, whereas other regions demonstrated an initial decline followed by a surge in successive birth cohorts. Conclusions: Resources dedicated to CVD care for WCBA are largely insufficient, especially in low SDI regions. Thus, there is an urgent need to allocate cardiovascular healthcare resources variably across different SDI regions, aiming to diminish risks among successively younger birth cohorts. Throughout this endeavor, the formulation of targeted policies and the judicious distribution of resources are essential to reduce risks for women across all age groups.

Transnational inequities in cardiovascular diseases from 1990 to 2019: exploration based on the global burden of disease study 2019.

Background: To describe the burden and examine transnational inequities in overall cardiovascular disease (CVD) and ten specific CVDs across different levels of societal development. Methods: Estimates of disability-adjusted life-years (DALYs) for each disease and their 95% uncertainty intervals (UI) were extracted from the Global Burden of Diseases (GBD). Inequalities in the distribution of CVD burdens were quantified using two standard metrics recommended absolute and relative inequalities by the World Health Organization (WHO), including the Slope Index of Inequality (SII) and the relative concentration Index. Results: Between 1990 and 2019, for overall CVD, the Slope Index of Inequality changed from 3760.40 (95% CI: 3758.26 to 3756.53) in 1990 to 3400.38 (95% CI: 3398.64 to 3402.13) in 2019. For ischemic heart disease, it shifted from 2833.18 (95% CI: 2831.67 to 2834.69) in 1990 to 1560.28 (95% CI: 1559.07 to 1561.48) in 2019. Regarding hypertensive heart disease, the figures changed from-82.07 (95% CI: -82.56 to-81.59) in 1990 to 108.99 (95% CI: 108.57 to 109.40) in 2019. Regarding cardiomyopathy and myocarditis, the data evolved from 273.05 (95% CI: 272.62 to 273.47) in 1990 to 250.76 (95% CI: 250.42 to 251.09) in 2019. Concerning aortic aneurysm, the index transitioned from 104.91 (95% CI: 104.65 to 105.17) in 1990 to 91.14 (95% CI: 90.94 to 91.35) in 2019. Pertaining to endocarditis, the figures shifted from-4.50 (95% CI: -4.64 to-4.36) in 1990 to 16.00 (95% CI: 15.88 to 16.12) in 2019. As for rheumatic heart disease, the data transitioned from-345.95 (95% CI: -346.47 to-345.42) in 1990 to-204.34 (95% CI: -204.67 to-204.01) in 2019. Moreover, the relative concentration Index for overall CVD and each specific type also varied from 1990 to 2019. Conclusion: There's significant heterogeneity in transnational health inequality for ten specific CVDs. Countries with higher levels of societal development may bear a relatively higher CVD burden except for rheumatic heart disease, with the extent of inequality changing over time.

U-shaped stereoscopic design strategy toward N-doped nanographene segment.

There have been scarce reports about stereoscopic design of N-heteroacenes (NHAs), especially for the electron-deficient π-building blocks. Herein, we report the design and synthesis of a U-shaped bis(pyrene-quinoxaline) (BPQ). Single crystal X-ray diffraction reveals the herringbone stacking pattern and the presence of regular and incompletely closed pores.

Threshold-modifying effect of the systemic inflammatory response index on kidney function decline in hypertensive patients.

BACKGROUND: Chronic kidney disease (decreased kidney function) is common in hypertensive patients. The SIRI is a novel immune biomarker. We investigated the correlation between the SIRI and kidney function in hypertensive patients. METHODS: The present study analyzed data from participants who suffered from hypertension in the NHANES from 2009 to 2018. Multivariate regression analysis and subgroup analysis were used to clarify whether the SIRI was an independent risk factor for decreased kidney function. RCSs were utilized to evaluate the correlation between the SIRI and the eGFR and between the SIRI and the ACR. In addition, we modeled the mediating effect of the SIRI on the eGFR and the ACR using blood pressure as a mediating variable. RESULTS: The highest SIRI was an independent risk factor for a decreased eGFR [odds ratio (OR) = 1.46, 95% CI (1.15, 1.86)] and an increased ACR [OR = 2.26, 95% CI (1.82, 2.82)] when the lowest quartile was used as the reference. The RCS results indicated an inverted U-shaped relationship between the SIRI and the eGFR and between the SIRI and the ACR (the inflection points were 1.86 and 3.09, respectively). The mediation effect analysis revealed that the SIRI was the main factor influencing kidney function, and diastolic blood pressure was a mediating variable. In particular, there was a fully mediating effect between the SIRI and UCr, with a mediating effect value of -0.61 (-0.90, -0.36). CONCLUSIONS: The association between the SIRI and renal function in hypertensive patients was significant and was particularly dominated by the association between the SIRI and the ACR. This difference may be due to the mediating effect of diastolic blood pressure.

Risk analysis of the association between different hemoglobin glycation index and poor prognosis in critical patients with coronary heart disease-A study based on the MIMIC-IV database.

BACKGROUND: The hemoglobin glycation index (HGI) is the difference between the observed and predicted values of glycosylated hemoglobin (HbA1c), which is closely associated with a variety of poor prognoses. However, there are still no studies on the correlation between HGI and poor prognosis in patients with critical coronary artery disease. The purpose of this study was to analyze the correlation between HGI and all-cause mortality in patients with critical coronary artery disease using the MIMIC-IV database. METHODS: The HGI was calculated by constructing a linear regression equation between HbA1c and fasting plasma glucose (FPG). A Kaplan‒Meier survival analysis model was constructed based on the HGI quartiles to clarify the differences in all-cause mortality rates between groups, and the log-rank test was used to assess the differences between groups. The hazard ratio (HR) of HGI as a risk factor for outcome events was assessed using the Cox proportional risk model and restricted cubic spline (RCS), with the Q2 group serving as the reference group. RESULTS: A total of 5260 patients were included in this study. The 30-day mortality rate of the patients was 4.94% and the mortality rate within 365 days was 13.12%. A low HGI was significantly associated with 30-day mortality (HR, 1.96; 95% CI, (1.38, 2.78); P < 0.001) and 365-day mortality (HR, 1.48; 95% CI, (1.19, 1.85); P < 0.001) in patients with critical coronary artery disease in the completely adjusted Cox proportional risk model. In addition, high levels of HGI were associated with 365-day mortality (HR, 1.31; 95% CI, (1.02, 1.69); P < 0.05). RCS analysis revealed a U-shaped relationship between HGI and outcome events. According to the stratified analysis, the interaction test revealed that the correlation between HGI and outcome events remained stable. CONCLUSION: There was a significant correlation between HGI and all-cause mortality in patients with critical coronary artery disease, particularly in those with low HGI. HGI can be used as a potential indicator for assessing the short- and long-term risk of mortality in such patients.

Origin and evolution of pentanucleotide repeat expansions at the familial cortical myoclonic tremor with epilepsy type1 - SAMD12 locus.

Familial cortical myoclonic tremor with epilepsy type 1 (FCMTE1) is caused by (TTTTA)exp(TTTCA)exp repeat expansions in SAMD12, while pure (TTTTA)exp is polymorphic. Our investigation focused on the origin and evolution of pure (TTTTA)exp and (TTTTA)exp(TTTCA)exp at this locus. We observed a founder effect between them. The phylogenetic analysis suggested that the (TTTTA)exp(TTTCA)exp might be generated from pure (TTTTA)exp through infrequent transformation events. Long-read sequencing revealed somatic generation of (TTTTA)exp(TTTCA)exp from pure (TTTTA)exp, likely via long segment (TTTCA) repeats insertion. Our findings indicate close relationships between the non-pathogenic (TTTTA)exp and the pathogenic (TTTTA)exp(TTTCA)exp, with dynamic interconversions. This sheds light on the genesis of pathogenic repeat expansions from ancestral premutation alleles. Our results may guide future studies in detecting novel repeat expansion disorders and elucidating repeat expansion mutational processes, thereby enhancing our understanding of human genomic variation.

Elastic Relaxor Ferroelectric by Thiol-ene Click Reaction.

As ferroelectrics hold significance and application prospects in wearable devices, the elastification of ferroelectrics becomes more and more important. Nevertheless, achieving elastic ferroelectrics requires stringent synthesis conditions, while the elastification of relaxor ferroelectric materials remains unexplored, presenting an untapped potential for utilization in energy storage and actuation for wearable electronics. The thiol-ene click reaction offers a mild and rapid reaction platform to prepare functional polymers. Therefore, we employed this approach to obtain an elastic relaxor ferroelectric by crosslinking an intramolecular carbon-carbon double bonds (CF=CH) polymer matrix with multiple thiol groups via a thiol-ene click reaction. The resulting elastic relaxor ferroelectric demonstrates pronounced relaxor-type ferroelectric behaviour. This material exhibits low modulus, excellent resilience, and fatigue resistance, maintaining a stable ferroelectric response even under strains up to 70 %. This study introduces a straightforward and efficient approach for the construction of elastic relaxor ferroelectrics, thereby expanding the application possibilities in wearable electronics.

Subcutaneous implantation of nodular goiter after transoral endoscopic thyroidectomy vestibular approach: A case study and review of literature.

BACKGROUND: Extrathyroid implantation or dissemination of thyroid tissue secondary to a thyroid procedure is rare. Most of these belonged to thyroid carcinoma with metastatic potential and uncommon for benign pathologies. METHODS: We report the case of a 31-year-old female who was identified to have multiple subcutaneous implantation of thyroid tissue 5 years after transoral endoscopic thyroidectomy vestibular approach. A comprehensive literature search on implantation of thyroid tissue secondary to thyroid procedures was performed. RESULTS: Accidental tearing of the capsule during previous surgery may lead to the subcutaneous implantation. Through literature review, a total 29 articles with 47 patients were identified. 33.3% were benign lesions, and implantation was mostly secondary to fine needle aspiration biopsy (46.5%). CONCLUSIONS: Subcutaneous or port site implantation after endoscopic thyroid surgery may occur in benign thyroid pathologies and therefore, oncologic principles must be strictly followed during surgery regardless of its histopathological nature.

High-Curie-Temperature Elastic Polymer Ferroelectric by Carbene Cross-Linking.

With the emergence of wearable electronics, ferroelectrics are poised to serve as key components for numerous potential applications. Currently, intrinsically elastic ferroelectrics featuring a network structure through a precise "slight cross-linking" approach have been realized. The resulting elastic ferroelectrics demonstrate a combination of stable ferroelectric properties and remarkable resilience under various strains. However, challenges arose as the cross-linking temperature was too high when integrating ferroelectrics with other functional materials, and the Curie temperature of this elastic ferroelectric was comparatively low. Addressing these challenges, we strategically chose a poly(vinylidene fluoride)-based copolymer with high vinylidene fluoride content to obtain a high Curie temperature while synthesizing a cross-linker with carbene intermediate for high reactivity to reduce the cross-linking temperature. At a relatively low temperature, we successfully fabricated elastic ferroelectrics through carbene cross-linking. The resulting elastic polymer ferroelectrics exhibit a higher Curie temperature and show a stable ferroelectric response under strains up to 50%. These materials hold significant potential for integration into wearable electronics.

Deep spatial proteomics reveals region-specific features of severe COVID-19-related pulmonary injury.

As a primary target of severe acute respiratory syndrome coronavirus 2, lung exhibits heterogeneous histopathological changes following infection. However, comprehensive insight into their protein basis with spatial resolution remains deficient, which hinders further understanding of coronavirus disease 2019 (COVID-19)-related pulmonary injury. Here, we generate a region-resolved proteomic atlas of hallmark pathological pulmonary structures by integrating histological examination, laser microdissection, and ultrasensitive proteomics. Over 10,000 proteins are quantified across 71 post-mortem specimens. We identify a spectrum of pathway dysregulations in alveolar epithelium, bronchial epithelium, and blood vessels compared with non-COVID-19 controls, providing evidence for transitional-state pneumocyte hyperplasia. Additionally, our data reveal the region-specific enrichment of functional markers in bronchiole mucus plugs, pulmonary fibrosis, airspace inflammation, and alveolar type 2 cells, uncovering their distinctive features. Furthermore, we detect increased protein expression associated with viral entry and inflammatory response across multiple regions, suggesting potential therapeutic targets. Collectively, this study provides a distinct perspective for deciphering COVID-19-caused pulmonary dysfunction by spatial proteomics.

The optimal QTc selection in patients of acute myocardial infarction with poor perioperative prognosis.

BACKGROUND: The predictive utility of QTc values, calculated through various correction formulas for the incidence of postoperative major adverse cardiovascular and cerebrovascular events (MACCE) in patients experiencing acute myocardial infarction (AMI), warrants further exploration. This study endeavors to ascertain the predictive accuracy of disparate QTc values for MACCE occurrences in patients with perioperative AMI. METHODS: A retrospective cohort of three hundred fourteen AMI patients, comprising 81 instances of in-hospital MACCE and 233 controls, was assembled, with comprehensive collection of baseline demographic and clinical data. QTc values were derived employing the correction formulas of Bazett, Fridericia, Hodges, Ashman, Framingham, Schlamowitz, Dmitrienko, Rautaharju, and Sarma. Analytical methods encompassed comparative statistics, Spearman correlation analysis, binary logistic regression models, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). RESULTS: QTc values were significantly elevated in the MACCE cohort compared to controls (P < 0.05). Spearman's correlation analysis between heart rate and QTc revealed a modest positive correlation for the Sarma formula (QTcBaz) (ρ = 0.46, P < 0.001). Within the multifactorial binary logistic regression, each QTc variant emerged as an independent risk factor for MACCE, with the Sarma formula-derived QTc (QTcSar) presenting the highest hazard ratio (OR = 1.025). ROC curve analysis identified QTcSar with a threshold of 446 ms as yielding the superior predictive capacity (AUC = 0.734), demonstrating a sensitivity of 60.5% and a specificity of 82.8%. DCA indicated positive net benefits for QTcSar at high-risk thresholds ranging from 0 to 0.66 and 0.71-0.96, with QTcBaz, prevalent in clinical settings, showing positive net benefits at thresholds extending to 0-0.99. CONCLUSION: For perioperative AMI patients, QTcSar proves more advantageous in monitoring QTc intervals compared to alternative QT correction formulas, offering enhanced predictive prowess for subsequent MACCE incidents.

Isolation of ACE2-dependent and -independent sarbecoviruses from Chinese horseshoe bats.

While the spike proteins from severe acute respiratory syndrome coronaviruses-1 and 2 (SARS-CoV and SARS-CoV-2) bind to host angiotensin-converting enzyme 2 (ACE2) to infect cells, the majority of bat sarbecoviruses cannot use ACE2 from any species. Despite their discovery almost 20 years ago, ACE2-independent sarbecoviruses have never been isolated from field samples, leading to the assumption these viruses pose little risk to humans. We have previously shown how spike proteins from a small group of ACE2-independent bat sarbecoviruses may possess the ability to infect human cells in the presence of exogenous trypsin. Here, we adapted our earlier findings into a virus isolation protocol and recovered two new ACE2-dependent viruses, RsYN2012 and RsYN2016A, as well as an ACE2-independent virus, RsHuB2019A. Although our stocks of RsHuB2019A rapidly acquired a tissue-culture adaption that rendered the spike protein resistant to trypsin, trypsin was still required for viral entry, suggesting limitations on the exogenous entry factors that support bat sarbecoviruses. Electron microscopy revealed that ACE2-independent sarbecoviruses have a prominent spike corona and share similar morphology to other coronaviruses. Our findings demonstrate a broader zoonotic threat posed by sarbecoviruses and shed light on the intricacies of coronavirus isolation and propagation in vitro. IMPORTANCE Several coronaviruses have been transmitted from animals to people, and 20 years of virus discovery studies have uncovered thousands of new coronavirus sequences in nature. Most of the animal-derived sarbecoviruses have never been isolated in culture due to cell incompatibilities and a poor understanding of the in vitro requirements for their propagation. Here, we built on our growing body of work characterizing viral entry mechanisms of bat sarbecoviruses in human cells and have developed a virus isolation protocol that allows for the exploration of these understudied viruses. Our protocol is robust and practical, leading to successful isolation of more sarbecoviruses than previous approaches and from field samples that had been collected over a 10-year longitudinal study.

N-linked glycoproteins and host proteases are involved in swine acute diarrhea syndrome coronavirus entry.

IMPORTANCE: Gaining insight into the cell-entry mechanisms of swine acute diarrhea syndrome coronavirus (SADS-CoV) is critical for investigating potential cross-species infections. Here, we demonstrated that pretreatment of host cells with tunicamycin decreased SADS-CoV attachment efficiency, indicating that N-linked glycosylation of host cells was involved in SADS-CoV entry. Common N-linked sugars Neu5Gc and Neu5Ac did not interact with the SADS-CoV S1 protein, suggesting that these molecules were not involved in SADS-CoV entry. Additionally, various host proteases participated in SADS-CoV entry into diverse cells with different efficiencies. Our findings suggested that SADS-CoV may exploit multiple pathways to enter cells, providing insights into intervention strategies targeting the cell entry of this virus.

Identification of TMEM53 as a novel SADS-CoV restriction factor that targets viral RNA-dependent RNA polymerase.

ABSTRACTZoonotic transmission of coronaviruses (CoVs) poses a serious public health threat. Swine acute diarrhea syndrome coronavirus (SADS-CoV), originating from a bat HKU2-related CoV, causes devastating swine diseases and poses a high risk of spillover to humans. Currently, licensed therapeutics that can prevent potential human outbreaks are unavailable. Identifying the cellular proteins that restrict viral infection is imperative for developing effective interventions and therapeutics. We utilized a large-scale human cDNA screening and identified transmembrane protein 53 (TMEM53) as a novel cell-intrinsic SADS-CoV restriction factor. The inhibitory effect of TMEM53 on SADS-CoV infection was found to be independent of canonical type I interferon responses. Instead, TMEM53 interacts with non-structural protein 12 (NSP12) and disrupts viral RNA-dependent RNA polymerase (RdRp) complex assembly by interrupting NSP8-NSP12 interaction, thus suppressing viral RdRp activity and RNA synthesis. Deleting the transmembrane domain of TMEM53 resulted in the abrogation of TMEM53-NSP12 interaction and TMEM53 antiviral activity. Importantly, TMEM53 exhibited broad antiviral activity against multiple HKU2-related CoVs. Our findings reveal a novel role of TMEM53 in SADS-CoV restriction and pave the way to host-directed therapeutics against HKU2-related CoV infection.

Characterization of a mouse-adapted strain of bat severe acute respiratory syndrome-related coronavirus.

Bats carry genetically diverse severe acute respiratory syndrome-related coronaviruses (SARSr-CoVs). Some of them utilize human angiotensin-converting enzyme 2 (hACE2) as a receptor and cannot efficiently replicate in wild-type mice. Our previous study demonstrated that the bat SARSr-CoV rRsSHC014S induces respiratory infection and lung damage in hACE2 transgenic mice but not wild-type mice. In this study, we generated a mouse-adapted strain of rRsSHC014S, which we named SMA1901, by serial passaging of wild-type virus in BALB/c mice. SMA1901 showed increased infectivity in mouse lungs and induced interstitial lung pneumonia in both young and aged mice after intranasal inoculation. Genome sequencing revealed mutations in not only the spike protein but the whole genome, which may be responsible for the enhanced pathogenicity of SMA1901 in wild-type BALB/c mice. SMA1901 induced age-related mortality similar to that observed in SARS and COVID-19. Drug testing using antibodies and antiviral molecules indicated that this mouse-adapted virus strain can be used to test prophylactic and therapeutic drug candidates against SARSr-CoVs. IMPORTANCE The genetic diversity of SARSr-CoVs in wildlife and their potential risk of cross-species infection highlights the importance of developing a powerful animal model to evaluate the antibodies and antiviral drugs. We acquired the mouse-adapted strain of a bat-origin coronavirus named SMA1901 by natural serial passaging of rRsSHC014S in BALB/c mice. The SMA1901 infection caused interstitial pneumonia and inflammatory immune responses in both young and aged BALB/c mice after intranasal inoculation. Our model exhibited age-related mortality similar to SARS and COVID-19. Therefore, our model will be of high value for investigating the pathogenesis of bat SARSr-CoVs and could serve as a prospective test platform for prophylactic and therapeutic candidates.

Intrinsically elastic polymer ferroelectric by precise slight cross-linking.

Ferroelectrics are an integral component of the modern world and are of importance in electrics, electronics, and biomedicine. However, their usage in emerging wearable electronics is limited by inelastic deformation. We developed intrinsically elastic ferroelectrics by combining ferroelectric response and elastic resilience into one material by slight cross-linking of plastic ferroelectric polymers. The precise slight cross-linking can realize the complex balance between crystallinity and resilience. Thus, we obtained an elastic ferroelectric with a stable ferroelectric response under mechanical deformation up to 70% strain. This elastic ferroelectric exerts potentials in applications related to wearable electronics, such as elastic ferroelectric sensors, information storage, and energy transduction.