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Two ultrastable luminescent covalent organic frameworks (COFs), PyTA‐BC and PyTA‐BC‐Ph, are synthesized through polycondensations of 4,4′,4″,4′″‐pyrene‐1,3,6,8‐tetrayl)tetraaniline (PyTA‐4NH2) with two carbazole‐based derivatives having different degrees of conjugation. The PyTA‐BC and PyTA‐BC‐Ph COFs exhibit ultrahigh thermal stabilities (up to 421 °C), excellent crystallinity, and high Brunauer–Emmett–Teller surface areas (up to 1445 m2 g−1). These COFs display strong fluorescence emissions in various solvents, with their emission maxima gradually red‐shifting upon increasing the polarity of the solvent (solvatochromism). Upon exposure to HCl, they respond very rapidly and sensitively in terms of changing their colors and fluorescence emission maxima. In the presence of a sacrificial electron donor, these COFs mediate the highly efficient photocatalytic evolution of H2 from water. In the absence of a noble metal cocatalyst, the COFs and ascorbic acid provide a photocatalytic H2 production of up to 1183 µmol g−1 h−1 (λ ≥ 420 nm); this value is the highest reported to date for a COF. Such COFs appear to be potentially useful as chemosensors for the naked‐eye and sensitive spectroscopic detection of HCl and as cocatalysts for the sustainable photocatalytic production of H2 from water. [ABSTRACT FROM AUTHOR]

Background: Influenza A viruses cause epidemics/severe pandemics that pose a great global health threat. Among eight viral RNA segments, the multiple functions of nucleoprotein (NP) play important roles in viral replication and transcription. Methods: To understand how NP contributes to the virus evolution, we analyzed the NP gene of H3N2 viruses in Taiwan and 14,220 NP sequences collected from Influenza Research Database. The identified genetic variations were further analyzed by mini-genome assay, virus growth assay, viral RNA and protein expression as well as ferret model to analyze their impacts on viral replication properties. Results: The NP genetic analysis by Taiwan and global sequences showed similar evolution pattern that the NP backbones changed through time accompanied with specific residue substitutions from 1999 to 2018. Other than the conserved residues, fifteen sporadic substitutions were observed in which the 31R, 377G and 450S showed higher frequency. We found 31R and 450S decreased polymerase activity while the dominant residues (31 K and 450G) had higher activity. The 31 K and 450G showed better viral translation and replication in vitro and in vivo. Conclusions: These findings indicated variations identified in evolution have roles in modulating viral replication in vitro and in vivo. This study demonstrates that the interaction between variations of NP during virus evolution deserves future attention. [ABSTRACT FROM AUTHOR]

Delirium is a common neuropsychiatric syndrome that is often overlooked in clinical settings. The most accurate instrument for screening delirium has not been established. This study aimed to compare the diagnostic accuracy of the 4 'A's Test (4AT), Nursing Delirium Screening Scale (Nu-DESC), and Confusion Assessment Method (CAM) in detecting delirium among older adults in clinical settings. These assessment tools feature concise item sets and straightforward administration procedures. Five electronic databases were systematically searched from their inception to September 7, 2022. Studies evaluating the sensitivity and specificity of the 4AT, Nu-DESC, and CAM against the Diagnostic and Statistical Manual of Mental Disorders or International Classification of Diseases as the reference standard were included. Bivariate random effects model was used to summarize the sensitivity and specificity results. A total of 38 studies involving 7378 patients were included. The 4AT, Nu-DESC, and CAM had comparable sensitivity in detecting delirium (0.76, 0.78, and 0.80, respectively). However, the specificity of the CAM was higher than that of the 4AT (0.98 vs 0.89, P =.01) and Nu-DESC 0.99 vs 0.90, P =.003). Diagnostic accuracy was moderated by the percentage of women, acute care setting, sample size, and assessors. The three tools exhibit comparable sensitivity, and the CAM has the highest specificity. Based on the feasibility of the tools, nurses and clinical staffs could employ the Nu-DESC and the 4AT on screening out positive delirium cases and integrate these tools into daily practice. Further investigations are warranted to verify our findings. • The 4 'A's Test (4AT), Nursing Delirium Screening Scale (Nu-DESC), and Confusion Assessment Method (CAM) are commonly used for delirium detection. • The 4AT, Nu-DESC, and CAM had comparable pooled sensitivity in screening delirium (0.76, 0.78, and 0.80, respectively). • The CAM had the optimal ability to exclude patients without delirium. • Nu-DESC is suitable for screening delirium among older adults through daily nursing practice in few minutes. [ABSTRACT FROM AUTHOR]

Ultrasound strain imaging has been proposed to quantitatively assess myocardial contractility. Cross-correlation- based 2-D speckle tracking (ST) and auto-correlationbased tissue Doppler imaging (TDI) [often called Doppler tissue imaging (DTI)] are competitive ultrasound techniques for this application. Compared with 2-D ST, TDI, as a 1-D method, is sensitive to beam angle and suffers from low strain signal-to-noise ratio because a high pulse repetition frequency is required to avoid aliasing in velocity estimation. In addition, ST and TDI are fundamentally different in the way that physical parameters such as the mechanical strain are derived, resulting in different estimation accuracy and interpretation. In this study, we directly compared the accuracy of TDI and 2-D ST estimates of instantaneous axial normal strain and accumulated axial normal strain using a simulated heart. We then used an isolated rabbit heart model of acute ischemia produced by left descending anterior artery ligation to evaluate the performance of the two methods in detecting abnormal motion. Results showed that instantaneous axial normal strains derived using TDI (0.36% error) were less accurate with larger variance than those derived from 2-D ST (0.08% error) given the same spatial resolution. In addition to poorer accuracy, accumulated axial normal strain estimates derived using TDI suffered from bias, because the accumulation method for TDI cannot trace along the actual tissue displacement path. Finally, we demonstrated the advantage 2-D ST has over TDI to reduce dependency on beam angle for lesion detection by estimating strains based on the principal stretches and their corresponding principal axes. [ABSTRACT FROM PUBLISHER]

Lead-tin perovskite solar cells (Pb-Sn PSCs) are a more environmentally friendly alternative to the mainstream lead-based PSCs, but their development has been hampered by their instability due to the strong tendency of the Sn2+ constituent to oxidize. This study examines the effects of three types of hydrazine compound—phenylhydrazine hydrochloride (PH•HCl), 4-fluorophenylhydrazine hydrochloride (FPH•HCl), and 1-[2,5-bis(trifluoromethyl)phenyl]hydrazine hydrochloride (BTFMPH•HCl)—as additives to Pb-Sn perovskite precursor solutions on the stability and performance of Pb-Sn PSC devices, taking advantages of the hydrazine functional group's ability to suppress oxidation of Sn2+, and of the hydrophobicity provided by the phenyl structure and/or fluorine (F) contents of the selected compounds. All of the three additives significantly improved the stability of the resultant Pb-Sn PSC devices, with the additives containing more F contents (BTFMPH•HCl > FPH•HCl > PH•HCl) showing slightly greater improvements. The PH•HCl additive markedly enhanced the power conversion efficiency (PCE) while reducing the hysteresis ratio of the PSC devices thanks to its multifaceted effects including improving morphology, reducing non-radiative losses, alleviating recombination defects, and enhancing charge-carrier mobility of the Pb-Sn perovskite layer, as elucidated by a series of photo-luminescence and electrical characterizations. Both the BTFMPH•HCl and FPH•HCl additives slightly degraded the device PCE due to their poorer resultant perovskite morphology, which was attributed to their lower affinity with the perovskite as a result of their F contents. Our results provide useful insights in selecting and designing hydrazine-based additives for PSC. • Efficiency and stability of Pb-Sn perovskite solar cells were enhanced with novel hydrazine additives. • Relationships between chemical structure and performance of the hydrazine additives were determined. • Mechanisms of the enhancement effects of the hydrazine additives were elucidated. • Results of this study provide useful insights in selecting and designing additives for perovskite solar cells. [ABSTRACT FROM AUTHOR]

Wild poliovirus (WPV) persists in diverse locales worldwide, spreading outward from endemic areas. In response to the international threat of WPV transmission and changes in the national vaccination policy, we established an environmental surveillance system to monitor the circulation of wild and vaccine-related poliovirus in Taiwan. From July 2012 to December 2013, we collected sewage specimens every month from 10 sewage treatment plants located throughout Taiwan. The specimens were concentrated by the two-phase separation method and then inoculated into L20B, RD, and A549 cells for virus isolation. Viral isolates were identified and serotyped by immunofluorescence assay or molecular analysis. A total of 300 sewage samples were collected, and the results showed 163 samples (54.3%) were positive for virus, and 268 isolates were identified. Among these, 75 samples (25%) were positive for enterovirus (EV), but no poliovirus was found. In addition, 92 isolates were identified as enteroviruses and the most common serotypes were coxsackievirus B4, coxsackievirus B3, and coxsackievirus B2. Interestingly, 102 (34%) and 82 (27.3%) specimens were positive for mammalian orthoreovirus (MRV) and adenovirus, respectively. This study confirmed that sewage surveillance can be a useful additional modality for monitoring the possible presence of wild-type or vaccine-derived poliovirus in wastewater, and can indicate the current types of viruses circulating in the population. Furthermore, since MRV was found in children with acute necrotizing encephalopathy and meningitis, the high incidence of MRV detected by environmental surveillance warrants further investigation. [ABSTRACT FROM AUTHOR]

Three aromatic diamines, 2,2′-diiodo-4,4′-oxydianiline (DI-ODA 2), 2,2′-bis[ p-(trifluoromethyl)phenyl]-4,4′-oxydianiline (BTFP-ODA 3) and 2,8-diaminodibenzofuran (DADBF 5) were synthesized by using 4,4-oxydianiline (4,4′-ODA) as the starting material. New aromatic polyamides 6, 7 and 8 were prepared from these three diamines and six commercially available aromatic diacids by direct polycondensation, respectively. Polyamides 6 and 7 contained bulky iodide and p-trifluoromethylphenyl substitutents that would hinder the chain packing and increase the free volume. They exhibited good optical transparency in visible light region and showed excellent solubility in organic solvents such as DMSO, DMAc, DMF and NMP. Polyamides 8 containing planar dibenzofuran moieties had the highest glass transition temperatures and decomposition temperatures among these polyamides. Polyamides 6 had the lowest decomposition temperatures due to the presence of weak carbon-iodine bond. All of these polyamides showed amorphous nature evidenced by wide angle X-ray diffraction. No endothermic peaks were observed from DSC thermograms up to their decomposition temperatures. High optical transparency and excellent solubility combined with good thermal stability make these polyamides attractive for potential soft electronics applications. [ABSTRACT FROM AUTHOR]

Abstract: Background: β-thalassemia represents a great heterogeneity as over 200 mutations have been identified for the β-globin gene responsible for this disease. A rapid genotyping test with high accuracy, selectivity, and reproducibility suitable for the determination of known mutations is needed for prenatal screening and post-natal diagnosis of this disease in clinical setting. Design and methods: We have performed the validation of a DHPLC assay for direct genotyping of known causative mutations in β-globin gene using the chromatographic pattern-based strategy under partially-denaturing conditions. Results: DHPLC assay was established based on the analysis of 795 DNA samples from a group of various genotypes for the 20 mutations and 8 polymorphisms in β-globin gene then validated on 319 tests in a blind study. The results obtained with this assay were in concordance with the results obtained by DNA sequence analysis. Conclusion: This simple method can meet the requirements of direct genotyping of known β-thalassemia mutations and/or polymorphisms in the clinical setting for Chinese and in general as a model for other populations. [Copyright &y& Elsevier]

Background: Influenza A virus (IAV) evolves strategies to counteract the host antiviral defense for establishing infection. The influenza A virus (IAV) non-structural protein 1 (NS1) is a key viral factor shown to counteract type I IFN antiviral response mainly through targeting RIG-I signaling. Growing evidence suggests that viral RNA sensors RIG-I, TLR3, and TLR7 function to detect IAV RNA in different cell types to induce type I IFN antiviral response to IAV infection. Yet, it remains unclear if IAV NS1 can exploit a common mechanism to counteract these RNA sensing pathways to type I IFN production at once, then promoting viral propagation in the host. Methods: Luciferase reporter assays were conducted to determine the effect of NS1 and its mutants on the RIG-I and TLR3 pathways to the activation of the IFN-β and NF-κB promoters. Coimmunoprecipitation and confocal microscopic analyses were used to the interaction and colocalization between NS1 and TRAF3. Ubiquitination assays were performed to study the effect of NS1 and its mutants on TRAF3 ubiquitination. A recombinant mutant virus carrying NS1 E152A/E153A mutations was generated by reverse genetics for biochemical, ex vivo, and in vivo analyses to explore the importance of NS1 E152/E153 residues in targeting the RNA sensing-TRAF3-type I IFN axis and IAV pathogenicity. Results: Here we report that NS1 subverts the RIG-I, TLR3, and TLR7 pathways to type I IFN production through targeting TRAF3 E3 ubiquitin ligase. NS1 harbors a conserved FTEE motif (a.a. 150-153), in which the E152/E153 residues are critical for binding TRAF3 to block TRAF3 ubiquitination and type I IFN production by these RNA sensing pathways. A recombinant mutant virus carrying NS1 E152A/E153A mutations induces higher type I IFN production ex vivo and in vivo, and exhibits the attenuated phenotype in infected mice, indicating the importance of E152/E153 residues in IAV pathogenicity. Conclusions: Together our work uncovers a novel mechanism of IAV NS1-mediated immune evasion to promote viral infection through targeting the RNA sensing-TRAF3-type I IFN axis. [ABSTRACT FROM AUTHOR]

The physical investigation of surfaces and their properties crucially depends on their quality. Such investigations are commonly performed in an ultra-high vacuum environment. Thereby, the transfer of samples among different setups and under ambient conditions is desirable. The usage of a capping layer for the protection of surfaces against contaminations during long-time storage and transfer, and the subsequent temperature-controlled decapping is an established approach. However, a residual-free removal of the capping layer may present a challenge. Here, we systematically investigate the decapping process of a tellurium protected topological insulator Bi2Te3. We give evidence for the material segregation from the contaminated capping layer surface to the substrates. Therefore, a simple, temperature controlled decapping is not sufficient. We demonstrate that near perfect surfaces can be reliably obtained even after long-time storage through a combination of an initial argon ion sputtering process and a following heating for decapping. This approach is suitable for dedicated analysis systems as well as for industrial applications, large throughput of samples of arbitrary shapes, and is easily implemented in existing setups. [ABSTRACT FROM AUTHOR]

Abstract Objective The aims of this study were to establish the reference intervals for HbA2 and HbF in a Guizhou population of reproductive age, and to determine the cut-off value of HbA 2 for β-thalassemia carrier screening. Methods Hemoglobin analysis was performed on 832 individuals without hypochromic microcytic anemia to calculate the reference intervals for HbA 2 and HbF. Three hundred and ninety one β-thalassemia carriers and non β-thalassemia individuals were analyzed for their HbA 2 levels followed by detecting β-globin gene mutations, then cut-off value of HbA 2 for β-thalassemia carrier screening was determined using ROC curve analysis. Results The reference interval for HbA 2 in overall normal individuals was 2.3%–3.1%, and reference intervals for HbF in normal males and females (including normal females and pregnant women) were 0–0.5% and 0–1.0% respectively. The cut-off values of HbA 2 for β-thalassemia carrier screening in males, non-pregnant women, pregnant women and the overall set were 4.40%, 3.75%, 3.70% and 3.95% respectively. Conclusion Gender and pregnancy status had no obvious influence on reference interval for HbA 2. The HbF level was higher in females than in males, but pregnancy status had no obvious influence on HbF level. Cut-off value of HbA 2 for β-thalassemia carrier screening was obviously affected by gender but not by pregnancy status. Highlights • Establish the reference intervals for HbA 2 and HbF • Determine the cut-off value for HbA 2 • Select the optimal reference intervals and cut-off value for local population [ABSTRACT FROM AUTHOR]

We describe an inexpensive alternative to conventional hydrophones for measuring ultrasonic fields. The hydrophone, composed of common laboratory supplies, depends on the acoustoelectric (AE) effect, a well-known interaction between electrical current and pressure. Beam patterns of a 540 kHz annular transducer captured using a bowtie-graphite hydrophone were consistent with patterns obtained using conventional, more expensive hydrophones. The AE signal was proportional to both the applied bias current (1.83 μV/mA) and pressure (13.3 μV/MPa) with sensitivity better than 50 kPa. Disposable AE hydrophones may be an attractive alternative for clinical applications that require close monitoring of high intensity acoustic fields. [ABSTRACT FROM AUTHOR]

Abstract: Ultrasound strain imaging using 2-D speckle tracking has been proposed to quantitatively assess changes in myocardial contractility caused by ischemia. Its performance must be demonstrated in a controlled model system as a step toward routine clinical application. In this study, a well-controlled 2-D cardiac elasticity imaging technique was developed using two coplanar and orthogonal linear probes simultaneously imaging an isolated retroperfused rabbit heart. Acute ischemia was generated by left anterior descending (LAD) artery ligation. An excitation-contraction decoupler, 2,3-butanedione monoxime, was applied at a 4-mM concentration to reversibly reduce myocardial contractility. Results using a single probe demonstrate that directional changes in the in-plane principal deformation axes can help locate the bulging area as a result of LAD ligation, which matched well with corresponding Evans Blue staining, and strains or strain magnitude, based on principal stretches, can characterize heart muscle contractility. These two findings using asymmetric displacement accuracy (i.e., normal single-probe measurements with good axial but poor lateral estimates) were further validated using symmetric displacement accuracy (i.e., dual-probe measurements using only accurate axial tracking estimates from each). However, the accuracy of 2-D cardiac strain imaging using a single probe depends on the probe''s orientation because of the large variance in lateral displacement estimates. (E-mail: cxjia@umich.edu) [Copyright &y& Elsevier]

Abstract: Genetic recombination is a well-known phenomenon for enteroviruses. In this study, we determined the phylogenetic relationships of five distinct regions of the EV71 genome for 73 EV71 isolates from 1986 and from 1998 to 2005 in Taiwan. Phylogenetic analyses showed that the 5′-UTR, VP4-VP2, VP1, and 3D regions of EV71 isolated in 2004 and 2005 were grouped into genotype C. However, the 2B region of these isolates differed in that it grouped with genotype B, indicating recombination within EV71 had occurred. This intratypic recombination was first seen in 2002 and became predominant in 2004 and 2005. The simplot and bootscan analyses identified two recombination points located at the 3′-termini of the 2A and 3C regions. This intratypic recombination was identified among naturally circulating EV71 isolates in Taiwan, therefore, it suggests that nonstructural genes may recombine to produce new EV71 variants. [Copyright &y& Elsevier]

Background: Delirium is a common symptom following a traumatic brain injury (TBI) that is often overlooked by healthcare professionals. Early detection of post-traumatic delirium is crucial to improving patient outcomes and quality of life. The four As Test (4AT: alertness, attention, abbreviated mental test-4, and acute mental changes) is a brief and rapid tool for delirium assessment with acceptable reliability and validity. However, the 4AT has not yet been translated for use in the Taiwanese population., Objective: To translate the 4AT into Traditional Chinese (TC-4AT), assess its reliability and validity, and explore the clinical effects of delirium in patients with TBI., Methods: This prospective observational study was conducted at the neurosurgery wards of two Taiwanese hospitals. Patients who were aged 20 years and older, were diagnosed with a TBI, and had a Glasgow Coma Scale score between 13 and 15 were included. Interrater reliability was assessed, and validity was verified using criterion-related comparisons with the Short Confusion Assessment Method (Short CAM). The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria were employed to assess the sensitivity and specificity of the TC-4AT for screening post-TBI delirium., Results: A total of 100 patients with an average age of 67 years were enrolled, of whom 10% were diagnosed with delirium based on the DSM-5 criteria. The interrater reliability of the TC-4AT was 1.00. Patients with delirium tended to have a longer hospital stay than those without delirium (13 days vs. 7 days) although the difference was nonsignificant (P = 0.28). In terms of criterion validity, patients diagnosed with delirium using the Short CAM had a significantly higher score on the TC-4AT than those not diagnosed with delirium (P < 0.001). The receiver operating characteristic curve indicated that the optimal cutoff point was 4, with sensitivity, specificity, and area under the characteristic curve of 0.90, 0.94, and 0.96, respectively., Conclusion: The TC-4AT is an accurate tool for delirium assessment that aids early detection and informs decision-making in preventive care., (Copyright © 2025 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.)

Purpose: To analyze the composition of abnormal hemoglobin and the relationship between genotype and phenotype by screening abnormal hemoglobin in a subpopulation of Guizhou, China., Patients and Methods: Routine blood evaluation, capillary electrophoresis of hemoglobin, and mutation of α - and β - thalassemia genes were evaluated in 19,976 individuals for thalassemia screening in Guizhou. Sanger sequencing of HBA1, HBA2 and HBB genes was performed in samples with abnormal bands or unexplained increases of normal bands. The types of abnormal hemoglobin were obtained by sequence analysis., Results: Abnormal hemoglobin was detected in 84 individuals (detection rate, 0.42%). Ten types each of α and β globin chain variants were detected, including most commonly Hb E, Hb New York and Hb Port Phillip. In this study, the abnormal Hb Mizuho was identified for the first time in a Chinese population, and a novel abnormal hemoglobin Hb Guiyang (HBA2: c.151C > A) was detected for the first time. Except for Hb Mizuho, other abnormal hemoglobin heterozygotes without thalassemia or iron deficiency had no significant hematological changes., Conclusion: This study enriched the molecular epidemiological data of abnormal hemoglobin in Guizhou, China and provided reference data for genetic counseling and prenatal diagnosis of abnormal hemoglobin., Competing Interests: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article., (© 2024 Chen et al.)

Dengue virus (DENV) causes approximately 390 million dengue infections worldwide every year. There were 22,777 reported DENV infections in Tainan, Taiwan in 2015. In this study, we sequenced the C-prM-E genes from 45 DENV 2015 strains, and phylogenetic analysis based on C-prM-E genes revealed that all strains were classified as DENV serotype 2 Cosmopolitan genotype. Sequence analysis comparing different DENV-2 genotypes and Cosmopolitan DENV-2 sequences prior to 2015 showed a clade replacement event in the DENV-2 Cosmopolitan genotype. Additionally, a major substitution C-A314G (K73R) was found in the capsid region which may have contributed to the clade replacement event. Reverse genetics virus rgC-A314G (K73R) showed slower replication in BHK-21 and C6/36 cells compared to wildtype virus, as well as a decrease in NS1 production in BHK-21-infected cells. After a series of passaging, the C-A314G (K73R) mutation reverted to wildtype and was thus considered to be unstable. Next generation sequencing (NGS) of three sera collected from a single DENV2-infected patient at 1-, 2-, and 5-days post-admission was employed to examine the genetic diversity over-time and mutations that may work in conjunction with C-A314G (K73R). Results showed that the number of haplotypes decreased with time in the DENV-infected patient. On the fifth day after admission, two new haplotypes emerged, and a single non-synonymous NS4A-L115I mutation was identified. Therefore, we have identified a persistent mutation C-A314G (K73R) in all of the DENV-2 isolates, and during the course of an infection, a single new non-synonymous mutation in the NS4A region appears in the virus population within a single host. The C-A314G (K73R) thus may have played a role in the DENV-2 2015 outbreak while the NS4A-L115I may be advantageous during DENV infection within the host., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Tsai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Enterovirus A71 (EV-A71) can induce severe neurological complications and even fatal encephalitis in children, and it has caused several large outbreaks in Taiwan since 1998. We previously generated VP1 codon-deoptimized (VP1-CD) reverse genetics (rg) EV-A71 viruses (rgEV-A71s) that harbor a high-fidelity (HF) 3D polymerase. These VP1-CD-HF rgEV-A71s showed lower replication kinetics in vitro and decreased virulence in an Institute of Cancer Research (ICR) mouse model of EV-A71 infection, while still retaining their antigenicity in comparison to the wild-type virus. In this study, we aimed to further investigate the humoral and cellular immune responses elicited by VP1-CD-HF rgEV-A71s to assess the potential efficacy of these EV-A71 vaccine candidates. Following intraperitoneal (i.p.) injection of VP1-CD-HF rgEV-A71s in mice, we observed a robust induction of EV-A71-specific neutralizing IgG antibodies in the antisera after 21 days. Splenocytes isolated from VP1-CD-HF rgEV-A71s-immunized mice exhibited enhanced proliferative activities and cytokine production (IL-2, IFN-γ, IL-4, IL-6, and TNF-α) upon re-stimulation with VP1-CD-HF rgEV-A71, as compared to control mice treated with adjuvant only. Importantly, administration of antisera from VP1-CD-HF rgEV-A71s-immunized mice protected against lethal EV-A71 challenge in neonatal mice. These findings highlight that our generated VP1-CD-HF rgEV-A71 viruses are capable of inducing both cellular and humoral immune responses, supporting their potential as next-generation EV-A71 vaccines for combating EV-A71 infection.IMPORTANCEEV-A71 can cause severe neurological diseases and cause death in young children. Here, we report the development of synthetic rgEV-A71s with the combination of codon deoptimization and high-fidelity (HF) substitutions that generate genetically stable reverse genetics (rg) viruses as potential attenuated vaccine candidates. Our work provides insight into the development of low-virulence candidate vaccines through a series of viral genetic editing for maintaining antigenicity and genome stability and suggests a strategy for the development of an innovative next-generation vaccine against EV-A71., Competing Interests: The authors declare no conflict of interest.

Photomemristors have been regarded as one of the most promising candidates for next-generation hardware-based neuromorphic computing due to their potentials of fast data transmission and low power consumption. However, intriguingly, so far, photomemristors seldom display truly nonvolatile memory characteristics with high light sensitivity. Herein, we demonstrate ultrasensitive photomemristors utilizing two-dimensional (2D) Ruddlesden-Popper (RP) perovskites with a highly polar donor-acceptor-type push-pull organic cation, 4-(5-(2-aminoethyl)thiophen-2-yl)benzonitrile + (EATPCN + ), as charge-trapping layers. High linearity and almost zero-decay retention are observed in (EATPCN) 2 PbI 4 devices, which are very distinct from that of the traditional 2D RP perovskite devices consisting of nonpolar organic cations, such as phenethylamine + (PEA + ) and octylamine + (OA + ), and traditional 3D perovskite devices consisting of methylamine + (MA + ). The 2-fold advantages, including desirable spatial crystal arrangement and engineered energetic band alignment, clarify the mechanism of superior performance in (EATPCN) 2 PbI 4 devices. The optimized (EATPCN) 2 PbI 4 photomemristor also shows a memory window of 87.9 V and an on/off ratio of 10 6 with a retention time of at least 2.4 × 10 5 s and remains unchanged after >10 5 writing-reading-erasing-reading endurance cycles. Very low energy consumptions of 1.12 and 6 fJ for both light stimulation and the reading process of each status update are also demonstrated. The extremely low power consumption and high photoresponsivity were simultaneously achieved. The high photosensitivity surpasses that of a state-of-the-art commercial pulse energy meter by several orders of magnitude. With their outstanding linearity and retention, rabbit images have been rebuilt by (EATPCN) 2 PbI 4 photomemristors, which truthfully render the image without fading over time. Finally, by utilizing the powerful ∼8 bits of nonvolatile potentiation and depression levels of (EATPCN) 2 PbI 4 photomemristors, the accuracies of the recognition tasks of CIFAR-10 image classification and MNIST handwritten digit classification have reached 89% and 94.8%, respectively. This study represents the first report of utilizing a functional donor-acceptor type of organic cation in 2D RP perovskites for high-performance photomemristors with characteristics that are not found in current halide perovskites.

Enterovirus A71 (EV-A71) is a non-enveloped virus possessing 4 capsid proteins: VP1-VP4. The outermost capsid protein, VP1, plays roles in both antigenicity and virulence of the virus. The concept of generating other EV-A71 genotypes of reverse genetics (rg) viruses by replacing VP1 can be made possible with synthetic biotechnology, allowing us to redesign organisms, creating unavailable ones. To determine suitable vaccine candidates against EV-A71 infections, we combined synthetic biotechnology, rg-virus production and high-fidelity determinants to produce genetically stable viruses. With the use of antigenic cartography, we are able to view the antigenic distance among various points. We analyzed and generated various EV-A71 VP1 sequences from Taiwan and Southeast Asian (SEA) countries, which were then used to produce recombinant rg-viruses and the viral proteins were purified for immunization of mice and rabbits. Antisera against various EV-A71 genotypes were used in neutralization assays against various Taiwan and SEA EV-A71 genotypes. Based on neutralization data from mice and rabbit antisera, we found that antisera produced from several genotypes were able to effectively neutralize the various Taiwan and SEA EV-A71 genotypes. Additionally, comparing the antigenic maps produced from mouse, rabbit and human antisera against different EV-A71 genotypes, a difference in clustering was seen and the spacing between points also differed. Based on antigenic mapping and neutralizing activities, B4 7008-HF and C4 M79 may be good potential vaccine candidates against EV-A71., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Broadly neutralizing ability is critical for developing the next-generation SARS-CoV-2 vaccine. We collected sera samples between December 2021-January 2022 from 113 Taiwan naïve participants after their second dose of homologous vaccine (AZD1222, mRNA-1273, BNT162-b2, and MVC-COV1901) and compared the differences in serological responses of various SARS-CoV-2 vaccines. Compared to AZD1222, the two mRNA vaccines could elicit a higher level of anti-S1-RBD binding antibodies with higher broadly neutralizing ability evaluated using pseudoviruses of various SARS-CoV-2 lineages. The antigenic maps produced from the neutralization data implied that Omicron represents very different antigenic characteristics from the ancestral lineage. These results suggested that constantly administering the vaccine with ancestral Wuhan spike is insufficient for the Omicron outbreak. In addition, we found that anti-ACE2 autoantibodies were significantly increased in all four vaccinated groups compared to the unvaccinated pre-pandemic group, which needed to be investigated in the future., Competing Interests: Author Y-CC is employed by Leadgene Biomedical, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationship that could be considered a potential conflict of interest., (Copyright © 2022 Chao, Cheng, Huang, Chuang, Yeh and Wang.)

Coxsackievirus A16 (CVA16) is well known for causing hand-foot-and-mouth disease (HFMD) and outbreaks were frequently reported in Taiwan in the past twenty years. The epidemiology and genetic variations of CVA16 in Taiwan from 1998 to 2021 were analyzed in this study. CVA16 infections usually occurred in early summer and early winter, and showed increased incidence in 1998, 2000-2003, 2005, 2007-2008, and 2010 in Taiwan. Little or no CVA16 was detected from 2017 to 2021. CVA16 infection was prevalent in patients between 1 to 3 years old. A total of 69 isolates were sequenced. Phylogenetic analysis based on the VP1 region showed that CVA16 subgenotype B1 was dominantly isolated in Taiwan from 1998 to 2019, and B2 was identified only from isolates collected in 1999 and 2000. There was a high frequency of synonymous mutations in the amino acid sequences of the VP1 region among CVA16 isolates, with the exception of position 145 which showed positive selection. The recombination analysis of the whole genome of CVA16 isolates indicated that the 5'-untranslated region and the non-structural protein region of CVA16 subgenotype B1 were recombined with Coxsackievirus A4 (CVA4) and enterovirus A71 (EVA71) genotype A, respectively. The recombination pattern of subgenotype B2 was similar to B1, however, the 3D region was similar to EVA71 genotype B. Cross-neutralization among CVA16 showed that mouse antisera from various subgenotypes viruses can cross-neutralize different genotype with high neutralizing antibody titers. These results suggest that the dominant CVA16 genotype B1 can serve as a vaccine candidate for CVA16.