Comparative analysis of symptom profile and risk of death associated with infection by SARS-CoV-2 and its variants in Hong Kong.

The recurrent multiwave nature of coronavirus disease 2019 (COVID-19) necessitates updating its symptomatology. We characterize the effect of variants on symptom presentation, identify the symptoms predictive and protective of death, and quantify the effect of vaccination on symptom development. With the COVID-19 cases reported up to August 25, 2022 in Hong Kong, an iterative multitier text-matching algorithm was developed to identify symptoms from free text. Multivariate regression was used to measure associations between variants, symptom development, death, and vaccination status. A least absolute shrinkage and selection operator technique was used to identify a parsimonious set of symptoms jointly associated with death. Overall, 70.9% (54 450/76 762) of cases were symptomatic with 102 symptoms identified. Intrinsically, the wild-type and delta variant caused similar symptoms among unvaccinated symptomatic cases, whereas the wild-type and omicron BA.2 subvariant had heterogeneous patterns, with seven symptoms (fatigue, fever, chest pain, runny nose, sputum production, nausea/vomiting, and sore throat) more frequent in the BA.2 cohort. With ≥2 vaccine doses, BA.2 was more likely than delta to cause fever among symptomatic cases. Fever, blocked nose, pneumonia, and shortness of breath remained jointly predictive of death among unvaccinated symptomatic elderly in the wild-type-to-omicron transition. Number of vaccine doses required for reducing occurrence varied by symptoms. We substantiate that omicron has a different clinical presentation compared to previous variants. Syndromic surveillance can be bettered with reduced reliance on symptom-based case identification, increased weighing on symptoms predictive of death in outcome prediction, individual-based risk assessment in care homes, and incorporating free-text symptom reporting.

LncRNA FOXD1-AS1 regulates pancreatic cancer stem cell properties and 5-FU resistance by regulating the miR-570-3p/SPP1 axis as a ceRNA.

Cancer stem cells (CSCs) play a pivotal role in the pathogenesis of human cancers. Previous studies have highlighted the role of long non-coding RNA (lncRNA) in modulating the stemness of CSCs. In our investigation, we identified an upregulation of lncRNA FOXD1-AS1 in CSCs. The enforced expression of lncRNA FOXD1-AS1 promotes tumorigenesis and self-renewal in pancreatic cancer CSCs. Conversely, the knockdown of lncRNA FOXD1-AS1 inhibits tumorigenesis and self-renewal in pancreatic cancer CSCs. Furthermore, our findings reveal that lncRNA FOXD1-AS1 enhances self-renewal and tumorigenesis in pancreatic cancer CSCs by up-regulating osteopontin/secreted phosphoprotein 1(SPP1) and acting as a ceRNA to sponge miR-570-3p in pancreatic cancer (PC) CSCs. Additionally, lncRNA FOXD1-AS1 depleted pancreatic cancer cells exhibit heightened sensitivity to 5-FU-indued cell growth inhibition and apoptosis. Analysis of patient-derived xenografts (PDX) indicates that a low level of lncRNA FOXD1-AS1 may serve as a predictor of 5-FU benefits in PC patients. Moreover, the introduction of SPP1 can reverse the sensitivity of lncRNA FOXD1-AS1-knockdown PC cells to 5-FU-induced cell apoptosis. Importantly, molecular studies have indicated that the elevated levels of lncRNAFOXD1-AS1 in PC are facilitated through METTL3 and YTHDF1-dependent m6A methylation. In summary, our results underscore the critical functions of lncRNA FOXD1-AS1 in the self-renewal and tumorigenesis of pancreatic cancer CSCs, positioning lncRNA FOXD1-AS1 as a promising therapeutic target for PC.

Probe Substrate Dependencies in CYP3A4 Allosteric Inhibition: A Novel Molecular Mechanism Involving F-F' Loop Perturbations.

The biochemical basis for substrate dependences in apparent inhibition constant values (Ki) remains unknown. Our study aims to elucidate plausible structural determinants underpinning these observations. In vitro steady-state inhibition assays conducted using human recombinant CYP3A4 enzyme and testosterone substrate revealed that fibroblast growth factor receptor (FGFR) inhibitors erdafitinib and pemigatinib noncompetitively inhibited CYP3A4 with apparent Ki values of 10.2 ± 1.1 and 3.3 ± 0.9 µM, respectively. However, when rivaroxaban was adopted as the probe substrate, there were 2.0- and 3.2-fold decreases in its apparent Ki values. To glean mechanistic insights into this phenomenon, erdafitinib and pemigatinib were docked to allosteric sites in CYP3A4. Subsequently, molecular dynamics (MD) simulations of apo- and holo-CYP3A4 were conducted to investigate the structural changes induced. Comparative structural analyses of representative MD frames extracted by hierarchical clustering revealed that the allosteric inhibition of CYP3A4 by erdafitinib and pemigatinib did not substantially modulate its active site characteristics. In contrast, we discovered that allosteric binding of the FGFR inhibitors reduces the structural flexibility of the F-F' loop region, an important gating mechanism to regulate access of the substrate to the catalytic heme. We surmised that the increased rigidity of the F-F' loop engenders a more constrained entrance to the CYP3A4 active site, which in turn impedes access to the larger rivaroxaban molecule to a greater extent than testosterone and culminates in more potent inhibition of its CYP3A4-mediated metabolism. Our findings suggest a potential mechanism to rationalize probe substrate dependencies in Ki arising from the allosteric noncompetitive inhibition of CYP3A4.

The role of quercetin in ameliorating bleomycin-induced pulmonary fibrosis: insights into autophagy and the SIRT1/AMPK signaling pathway.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a disease of unknown etiology characterized by a constant incidence rate. Unfortunately, effective pharmacological treatments for this condition are lacking and the identification of novel therapeutic approaches and underlying pathological mechanisms are required. This study investigated the potential of quercetin in alleviating pulmonary fibrosis by promoting autophagy and activation of the SIRT1/AMPK pathway. METHODS: Mouse models of IPF were divided into four treatment groups: control, bleomycin (BLM), quercetin (Q), and quercetin + EX-527 (Q + E) treatment. Pulmonary fibrosis was induced in the mouse models through intratracheal instillation of BLM. Various indexes were identified through histological staining, Western blotting analysis, enzyme-linked immunosorbent assay, immunohistochemistry, and transmission electron microscopy. RESULTS: Quercetin treatment ameliorated the pathology of BLM-induced pulmonary fibrosis of mice by reducing α-smooth muscle actin (α-SMA), collagen I (Col I), and collagen III (Col III) levels, and also improved the level of E-cadherin in lung tissue. Furthermore, Quercetin significantly enhanced LC3II/LC3I levels, decreased P62 expression, and increased the number of autophagosomes in lung tissue. These effects were accompanied by the activation of the SIRT1/AMPK pathway. Treatment with EX-527, an inhibitor for SIRT1, reversed all effects induced by quercetin. CONCLUSION: This study showed that quercetin could alleviate pulmonary fibrosis and improve epithelial-mesenchymal transition by acting on the SIRT1/AMPK signaling pathway, which may be achieved by regulating the level of autophagy.

Real-world safety and effectiveness of pirfenidone and nintedanib in the treatment of idiopathic pulmonary fibrosis: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Multiple randomized controlled studies have shown that pirfenidone and nintedanib are effective and safe for treating idiopathic pulmonary fibrosis. This study aimed to evaluate their efficacy, safety, and tolerability in a real-world setting. METHODS: We searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases for real-world studies published up to March 3, 2023, on pirfenidone and nintedanib for idiopathic pulmonary fibrosis. RESULTS: A total of 74 studies with 23,119 participants were included. After 12 months of treatment, the change from baseline in percent predicted FVC (%FVC) was - 0.75% for pirfenidone and - 1.43% for nintedanib. The change from baseline in percent predicted DLCO (%DCLO) was - 2.32% for pirfenidone and - 3.95% for nintedanib. The incidence of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) was 12.5% for pirfenidone and 14.4% for nintedanib. The IPF-related mortality rates of pirfenidone and nintedanib were 13.4% and 7.2%, respectively. The all-cause mortality was 20.1% for pirfenidone and 16.6% for nintedanib. In the pirfenidone group, 16.6% of patients discontinued treatment because of adverse events, and in the nintedanib group, 16.2% of patients discontinued treatment because of adverse events. The incidence of adverse events was 56.4% and 69.7% for pirfenidone and nintedanib, respectively. CONCLUSION: The results of this study indicate that pirfenidone and nintedanib are both effective in slowing down the decline of lung function in IPF patients in real-world settings. The incidence of adverse events with pirfenidone is lower than that with nintedanib, but both are below the clinical trial data, and no new major adverse events have been observed. The discontinuation rates due to adverse reactions of the two drugs are consistent with clinical trial data, indicating good tolerability. However, the mortality rates and AE-IPF incidence rates of these two drugs in real-world settings are higher than those in previous clinical trials, with pirfenidone patients showing a higher mortality rate. Further large-sample studies are needed to investigate the risks of these drugs in these aspects. Additionally, we recommend that future real-world studies pay more attention to patients' subjective symptoms and conduct stratified analyses of the efficacy and safety of pirfenidone and nintedanib based on factors such as patients' baseline lung function, comorbidities, and age, in order to provide more personalized medication advice for IPF patients in clinical practice.

Developmental toxicity and mechanism of polychlorinated biphenyls 126 and nano-polystyrene combined exposure to zebrafish larvae.

3,3',4,4',5-Pentachlorobiphenyl (PCB126) is the most toxic congener of dioxin-like polychlorinated biphenyls (DL PCBs), while nanoplastics (NPs) have recently emerged as significant marine pollutants, both posing threats to aquatic organisms and human health. They coexist in the environment, but their comprehensive toxicological effects remain unclear. In this study, zebrafish embryos were simultaneously exposed to PCB126 and 80-nanometer nanoplastyrene (NPS). Researchers utilized fluorescence microscopy, qPCR, histopathological examination, and transcriptomic sequencing to investigate the developmental toxicity of different concentrations of PCB126 and NPS individually or in combination on zebrafish embryos and larvae. Results indicate that the chorion significantly impedes the accumulation of NPS (p < 0.05). It is noteworthy that this barrier effect diminishes upon simultaneous exposure to PCB126. In this experiment, the semi-lethal concentration of PCB126 for larvae was determined to be 6.33 µg/L. Exposure to PCB126 induces various deformities, primarily mediated through the aryl hydrocarbon receptor (AHR). Similarly, exposure to NPS also activates AHR, leading to developmental impairments. Furthermore, transcriptomic sequencing revealed similar effects of PCB126 and NPS on the gene expression trends in zebrafish larvae, but combined exposure to both exacerbates the risk of cancer and induces more severe cardiac toxicity. At this level, co-exposure to PCB126 and NPS adversely affects the development of zebrafish larvae. This study contributes to a deeper understanding of the in vivo accumulation of DL polychlorinated biphenyls and microplastics in actual aquatic environments and their impact on fish development.

Fast water transport and molecular sieving through ultrathin ordered conjugated-polymer-framework membranes.

The development of membranes that block solutes while allowing rapid water transport is of great importance. The microstructure of the membrane needs to be rationally designed at the molecular level to achieve precise molecular sieving and high water flux simultaneously. We report the design and fabrication of ultrathin, ordered conjugated-polymer-framework (CPF) films with thicknesses down to 1 nm via chemical vapour deposition and their performance as separation membranes. Our CPF membranes inherently have regular rhombic sub-nanometre (10.3 × 3.7 Å) channels, unlike membranes made of carbon nanotubes or graphene, whose separation performance depends on the alignment or stacking of materials. The optimized membrane exhibited a high water/NaCl selectivity of ∼6,900 and water permeance of ∼112 mol m-2 h-1 bar-1, and salt rejection >99.5% in high-salinity mixed-ion separations driven by osmotic pressure. Molecular dynamics simulations revealed that water molecules quickly and collectively pass through the membrane by forming a continuous three-dimensional network within the hydrophobic channels. The advent of ordered CPF provides a route towards developing carbon-based membranes for precise molecular separation.

Work-Family Balance and Managing Spillover Effects Communicatively during COVID-19: Nurses' Perspectives.

Work-family balance has received meaningful attention from researchers and practitioners alike. Work and family are usually seen as two separate domains that are interdependent, with boundaries that have some level of permeability. Crisis situations can alter permeability of these boundaries, enhancing integration of the two domains due to exchange of ideas and spillover of concerns between these domains. This study looks at how these boundaries are impacted for nurses working directly with COVID-19 patients. The study conducted 24 semi-structured interviews with nurses. Through a thematic analysis the study found that the work-family boundaries have blurred due to concerns around the contagiousness and anxiety associated with the virus. In order to cope with these spillover and possible crossover effects, nurses use prosocial distortion and avoidance and create sub-boundaries at home.

Bone marrow mesenchymal stem cell-derived exosomal miR-193b-5p reduces pyroptosis after ischemic stroke by targeting AIM2.

BACKGROUND: Ischemic stroke represents a major factor causing global morbidity and death. Bone marrow mesenchymal stem cell (BMSC)-derived exosomes (Exos) have important effects on treating ischemic stroke. Here, we investigated the therapeutic mechanism by which BMSC-derived exosomal miR-193b-5p affects ischemic stroke. METHODS: luciferase assay was performed to evaluate the regulatory relationship of miR-193b-5p with absent in melanoma 2 (AIM2). Additionally, an oxygen-glucose deprivation/reperfusion (OGD/R) model was constructed for the in vitro assay, while a middle cerebral artery occlusion (MCAO) model was developed for the in vivo assay. After exosome therapy, lactate dehydrogenase and MTT assays were conducted to detect cytotoxicity and cell viability, while PCR, ELISA, western blotting assay, and immunofluorescence staining were performed to detect changes in the levels of pyroptosis-related molecules. TTC staining and TUNEL assays were performed to assess cerebral ischemia/reperfusion (I/R) injury. RESULTS: In the luciferase assay, miR-193b-5p showed direct binding to the 3'-untranslated region of AIM2. In both in vivo and in vitro assays, the injected exosomes could access the sites of ischemic injury and could be internalized. In the in vitro assay, compared to normal BMSC-Exos, miR-193b-5p-overexpressing BMSC-Exos showed greater effects on increasing cell viability and attenuating cytotoxicity; AIM2, GSDMD-N, and cleaved caspase-1 levels; and IL-1ß/IL-18 generation. In the in vivo assay, compared to normal BMSC-Exos, miR-193b-5p-overexpressing BMSC-Exos showed greater effects on decreasing the levels of these pyroptosis-related molecules and infarct volume. CONCLUSION: BMSC-Exos attenuate the cerebral I/R injury in vivo and in vitro by inhibiting AIM2 pathway-mediated pyroptosis through miR-193b-5p delivery.

The polymorphisms in cGAS-STING pathway are associated with mitochondrial DNA copy number in coke oven workers.

OBJECTIVE: To evaluate the interaction effects of Polycyclic aromatic hydrocarbons (PAHs) exposure and variants in cGAS-STING genes on mitochondrial DNA copy number (mtDNAcn) in workers. METHODS: The mtDNAcn was determined by real-time quantitative polymerase-chain reaction in 544 PAHs-exposed workers and 238 office workers. The polymorphisms were detected by flight mass spectrometry. RESULTS: The mtDNAcn in PAHs exposure group was significantly lower than non-occupational exposure population (P < 0.00). The cGAS rs610913 CA+AA had significant interaction effects with STING rs11554776 GG+GA (P = 0.035), rs7380824 CC+CT (P = 0.026), and rs78233829 GC+CC (P = 0.034) on mtDNAcn. The generalized linear model results showed that the influencing factors of mtDNAcn include PAHs exposure (P < 0.001) and the interaction of PAHs exposure and cGAS rs 311678 AA+AG (P = 0.047). CONCLUSION: The influencing factors of mtDNAcn include PAHs exposure and the interaction of PAHs exposure and cGAS rs 311678 AA+AG.

Role of Circular RNAs in Atherosclerosis through Regulation of Inflammation, Cell Proliferation, Migration, and Apoptosis: Focus on Atherosclerotic Cerebrovascular Disease.

Atherosclerosis (AS) is a disease dangerous to human health and the main pathological cause of ischemic cardiovascular diseases. Although its pathogenesis is not fully understood, numerous basic and clinical studies have shown that AS is a chronic inflammatory disease existing in all stages of atherogenesis. It may be a common link or pathway in the pathogenesis of multiple atherogenic factors. Inflammation is associated with AS complications, such as plaque rupture and ischemic cerebral infarction. In addition to inflammation, apoptosis plays an important role in AS. Apoptosis is a type of programmed cell death, and different apoptotic cells have different or even opposite roles in the process of AS. Unlike linear RNA, circular RNA (circRNA) a covalently closed circular non-coding RNA, is stable and can sponge miRNA, which can affect the stages of AS by regulating downstream pathways. Ultimately, circRNAs play very important roles in AS by regulating inflammation, apoptosis, and some other mechanisms. The study of circular RNAs can provide new ideas for the prediction, prevention, and treatment of AS.

Aryl-to-Vinyl 1,4-Nickel Migration/Reductive Cross-Coupling Reaction for the Stereoselective Synthesis of Multisubstituted Olefins.

The aryl-to-vinyl nickel 1,4-migration (1,4-Ni migration) reaction has been reported for the first time. The generated alkenyl Ni species undergo a reductive coupling reaction with unactivated brominated alkanes affording a series of trisubstituted olefins. This tandem reaction exhibits mild conditions, a broad substrate scope, high regioselectivity, and excellent Z/E stereoselectivity. A series of controlled experiments have shown that the critical 1,4-Ni migration process is reversible. In addition, the alkenyl nickel intermediates obtained after migration are highly Z/E stereoselective and do not undergo Z/E isomerization. The obtained trace isomerization products are caused by the instability of the product.

Direct and Sequential Bioactivation of Pemigatinib to Reactive Iminium Ion Intermediates Culminates in Mechanism-Based Inactivation of Cytochrome P450 3A.

We recently established the mechanism-based inactivation (MBI) of cytochrome P450 3A (CYP3A) by the fibroblast growth factor receptor (FGFR) inhibitors erdafitinib and infigratinib. Serendipitously, our preliminary data have also revealed that pemigatinib (PEM), another clinically approved FGFR1-3 inhibitor, similarly elicited time-dependent inhibition of CYP3A. This was rather unexpected, as it was previously purported that PEM did not pose any metabolism-dependent liabilities due to the absence of glutathione-related conjugates in metabolic profiling experiments conducted in human liver microsomes. Here, we confirmed that PEM inhibited both CYP3A isoforms in a time-, concentration-, and cofactor-dependent manner consistent with MBI, with inactivator concentration at half-maximum rate constant, maximum inactivation rate constant, and partition ratio of 8.69 and 11.95 µM, 0.108 and 0.042 min-1, and approximately 44 and approximately 47 for CYP3A4 and CYP3A5, respectively. Although the rate of inactivation was diminished by coincubation with an alternative substrate or direct inhibitor of CYP3A, the inclusion of nucleophilic trapping agents afforded no such protection. Furthermore, the lack of catalytic activity recovery following dialysis and oxidation with potassium ferricyanide coupled with the absence of a spectrally resolvable peak in the Soret region collectively implied that the underlying mechanism of inactivation was not elicited via the formation of pseudo-irreversible metabolite-intermediate complexes. Finally, utilizing cyanide trapping and high-resolution mass spectrometry, we illuminated the direct and sequential oxidative bioactivation of PEM and its major O-desmethylated metabolite at its distal morpholine moiety to reactive iminium ion hard electrophilic species that could covalently inactivate CYP3A via MBI. SIGNIFICANCE STATEMENT: This study reports for the first time the covalent MBI of CYP3A by PEM and deciphered its bioactivation pathway involving the metabolic activation of PEM and its major O-desmethylated metabolite to reactive iminium ion intermediates. Following which, a unique covalent docking methodology was harnessed to unravel the structural and molecular determinants underpinning its inactivation. Findings from this study lay the foundation for future investigation of clinically relevant drug-drug interactions between PEM and concomitant substrates of CYP3A.

Effects of Environmental and Spatial Variables on Bacteria in Zhanjiang Mangrove Sediments.

The bottom mud of mangroves contains numerous microbial groups that play an important role in the main ecological functions of the mangrove ecosystem. The diversity and functional and environmental factors related to microbial communities, in terms of the assembly process and in environmental adaptation of the abundance and rare bacterial communities in the mangrove ecosystem, have not been fully explored. We used 16S high-throughput sequencing and operational taxonomic unit analysis to compare the diversity and composition of bacterial communities in different tidal zones in the sediments of the Zhanjiang Gaoqiao Mangrove Nature Reserve, compare the ecological adaptation thresholds and phylogenetic signals of bacterial communities under different environmental gradients, and examine the factors affecting the composition of the bacterial community. The diversity of microbial species and structure and function of the mangrove sediments were affected by the environment, showing the trend: mid tide zone > climax zone > low tide zone. Organic matter content, oxygen content, pH, and total phosphorus were identified as important environmental factors determining the functional diversity of bacterial communities and survival, while pH influences species evolution. The abundant taxa showed a wider response threshold and stronger phylogenetic signals of ecological preference across environmental gradients compared to rare taxa. The abundant bacterial groups have broader environmental adaptability than rare bacterial groups, and different environmental factors affect different communities and functions in the mangrove ecological environment. These results elucidate the mechanism underlying the generation and maintenance of bacterial diversity in response to global environmental changes.

Functional analysis of the long-range regulatory element of BMP2 gene.

Recently, several pedigree-based studies have shown that abnormal replication of an enhancer element regulatory region in the downstream of the bone morphogenetic protein 2 (BMP2) gene is the cause of brachydactyly type A2 (BDA2). However, the exact molecular function of this regulatory region is unclear, and even conflicting results have emerged. In this study, based on bioinformatics analysis, we amplified target fragments of different lengths in this regulatory region by PCR technology, including a highly conserved 2.1 kb core sequence and 3 fragments that can completely cover the core 2.1 kb fragment. Then, the gene recombination vectors were constructed, and the biological function of these fragments was analyzed by the dual-luciferase reporter gene technology system. We found that the highly conserved 2.1 kb fragment did not have enhancer activity, while all of three truncated fragments showed strong enhancer activity. The results suggest that the expression regulation mode of the BMP2 gene is very complex. For the downstream regulatory region, selecting fragments of different lengths may have different effects on the regulation of BMP2 expression, which may due to the fragments with different lengths carrying different regulatory elements in the number of types. In summary, this study revealed the complexity of BMP2 gene regulatory elements, and provided new clues and directions for the subsequent in-depth exploration of the molecular pathogenic mechanism of BDA2.

Effect of prior outbreak work experience to future outbreak responses for nurses in Hong Kong: A cross-sectional study.

Background: During the early phase of the Coronavirus Disease 2019 (COVID-19) epidemic, health care workers had elevated levels of psychological distress. Historical exposure to disease outbreak may shape different pandemic responses among experienced health care workers. Aim: Considering the unique experience of the 2003 SARS outbreak in Hong Kong, this study examined the association between prior epidemic work experience and anxiety levels, and the mediating role of perceived severity of COVID-19 and SARS in nurses. Methods: In March 2020, a cross-sectional survey targeting practising nurses in Hong Kong was conducted during the early phase of the COVID-19 epidemic. The interrelationships among participants' work experience during the SARS outbreak, perceived severity of SARS and COVID-19, and anxiety level were elucidated using structural equation model (SEM). Findings: Of 1,061 eligible nurses, a majority were female (90%) with a median age of 39 years (IQR = 32-49). A significant and negative indirect association was identified between SARS experience and anxiety levels (B=-0.04, p=0.04) in the SEM with a satisfactory fitness (CFI=0.95; RMSEA=0.06). SARS-experienced nurses perceived SARS to be less severe (B=-0.17, p=0.01), translated an equivalent perception to COVID-19 (B=1.29, p<0.001) and resulted in a lower level of anxiety (B=0.19, p<0.001). Conclusions: The less vigorous perception towards the severity of SARS and COVID-19 may explain SARS-experienced nurses' less initial epidemic-induced anxiety. The possible role of outbreak-experienced nurses in supporting outbreak-inexperienced nurses, both emotionally and technically, should be considered when an epidemic commences. Interventions aiming to facilitate the understanding of emerging virus should also be in place.

Experimental and Computational Studies of Palladium-Catalyzed Spirocyclization via a Narasaka-Heck/C(sp3 or sp2)-H Activation Cascade Reaction.

The first synthesis of highly strained spirocyclobutane-pyrrolines via a palladium-catalyzed tandem Narasaka-Heck/C(sp3 or sp2)-H activation reaction is reported here. The key step in this transformation is the activation of a δ-C-H bond via an in situ generated σ-alkyl-Pd(II) species to form a five-membered spiro-palladacycle intermediate. The concerted metalation-deprotonation (CMD) process, rate-determining step, and energy barrier of the entire reaction were explored by density functional theory (DFT) calculations. Moreover, a series of control experiments was conducted to probe the rate-determining step and reversibility of the C(sp3)-H activation step.

Psychobehavioral Responses and Likelihood of Receiving COVID-19 Vaccines during the Pandemic, Hong Kong.

To access temporal changes in psychobehavioral responses to the coronavirus disease (COVID-19) pandemic, we conducted a 5-round (R1-R5) longitudinal population-based online survey in Hong Kong during January-September 2020. Most respondents reported wearing masks (R1 99.0% to R5 99.8%) and performing hand hygiene (R1 95.8% to R5 97.7%). Perceived COVID-19 severity decreased significantly, from 97.4% (R1) to 77.2% (R5), but perceived self-susceptibility remained high (87.2%-92.8%). Female sex and anxiety were associated with greater adoption of social distancing. Intention to receive COVID-19 vaccines decreased significantly (R4 48.7% to R5 37.6%). Greater anxiety, confidence in vaccine, and collective responsibility and weaker complacency were associated with higher tendency to receive COVID-19 vaccines. Although its generalizability should be assumed with caution, this study helps to formulate health communication strategies and foretells the initial low uptake rate of COVID-19 vaccines, suggesting that social distancing should be maintained in the medium term.

Electrically controllable terahertz metamaterials with large tunabilities and low operating electric fields using electrowetting-on-dielectric cells.

A simple method that is compatible with all geometrical structures of terahertz (THz) metamaterials for increasing their frequency tunabilities and decreasing their operating electric fields is proposed. This method uses the displacement of glycerol droplets with various volumes to tune the resonance frequency of a THz metamaterial in an electrowetting-on-dielectric (EWOD) cell. The experimental results reveal that the THz metamaterial has a large frequency tunability of 28% at an operating electric field that is smaller than 0.2 V/µm as the glycerol droplets move in and out of the path of a THz beam. The frequency tunability is large because the near field of the metamaterial "experiences" a large difference between the refractive indices of glycerol and air. The EWOD cell with the THz metamaterial is a great achievement for developing electrically controllable band-stop filters with large frequency tunabilities and small operating electric fields.

Epidemiology, clinical spectrum, viral kinetics and impact of COVID-19 in the Asia-Pacific region.

COVID-19 has hit the world by surprise, causing substantial mortality and morbidity since 2020. This narrative review aims to provide an overview of the epidemiology, induced impact, viral kinetics and clinical spectrum of COVID-19 in the Asia-Pacific Region, focusing on regions previously exposed to outbreaks of coronavirus. COVID-19 progressed differently by regions, with some (such as China and Taiwan) featured by one to two epidemic waves and some (such as Hong Kong and South Korea) featured by multiple waves. There has been no consensus on the estimates of important epidemiological time intervals or proportions, such that using them for making inferences should be done with caution. Viral loads of patients with COVID-19 peak in the first week of illness around days 2 to 4 and hence there is very high transmission potential causing community outbreaks. Various strategies such as government-guided and suppress-and-lift strategies, trigger-based/suppression approaches and alert systems have been employed to guide the adoption and easing of control measures. Asymptomatic and pre-symptomatic transmission is a hallmark of COVID-19. Identification and isolation of symptomatic patients alone is not effective in controlling the ongoing outbreaks. However, early, prompt and coordinated enactment predisposed regions to successful disease containment. Mass COVID-19 vaccinations are likely to be the light at the end of the tunnel. There is a need to review what we have learnt in this pandemic and examine how to transfer and improve existing knowledge for ongoing and future epidemics.