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Mercury (Hg) is a toxic element which impacts on biological systems and ecosystems. Because the toxicity of Hg species is highly dependent on their concentration levels and chemical forms, the sensitive identification of the chemical forms of Hg—i.e., Hg speciation—is of major significance in providing meaningful information about the sources of Hg exposure. In this study, a microfluidic-based device made of high-clarity poly(methyl methacrylate) (PMMA) was fabricated. Then, titanium dioxide nanoparticles (nano-TiO2s) were attached to the treated channel’s interior with the aid of poly(diallyldimethylammonium chloride) (PDADMAC). After coupling the nano-TiO2-coated microfluidic-based photocatalyst-assisted reduction device (the nano-TiO2-coated microfluidic-based PCARD) with high-performance liquid chromatography (HPLC) and inductively coupled plasma mass spectrometry (ICP-MS), a selective and sensitive, hyphenated system for Hg speciation was established. Validation procedures demonstrated that the method could be satisfactorily applied to the determination of mercury ions (Hg2+) and methylmercury ions (CH3Hg+) in both human urine and water samples. Remarkably, the zeta potential measured clearly indicated that the PDADMAC-capped nano-TiO2s with a predominance of positive charges indeed provided a steady force for firm attachment to the negatively charged device channel. The cause of the durability of the nano-TiO2-coated microfluidic-based PCARD was clarified thus.

To study the permeability of the blood–brain barrier (BBB) to arsenates, arsenite, monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), molybdate, and methylmercury, and the transfer behavior of these species, we constructed an automatic online analytical system comprising a microdialysis sampling device, a minicolumn packed with nonfunctionalized poly(vinyl chloride) beads, and an inductively coupled plasma mass spectrometer for continuous in-vivo measurement of their dynamic variation in the extracellular space of the brains of living rats. By using ion–polymer interactions as a novel working mechanism for sample pretreatment of volume-limited microdialysate, we simplified the operating procedure of conventional solid-phase extraction and reduced the contribution to the blank of the chemicals used. After optimizing this hyphenated system, we measured its performance by analysis of NIST standard reference materials 1640a (trace elements in natural water) and 2672a (trace elements in human urine) and by in-vivo monitoring of the dynamic variation of the compounds tested in the extracellular fluid (ECF) of rat brain. We found that intraperitoneal administration led to observable BBB permeability of arsenates, arsenite, DMA, MMA, and molybdate. Nevertheless, the limited sensitivity of the system and the size of microdialysis samples meant that detection of MeHg in ECF remained problematic, even when we administered a dose of 20 mg MeHg kg –1 body weight. On the basis of these practical demonstrations, we suggest that our analytical system could be used not only for dynamic monitoring of the transfer kinetics of the four arsenicals and molybdate in the rat brain but also to describe associated neurotoxicity in terms of exposure to toxic metals and their species.

Serological and plasmablast responses and plasmablast-derived IgG monoclonal antibodies (MAbs) have been analysed in three COVID-19 patients with different clinical severities. Potent humoral responses were detected within 3 weeks of onset of illness in all patients and the serological titre was elicited soon after or concomitantly with peripheral plasmablast response. An average of 13.7% and 3.5% of plasmablast-derived MAbs were reactive with virus spike glycoprotein or nucleocapsid, respectively. A subset of anti-spike (10 of 32) antibodies cross-reacted with other betacoronaviruses tested and harboured extensive somatic mutations, indicative of an expansion of memory B cells upon SARS-CoV-2 infection. Fourteen of 32 anti-spike MAbs, including five anti-receptor-binding domain (RBD), three anti-non-RBD S1 and six anti-S2, neutralised wild-type SARS-CoV-2 in independent assays. Anti-RBD MAbs were further grouped into four cross-inhibiting clusters, of which six antibodies from three separate clusters blocked the binding of RBD to ACE2 and five were neutralising. All ACE2-blocking anti-RBD antibodies were isolated from two recovered patients with prolonged fever, which is compatible with substantial ACE2-blocking response in their sera. Finally, the identification of non-competing pairs of neutralising antibodies would offer potential templates for the development of prophylactic and therapeutic agents against SARS-CoV-2.

This paper aims to develop a multisensor data fusion technology-based smart home system by integrating wearable intelligent technology, artificial intelligence, and sensor fusion technology. We have developed the following three systems to create an intelligent smart home environment: (1) a wearable motion sensing device to be placed on residents’ wrists and its corresponding 3D gesture recognition algorithm to implement a convenient automated household appliance control system; (2) a wearable motion sensing device mounted on a resident’s feet and its indoor positioning algorithm to realize an effective indoor pedestrian navigation system for smart energy management; (3) a multisensor circuit module and an intelligent fire detection and alarm algorithm to realize a home safety and fire detection system. In addition, an intelligent monitoring interface is developed to provide in real-time information about the smart home system, such as environmental temperatures, CO concentrations, communicative environmental alarms, household appliance status, human motion signals, and the results of gesture recognition and indoor positioning. Furthermore, an experimental testbed for validating the effectiveness and feasibility of the smart home system was built and verified experimentally. The results showed that the 3D gesture recognition algorithm could achieve recognition rates for automated household appliance control of 92.0%, 94.8%, 95.3%, and 87.7% by the 2-fold cross-validation, 5-fold cross-validation, 10-fold cross-validation, and leave-one-subject-out cross-validation strategies. For indoor positioning and smart energy management, the distance accuracy and positioning accuracy were around 0.22% and 3.36% of the total traveled distance in the indoor environment. For home safety and fire detection, the classification rate achieved 98.81% accuracy for determining the conditions of the indoor living environment.

In this study, we evaluated the efficacy of hydroxychloroquine (HCQ) against coronavirus disease 2019 (COVID-19) via a randomized controlled trial (RCT) and a retrospective study. Subjects admitted to 11 designated public hospitals in Taiwan between April 1 and May 31, 2020, with COVID-19 diagnosis confirmed by pharyngeal real-time RT-PCR for SARS-CoV-2, were randomized at a 2:1 ratio and stratified by mild or moderate illness. HCQ (400 mg twice for 1 d or HCQ 200 mg twice daily for 6 days) was administered. Both the study and control group received standard of care (SOC). Pharyngeal swabs and sputum were collected every other day. The proportion and time to negative viral PCR were assessed on day 14. In the retrospective study, medical records were reviewed for patients admitted before March 31, 2020. There were 33 and 37 cases in the RCT and retrospective study, respectively. In the RCT, the median times to negative rRT-PCR from randomization to hospital day 14 were 5 days (95% CI; 1, 9 days) and 10 days (95% CI; 2, 12 days) for the HCQ and SOC groups, respectively (p = 0.40). On day 14, 81.0% (17/21) and 75.0% (9/12) of the subjects in the HCQ and SOC groups, respectively, had undetected virus (p = 0.36). In the retrospective study, 12 (42.9%) in the HCQ group and 5 (55.6%) in the control group had negative rRT-PCR results on hospital day 14 (p = 0.70). Neither study demonstrated that HCQ shortened viral shedding in mild to moderate COVID-19 subjects.

Most metals dissolve in aqueous solution in ionic form that tasks of purifying contaminated environments are always challenging for us, and the accurate prediction in the adsorption process is essential to identify determinants in surface science. We propose the simple representations of parameters described by Conceptual Density Functional Theory for hydrated metal ions. Different calculation methods through density functional theory (DFT) are developed and corresponding performance is revealed that the high correlation occurs between the global electronegativity and inner-sphere adsorption energy of hydrated metal ions by carboxyl-functionalized single-walled carbon nanotubes, in particular, the calculation concept involving fractional occupation numbers that R-square is above 0.8. The hydration energy is not negligible when determining the adsorption energy and it promotes the stability of the complexes in aqueous phase. That metal ions with trivalent charge exhibit stronger hydration energy than those with divalent charge is found. Meanwhile, the efficient system simulated by the meaningful fractional occupation methods for the wastewater treatment and optimal materials designing could be rationalized and accelerated.

Conflicting data exists regarding the baseline determinants of virological nonsuppression outcomes in treatment-experienced people living with human immunodeficiency virus (PWH) switching to antiretroviral treatment (ART) with bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) or dolutegravir/lamivudine (DTG/3TC) in Asia. This retrospective observational study, conducted at a designated HIV-care hospital from October 2019 to January 2023, aimed to address this gap. We assessed the odds of virological nonsuppression (VNS) at weeks 48 using logistic regression. A total of 988 patients were included, 35 patients (3.5%) with VNS at week 48. Pre-existing primary resistance-associated mutations (RAM) to nucleoside reverse transcriptase inhibitor (NRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) were identified in 11.0% (51/465) and 14.4% (67/465), respectively. The identified risk factor was a record of virological failure ≥2 times (AOR 5.32, 95% CI 2.04–13.85), while an HIV viral load <50 copies/mL within the past three months before switch (AOR: 0.27, 95% CI 0.11–0.72) was identified as a protective factor. No cases of acquired drug resistance-associated mutations were detected at week 48. Additionally, DTG/3TC was noninferior to BIC/FTC/TAF in achieving or maintaining HIV RNA levels of <50 copies/mL, within a -10% noninferiority margin in the per-protocol analysis (responder proportion: 98.2% vs. 95.0%, respectively; adjusted treatment difference [95% CI], 3.2% [0.7% to 5.3%]). In conclusion, DTG/3TC and BIC/FTC/TAF demonstrated good effectiveness in a real-world cohort, but frequent virological failure before the switch might impact the benefits of these regimens in the short term of follow-up.

Few studies have demonstrated the interplay between human immunodeficiency virus (HIV), anal human papillomavirus (HPV), and anal microbiota, especially in persons living with HIV who are men who have sex with men. We, therefore, explored these interrelationships in a cohort of persons living with HIV, mainly comprising men who have sex with men. HPV genotyping using a commercial genotyping kit and ThinPrep cytology interpreted by Bethesda systems was performed on samples from 291 patients. Samples were characterized by high-throughput sequencing of dual-index barcoded 16s rRNA (V3–4). Bacterial diversity was diminished in individuals living with HIV with CD4+ T cells <500 cells/μL and anal cytology yielding atypical squamous cells of undetermined significance or higher grades (ASCUS+) with detectable HPV 16/18 compared with those with CD4+ T cells ≥500 cells/μL with ASCUS+ and HPV 16/18 and those with normal anal cytology or inflammation without HPV 16/18. Enterobacteriaceae, Ruminococcus , and Bacilli were significantly abundant in persons living with HIV with CD4+ T cells <500 cells/μL with ASCUS+ and HPV 16/18. Bacterial diversity, composition, and homogeneity of dispersion were different in individuals living with HIV with low CD4+ T cells with ASCUS+ and HPV 16/18, and understanding the interaction among immunocompromised hosts, oncogenic HPVs, and microbiota is essential, and the contribution of these factors to anal precancerous lesions needs more in-depth exploration.

Background Although the nucleolus involves two major functions: pre-rRNA processing and ribosome biogenesis/assembly, increasing evidence indicates that it also plays important roles in response to abiotic stress. However, the possible regulatory mechanisms underlying the nucleolar proteins responsive to abiotic stress are largely unknown. High salinity is one of the major abiotic stresses, which hinders plant growth and productivity. Here, genetic screening approach was used to identify a salt hypersensitive mutant 9 ( sahy9 ) mutant, also known as apum23 , in Arabidopsis thaliana . Functional characterization of SAHY9/APUM23 through analyses of gene/protein expression profiles and metabolites was performed to decipher the possible regulatory mechanisms of the nucleolar protein SAHY9/APUM23 in response to salt stress. Results Seedlings of the sahy9/apum23 mutant displayed postgermination developmental arrest and then became bleached after prolonged culture under various salt stresses. Transcriptomic and proteomic analyses of salt-treated sahy9/apum23 and wild-type seedlings revealed differential expression of genes/proteins that have similar functional categories of biological processes, primarily those involved in cellular and metabolic processes as well as abiotic and biotic stress responses. However, the consistency of differential gene expression at both the transcript and protein levels was low (~ 12%), which suggests the involvement of posttranscriptional processing during the salt response. Furthermore, the altered expression of genes and proteins mediated by SAHY9/APUM23 regarding salt sensitivity involves abscisic acid (ABA) biosynthesis and signaling, abiotic stress responses, and ribosome biogenesis-related genes. Importantly, NCED3 , ABI2 , PP2CA , and major ABA-responsive marker genes, such as RD20 and RD29B , were down-regulated at both the transcript and protein levels in conjunction with lower contents of ABA and changes in the expression of a subset of LEA proteins in sahy9/apum23 mutants under salt stress. Moreover, the salt hypersensitivity of the sahy9/apum23 mutant was largely rescued by the exogenous application of ABA during salt stress. Conclusion Our results revealed that SAHY9/APUM23 regulated the expression of ribosome biogenesis-related genes and proteins, which further affected the ribosome composition and abundance, and potential posttranscriptional regulation. The salt hypersensitivity of sahy9/apum23 is associated with the ABA-mediated signaling pathway and the downstream stress-responsive network of this pathway.

The international and national HIV treatment guidelines in 2016 have focused on scaling up access to combination antiretroviral therapy (cART). We aimed to assess the trends and treatment outcomes of late cART initiation in Taiwan. Between June 2012 and May 2016, we retrospectively included antiretroviral-naive HIV-positive adults who initiated cART. Late initiation was defined as when cART was initiated in patients with a CD4 count <200 cells/mm3 or having experienced AIDS-defining illnesses. The treatment outcomes were assessed up to 6 months after starting cART. We included 3655 HIV-positive patients, and the majority of the patients were male (95.4%) with a median age of 31 years and initiated non-nucleoside reverse-transcriptase inhibitor-containing regimens (87.0%). The median CD4 count at cART initiation increased from 207 cells/mm3 in 2012 to 298 cells/mm3 in 2016, and the overall proportion of late cART initiation decreased from 49.1% in 2012 to 29.0% in 2016 (P for trend <0.001). Late cART initiation mainly resulted from late presentation for HIV care and was associated with older age (per 1-year increase, adjusted odds ratio [AOR], 1.05; 95% CI, 1.04-1.06), HBsAg seropositivity (AOR, 1.31; 95% CI, 1.04-1.64), HIV care in central and southern Taiwan, initiating cART in earlier year, non-intravenous drug users (AOR, 1.96; 95% CI, 1.33-2.86), and negative hepatitis C serostatus (AOR, 1.47; 95% CI, 1.04-2.08). Compared with non-late initiators, late initiators had a higher rate of all-cause mortality (1.7% vs. 0.3%) and regimen modification due to virological failure (7.1% vs. 2.6%). The predicting factors of all-cause mortality were late cART initiation (adjusted hazard ratio [AHR], 5.40; 95% CI, 2.14-13.65) and older age (AHR, 1.06; 95% CI, 1.03-1.10). While the proportion of late cART initiation decreased over time in Taiwan, late initiation remained in a substantial proportion of HIV-positive patients. The late initiators had higher risk for poor outcomes. The need for strategies to earlier detection of HIV infection and expediting cART initiation should be highlighted, especially among the older population.