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Seeking optimized infectious pathogen detection tools is of primary importance to lessen the spread of infections, allowing prompt medical attention for the infected. Among nucleic-acid-based sensing techniques, loop-mediated isothermal amplification is a promising method, as it provides rapid, sensitive, and specific detection of microbial and viral pathogens and has enormous potential to transform current point-of-care molecular diagnostics. In this review, the advances in LAMP-based point-of-care diagnostics assays developed during the past few years for rapid and sensitive detection of infectious pathogens are outlined. The numerous detection methods of LAMP-based biosensors are discussed in an end-point and real-time manner with ideal examples. We also summarize the trends in LAMP-on-a-chip modalities, such as classical microfluidic, paper-based, and digital LAMP, with their merits and limitations. Finally, we provide our opinion on the future improvement of on-chip LAMP methods. This review serves as an overview of recent breakthroughs in the LAMP approach and their potential for use in the diagnosis of existing and emerging diseases.

Strobilanthes cusia (Nees) Kuntze is a Chinese herbal medicine used in the treatment of respiratory virus infections. The methanol extract of S. cusia leaf contains chemical components such as β-sitosterol, indirubin, tryptanthrin, betulin, indigodole A, and indigodole B that have diverse biological activities. However, the antiviral action of S. cusia leaf and its components against human coronavirus remains to be elucidated. Human coronavirus NL63 infection is frequent among immunocompromised individuals, young children, and in the elderly. This study investigated the anti-Human coronavirus NL63 (HCoV-NL63) activity of the methanol extract of S. cusia leaf and its major components. The methanol extract of S. cusia leaf effectively inhibited the cytopathic effect (CPE) and virus yield (IC50 = 0.64 μg/mL) in HCoV-NL63-infected cells. Moreover, this extract potently inhibited the HCoV-NL63 infection in a concentration-dependent manner. Among the six components identified in the methanol extract of S. cusia leaf, tryptanthrin and indigodole B (5aR-ethyltryptanthrin) exhibited potent antiviral activity in reducing the CPE and progeny virus production. The IC50 values against virus yield were 1.52 μM and 2.60 μM for tryptanthrin and indigodole B, respectively. Different modes of time-of-addition/removal assay indicated that tryptanthrin prevented the early and late stages of HCoV-NL63 replication, particularly by blocking viral RNA genome synthesis and papain-like protease 2 activity. Notably, tryptanthrin (IC50 = 0.06 μM) and indigodole B (IC50 = 2.09 μM) exhibited strong virucidal activity as well. This study identified tryptanthrin as the key active component of S. cusia leaf methanol extract that acted against HCoV-NL63 in a cell-type independent manner. The results specify that tryptanthrin possesses antiviral potential against HCoV-NL63 infection.

Severe acute respiratory syndrome–associated coronavirus (SARS-CoV) initiates the cytokine/chemokine storm-mediated lung injury. The SARS-CoV unique domain (SUD) with three macrodomains (N, M, and C), showing the G-quadruplex binding activity, was examined the possible role in SARS pathogenesis in this study. The chemokine profile analysis indicated that SARS-CoV SUD significantly up-regulated the expression of CXCL10, CCL5 and interleukin (IL)-1β in human lung epithelial cells and in the lung tissues of the mice intratracheally instilled with the recombinant plasmids. Among the SUD subdomains, SUD-MC substantially activated AP-1-mediated CXCL10 expression in vitro. In the wild type mice, SARS-CoV SUD-MC triggered the pulmonary infiltration of macrophages and monocytes, inducing CXCL10-mediated inflammatory responses and severe diffuse alveolar damage symptoms. Moreover, SUD-MC actuated NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome-dependent pulmonary inflammation, as confirmed by the NLRP3 inflammasome inhibitor and the NLRP3−/− mouse model. This study demonstrated that SARS-CoV SUD modulated NLRP3 inflammasome-dependent CXCL10-mediated pulmonary inflammation, providing the potential therapeutic targets for developing the antiviral agents.

The Dual-Frequency Precipitation Radar (DPR), which consists of a Ku-band precipitation radar (KuPR) and a Ka-band precipitation radar (KaPR) on board the GPM Core Observatory , cannot observe precipitation at low altitudes near the ground contaminated by surface clutter. This near-surface region is called the blind zone. DPR estimates the clutter-free bottom (CFB), which is the lowest altitude not included in the blind zone, and estimates precipitation at altitudes higher than the CFB. High CFBs, which are common over mountainous areas, represent obstacles to detection of shallow precipitation and estimation of low-level enhanced precipitation. We compared KuPR data with rain gauge data from Da-Tun Mountain of northern Taiwan acquired from March 2014 to February 2020. A total of 12 cases were identified in which the KuPR missed some rainfall with intensity of >10 mm h −1 that was observed by rain gauges. Comparison of KuPR profile and ground-based radar profile revealed that shallow precipitation in the KuPR blind zone was missed because the CFB was estimated to be higher than the lower bound of the range free from surface echoes. In the original operational algorithm, CFB was estimated using only the received power data of the KuPR. In this study, the CFB was identified by the sharp increase in the difference between the received powers of the KuPR and the KaPR at altitude affected by surface clutter. By lowering the CFB, the KuPR succeeded in detection and estimation of shallow precipitation.

This study aimed to investigate the real experience and specific needs of patients undergoing holmium laser enucleation of the prostate, to provide appropriate nursing strategies for reference in the perioperative management of patients undergoing this type of surgery. The descriptive phenomenological research method in qualitative research was selected for this study. Purposive sampling method was used to select 10 patients who underwent holmium laser enucleation of the prostate in a tertiary hospital in Shanghai from May to June 2023 for semi-structured interviews, and the results of the interviews were compiled and analyzed using the Colaizzi seven-step analysis method. The surgical process experience and needs of patients undergoing holmium laser enucleation of the prostate were summarized and organized into three major themes and eight minor themes: (i) overall perception of the preoperative surgical process (unexpected admission experience, uncertain preoperative waiting time, and inadequate preoperative informational support), (ii) complex intraoperative sensory experience (unfamiliar surgical staff, cold surgical environment, and noisy surgical sounds), and (iii) postoperative continuity of care needs (diverse forms of health education, personalized health education content). These findings recommend to strengthen preoperative education to enhance patients’ cognitive preparedness, to improve intraoperative care by addressing complex environmental stimuli through humanistic nursing, and to provide diverse health education that supports continuity of care throughout the perioperative process. This will further improve the hospitalization experience of patients undergoing holmium laser enucleation of the prostate, meet practical needs, and provide a valuable reference for perioperative comfort management and nursing strategy development for this group of patients undergoing HoLEP.

Background Height is an important anthropometric measurement and is associated with many health-related outcomes. Genome-wide association studies (GWASs) have identified hundreds of genetic loci associated with height, mainly in individuals of European ancestry. Methods We performed genome-wide association analyses and replicated previously reported GWAS-determined single nucleotide polymorphisms (SNPs) in the Taiwanese Han population (Taiwan Biobank; n = 67,452). A genetic instrument composed of 251 SNPs was selected from our GWAS, based on height and replication results as the best-fit polygenic risk score (PRS), in accordance with the clumping and p -value threshold method. We also examined the association between genetically determined height (PRS 251 ) and measured height (phenotype). We performed observational (phenotype) and genetic PRS 251 association analyses of height and health-related outcomes. Results GWAS identified 6843 SNPs in 89 genomic regions with genome-wide significance, including 18 novel loci. These were the most strongly associated genetic loci ( EFEMP1 , DIS3L2 , ZBTB38 , LCORL , HMGA1 , CS , and GDF5 ) previously reported to play a role in height. There was a positive association between PRS 251 and measured height ( p < 0.001). Of the 14 traits and 49 diseases analyzed, we observed significant associations of measured and genetically determined height with only eight traits ( p < 0.05/[14 + 49]). Height was positively associated with body weight, waist circumference, and hip circumference but negatively associated with body mass index, waist-hip ratio, body fat, total cholesterol, and low-density lipoprotein cholesterol ( p < 0.05/[14 + 49]). Conclusions This study contributes to the understanding of the genetic features of height and health-related outcomes in individuals of Han Chinese ancestry in Taiwan.

Ocular corticosteroids are commonly used clinically. Unfortunately, their administration frequently leads to ocular hypertension, i.e., elevated intraocular pressure (IOP), which, in turn, can progress to a form of glaucoma known as steroid-induced glaucoma. The pathophysiology of this condition is poorly understood yet shares similarities with the most common form of glaucoma. Using nanotechnology, we created a mouse model of corticosteroid-induced ocular hypertension. This model functionally and morphologically resembles human ocular hypertension, having titratable, robust, and sustained IOPs caused by increased resistance to aqueous humor outflow. Using this model, we then interrogated the biomechanical properties of the trabecular meshwork (TM), including the inner wall of Schlemm’s canal (SC), tissues known to strongly influence IOP and to be altered in other forms of glaucoma. Specifically, using spectral domain optical coherence tomography, we observed that SC in corticosteroid-treated mice was more resistant to collapse at elevated IOPs, reflecting increased TM stiffness determined by inverse finite element modeling. Our noninvasive approach to monitoring TM stiffness in vivo is applicable to other forms of glaucoma and has significant potential to monitor TM function and thus positively affect the clinical care of glaucoma, the leading cause of irreversible blindness worldwide.

This study explores the mechanisms responsible for valley precipitation enhancement over Da-Tun Mountain under the prevailing northeasterly monsoonal flow. Da-Tun Mountain, located adjacent to the northern coast of Taiwan, is a small-scale (15 km), concave-like terrain feature with two ridge arms and a funnel-shaped valley. A typical valley precipitation enhancement event that occurred on 13 December 2018 was chosen for detailed analyses. Upstream conditions were characterized by the absence of convective available potential energy with a large-Froude-number (>1) flow regime. Observational and modeling results indicate a consistent, important signature of flow splitting due to partial blocking as the low-level northeasterly flow encountered the ridge arms. Fine-scale structures of airflow and precipitation evident from the simulations further reveal that the deflected flows over the two ridge arms interacted with each other to produce lateral convergence and enhanced precipitation inside the valley. The smaller-scale splitting flows tended to occur over the ridge arms as upstream moist Froude number decreased from relatively higher (5–11) to lower (3–5) values due to the temporal change in moist static stability. Quantitative diagnoses of vertical velocities performed over the region of primary precipitation support that upward motions associated with lateral convergence greatly overwhelmed the upslope-forced lifting over the valley region during the valley precipitation enhancement periods. However, vertical motions over the ridge arms with steeper slopes were dominantly contributed by the upslope forcing, but their intensities were also modulated by the flow-splitting-induced divergence.

SARS coronavirus (SARS-CoV) papain-like protease (PLpro) has been identified in TGF-β1 up-regulation in human promonocytes (Proteomics 2012, 12: 3193-205). This study investigates the mechanisms of SARS-CoV PLpro-induced TGF-β1 promoter activation in human lung epithelial cells and mouse models. SARS-CoV PLpro dose- and time-dependently up-regulates TGF-β1 and vimentin in A549 cells. Dual luciferase reporter assays with TGF-β1 promoter plasmids indicated that TGF-β1 promoter region between −175 to −60, the Egr-1 binding site, was responsible for TGF-β1 promoter activation induced by SARS-CoV PLpro. Subcellular localization analysis of transcription factors showed PLpro triggering nuclear translocation of Egr-1, but not NF-κB and Sp-1. Meanwhile, Egr-1 silencing by siRNA significantly reduced PLpro-induced up-regulation of TGF-β1, TSP-1 and pro-fibrotic genes. Furthermore, the inhibitors for ROS (YCG063), p38 MAPK (SB203580) and STAT3 (Stattic) revealed ROS/p38 MAPK/STAT3 pathway involving in Egr-1 dependent activation of TGF-β1 promoter induced by PLpro. In a mouse model with a direct pulmonary injection, PLpro stimulated macrophage infiltration into lung, up-regulating Egr-1, TSP-1, TGF-β1 and vimentin expression in lung tissues. The results revealed that SARS-CoV PLpro significantly triggered Egr-1 dependent activation of TGF-β1 promoter via ROS/p38 MAPK/STAT3 pathway, correlating with up-regulation of pro-fibrotic responses in vitro and in vivo .

Severe acute respiratory syndrome coronavirus (SARS-CoV) papain-like protease (PLPro) reportedly inhibits the production of type I interferons (IFNs) and pro-inflammatory cytokines in Toll-like receptor 3 (TLR3) and retinoic acid-inducible gene 1 (RIG-I) pathways. The study investigated the inhibitory effect and its antagonistic mechanism of SARS-CoV PLPro on TLR7-mediated cytokine production. TLR7 agonist (imiquimod (IMQ)) concentration-dependently induced activation of ISRE-, NF-κB- and AP-1-luciferase reporters, as well as the production of IFN-α, IFN-β, TNF-α, IL-6 and IL-8 in human promonocyte cells. However, SARS-CoV PLPro significantly inhibited IMQ-induced cytokine production through suppressing the activation of transcription factors IRF-3, NF-κB and AP-1. Western blot analysis with anti-Lys48 and anti-Lys63 ubiquitin antibodies indicated the SARS-CoV PLPro removed Lys63-linked ubiquitin chains of TRAF3 and TRAF6, but not Lys48-linked ubiquitin chains in un-treated and treated cells. The decrease in the activated state of TRAF3 and TRAF6 correlated with the inactivation of TBK1 in response to IMQ by PLPro. The results revealed that the antagonism of SARS-CoV PLPro on TLR7-mediated innate immunity was associated with the negative regulation of TRAF3/6-TBK1-IRF3/NF-κB/AP1 signals.