Effect of C-type lectin 16 on dengue virus infection in Aedes aegypti salivary glands.

C-type lectins (CTLs) are a family of carbohydrate-binding proteins and an important component of mosquito saliva. Although CTLs play key roles in immune activation and viral pathogenesis, little is known about their role in regulating dengue virus (DENV) infection and transmission. In this study, we established a homozygous CTL16 knockout Aedes aegypti mutant line using CRISPR/Cas9 to study the interaction between CTL16 and viruses in mosquito vectors. Furthermore, mouse experiments were conducted to confirm the transmission of DENV by CTL16-/- A. aegypti mutants. We found that CTL16 was mainly expressed in the medial lobe of the salivary glands (SGs) in female A. aegypti. CTL16 knockout increased DENV replication and accumulation in the SGs of female A. aegypti, suggesting that CTL16 plays an important role in DENV transmission. We also found a reduced expression of immunodeficiency and Janus kinase/signal transducer and activator of transcription pathway components correlated with increased DENV viral titer, infection rate, and transmission efficiency in the CTL16 mutant strain. The findings of this study provide insights not only for guiding future investigations on the influence of CTLs on immune responses in mosquitoes but also for developing novel mutants that can be used as vector control tools.

Integrating predictive coding and a user-centric interface for enhanced auditing and quality in cancer registry data.

Data curation for a hospital-based cancer registry heavily relies on the labor-intensive manual abstraction process by cancer registrars to identify cancer-related information from free-text electronic health records. To streamline this process, a natural language processing system incorporating a hybrid of deep learning-based and rule-based approaches for identifying lung cancer registry-related concepts, along with a symbolic expert system that generates registry coding based on weighted rules, was developed. The system is integrated with the hospital information system at a medical center to provide cancer registrars with a patient journey visualization platform. The embedded system offers a comprehensive view of patient reports annotated with significant registry concepts to facilitate the manual coding process and elevate overall quality. Extensive evaluations, including comparisons with state-of-the-art methods, were conducted using a lung cancer dataset comprising 1428 patients from the medical center. The experimental results illustrate the effectiveness of the developed system, consistently achieving F1-scores of 0.85 and 1.00 across 30 coding items. Registrar feedback highlights the system's reliability as a tool for assisting and auditing the abstraction. By presenting key registry items along the timeline of a patient's reports with accurate code predictions, the system improves the quality of registrar outcomes and reduces the labor resources and time required for data abstraction. Our study highlights advancements in cancer registry coding practices, demonstrating that the proposed hybrid weighted neural-symbolic cancer registry system is reliable and efficient for assisting cancer registrars in the coding workflow and contributing to clinical outcomes.

CLEC5A mediates Zika virus-induced testicular damage.

BACKGROUND: Zika virus (ZIKV) infection is clinically known to induce testicular swelling, termed orchitis, and potentially impact male sterility, but the underlying mechanisms remain unclear. Previous reports suggested that C-type lectins play important roles in mediating virus-induced inflammatory reactions and pathogenesis. We thus investigated whether C-type lectins modulate ZIKV-induced testicular damage. METHODS: C-type lectin domain family 5 member A (CLEC5A) knockout mice were generated in a STAT1-deficient immunocompromised background (denoted clec5a-/-stat1-/-) to enable testing of the role played by CLEC5A after ZIKV infection in a mosquito-to-mouse disease model. Following ZIKV infection, mice were subjected to an array of analyses to evaluate testicular damage, including ZIKV infectivity and neutrophil infiltration estimation via quantitative RT-PCR or histology and immunohistochemistry, inflammatory cytokine and testosterone detection, and spermatozoon counting. Furthermore, DNAX-activating proteins for 12 kDa (DAP12) knockout mice (dap12-/-stat1-/-) were generated and used to evaluate ZIKV infectivity, inflammation, and spermatozoa function in order to investigate the potential mechanisms engaged by CLEC5A. RESULTS: Compared to experiments conducted in ZIKV-infected stat1-/- mice, infected clec5a-/-stat1-/- mice showed reductions in testicular ZIKV titer, local inflammation and apoptosis in testis and epididymis, neutrophil invasion, and sperm count and motility. CLEC5A, a myeloid pattern recognition receptor, therefore appears involved in the pathogenesis of ZIKV-induced orchitis and oligospermia. Furthermore, DAP12 expression was found to be decreased in the testis and epididymis tissues of clec5a-/-stat1-/- mice. As for CLEC5A deficient mice, ZIKV-infected DAP12-deficient mice also showed reductions in testicular ZIKV titer and local inflammation, as well as improved spermatozoa function, as compared to controls. CLEC5A-associated DAP12 signaling appears to in part regulate ZIKV-induced testicular damage. CONCLUSIONS: Our analyses reveal a critical role for CLEC5A in ZIKV-induced proinflammatory responses, as CLEC5A enables leukocytes to infiltrate past the blood-testis barrier and induce testicular and epididymal tissue damage. CLEC5A is thus a potential therapeutic target for the prevention of injuries to male reproductive organs in ZIKV patients.

Prevalence of exposure to benzodiazepines among pregnant women in Taiwan: A nationwide longitudinal study.

Although more than one hundred studies have examined the prevalence of the use of benzodiazepines and benzodiazepine-like Z-hypnotics (BZDs) among pregnancy events, further analysis of the effects of dosage or type of BZDs is needed. The aim of this study was to examine the prevalence rate of BZDs use in pregnancy events, stratified by trimester over time, with characteristics of the dosage and type of BZDs. This is a retrospective population study based on linking three national databases. We examined the prevalence rates from 2004 to 2017, and contrasted the results based on >0 defined daily dose (DDD) and ≥0.5 DDD. We identified 2,630,944 pregnancy events with live births; 89,897 (3.4%) of the associated pregnancy events had used some form of BZD during pregnancy. The prevalence of BZDs use, as defined by >0 DDD, decreased from 4.1% in 2004 to 2.9% in 2017, indicating a decrease in sporadic use and an increase in stable use within therapeutic doses. Meanwhile, BZDs use defined by ≥0.5 DDD increased from 0.1% in 2004 to 0.4% in 2017. Zolpidem was the most frequently prescribed BZDs, as defined by >0 DDD or ≥0.5 DDD. This national cohort study demonstrates the importance of average dosage in the definition of BZDs use in pregnancy events, and it found opposite trends in the prevalence of use between different dosages.

Admittance analysis of broadband omnidirectional near-perfect absorber in epsilon-near-zero mode.

In this paper, we propose a broadband omnidirectional near-perfect absorber that transforms light energy into heat. In contrast to previous research on structural metamaterials, this study focuses on light absorption in the epsilon-near-zero (ENZ) layers without any structural patterns. Chromium (Cr) thin films were applied as ENZ layers. Using the admittance method, we found the proper thicknesses of SiO2 layers to match the incident medium and achieve perfect absorption. Also, the absorber is angular insensitive up to 60°. The temperature of the absorber increases from room temperature to 42°C, which is 4°C higher than the uncoated substrate at 38°C, after exposure to sunlight for 20 min.

Varying stress of SiOxCy thin films deposited by plasma polymerization.

SiOxCy thin films were deposited by plasma polymerization. The stress of the deposited SiOxCy thin films can be modified by adjusting the beam current, the anode voltage, and the flow rate of hexamethyldisiloxane (HMDSO) gas and oxygen. Reducing the beam current or increasing the flow rate of HMDSO gas increased the linear/cage structure ratio and turned the stress of the SiOxCy thin films from compressive to tensile. The linear/cage structure ratio can be adjusted by changing the composite parameter, W[FM]c/[FM]m, to control the stress of the deposited plasma polymer films. Multilayers of TiO2/SiO2/TiO2 were coated on a SiOxCy plasma polymer film herein, reducing their stress by 70% from 0.06 to 0.018 GPa. The refractive index is 1.55, and the absorption coefficient is less than 10-4 at 550 nm of the SiOxCy films. Superior optical performances of SiOxCy thin films make their use in optical thin films.

Endocytosis of PEGylated agents enhances cancer imaging and anticancer efficacy.

PEGylated nanoparticles and macromolecules are increasingly used in cancer imaging and anticancer treatment. The role of receptor-mediated endocytosis in the efficacy of these agents, however, has not been clearly defined. Here, we developed a matched pair of endocytic and nonendocytic receptors to directly and unambiguously assess this issue. The ligand-binding domains of the low-density lipoprotein receptor (LDLR) or a truncated LDLR lacking the NPXY endocytosis motif (DeltaLDLR) were replaced with an anti-polyethylene glycol antibody (alphaPEG) to form endocytic alphaPEG-LDLR and nonendocytic alphaPEG-DeltaLDLR receptors. The receptors were stably expressed at similar levels on the surface of HCC36 cells. HCC36/alphaPEG-LDLR cells, but not HCC36/alphaPEG-DeltaLDLR cells, rapidly endocytosed PEG-quantum dots and PEG-liposomal doxorubicin (Lipo-Dox) in vitro and in vivo. Lipo-Dox was significantly more cytotoxic to HCC36/alphaPEG-LDLR cells than to HCC36/alphaPEG-DeltaLDLR cells. HCC36/alphaPEG-LDLR tumors also accumulated significantly more PEGylated near-IR probes (PEG-NIR797) and PEG-liposomal-(111)In than HCC36/alphaPEG-DeltaLDLR tumors in vivo. Furthermore, Lipo-Dox more significantly suppressed the growth of established HCC36/alphaPEG-LDLR tumors as compared with HCC36/alphaPEG-DeltaLDLR tumors. Our data show that endocytosis of PEGylated probes and drugs enhances both cancer imaging and anticancer efficacy, indicating that endocytic receptors are superior targets for the design of cancer imaging probes and immunoliposomal drugs.

Measurement of poly(ethylene glycol) by cell-based anti-poly(ethylene glycol) ELISA.

Poly(ethylene glycol) (PEG) is increasingly used in clinical and experimental medicine. However, quantification of PEG and PEGylated small molecules remains laborious and unsatisfactory. In this report, we stably expressed a functional anti-PEG antibody on the surface of BALB 3T3 cells (3T3/alphaPEG cells) to develop a competitive enzyme-linked immunosorbent assay (ELISA) for PEG quantification. The alphaPEG cell-coated plate bound biotinylated PEG(5K) (CH(3)-PEG(5K)-biotin) and CH(3)-PEG(5K)-(131)I more effectively than did a traditional anti-PEG antibody-coated plate. Competitive binding between PEG (2, 5, 10, or 20 kDa) and a known amount of CH(3)-PEG(5K)-biotin allowed construction of a reproducible competition curve. The alphaPEG cell-based competition ELISA measured small molecules derivatized by PEG(2K), PEG(5K), PEG(10K), PEG(20K), and PEG(5K) at concentrations as low as 58.6, 14.6, 3.7, 3.7, and 14.6 ng/mL, respectively. Notably, the presence of serum or bovine serum albumin enhanced PEG measurement by the alphaPEG cell-based competition ELISA. Finally, we show here that the alphaPEG cell-based competition ELISA accurately delineated the pharmacokinetics of PEG(5K), comparable to those determined by direct measurement of radioactivity in blood after intravenous injection of CH(3)-PEG(5K)-(131)I into mice. This quantitative strategy may provide a simple and sensitive method for quantifying PEG and PEGylated small molecules in vivo.

The nature of international health security.

Health issues occasionally intersect security issues. Health security has been viewed as an essential part of human security. Policymakers and health professionals, however, do not share a common definition of health security. This article aims to characterize the notions of health security in order to clarify what constitutes the nexus of health and security. The concept of health security has evolved over time so that it encompasses many entities. Analyzing the health reports of four multilateral organizations (the United Nations, World Health Organization, Asia-Pacific Economic Cooperation, and the European Union) produced eight categories of most significant relevance to contemporary health security, allowing comparison of the definitions. The four categories are: emerging diseases; global infectious disease; deliberate release of chemical and biological materials; violence, conflict, and humanitarian emergencies. Two other categories of common concern are natural disasters and environmental change, as well as chemical and radioactive accidents. The final two categories, food insecurity and poverty, are discussed less frequently. Nevertheless, food security is emerging as an increasingly important issue in public health. Health security is the first line of defence against health emergencies. As globalization brings more complexities, dealing with the increased scale and extent of health security will require greater international effort and political support.