Bispecific antibodies promote natural killer cell-mediated elimination of HIV-1 reservoir cells.

The persistence of CD4+ T cells carrying latent human immunodeficiency virus-1 (HIV-1) proviruses is the main barrier to a cure. New therapeutics to enhance HIV-1-specific immune responses and clear infected cells will probably be necessary to achieve reduction of the latent reservoir. In the present study, we report two single-chain diabodies (scDbs) that target the HIV-1 envelope protein (Env) and the human type III Fcγ receptor (CD16). We show that the scDbs promoted robust and HIV-1-specific natural killer (NK) cell activation and NK cell-mediated lysis of infected cells. Cocultures of CD4+ T cells from people with HIV-1 on antiretroviral therapy (ART) with autologous NK cells and the scDbs resulted in marked elimination of reservoir cells that was dependent on latency reversal. Treatment of human interleukin-15 transgenic NSG mice with one of the scDbs after ART initiation enhanced NK cell activity and reduced reservoir size. Thus, HIV-1-specific scDbs merit further evaluation as potential therapeutics for clearance of the latent reservoir.

Irreversible synthesis of an ultrastrong two-dimensional polymeric material.

Polymers that extend covalently in two dimensions have attracted recent attention1,2 as a means of combining the mechanical strength and in-plane energy conduction of conventional two-dimensional (2D) materials3,4 with the low densities, synthetic processability and organic composition of their one-dimensional counterparts. Efforts so far have proven successful in forms that do not allow full realization of these properties, such as polymerization at flat interfaces5,6 or fixation of monomers in immobilized lattices7-9. Another frequently employed synthetic approach is to introduce microscopic reversibility, at the cost of bond stability, to achieve 2D crystals after extensive error correction10,11. Here we demonstrate a homogenous 2D irreversible polycondensation that results in a covalently bonded 2D polymeric material that is chemically stable and highly processable. Further processing yields highly oriented, free-standing films that have a 2D elastic modulus and yield strength of 12.7 ± 3.8 gigapascals and 488 ± 57 megapascals, respectively. This synthetic route provides opportunities for 2D materials in applications ranging from composite structures to barrier coating materials.

NFTest: automated testing of Nextflow pipelines.

MOTIVATION: The ongoing expansion in the volume of biomedical data has contributed to a growing complexity in the tools and technologies used in research with an increased reliance on complex workflows written in orchestration languages such as Nextflow to integrate algorithms into processing pipelines. The growing use of workflows involving various tools and algorithms has led to increased scrutiny of software development practices to avoid errors in individual tools and in the connections between them. RESULTS: To facilitate test-driven development of Nextflow pipelines, we created NFTest, a framework for automated pipeline testing and validation with customizability options for Nextflow features. It is open-source, easy to initialize and use, and customizable to allow for testing of complex workflows with test success configurable through a broad range of assertions. NFTest simplifies the testing burden on developers by automating tests once defined and providing a flexible interface for running tests to validate workflows. This reduces the barrier to rigorous biomedical workflow testing and paves the way toward reducing computational errors in biomedicine. AVAILABILITY AND IMPLEMENTATION: NFTest is an open-source Python framework under the GPLv2 license and is freely available at https://github.com/uclahs-cds/tool-NFTest. The call-sSNV Nextflow pipeline is available at: https://github.com/uclahs-cds/pipeline-call-sSNV.

Selectively Controlled Ferromagnets by Electric Fields in van der Waals Ferromagnetic Heterojunctions.

Charge transfer plays a key role at the interfaces of heterostructures, which can affect electronic structures and ultimately the physical properties of the materials. However, charge transfer is difficult to manipulate externally once the interface is formed. The recently discovered van der Waals ferromagnets with atomically sharp interfaces provided a perfect platform for the electrical control of interfacial charge transfer. Here, we report magnetoresistance experiments revealing electrically tunable charge transfer in Fe3GeTe2/Cr2Ge2Te6/Fe3GeTe2 all-magnetic van der Waals heterostructures, which can be exploited to selectively modify the switching fields of the top or bottom Fe3GeTe2 electrodes. The directional charge transfer from metallic Fe3GeTe2 to semiconducting Cr2Ge2Te6 is revealed by first-principles calculations, which remarkably modifies the magnetic anisotropy energy of Fe3GeTe2, leading to the dramatically suppressed coercivity. The electrically selective control of magnetism demonstrated in this study could stimulate the development of spintronic devices based on van der Waals magnets.

[Risk factors for embolism in children with refractory Mycoplasmapneumoniae pneumonia and construction of a nomogram model for prediction of embolism]. / éš¾æ²»æ€§è‚ºç‚Žæ”¯åŽŸä½“è‚ºç‚Žæ‚£å„¿åˆå¹¶æ “å¡žçš„å±é™©å› ç´ åˆ†æžåŠåˆ—çº¿å›¾é¢„æµ‹æ¨¡åž‹çš„æž„å»º.

OBJECTIVES: To study the risk factors for embolism in children with refractory Mycoplasma pneumoniae pneumonia (RMPP) and to construct a nomogram model for prediction of embolism. METHODS: This retrospective study included 175 children diagnosed with RMPP at Children's Hospital Affiliated toZhengzhou University from January 2019 to October 2023. They were divided into two groups based on the presence of embolism: the embolism group (n=62) and the non-embolism group (n=113). Multivariate logistic regression analysis was used to screen for risk factors of embolism in children with RMPP, and the R software was applied to construct the nomogram model for prediction of embolism. RESULTS: Multivariate logistic regression analysis indicated that higher levels of D-dimer, interleukin-6 (IL-6) and neutrophil to lymphocyte ratio (NLR), lung necrosis, and pleural effusion were risk factors for embolism in children with RMPP (P<0.05). The area under the curve of the nomogram model for prediction of embolism constructed based on the aforementioned risk factors was 0.912 (95%CI: 0.871-0.952, P<0.05). The Hosmer-Lemeshow goodness-of-fit test showed that the model had a good fit with the actual situation (P<0.05). Calibration and decision curve analysis indicated that the model had high predictive efficacy and clinical applicability. CONCLUSIONS: Higher levels of D-dimer, IL-6 and NLR, lung necrosis, and pleural effusion are risk factors for embolism in children with RMPP. The nomogram model based on these risk factors has high clinical value for predicting embolism in children with RMPP.

The Natural Stilbenoid (-)-Hopeaphenol Inhibits HIV Transcription by Targeting Both PKC and NF-κB Signaling and Cyclin-Dependent Kinase 9.

Despite effective combination antiretroviral therapy (cART), people living with HIV (PLWH) continue to harbor replication-competent and transcriptionally active virus in infected cells, which in turn can lead to ongoing viral antigen production, chronic inflammation, and increased risk of age-related comorbidities. To identify new agents that may inhibit postintegration HIV beyond cART, we screened a library of 512 pure compounds derived from natural products and identified (-)-hopeaphenol as an inhibitor of HIV postintegration transcription at low to submicromolar concentrations without cytotoxicity. Using a combination of global RNA sequencing, plasmid-based reporter assays, and enzyme activity studies, we document that hopeaphenol inhibits protein kinase C (PKC)- and downstream NF-κB-dependent HIV transcription as well as a subset of PKC-dependent T-cell activation markers, including interleukin-2 (IL-2) cytokine and CD25 and HLA-DRB1 RNA production. In contrast, it does not substantially inhibit the early PKC-mediated T-cell activation marker CD69 production of IL-6 or NF-κB signaling induced by tumor necrosis factor alpha (TNF-α). We further show that hopeaphenol can inhibit cyclin-dependent kinase 9 (CDK9) enzymatic activity required for HIV transcription. Finally, it inhibits HIV replication in peripheral blood mononuclear cells (PBMCs) infected in vitro and dampens viral reactivation in CD4+ cells from PLWH. Our study identifies hopeaphenol as a novel inhibitor that targets a subset of PKC-mediated T-cell activation pathways in addition to CDK9 to block HIV expression. Hopeaphenol-based therapies could complement current antiretroviral therapy otherwise not targeting cell-associated HIV RNA and residual antigen production in PLWH.

Neuropilin-1 Facilitates Pseudorabies Virus Replication and Viral Glycoprotein B Promotes Its Degradation in a Furin-Dependent Manner.

Pseudorabies virus (PRV), which is extremely infectious and can infect numerous mammals, has a risk of spillover into humans. Virus-host interactions determine viral entry and spreading. Here, we showed that neuropilin-1 (NRP1) significantly potentiates PRV infection. Mechanistically, NRP1 promoted PRV attachment and entry, and enhanced cell-to-cell fusion mediated by viral glycoprotein B (gB), gD, gH, and gL. Furthermore, through in vitro coimmunoprecipitation (Co-IP) and bimolecular fluorescence complementation (BiFC) assays, NRP1 was found to physically interact with gB, gD, and gH, and these interactions were C-end Rule (CendR) motif independent, in contrast to currently known viruses. Remarkably, we illustrated that the viral protein gB promotes NRP1 degradation via a lysosome-dependent pathway. We further demonstrate that gB promotes NRP1 degradation in a furin-cleavage-dependent manner. Interestingly, in this study, we generated gB furin cleavage site (FCS)-knockout PRV (Δfurin PRV) and evaluated its pathogenesis; in vivo, we found that Δfurin PRV virulence was significantly attenuated in mice. Together, our findings demonstrated that NRP1 is an important host factor for PRV and that NRP1 may be a potential target for antiviral intervention. IMPORTANCE Recent studies have shown accelerated PRV cross-species spillover and that PRV poses a potential threat to humans. PRV infection in humans always manifests as a high fever, tonic-clonic seizures, and encephalitis. Therefore, understanding the interaction between PRV and host factors may contribute to the development of new antiviral strategies against PRV. NRP1 has been demonstrated to be a receptor for several viruses that harbor CendR, including SARS-CoV-2. However, the relationships between NRP1 and PRV are poorly understood. Here, we found that NRP1 significantly potentiated PRV infection by promoting PRV attachment and enhanced cell-to-cell fusion. For the first time, we demonstrated that gB promotes NRP1 degradation via a lysosome-dependent pathway. Last, in vivo, Δfurin PRV virulence was significantly attenuated in mice. Therefore, NRP1 is an important host factor for PRV, and NRP1 may be a potential target for antiviral drug development.

Value of Radiomic Analysis Combined With Diffusion Tensor Imaging in Early Diagnosis of HIV-Associated Neurocognitive Disorders.

BACKGROUND: The combination of radiomics and diffusion tensor imaging (DTI) may have potential clinical value in the early stage of HIV-associated neurocognitive disorders (HAND). PURPOSE: To investigate the value of DTI-based radiomics in the early stage of HAND in people living with HIV (PLWH). STUDY TYPE: Retrospective. POPULATION: A total of 138 male PLWH were included, including 68 with intact cognition (IC) and 70 with asymptomatic neurocognitive impairment (ANI). Seventy healthy controls (HCs) were recruited for tract-based spatial statistics (TBSS) analysis. All PLWHs were randomly divided into training and validation cohorts at a 7:3 ratio. FIELD STRENGTH/SEQUENCE: A 3 T, single-shot spin-echo echo planar imaging (EPI). ASSESSMENT: The differences between the PLWH groups were compared using TBSS and region of interest (ROI) analysis. Radiomic features were extracted from the corpus callosum (CC) on DTI postprocessed images, including fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD). The performance of the radiomic signatures was evaluated by ROC curve analysis. The radiomic signature with the highest area under the curve (AUC) was combined with clinical characteristics to construct a nomogram. Decision curve analysis (DCA) was performed to evaluate the ability of different methods in discriminating ANI. STATISTICAL TESTS: Chi-square test, independent-samples t test, Kruskal-Wallis test, Mann-Whitney U test, threshold-free cluster enhancement (TFCE), ROC curve analysis, DCA, multivariate logistic regression analysis, Hosmer-Lemeshow test. P < 0.05 with TFCE corrected and P < 0.0001 without TFCE corrected were considered statistically significant. RESULTS: The ANI group showed lower FA and higher AD than the IC group. In the validation cohort, the AUCs of the FA-, AD-, MD- and RD-based radiomic signatures and the clinicoradiomic nomogram were 0.829, 0.779, 0.790, 0.864, and 0.874, respectively. DCA revealed that the nomogram was of greater clinical value than TBSS analysis, the clinical models, and the RD-based radiomic signature. DATA CONCLUSION: The combination of DTI and radiomics is correlated with early stage of HAND in PLWH. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

Discretized hexagonal boron nitride quantum emitters and their chemical interconversion.

Quantum emitters in two-dimensional hexagonal boron nitride (hBN) are of significant interest because of their unique photophysical properties, such as single-photon emission at room temperature, and promising applications in quantum computing and communications. The photoemission from hBN defects covers a wide range of emission energies but identifying and modulating the properties of specific emitters remain challenging due to uncontrolled formation of hBN defects. In this study, more than 2000 spectra are collected consisting of single, isolated zero-phonon lines (ZPLs) between 1.59 and 2.25 eV from diverse sample types. Most of ZPLs are organized into seven discretized emission energies. All emitters exhibit a range of lifetimes from 1 to 6 ns, and phonon sidebands offset by the dominant lattice phonon in hBN near 1370 cm-1. Two chemical processing schemes are developed based on water and boric acid etching that generate or preferentially interconvert specific emitters, respectively. The identification and chemical interconversion of these discretized emitters should significantly advance the understanding of solid-state chemistry and photophysics of hBN quantum emission.

The Australia Smoking and Vaping Model: The Potential Impact of Increasing Access to Nicotine Vaping Products.

BACKGROUND: We model the potential impact of relaxing current nicotine vaping product (NVP) restrictions on public health in Australia. AIMS AND METHODS: A Restricted NVP Scenario was first developed to project current smoking and vaping rates, where a U.S. smoking model was calibrated to recent Australian trends. To model less restrictive NVP policies, a Permissive NVP Scenario applied rates of switching from smoking to vaping, initiation into NVP and cigarette use, and cessation from smoking and vaping based on U.S. trends. The model measures vaping risk relative to the excess mortality rate of smoking. The public health impacts are measured as the difference between smoking- and vaping-attributable deaths (SVADs) and life years lost (LYLs) in the Restricted and Permissive NVP Scenarios. Sensitivity analysis is conducted regarding the NVP excess risk and other factors. RESULTS: Assuming an NVP excess risk of 5% that of smoking, 104.2 thousand SVADs (7.7% reduction) and 2.05 million LYLs (17.3% reduction) are averted during 2017-2080 in the Permissive NVP Scenario compared to the Restricted NVP Scenario. Assuming 40% NVP excess risk, 70 thousand SVADs and 1.2 million LYLs are averted. The impact is sensitive to the rate at which smokers switch to NVPs and quit smoking, and relatively insensitive to the smoking initiation and NVP initiation and cessation rates. CONCLUSIONS: The model suggests the potential for public health gains to be achieved by relaxing NVP access regulations. However, the model would benefit from better information regarding the impact of NVPs on smoking under a relaxation of current restrictions. IMPLICATIONS: Australia has implemented a strong array of cigarette-oriented policies, but has restricted access to NVPs. The Smoking and Vaping Model offers a framework for modeling hypothetical policy scenarios. The Australian model shows the potential for public health gains by maintaining cigarette-oriented policies while relaxing the current restrictive NVP policy. Modeling results under a permissive NVP policy are particularly sensitive to the estimated rates of smoking cessation and switching to vaping, which are not well established and will likely depend on past and future cigarette-oriented policies and the specific NVP policies implemented in Australia.

Fluorine-Containing Covalent Organic Frameworks: Synthesis and Application.

Covalent organic frameworks (COFs) are a type of crystalline porous polymers that possess ordered structures and eternal pores. Because of their unique structural characteristics and diverse functional groups, COFs have been used in various application fields, such as adsorption, catalysis, separation, ion conduction, and energy storage. Among COFs, the fluorine-containing COFs (fCOFs) have been developed for special applications by virtue of special physical and chemical properties resulting from fluorine element, which is a nonmetallic halogen element and possesses strong electronegativity. In the organic chemistry field, introducing fluorine into chemicals enables those chemicals to exhibit many interesting properties, and fluorine chemistry increasingly plays an important role in the history of chemical development. The introduction of fluorine in COFs can enhance the crystallinity, porosity, and stability of COFs, making COFs having superior performances and some new applications. In this review, the synthesis and application of fCOFs are systematically summarized. The application involves photocatalytic production of hydrogen peroxide, photocatalytic water splitting, electrocatalytic CO2 reduction, adsorption for different substances (H2 , pesticides, per-/polyfluoroalkyl substances, polybrominated diphenyl ethers, bisphenols, and positively charged organic dye molecules), oil-water separation, energy storage (e.g., zinc-ion batteries, lithium-sulfur batteries), and proton conduction. Perspectives of remaining challenges and possible directions for fCOFs are also discussed.

Public health impact of a US ban on menthol in cigarettes and cigars: a simulation study.

INTRODUCTION: The US Food and Drug Administration most recently announced its intention to ban menthol cigarettes and cigars nationwide in April 2021. Implementation of the ban will require evidence that it would improve public health. This paper simulates the potential public health impact of a ban on menthol in cigarettes and cigars through its impacts on smoking initiation, smoking cessation and switching to nicotine vaping products (NVPs). METHODS: After calibrating an established US simulation model to reflect recent use trends in cigarette and NVP use, we extended the model to incorporate menthol and non-menthol cigarette use under a status quo scenario. Applying estimates from a recent expert elicitation on the behavioural impacts of a menthol ban, we developed a menthol ban scenario with the ban starting in 2021. We estimated the public health impact as the difference between smoking and vaping-attributable deaths and life-years lost in the status quo scenario and the menthol ban scenario from 2021 to 2060. RESULTS: As a result of the ban, overall smoking was estimated to decline by 15% as early as 2026 due to menthol smokers quitting both NVP and combustible use or switching to NVPs. These transitions are projected to reduce cumulative smoking and vaping-attributable deaths from 2021 to 2060 by 5% (650 000 in total) and reduce life-years lost by 8.8% (11.3 million). Sensitivity analyses showed appreciable public health benefits across different parameter specifications. CONCLUSIONS AND RELEVANCE: Our findings strongly support the implementation of a ban on menthol in cigarettes and cigars.

The obesity paradox in ST-segment elevation myocardial infarction patients: A meta-analysis.

OBJECTIVE: The aim of this study was to investigate whether there was a difference in survival after initial percutaneous coronary intervention (PCI) among ST-segment elevation myocardial infarction (STEMI) patients with different body mass index (BMI). METHODS: Literature retrieval was conducted on PubMed, Web of Science, Embase, CNKI, and Wanfang databases to obtain the published studies on the survival of STEMI patients with different BMI after initial PCI from the establishment of the database to 2022. All statistical analyses were performed using STATA16.0. RESULTS: Two hundred thirty-nine studies were retrieved, and 12 studies were eventually included. Meta-analysis showed that overweight patients [OR = 0.66, 95% CI (0.58, 0.76), p < .001] and obese patients [OR = 0.60, 95% CI (0.51, 0.72), p < .001] had lower in-hospital mortality than healthy-weight patients. Overweight patients [OR = 0.66, 95% CI (0.58, 0.74), p < .001] and obese patients [OR = 0.62, 95% CI (0.53, 0.72), p < .001] had lower short-term mortality than healthy-weight patients. In addition, overweight patients [OR = 0.63, 95% CI (0.58, 0.69), p < .001] and obese patients [OR = 0.59, 95% CI (0.52, 0.66), p < .001] also had lower long-term mortality than healthy-weight patients. There was no significant difference in in-hospital mortality [OR = 1.06, 95% CI (0.89, 1.27), p > .05], short-term mortality [OR = 1.04, 95% CI (0.89, 1.22), p > .05], and long-term mortality [OR = 1.07, 95% CI (0.95, 1.20), p > .05] between overweight and obese patients. CONCLUSION: This meta-analysis confirmed an obesity paradox in STEMI patients following PCI. The obesity paradox exists in in-hospital, short-term, and long-term conditions.

The smoking and vaping model, A user-friendly model for examining the country-specific impact of nicotine VAPING product use: application to Germany.

BACKGROUND: Simulation models play an increasingly important role in tobacco control. Models examining the impact of nicotine vaping products (NVPs) and smoking tend to be highly specialized and inaccessible. We present the Smoking and Vaping Model (SAVM),a user-friendly cohort-based simulation model, adaptable to any country, that projects the public health impact of smokers switching to NVPs. METHODS: SAVM compares two scenarios. The No-NVP scenario projects smoking rates in the absence of NVPs using population projections, deaths rates, life expectancy, and smoking prevalence. The NVP scenario models vaping prevalence and its impact on smoking once NVPs became popular. NVP use impact is estimated as the difference in smoking- and vaping-attributable deaths (SVADs) and life-years lost (LYLs) between the No-NVP and NVP scenarios. We illustrate SAVM's adaptation to the German adult ages 18+ population, the Germany-SAVM by adjusting the model using population, mortality, smoking and NVP use data. RESULTS: Assuming that the excess NVP mortality risk is 5% that of smoking, Germany-SAVM projected 4.7 million LYLs and almost 300,000 SVADs averted associated with NVP use from 2012 to 2060. Increasing the excess NVP mortality risk to 40% with other rates constant resulted in averted 2.8 million LYLs and 200,000 SVADs during the same period. CONCLUSIONS: SAVM enables non-modelers, policymakers, and other stakeholders to analyze the potential population health effects of NVP use and public health interventions.

Linkages Make a Difference in the Photoluminescence of Covalent Organic Frameworks.

Covalent organic frameworks (COFs) with structural designability and tunability of photophysical properties enable them to be a promising class of organic luminescent materials by incorporating well-designed fluorescent units directly into the periodic skeletons. The photophysical properties of COFs are mainly affected by the structural features, which determine the conjugation degree, charge delocalization ability, and exciton dynamics of COFs. To understand the relationship between COF structures and their photophysical properties, two COFs with the same pyrene chromophore units but different linkages (imine or vinylene) were designed and synthesized. Interestingly, different linkages endow COFs with huge differences in solid-state photoluminescence quantum yield (PLQY) for imine- and vinylene-linked pyrene-based COFs, which possess PLQY values of 0.34 % and 15.43 %, respectively. The femtosecond-transient absorption spectra and time-dependent density functional theory reveal the different charge-transfer pathways in imine- and vinylene-linked COFs, which influence the exciton relaxation way and fluorescence intensity. In addition, an effective white-light device was obtained by coating the vinylene-linked COF on a light-emitting diode strip.

A Fully Conjugated Covalent Organic Framework with Oxidative and Reductive Sites for Photocatalytic Carbon Dioxide Reduction with Water.

Constructing a powerful photocatalytic system that can achieve the carbon dioxide (CO2 ) reduction half-reaction and the water (H2 O) oxidation half-reaction simultaneously is a very challenging but meaningful task. Herein, a porous material with a crystalline topological network, named viCOF-bpy-Re, was rationally synthesized by incorporating rhenium complexes as reductive sites and triazine ring structures as oxidative sites via robust -C=C- bond linkages. The charge-separation ability of viCOF-bpy-Re is promoted by low polarized π-bridges between rhenium complexes and triazine ring units, and the efficient charge-separation enables the photogenerated electron-hole pairs, followed by an intramolecular charge-transfer process, to form photogenerated electrons involved in CO2 reduction and photogenerated holes that participate in H2 O oxidation simultaneously. The viCOF-bpy-Re shows the highest catalytic photocatalytic carbon monoxide (CO) production rate (190.6 µmol g-1 h-1 with about 100 % selectivity) and oxygen (O2 ) evolution (90.2 µmol g-1 h-1 ) among all the porous catalysts in CO2 reduction with H2 O as sacrificial agents. Therefore, a powerful photocatalytic system was successfully achieved, and this catalytic system exhibited excellent stability in the catalysis process for 50 hours. The structure-function relationship was confirmed by femtosecond transient absorption spectroscopy and density functional theory calculations.

Cyclic silicon waveguide four-mode converter for mode division multiplexing transmission.

In this paper, a novel cyclic mode converter (CMC) is proposed and fabricated to implement cyclic mode permutation (CMP) on-chip for differential mode delay and mode-dependent loss elimination in the mode division multiplexing (MDM) transmission system. Cascaded by three optimally designed mode converters that do not affect the non-target modes, the proposed CMC can realize the conversion of any input mode among the TE0/TE1/TM0/TM1 modes. The three-dimensional finite-difference time-domain (3D-FDTD) simulation results show that the insertion loss of our device is less than 0.59 dB, and the crosstalk of each mode is lower than -15 dB under the range of 1500-1600 nm. The flat spectral response of this CMC is maintained even in the presence of fabrication errors up to±10 nm, showing great robustness. The experimental results also prove that at the center wavelength of 1550 nm the measured insertion loss of each mode is below 2.22 dB, and the crosstalk of each mode is lower than -15 dB. The proposed CMC provides a new idea for effectively reducing link damage in the MDM transmission system.

Tobacco Couponing: A Systematic Review of Exposures and Effects on Tobacco Initiation and Cessation.

INTRODUCTION: Tobacco couponing continues to be part of contemporary tobacco marketing in the United States. We performed a systematic review of the evidence of tobacco product coupon receipt and redemption to inform regulation. AIMS AND METHODS: We searched EMBASE OVID and Medline databases for observational (cross-sectional and longitudinal) studies that examined the prevalence of tobacco coupon receipt and coupon redemption across different subpopulations, as well as studies of the association between coupon receipt and redemption with tobacco initiation and cessation at follow-up. We extracted unadjusted and adjusted odds ratios for the associations between coupon exposure (receipt, redemption) and tobacco use outcomes (initiation, cessation) and assessed each studies' potential risk of bias. RESULTS: Twenty-seven studies met the criteria for inclusion. Of 60 observations extracted, 37 measured coupon receipt, nine measured coupon redemption, eight assessed tobacco use initiation, and six assessed cessation. Tobacco product coupon receipt and redemption tended to be more prevalent among younger adults, women, lower education individuals, members of sexual and gender minorities, and more frequent tobacco users. Coupon receipt at baseline was associated with greater initiation. Coupon receipt and redemption at baseline were associated with lower cessation at follow-up among tobacco users. Results in high-quality studies did not generally differ from all studies. CONCLUSIONS: Tobacco product coupon receipt and redemption are often more prevalent among price-sensitive subpopulations. Most concerning, our results suggest coupon receipt may be associated with higher tobacco initiation and lower tobacco cessation. Couponing thereby increases the toll of tobacco use and could prove to be a viable public health policy intervention point. IMPLICATIONS: A systematic review was conducted of the scientific literature about the receipt, redemption, and effects on tobacco initiation and cessation of tobacco product couponing. This review found that tobacco coupons are more often received by price-sensitive persons and these coupons serve to increase tobacco initiation and decrease tobacco cessation. Policy efforts to address these consequences may help curb tobacco's harms and address health inequities.

Ansellone J, a Potent in Vitro and ex Vivo HIV-1 Latency Reversal Agent Isolated from a Phorbas sp. Marine Sponge.

Five new minor sesterterpenoids, ansellones H (4), I (5), J (6), and K (7) and phorone C (8), have been isolated from a Phorbas sp. marine sponge collected in British Columbia. Their structures have been elucidated by detailed analysis of NMR and MS data. Ansellone J (6) and phorone C (8) are potent in vitro HIV-1 latency reversal agents that are more potent than the reference compound and control protein kinase C activator prostratin (3). The most potent Phorbas sesterterpenoid, ansellone J (6), was evaluated for HIV latency reversal in a primary cell context using CD4+ T cells obtained directly from four combination antiretroviral therapy-suppressed donors with HIV. To a first approximation, ansellone J (6) induced HIV latency reversal at levels similar to prostratin (3) ex vivo, but at a 10-fold lower concentration.

Public health impact of a US menthol cigarette ban on the non-Hispanic black population: a simulation study.

INTRODUCTION: With the US Food and Drug Administration recently proposing to implement a ban on menthol cigarettes, it is critical to estimate the potential public health effects of such a ban. With high rates of menthol cigarette use and important smoking-related health disparity implications, the impact of the ban on the non-Hispanic black (NHB) population merits strong consideration. METHODS: We apply the previously developed Menthol Smoking and Vaping Model to the NHB population. A status quo scenario is developed using NHB-specific population, smoking and vaping initiation, cessation and death rates. Estimates from a recent expert elicitation on behavioural impacts of a menthol cigarette ban on the NHB population are used to develop a menthol ban scenario implemented in 2021. The public health impacts of the menthol ban are estimated as the difference between smoking and vaping attributable deaths (SVADs) and life years lost (LYLs) in the status quo and the menthol ban scenarios from 2021 to 2060. RESULTS: Under the menthol ban scenario, overall smoking is projected to decline by 35.7% in 2026 and by 25.3% in 2060 relative to the status quo scenario. With these reductions, SVADs are estimated to fall by about 18.5% and LYLs by 22.1%, translating to 255 895 premature deaths averted, and 4.0 million life years gained over a 40-year period. CONCLUSIONS: A menthol cigarette ban will substantially reduce the smoking-associated health impact on the NHB population, thereby reducing health disparities.