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Abstract A highly miniaturised electrically small square loop antenna has been designed for operation at 2.5 GHz. The antenna is loaded using a simple series combination of two lumped inductors and two interdigitated capacitors in order to realise inherent impedance matching at a given miniaturisation level with respect to a specified source impedance, without using any external matching network. The designed antenna has an overall size of 0.061λ0 × 0.061λ0, which is approximately 75.6% miniaturised in terms of total loop length and 94% miniaturised in terms of overall footprint. The designed antenna is fabricated and the corresponding impedance matching and radiation patterns are measured, which are found to be in reasonable agreement with their simulated counterparts. Moreover, an investigation with two closely spaced electrically small SLAs, one for transmitting and the other for receiving, is carried out in this work in pursuit of maximising the isolation, which plays a crucial role in the Tx/Rx systems.

Deciphering the mechanisms underlying viral persistence is critical to achieving a cure for human immunodeficiency virus (HIV) infection. Here, we implement a systems approach to discover molecular signatures of HIV latently infected CD4+ T cells, identifying the immunosuppressive, adenosine-producing ectonucleotidase CD73 as a key surface marker of latent cells. Hypoxic conditioning, reflecting the lymphoid tissue microenvironment, increases the frequency of CD73+ CD4+ T cells and promotes HIV latency. Transcriptomic profiles of CD73+ CD4+ T cells favor viral quiescence, immune evasion, and cell survival. CD73+ CD4+ T cells are capable of harboring a functional HIV reservoir and reinitiating productive infection ex vivo. CD73 or adenosine receptor blockade facilitates latent HIV reactivation in vitro, mechanistically linking adenosine signaling to viral quiescence. Finally, tissue imaging of lymph nodes from HIV-infected individuals on antiretroviral therapy reveals spatial association between CD73 expression and HIV persistence in vivo. Our findings warrant development of HIV-cure strategies targeting the hypoxia-CD73-adenosine axis.

Arthroscopic shoulder surgeries are routinely practiced in many orthopedic centers for diagnostic and therapeutic purposes. The patient is commonly made to lie in a lateral position to carry out the procedure. We had a 71-year-old patient who underwent right shoulder arthroscopy for rotator cuff injury; the duration of surgery was 300 min. The patient developed subcutaneous edema over the neck and anterior chest. Further evaluation revealed airway edema as well. The patient was shifted to ICU for monitoring and overnight ventilation. Other radiological investigations confirmed the edema in subcutaneous and deep tissues of the neck and chest. The patient was extubated the next day morning after the edema improved. She was shifted to the ward for further management. Airway edema after shoulder arthroscopy, though uncommon, can be predicted in susceptible patients with prolonged surgeries and excess fluid irrigation. Timely diagnosis and intervention with coordination among the treating teams can result in positive outcomes.

Abstract The receptor-binding site of influenza A virus hemagglutinin partially overlaps with major antigenic sites and constantly evolves. In this study, we observe that mutations G186D and D190N in the hemagglutinin receptor-binding site have coevolved in two recent human H3N2 clades. X-ray crystallography results show that these mutations coordinately drive the evolution of the hemagglutinin receptor binding mode. Epistasis between G186D and D190N is further demonstrated by glycan binding and thermostability analyses. Immunization and neutralization experiments using mouse and human samples indicate that the evolution of receptor binding mode is accompanied by a change in antigenicity. Besides, combinatorial mutagenesis reveals that G186D and D190N, along with other natural mutations in recent H3N2 strains, alter the compatibility with a common egg-adaptive mutation in seasonal influenza vaccines. Overall, our findings elucidate the role of epistasis in shaping the recent evolution of human H3N2 hemagglutinin and substantiate the high evolvability of its receptor-binding mode.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused a global economic and health crisis. Recently, plasma levels of galectin-9 (Gal-9), a β-galactoside-binding lectin involved in immune regulation and viral immunopathogenesis, were reported to be elevated in the setting of severe COVID-19 disease. However, the impact of Gal-9 on SARS-CoV-2 infection and immunopathology remained to be elucidated. In this study, we demonstrate that Gal-9 treatment potently enhances SARS-CoV-2 replication in human airway epithelial cells (AECs), including immortalized AECs and primary AECs cultured at the air-liquid interface. Gal-9-glycan interactions promote SARS-CoV-2 attachment and entry into AECs in an angiotensin-converting enzyme 2 (ACE2)-dependent manner, enhancing the binding of the viral spike protein to ACE2. Transcriptomic analysis revealed that Gal-9 and SARS-CoV-2 infection synergistically induced the expression of key pro-inflammatory programs in AECs, including the IL-6, IL-8, IL-17, EIF2, and TNFα signaling pathways. Our findings suggest that manipulation of Gal-9 should be explored as a therapeutic strategy for SARS-CoV-2 infection.

Fruit crops are essential for human nutrition and health, yet high level of heavy metal levels in soils can degrade fruit quality. These metals accumulate in plant roots and tissues due to factors like excessive fertilizer and pesticide use, poor waste management, and unscientific agricultural practices. Such accumulation can adversely affect plant growth, physiology, and yield. Consuming fruits contaminated with toxic metals poses significant health risks, including nervous system disorders and cancer. Various strategies, such as organic manuring, biomaterials, and modified cultivation practices have been widely researched to reduce heavy metal accumulation. Recently, silicon (Si) application has emerged as a promising and cost-effective solution for addressing biological and environmental challenges in food crops. Si, which can be applied to the soil, through foliar application or a combination of both, helps reduce toxic metal concentrations in soil and plants. Despite its potential, there is currently no comprehensive review that details Si's role in mitigating heavy metal stress in fruit crops. This review aims to explore the potential of Si in reducing heavy metal-induced damage in fruit crops while enhancing growth by alleviating heavy metal toxicity.

By understanding the potential benefits of Gate Stack Dual Material double gate MOSFET (DG MOSFET), this research aims to contribute to the investigation of its electrical characteristics with improved performance and dependability. A detailed investigation is conducted into the temperature dependent electrical properties at different temperatures. A detailed analysis is conducted on the enhanced gate controllability in lower technology nodes and the protection against short channel effects. Together with the DC performances, this research also analyzes the suggested device's analog performance. The device's performance matrix was presented for temperatures ranging from 70 K to 800 K. The results showsthe improvement the drain current, transconductance, and transconductance generation factor(TGF) with decrease in temperature.

Abstract The ongoing evolution of SARS-CoV-2 to evade vaccines and therapeutics underlines the need for innovative therapies with high genetic barriers to resistance. Therefore, there is pronounced interest in identifying new pharmacological targets in the SARS-CoV-2 viral life cycle. The small molecule PAV-104, identified through a cell-free protein synthesis and assembly screen, was recently shown to target host protein assembly machinery in a manner specific to viral assembly. In this study, we investigate the capacity of PAV-104 to inhibit SARS-CoV-2 replication in human airway epithelial cells (AECs). We show that PAV-104 inhibits >99% of infection with diverse SARS-CoV-2 variants in immortalized AECs, and in primary human AECs cultured at the air-liquid interface (ALI) to represent the lung microenvironment in vivo. Our data demonstrate that PAV-104 inhibits SARS-CoV-2 production without affecting viral entry, mRNA transcription, or protein synthesis. PAV-104 interacts with SARS-CoV-2 nucleocapsid (N) and interferes with its oligomerization, blocking particle assembly. Transcriptomic analysis reveals that PAV-104 reverses SARS-CoV-2 induction of the type-I interferon response and the maturation of nucleoprotein signaling pathway known to support coronavirus replication. Our findings suggest that PAV-104 is a promising therapeutic candidate for COVID-19 with a mechanism of action that is distinct from existing clinical management approaches.

Catalytic asymmetric α-alkylation of carbonyl compounds represents a long-standing challenge in synthetic organic chemistry. Herein, we advance a dual biocatalytic platform for the efficient asymmetric alkylation of α-keto acids. First, guided by our recently obtained crystal structures, we develop SgvMVAV as a general biocatalyst for the enantioselective methylation, ethylation, allylation and propargylation of a range of α-keto acids with total turnover numbers (TTNs) up to 4,600. Second, we mine a family of bacterial HMTs from Pseudomonas species sharing less than 50% sequence identities with known HMTs and evaluated their activities in SAM regeneration. Our best performing HMT from P. aeruginosa, PaHMT, displays the highest SAM regeneration efficiencies (TTN up to 7,700) among HMTs characterized to date. Together, the synergistic use of SgvMVAV and PaHMT affords a fully biocatalytic protocol for asymmetric methylation featuring a record turnover efficiency, providing a solution to the notorious problem of asymmetric alkylation.

Poor visualization of polyps can limit colorectal cancer screening. Fluorescent antibodies to mucin5AC (MUC5AC), a glycoprotein upregulated in adenomas and colorectal cancer, could improve screening colonoscopy polyp detection rate. Adenomatous polyposis coli flox mice with a Cdx2-Cre transgene (CPC-APC) develop colonic polyps that contain both dysplastic and malignant tissue. Mice received MUC5AC-IR800 or IRdye800 as a control IV and were sacrificed after 48 h for near-infrared imaging of their colons. A polyp-to-background ratio (PBR) was calculated for each polyp by dividing the mean fluorescence intensity of the polyp by the mean fluorescence intensity of the background tissue. The mean 25 μg PBR was 1.70 (±0.56); the mean 50 μg PBR was 2.64 (±0.97); the mean 100 μg PBR was 3.32 (±1.33); and the mean 150 μg PBR was 3.38 (±0.87). The mean PBR of the dye-only control was 2.22 (±1.02), significantly less than the 150 μg arm (p-value 0.008). The present study demonstrates the ability of fluorescent anti-MUC5AC antibodies to specifically target and label colonic polyps containing high-grade dysplasia and intramucosal adenocarcinoma in CPC-APC mice. This technology can potentially improve the detection rate and decrease the miss rate of advanced colonic neoplasia and early cancer at colonoscopy.

BackgroundUndergraduate programs in public health are becoming increasingly popular in the United States (US). The recent pandemic, growing climate instability, and the aging baby boomers have led to higher demands for skilled public health professionals at various levels of the workforce. This study examines the nature of courses being delivered in undergraduate public health programs across the United States. The goal is to assess domains, themes, competencies, and other specialized skills that are currently covered in these academic programs.MethodologyA search was conducted in February 2023 using the online CEPH program database to identify undergraduate public health programs in the US. In total, 86 institutions and 90 CEPH-accredited undergraduate public health programs were identified. Lists of public health courses were retrieved from each program, and a total of 2,259 unduplicated courses were extracted and analyzed. A content analysis of the extracted topics was conducted to generate 38 common themes among the courses offered. Coded course themes were mapped to the public health domains and competencies listed by the ASPPH and CEPH to evaluate the distribution of themes across course offerings.ResultsAnalysis of course themes found that Foundations of Public Health, Epidemiology, Public Health Management, Policy, and Leadership, Climate and Environmental Health, and Global Health Issues were the most prevalent. When course themes were mapped onto the ASPPH and CEPH domains of critical public health learning, “overview of public health” and “determinants of health” were the most populated domains. Programs had different emphases according to their approach, but overall, about two-thirds of course themes were focused on foundational and theoretical concepts of public health, and one-third were directed toward practical applications of public health concepts.ConclusionAs the demand for skilled public health workers continues to rise, programs will need to watch the skills and competencies required in the current working environment, as well as the ASPPH and CEPH criteria, and adjust their approach accordingly. Given the rapid changes in the public health landscape, schools and programs of public health should evaluate their curricula to ensure that they are meeting the needs of the workforce and the world.

This study investigates the prevalence and dynamics of pomegranate wilt disease induced by Meloidogyne incognita across the Kullu, Mandi and Solan districts of Himachal Pradesh (India), revealed notable spatial and temporal variations in nematode populations and galling severity across the regions. The highest average nematode infestation of 9.25 % was observed at Nauni with highest counts of average second-stage juvenile (J2) larvae (449 larvae per 100 cc of soil) followed by Hurla (Kullu) with 7.42 % infestation. Correlation analysis reveals a strong positive relationship between larval population and galling severity suggesting a potential link between nematode levels and plant damage. Common disease symptoms were leaf size reduction, yellowing and gradual decline of pomegranate plants, often observed in patches within orchards. Microscopic identification revealed distinctive pear-shaped body of mature females while J2 larvae displayed vermiform shapes and the associated species of M. incognita was confirmed through examination of the perineal pattern. Pathogenicity test reveals initiation of leaf yellowing symptom after 45 days of inoculation of larval suspension and root galling was observed after 60 days onward followed by plant decline under greenhouse conditions. Results from pot and field experiments demonstrated the efficacy of Fluopyram and Fluensulfone in reducing nematode populations and galling severity. Treatment with drenching of Fluopyram at the rate of 2 ml/L reduced 98.56 % larvae under field and 99.00 % larvae/100 cc soil under pot conditions. Statistical analysis (paired t-test and MANOVA) confirms significant differences in galling severity and larval population before and after drenching. The study also underscores the importance of weed management in disease mitigation as several weed species (Chenopodium album and Solanum nigrum) were identified as potential reservoirs for M. incognita in infested pomegranate plant basin. This investigation contributes to the advancement of management practices for pomegranate cultivation that addresses both nematode and weed infestations ultimately enhancing crop resilience and productivity.

Summary: Lipids have emerged as potent regulators of immune cell function. In the skin, adipocyte lipolysis increases the local pool of free fatty acids and is essential for coordinating early macrophage inflammation following injury. Here, we investigate G-protein-coupled receptor 84 (GPR84), a medium-chain fatty acid (MCFA) receptor, for its potential to propagate pro-inflammatory signaling after skin injury. GPR84 signaling was identified as a key component of regulating myeloid cell numbers and subsequent tissue repair through in vivo administration of a pharmacological antagonist and the MCFA decanoic acid. We found that impaired injury-induced dermal adipocyte lipolysis is a hallmark of diabetes, and lipidomic analysis demonstrated that MCFAs are significantly reduced in diabetic murine wounds. Furthermore, local administration of decanoic acid rescued myeloid cell numbers and tissue repair during diabetic wound healing. Thus, GPR84 is a readily targetable lipid signaling pathway for manipulating injury-induced tissue inflammation with beneficial effects on acute diabetic healing.

Gene silencing without gene editing holds great potential for the development of safe therapeutic applications. Here, we describe a novel strategy to concomitantly repress multiple genes using zinc finger proteins fused to Krüppel-Associated Box repression domains (ZF-Rs). This was achieved via the optimization of a lentiviral system tailored for the delivery of ZF-Rs in hematopoietic cells. We showed that an optimal design of the lentiviral backbone is crucial to multiplex up to three ZF-Rs or two ZF-Rs and a chimeric antigen receptor. ZF-R expression had no impact on the integrity and functionality of transduced cells. Furthermore, gene repression in ZF-R-expressing T cells was highly efficient in vitro and in vivo during the entire monitoring period (up to 10 weeks), and it was accompanied by epigenetic remodeling events. Finally, we described an approach to improve ZF-R specificity to illustrate the path toward the generation of ZF-Rs with a safe clinical profile. In conclusion, we successfully developed an epigenetic-based cell engineering approach for concomitant modulation of multiple gene expressions that bypass the risks associated with DNA editing.