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1.
Nature ; 589(7843): 603-607, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33166988

RESUMO

The ongoing coronavirus disease 2019 (COVID-19) pandemic is associated with substantial morbidity and mortality. Although much has been learned in the first few months of the pandemic, many features of COVID-19 pathogenesis remain to be determined. For example, anosmia is a common presentation, and many patients with anosmia show no or only minor respiratory symptoms1. Studies in animals infected experimentally with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of COVID-19, provide opportunities to study aspects of the disease that are not easily investigated in human patients. Although the severity of COVID-19 ranges from asymptomatic to lethal2, most experimental infections provide insights into mild disease3. Here, using K18-hACE2 transgenic mice that were originally developed for SARS studies4, we show that infection with SARS-CoV-2 causes severe disease in the lung and, in some mice, the brain. Evidence of thrombosis and vasculitis was detected in mice with severe pneumonia. Furthermore, we show that infusion of convalescent plasma from a recovered patient with COVID-19 protected against lethal disease. Mice developed anosmia at early time points after infection. Notably, although pre-treatment with convalescent plasma prevented most signs of clinical disease, it did not prevent anosmia. Thus, K18-hACE2 mice provide a useful model for studying the pathological basis of both mild and lethal COVID-19 and for assessing therapeutic interventions.


Assuntos
Anosmia/virologia , COVID-19/fisiopatologia , COVID-19/terapia , Modelos Animais de Doenças , SARS-CoV-2/patogenicidade , Animais , Anosmia/fisiopatologia , Anosmia/terapia , Encéfalo/imunologia , Encéfalo/patologia , Encéfalo/virologia , COVID-19/imunologia , COVID-19/virologia , Epitélio/imunologia , Epitélio/virologia , Feminino , Humanos , Imunização Passiva , Inflamação/patologia , Inflamação/terapia , Inflamação/virologia , Pneumopatias/patologia , Pneumopatias/terapia , Pneumopatias/virologia , Masculino , Camundongos , Seios Paranasais/imunologia , Seios Paranasais/virologia , SARS-CoV-2/crescimento & desenvolvimento , SARS-CoV-2/imunologia , Resultado do Tratamento , Soroterapia para COVID-19
2.
Am J Respir Cell Mol Biol ; 70(3): 165-177, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37976469

RESUMO

Chronic obstructive pulmonary disease (COPD) remains a major public health challenge that contributes greatly to mortality and morbidity worldwide. Although it has long been recognized that the epithelium is altered in COPD, there has been little focus on targeting it to modify the disease course. Therefore, mechanisms that disrupt epithelial cell function in patients with COPD are poorly understood. In this study, we sought to determine whether epigenetic reprogramming of the cell-cell adhesion molecule E-cadherin, encoded by the CDH1 gene, disrupts epithelial integrity. By reducing these epigenetic marks, we can restore epithelial integrity and rescue alveolar airspace destruction. We used differentiated normal and COPD-derived primary human airway epithelial cells, genetically manipulated mouse tracheal epithelial cells, and mouse and human precision-cut lung slices to assess the effects of epigenetic reprogramming. We show that the loss of CDH1 in COPD is due to increased DNA methylation site at the CDH1 enhancer D through the downregulation of the ten-eleven translocase methylcytosine dioxygenase (TET) enzyme TET1. Increased DNA methylation at the enhancer D region decreases the enrichment of RNA polymerase II binding. Remarkably, treatment of human precision-cut slices derived from patients with COPD with the DNA demethylation agent 5-aza-2'-deoxycytidine decreased cell damage and reduced air space enlargement in the diseased tissue. Here, we present a novel mechanism that targets epigenetic modifications to reverse the tissue remodeling in human COPD lungs and serves as a proof of concept for developing a disease-modifying target.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Humanos , Animais , Camundongos , Doença Pulmonar Obstrutiva Crônica/genética , Diferenciação Celular , Metilação de DNA , Progressão da Doença , Epigênese Genética , Oxigenases de Função Mista , Proteínas Proto-Oncogênicas
3.
Biotechnol Bioeng ; 121(1): 71-81, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37661712

RESUMO

Many of the infectious diseases are ubiquitous in nature and pose a threat to global and public health. The original cause for such type of serious maladies can be summarized as the scarcity of appropriate analysis and treatment methods. Pulmonary diseases are considered one of the life-threatening lung diseases that affect millions of people globally. It consists of several types, namely, asthma, lung cancer, tuberculosis, chronic obstructive pulmonary disease, and several respiratory-related infections. This is due to the limited access to well-equipped healthcare facilities for early disease diagnosis. This needs the availability of processes and technologies that can help to stop this harmful disease-diagnosing practice. Various approaches for diagnosing various lung diseases have been developed over time, namely, autopsy, chest X-rays, low-dose CT scans, and so forth. The need of the hour is to develop a rapid, simple, portable, and low-cost method for the diagnosis of pulmonary diseases. So nowadays, biosensors have been becoming one of the highest priority research areas as a potentially useful tool for the early diagnosis and detection of many pulmonary lung diseases. In this review article, various types of biosensors and their applications in the diagnosis of lung-related disorders are expansively explained.


Assuntos
Asma , Técnicas Biossensoriais , Pneumopatias , Neoplasias Pulmonares , Doença Pulmonar Obstrutiva Crônica , Infecções Respiratórias , Humanos , Pneumopatias/diagnóstico , Asma/diagnóstico , Asma/terapia , Pulmão , Técnicas Biossensoriais/métodos
4.
Org Biomol Chem ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38919997

RESUMO

Brønsted acid catalyzed regioselective ring opening of aziridines by phenols and thiophenols have been reported. Involvement of a series of aziridines with a range of phenols and thiophenols offer the generality of the reported protocol. Completion of the reaction at room temperature within very short time brings the uniqueness of the developed technique. To emphasis on the application of the developed methodology, the products have been used for the further synthesis of a range of useful and novel heterocyclic molecules such as indolines, indoles, benzothiazines, dihydrobenzothiazines, benzo-oxazines and benzochromenes.

5.
Phys Chem Chem Phys ; 26(6): 5387-5398, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38270198

RESUMO

Here, we report a comparison study on the synthesis and characterization of perovskite SrSnO3 (SSO) and Sr2SnO4 (S2SO). Rietveld refinement studies were performed on both prepared samples and suggest that they crystallized in cubic (SSO) and tetragonal (S2SO) structures. Fourier-transform infrared (FTIR) and Raman spectroscopy studies supported the XRD observations. Improved dielectric parameters were observed for S2SO over SSO due to differences in dislocation density, larger crystallite size, and denser microstructure. The electrical conduction and relaxation processes followed the Arrhenius type in both samples through the migration of oxygen vacancies via the Sn-site and the transfer of electrons between the Sn sites in two different temperature regions. These processes in the samples occurred via correlated barrier hopping (CBH) in SSO and the non-overlapping of small-polaron tunnelling (NSPT) in S2SO. The conduction and relaxation processes had similar sources of charge carriers but differed in the concentration and mobility of charge carriers. The presented materials can be utilized for dielectric capacitors, sensors, and mixed ionic and electronic conductor-based electrodes in IT-SOFC applications.

6.
Rheumatol Int ; 44(5): 819-829, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38082159

RESUMO

Antiphospholipid antibodies (APLA) are present in one-third of systemic lupus erythematosus (SLE) patients, and they are associated with both criteria and non-criteria manifestations. We studied the prevalence, clinical associations, and impact on mortality of APLA in SLE patients from India. Among the Indian SLE inception cohort (INSPIRE), patients who had data on all five routinely performed APLAs [lupus anticoagulant (LA), IgG and IgM anticardiolipin antibody (aCL) and anti-ß2-glycoprotein I(ß2GPI)] at enrolment were selected. Patients were divided into four categories based on the presence/absence of APLA associated manifestations and presence/absence of the APLA viz SLE-APS, SLE-APLA, SLE: events but no APLA, and SLE: no events, no APLA (reference group). 1035 SLE patients at least 1 APLA antibody was detected in 372 (35.9%). LA was present in 206 (19.9%), aCL in 126 (12.2%) and ß2-GPI in 178 (17.2%). There were 88 thrombotic events in 83 patients (8.0%); 73 (82.9%) being arterial; APLA positivity was present in 37 (44.6%) [AOR 1.70 (1.054, 2.76)]. SLE-APS patients were younger and had higher mortality [AOR 4.11 (1.51, 11.3)], neuropsychiatric and hematologic disease. SLE-APLA also had a higher mortality rate [AOR 2.94 (1.06, 8.22)] than the reference group. The mortality was highest in the subset of patients with thrombotic events in the presence of APLA [AOR 7.67 (1.25, 46.9)]. The mere presence of APLA also conferred higher mortality even in the absence of thrombotic events [AOR 3.51 (1.43, 8.63)]. Hematologic manifestations (36.1%) were the most common non-criteria-manifestation. One-third of SLE patients have APLA and its presence is associated with non-criteria hematologic manifestations, arterial thrombosis and higher mortality rate.


Assuntos
Síndrome Antifosfolipídica , Lúpus Eritematoso Sistêmico , Trombose , Humanos , Anticorpos Antifosfolipídeos , Anticorpos Anticardiolipina , Lúpus Eritematoso Sistêmico/complicações , Síndrome Antifosfolipídica/complicações , Inibidor de Coagulação do Lúpus
7.
PLoS Genet ; 17(7): e1009460, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34314427

RESUMO

Visual perception of the environment is mediated by specialized photoreceptor (PR) neurons of the eye. Each PR expresses photosensitive opsins, which are activated by a particular wavelength of light. In most insects, the visual system comprises a pair of compound eyes that are mainly associated with motion, color or polarized light detection, and a triplet of ocelli that are thought to be critical during flight to detect horizon and movements. It is widely believed that the evolutionary diversification of compound eye and ocelli in insects occurred from an ancestral visual organ around 500 million years ago. Concurrently, opsin genes were also duplicated to provide distinct spectral sensitivities to different PRs of compound eye and ocelli. In the fruit fly Drosophila melanogaster, Rhodopsin1 (Rh1) and Rh2 are closely related opsins that originated from the duplication of a single ancestral gene. However, in the visual organs, Rh2 is uniquely expressed in ocelli whereas Rh1 is uniquely expressed in outer PRs of the compound eye. It is currently unknown how this differential expression of Rh1 and Rh2 in the two visual organs is controlled to provide unique spectral sensitivities to ocelli and compound eyes. Here, we show that Homothorax (Hth) is expressed in ocelli and confers proper rhodopsin expression. We find that Hth controls a binary Rhodopsin switch in ocelli to promote Rh2 expression and repress Rh1 expression. Genetic and molecular analysis of rh1 and rh2 supports that Hth acts through their promoters to regulate Rhodopsin expression in the ocelli. Finally, we also show that when ectopically expressed in the retina, hth is sufficient to induce Rh2 expression only at the outer PRs in a cell autonomous manner. We therefore propose that the diversification of rhodpsins in the ocelli and retinal outer PRs occurred by duplication of an ancestral gene, which is under the control of Homothorax.


Assuntos
Proteínas de Drosophila/genética , Drosophila melanogaster/metabolismo , Proteínas de Homeodomínio/genética , Fenômenos Fisiológicos Oculares/genética , Rodopsina/genética , Animais , Animais Geneticamente Modificados , Drosophila melanogaster/genética , Regulação da Expressão Gênica , Proteínas de Membrana/genética , Células Fotorreceptoras/metabolismo , Regiões Promotoras Genéticas , Retina/fisiologia
8.
J Oral Rehabil ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778703

RESUMO

BACKGROUND: In postmenopausal women (PMW), vasomotor symptoms, emotional oscillations and sleep disturbances can affect physiological and psychological functioning. However, the effect of menopause on oral health-related parameters is not been thoroughly studied. OBJECTIVE: To evaluate oral health, taste perception, eating habits, nutritional status and emotional well-being in PMW compared with a group of young and healthy pre-menopausal women (PrMW). MATERIALS AND METHODS: Two groups (Group I: PMW and Group II: PrMW) with 30 participants each, participated in the cross-sectional study. The study proforma contained measures of oral health, taste perception, nutritional status and anxiety levels of the women in both groups using validated and previously used tools were designed and implemented. The data were analysed with student t, Mann-Whitney U, and chi-squared tests to evaluate the differences between the two groups. RESULTS: The cross-sectional study indicates no major differences in oral health, taste perception, nutritional and emotional status between PMW and PrMW. Nonetheless, there was a significant difference in perception of 'front teeth lengthening in size' and change in hot and cold sensations between the groups. Furthermore, the study group with PMW tends to have fewer natural teeth than the reference group. CONCLUSION: Overall, menopause does not appear to affect oral health, taste perception, nutrition or emotional health. It is suggested that oral health and taste perception, as well as nutritional and emotional status, are associated with gradual aging processes that may or may not be affected by menopause.

9.
Gen Dent ; 72(3): 34-40, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38640004

RESUMO

The majority of problematic conditions resulting from dental implant treatment are inflammatory in character, but certain isolated occurrences of primary oral squamous cell carcinoma (OSCC) have been discovered in the area of implants. The goal of this study was to examine whether there is a link between dental implants and the development of OSCC in patients who have a history of a potentially malignant lesion (PML) or malignancy. Using the keywords "carcinoma" AND "dental implants," a search was conducted in the MEDLINE (PubMed), National Center for Biotechnology Information, and Google Scholar databases for case reports and case series in which OSCC was discovered as a primary cancer in the region of dental implants. An initial search identified 260 articles, 247 of which were excluded based on study inclusion or exclusion criteria, leaving 13 articles chosen for inclusion and a total of 30 patients who developed primary oral cancer surrounding osseointegrated titanium-based dental implants. In the studies included in the present review, 22 (73%) of 30 patients with peri-implant cancer had a history of PML or carcinoma. There is no statistical evidence of a direct association between dental implants and OSCC in patients with a history of a PML or malignant lesion. There have been some case reports of OSCC in the region of dental implants in patients with a history of a PML or malignant lesion, but further studies are needed to prove a definitive relationship.


Assuntos
Carcinoma de Células Escamosas , Implantes Dentários , Neoplasias Bucais , Humanos , Implantes Dentários/efeitos adversos , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/etiologia
10.
Angew Chem Int Ed Engl ; 63(15): e202319162, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38235942

RESUMO

Natural products are attractive components to tailor environmentally friendly advanced new materials. We present surface-confined metallosupramolecular engineering of coordination polymers using natural dyes as molecular building blocks: indigo and the related Tyrian purple. Both building blocks yield identical, well-defined coordination polymers composed of (1 dehydroindigo : 1 Fe) repeat units on two different silver single crystal surfaces. These polymers are characterized atomically by submolecular resolution scanning tunnelling microscopy, bond-resolving atomic force microscopy and X-ray photoelectron spectroscopy. On Ag(100) and on Ag(111), the trans configuration of dehydroindigo results in N,O-chelation in the polymer chains. On the more inert Ag(111) surface, the molecules additionally undergo thermally induced isomerization from the trans to the cis configuration and afford N,N- plus O,O-chelation. Density functional theory calculations confirm that the coordination polymers of the cis-isomers on Ag(111) and of the trans-isomers on Ag(100) are energetically favoured. Our results demonstrate post-synthetic linker isomerization in interfacial metal-organic nanosystems.

11.
J Med Ultrasound ; 32(1): 83-85, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38665335

RESUMO

Inflammatory necrosis of the falciform ligament is an extremely rare cause of acute right upper quadrant pain. Due to overlapping symptoms with pathologies affecting the gall bladder and liver, this poses a diagnostic challenge with limited existing literature. Here, we report a case of a 62-year-old female patient presenting in the accident and emergency department with right upper quadrant pain. The patient underwent ultrasonography and revealed thickened and echogenic falciform ligament. Further, a computed tomography revealed swollen falciform ligament with associated fat stranding. The patient was kept under conservative management and improved over 2 weeks.

12.
J Am Chem Soc ; 145(3): 1945-1954, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36638828

RESUMO

The design and regulation of multiple room-temperature phosphorescence (RTP) processes are formidably challenging due to the restrictions imposed by Kasha's rule. Here, we report a general design principle for materials that show multiple RTP processes, which is informed by our study of four compounds where there is modulation of the linker hybridization between donor (D) and acceptor (A) groups. Theoretical modeling and photophysical experiments demonstrate that multiple RTP processes can be achieved in sp3 C-linked D-A compounds due to the arrest of intramolecular electronic communication between two triplet states (T1H and T1L) localized on the donor and acceptor or between two triplet states, one localized on the donor and one delocalized across aggregated acceptors. However, for the sp2 C-linked D-A counterparts, RTP from one locally excited T1 state is observed because of enhanced excitonic coupling between the two triplet states of molecular subunits. Single-crystal and reduced density gradient analyses reveal the influence of molecular packing on the coincident phosphorescence processes and the origin of the observed aggregate phosphorescence. These findings provide insights into higher-lying triplet excited-state dynamics and into a fundamental design principle for designing compounds that show multiple RTP.

13.
J Am Chem Soc ; 145(1): 422-435, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36537351

RESUMO

The development of an efficient photocatalyst for C2 product formation from CO2 is of urgent importance toward the deployment of solar-fuel production. Here, we report a template-free, cost-effective synthetic strategy to develop a carbazole-derived porous organic polymer (POP)-based composite catalyst. The composite catalyst is comprised of In2.77S4 and porous organic polymer (POP) and is held together by induced-polarity-driven electrostatic interaction. Utilizing the synergy of the catalytically active In centers and light-harvesting POPs, the catalyst showed 98.9% selectivity toward the generation of C2H4, with a formation rate of 67.65 µmol g-1 h-1. Two different oxidation states of the In2.77S4 spinel were exploited for the C-C coupling process, and this was investigated by X-ray photoelectron spectroscopy (XPS), X-ray absorption spectroscopy (XAS), and density functional theory (DFT) calculations. The role of POP was elucidated via several photophysical and photoelectrochemical studies. The electron transfer was mapped by several correlated approaches, which assisted in establishing the Z-scheme mechanism. Furthermore, the mechanism of C2H4 formation was extensively investigated using density functional theory (DFT) calculations from multiple possible pathways.

14.
Clin Immunol ; 251: 109328, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37086957

RESUMO

Regulatory T cells (Tregs) are a unique subset of lymphocytes that play a vital role in regulating the immune system by suppressing unwanted immune responses and thus preventing autoimmune diseases and inappropriate inflammatory reactions. In preclinical and clinical trials, these cells have demonstrated the ability to prevent and treat graft vs. host disease, alleviate autoimmune symptoms, and promote transplant tolerance. In this review, we provide a background on Treg cells with a focus on important Treg cell markers and Treg subsets, and outline the methodology currently used for manufacturing adoptive regulatory T cell therapies (TRACT). Finally, we discuss the approaches and outcomes of several clinical trials in which Tregs have been adoptively transferred to patients.


Assuntos
Doenças Autoimunes , Doença Enxerto-Hospedeiro , Humanos , Linfócitos T Reguladores , Imunoterapia Adotiva/métodos , Doenças Autoimunes/terapia
15.
Small ; : e2302498, 2023 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-37309278

RESUMO

Graphene coatings developed by chemical vapor deposition (CVD) that possess extraordinary/unique characteristics as barrier against aggressive environment can improve the corrosion resistance of Ni and Cu by up to two orders of magnitude. However, because of some compelling technical reasons, it has thus far been a nontrivial challenge to develop graphene coatings on the most commonly used engineering alloy, mild steel (MS). To circumvent the challenge simply by first electroplating MS with a Ni layer is attempted, and then developing CVD graphene over the Ni layer. However, this approach proved too simplistic and does not work. This necessitated an innovative surface modification of MS (based on basic metallurgical principles) that enabled successful CVD of graphene coating on MS. The graphene coating thus developed is demonstrated to improve the corrosion resistance of mild steel by two orders of magnitude in an aggressive chloride solution, through electrochemical testing. This improvement was not only sustained for the entire test duration of >1000 h; but there is a clear trend for the resistance to be possibly everlasting. The optimized surface modification that enabled development of CVD graphene coating on mild steel is generic in nature, and it should enable graphene coating on other alloy systems, which would otherwise not be possible.

16.
Small ; : e2305320, 2023 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-37736693

RESUMO

Bipolar plates, a critical component of proton exchange membrane fuel cell (PEMFC), are constructed out of alloys of Ti, Pt, Cr, or graphitic materials that have limitations. Electrical conductivity, cost, and corrosion resistance are among the critical considerations for bi-polar plate material. Graphene, which possesses impressive conductivity and toughness, is an attractive option as coating on metallic substrates of PEMFC bipolar plates. This study investigates corrosion resistance and its durability due to graphene developed by chemical vapor deposition on a pure Ni-Cu alloy and a commercial Ni-Cu alloy in 0.5 m H2 SO4 environment, with a view to exploring use of graphene coated Ni-Cu alloys for the construction of PEMFC bipolar plates. The graphene coating on the pure alloy shows remarkably superior corrosion resistance than the commercial alloy that is attributed to the former's ability to develop considerably defect-free graphene.

17.
Planta ; 258(3): 49, 2023 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-37480390

RESUMO

MAIN CONCLUSION: Morphological, phytochemical, and transcriptome analyses revealed candidate genes involved in the biosynthesis of volatile monoterpenes and development of glandular trichomes in Monarda citriodora. Monarda citriodora Cerv. ex Lag. is a valuable aromatic plant due to the presence of monoterpenes as major constituents in its essential oil (EO). Thus, it is of sheer importance to gain knowledge about the site of the biosynthesis of these terpenoid compounds in M. citriodora, as well as the genes involved in their biosynthesis. In this study, we studied different types of trichomes and their relative densities in three different developmental stages of leaves, early stage of leaf development (L1), mid-stage of leaf development (L2), and later stage of leaf development (L3) and the histochemistry of trichomes for the presence of lipid and terpenoid compounds. Further, the phytochemical analysis of this plant through GC-MS indicated a higher content of monoterpenes (thymol, thymoquinone, γ-terpinene, p-cymene, and carvacrol) in the L1 stage with a substantial decrease in the L3 stage of leaf development. This considerable decrease in the content of monoterpenes was attributed to the decrease in the trichome density from L1 to L3. Further, we developed a de novo transcriptome assembly by carrying out RNA sequencing of different plant parts of M. citriodora. The transcriptome data revealed several putative unigenes involved in the biosynthesis of specialized terpenoid compounds, as well as regulatory genes involved in glandular trichome development. The data generated in the present study build a strong foundation for further improvement of M. citriodora, in terms of quantity and quality of its essential oil, through genetic engineering.


Assuntos
Monarda , Óleos Voláteis , Monoterpenos , Terpenos , Perfilação da Expressão Gênica , Compostos Fitoquímicos
18.
J Virol ; 96(11): e0036422, 2022 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-35588276

RESUMO

Effective broad-spectrum antivirals are critical to prevent and control emerging human coronavirus (hCoV) infections. Despite considerable progress made toward identifying and evaluating several synthetic broad-spectrum antivirals against hCoV infections, a narrow therapeutic window has limited their success. Enhancing the endogenous interferon (IFN) and IFN-stimulated gene (ISG) response is another antiviral strategy that has been known for decades. However, the side effects of pegylated type-I IFNs (IFN-Is) and the proinflammatory response detected after delayed IFN-I therapy have discouraged their clinical use. In contrast to IFN-Is, IFN-λ, a dominant IFN at the epithelial surface, has been shown to be less proinflammatory. Consequently, we evaluated the prophylactic and therapeutic efficacy of IFN-λ in hCoV-infected airway epithelial cells and mice. Human primary airway epithelial cells treated with a single dose of IFN-I (IFN-α) and IFN-λ showed similar ISG expression, whereas cells treated with two doses of IFN-λ expressed elevated levels of ISG compared to that of IFN-α-treated cells. Similarly, mice treated with two doses of IFN-λ were better protected than mice that received a single dose, and a combination of prophylactic and delayed therapeutic regimens completely protected mice from a lethal Middle East respiratory syndrome CoV (MERS-CoV) infection. A two-dose IFN-λ regimen significantly reduced lung viral titers and inflammatory cytokine levels with marked improvement in lung inflammation. Collectively, we identified an effective regimen for IFN-λ use and demonstrated the protective efficacy of IFN-λ in MERS-CoV-infected mice. IMPORTANCE Effective antiviral agents are urgently required to prevent and treat individuals infected with SARS-CoV-2 and other emerging viral infections. The COVID-19 pandemic has catapulted our efforts to identify, develop, and evaluate several antiviral agents. However, a narrow therapeutic window has limited the protective efficacy of several broad-spectrum and CoV-specific antivirals. IFN-λ is an antiviral agent of interest due to its ability to induce a robust endogenous antiviral state and low levels of inflammation. Here, we evaluated the protective efficacy and effective treatment regimen of IFN-λ in mice infected with a lethal dose of MERS-CoV. We show that while prophylactic and early therapeutic IFN-λ administration is protective, delayed treatment is detrimental. Notably, a combination of prophylactic and delayed therapeutic administration of IFN-λ protected mice from severe MERS. Our results highlight the prophylactic and therapeutic use of IFN-λ against lethal hCoV and likely other viral lung infections.


Assuntos
Antivirais , Infecções por Coronavirus , Interferons , Coronavírus da Síndrome Respiratória do Oriente Médio , Animais , Antivirais/farmacologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Humanos , Interferons/farmacologia , Camundongos , Interferon lambda
19.
Chemistry ; 29(63): e202301932, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37632841

RESUMO

A reaction of fundamental and commercial importance is acetylene semi-hydrogenation. Acetylene impurity in the ethylene feedstock used in the polyethylene industry poisons the Ziegler-Natta catalyst which adversely affects the polymer quality. Pd based catalysts are most often employed for converting acetylene into the main reactant, ethylene, however, it often involves a tradeoff between the conversion and the selectivity and generally requires high temperatures. In this work, bimetallic Pd-Zn nanoparticles capped by hexadecylamine (HDA) have been synthesized by co-digestive ripening of Pd and Zn nanoparticles and studied for semi-hydrogenation of acetylene. The catalyst showed a high selectivity of ~85 % towards ethylene with a high ethylene productivity to the tune of ~4341 µmol g-1 min-1 , at room temperature and atmospheric pressure. It also exhibited excellent stability with ethylene selectivity remaining greater than 85 % even after 70 h on stream. To the best of the authors' knowledge, this is the first report of room temperature acetylene semi-hydrogenation, with the catalyst effecting high amount of acetylene conversion to ethylene retaining excellent selectivity and stability among all the reported catalysts thus far. DFT calculations show that the disordered Pd-Zn nanocatalyst prepared by a low temperature route exhibits a change in the d-band center of Pd and Zn which in turn enhances the selectivity towards ethylene. TPD, XPS and a range of catalysis experiments provided in-depth insights into the reaction mechanism, indicating the key role of particle size, surface area, Pd-Zn interactions, and the capping agent.

20.
Langmuir ; 39(9): 3301-3311, 2023 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-36802633

RESUMO

Liquid infiltration is one of the commonly adapted flow mechanisms in microscale/nanoscale heat-transfer applications. The theoretical modeling of dynamic infiltration profile in the microscale/nanoscale requires a deep study, because the acting forces are entirely different from those of a large-scale system. Herein, a model equation is developed from the fundamental force balance at the microscale/nanoscale level, to capture the dynamic infiltration flow profile. Molecular kinetic theory (MKT) is used to predict the dynamic contact angle. Molecular dynamics (MD) simulations are performed to study the capillary infiltration in two different geometries. The infiltration length is computed from the simulation results. The model is also evaluated over surfaces having different surface wettability. The generated model provides a better estimation of the infiltration length, compared to the well-established models. The developed model is expected to aid in the designing of microscale/nanoscale devices where liquid infiltration plays a key role.

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