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1.
Artigo em Inglês | MEDLINE | ID: mdl-38772909

RESUMO

Neutrophils are the first leukocytes to be recruited to sites of inflammation in response to chemotactic factors released by activated macrophages and pulmonary epithelial and endothelial cells in bacterial pneumonia, a common cause of acute respiratory distress syndrome (ARDS). Although neutrophilic inflammation facilitates the elimination of pathogens, neutrophils also may cause bystander tissue injury. Even though neutrophils in alveolar spaces is a key feature of acute lung injury and ARDS especially from pneumonia, their contribution to the pathogenesis of lung injury is uncertain. The goal of this study was to elucidate the role of neutrophils in a clinically relevant model of bacterial pneumonia. We investigated the effect of reducing neutrophils in a mouse model of pneumococcal pneumonia treated with antibiotics. Neutrophils were reduced with anti-Ly6G monoclonal antibody 24 hours before and immediately preceding infection. Mice were inoculated intranasally with Streptococcus pneumoniae and received ceftriaxone 12 hours after bacterial inoculation. Neutrophil reduction in mice treated with ceftriaxone attenuated hypoxemia, alveolar permeability, epithelial injury, pulmonary edema, and inflammatory biomarker release induced by bacterial pneumonia, even though bacterial loads in the distal air spaces of the lung were modestly increased as compared to antibiotic treatment alone. Thus, when appropriate antibiotics are administered, lung injury in the early phase of bacterial pneumonia is mediated in part by neutrophils. In the early phase of bacterial pneumonia, neutrophils contribute to the severity of lung injury, although they also participate in host defense.

2.
Res Sq ; 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38464245

RESUMO

Background: Streptococcus pneumoniae is the most common bacterial cause of community acquired pneumonia and the acute respiratory distress syndrome (ARDS). Some clinical trials have demonstrated a beneficial effect of corticosteroid therapy in community acquired pneumonia, COVID-19, and ARDS, but the mechanisms of this benefit remain unclear. The objective of this study was to investigate the effects of corticosteroids on the pulmonary biology of pneumococcal pneumonia in an observational cohort of mechanically ventilated patients and in a mouse model of bacterial pneumonia with Streptococcus pneumoniae. Methods: We studied gene expression with lower respiratory tract transcriptomes from a cohort of mechanically ventilated patients and in mice. We also carried out comprehensive physiologic, biochemical, and histological analyses in mice to identify the mechanisms of lung injury in Streptococcus pneumoniae with and without adjunctive steroid therapy. Results: Transcriptomic analysis identified pleiotropic effects of steroid therapy on the lower respiratory tract in critically ill patients with pneumococcal pneumonia, findings that were reproducible in mice. In mice with pneumonia, dexamethasone in combination with ceftriaxone reduced (1) pulmonary edema formation, (2) alveolar protein permeability, (3) proinflammatory cytokine release, (4) histopathologic lung injury score, and (5) hypoxemia but did not increase bacterial burden. Conclusions: The gene expression studies in patients and in the mice support the clinical relevance of the mouse studies, which replicate several features of pneumococcal pneumonia and steroid therapy in humans. In combination with appropriate antibiotic therapy in mice, treatment of pneumococcal pneumonia with steroid therapy reduced hypoxemia, pulmonary edema, lung permeability, and histologic criteria of lung injury, and also altered inflammatory responses at the protein and gene expression level. The results from these studies provide evidence for the mechanisms that may explain the beneficial effects of glucocorticoid therapy in patients with community acquired pneumonia from Streptococcus Pneumoniae.

3.
Opt Express ; 32(2): 1625-1634, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38297710

RESUMO

Based on enhanced Vernier effect, a compact fiber sensor with ultrahigh sensitivity is proposed for simultaneous transverse load (TL) and temperature measurements. A single mode fiber (SMF) is spliced with a segment of hollow-core fiber (HCF) coated with polydimethylsiloxane (PDMS), some PDMS is injected into the HCF, forming a Vernier sensor with an air cavity adjacent to a PDMS cavity. It is shown that TL and temperature changes give rise to opposite and remarkable different variations in lengths of the two cavities, thereby enhancing Vernier effect and in favor of simultaneous measurements of TL and temperature. Moreover, the limited sensitivity magnification due to the length mismatch between the two cavities is compensated for by reconstructing the Vernier envelope with a broadened free spectrum range (FSR) from output signal. As a result, the highest TL sensitivity reported so far of -2637.47 nm/N and a good condition number of 69.056 for the sensitivity coefficient matrix have been achieved.

4.
Int J Surg ; 110(2): 1183-1195, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38051918

RESUMO

BACKGROUND AND AIMS: Abdominal gunshot wounds (GSWs), a clinically devastating injury, can result in a variety of severe and lethal complications. Traditionally, exploratory laparotomy is the first-line approach for the management of abdominal GSWs, but it is associated with a considerable amount of unnecessary surgeries. At present, selective non-operative management (SNOM) of abdominal GSWs is becoming an effective and well-recognized approach, but it remains widely disputed since many surgeons are skeptical about the validity of SNOM in clinical practice. This meta-analysis aims to estimate the outcomes of SNOM and immediate laparotomy in patients with GSWs by collecting the currently available evidence. METHODS: The PubMed , EMBASE , and Cochrane Library databases were searched. A random-effects model was employed. A pooled proportion with 95% confidence intervals (CIs) was calculated. Heterogeneity was evaluated using Cochran's Q test and I2 statistics. RESULTS: Overall, 53 studies involving 60 291 participants were included. The pooled proportions of SNOM and SNOM failure were 27.0% (95% CI=24.0-30.0%) and 10.0% (95% CI=7.0-13.0%), respectively. The pooled mortality after SNOM and SNOM failure were 0.0% (95% CI=0.0-1.0%) and 0.0% (95% CI=0.0-0.0%), respectively. The pooled proportions of immediate laparotomy and unnecessary immediate laparotomy were 73.0% (95% CI=70.0-76.0%) and 10.0% (95% CI=8.0-13.0%), respectively. The pooled mortality after immediate laparotomy and unnecessary immediate laparotomy was 10.0% (95% CI=8.0-13.0%) and 0.0% (95% CI=0.0-1.0%), respectively. Heterogeneity was statistically significant in nearly all meta-analyses. CONCLUSION: Immediate laparotomy is still the mainstay approach for the management of abdominal GSWs. Approximately one-third of patients with abdominal GSWs undergo SNOM. SNOM failure is not frequent, and its related mortality is also rare.


Assuntos
Traumatismos Abdominais , Ferimentos por Arma de Fogo , Adulto , Humanos , Ferimentos por Arma de Fogo/cirurgia , Traumatismos Abdominais/cirurgia , Laparotomia , Bases de Dados Factuais
5.
ACS Sens ; 8(12): 4774-4781, 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38051949

RESUMO

Wearable sweat sensors provide real-time monitoring of biomarkers, enabling individuals to gain real-time insight into their health status. Current sensors primarily rely on electrochemical mechanisms, limiting their capacity for the concurrent detection of multiple analytes. Surface-enhanced Raman scattering spectroscopy offers an alternative approach by providing molecular fingerprint information to facilitate the identification of intricate analytes. In this study, we combine a wearable Janus fabric for efficient sweat collection and a grapefruit optical fiber embedded with Ag nanoparticles as a sensitive SERS probe. The Janus fabric features a superhydrophobic side in contact with the skin and patterned superhydrophilic regions on the opposite surface, facilitating the unidirectional flow of sweat toward these hydrophilic zones. Grapefruit optical fibers feature sharp tips with the ability to penetrate transparent dressings. Its microchannels extract sweat through capillary force, and nanoliter-scale volumes of sweat are sufficient to completely fill them. The Raman signal of sweat components is greatly enhanced by the plasmonic hot spots and accumulates along the fiber length. We demonstrate sensitive detection of sodium lactate and urea in sweat with a detection limit much lower than the physiological concentration levels. Moreover, the platform shows its capability for multicomponent detection and extends to the analysis of real human sweat.


Assuntos
Nanopartículas Metálicas , Dispositivos Eletrônicos Vestíveis , Humanos , Suor/química , Fibras Ópticas , Análise Espectral Raman/métodos , Prata/análise , Têxteis
6.
Ann Clin Microbiol Antimicrob ; 22(1): 99, 2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-37946238

RESUMO

BACKGROUND: Clinically, a large part of inflammatory bowel disease (IBD) patients is complicated by oral lesions. Although previous studies proved oral microbial dysbiosis in IBD patients, the bacterial community in the gastrointestinal (GI) tract of those IBD patients combined with oral ulcers has not been profiled yet. METHODS: In this study, we enrolled four groups of subjects, including healthy controls (CON), oral ulcer patients (OU), and ulcerative colitis patients with (UC_OU) and without (UC) oral ulcers. Bio-samples from three GI niches containing salivary, buccal, and fecal samples, were collected for 16S rRNA V3-V4 region sequencing. Bacterial abundance and related bio-functions were compared, and data showed that the fecal microbiota was more potent than salivary and buccal microbes in shaping the host immune system. ~ 22 UC and 10 UC_OU 5-aminosalicylate (5-ASA) routine treated patients were followed-up for six months; according to their treatment response (a decrease in the endoscopic Mayo score), they were further sub-grouped as responding and non-responding patients. RESULTS: We found those UC patients complicated with oral ulcers presented weaker treatment response, and three oral bacterial genera, i.e., Fusobacterium, Oribacterium, and Campylobacter, might be connected with treatment responding. Additionally, the salivary microbiome could be an indicator of treatment responding in 5-ASA routine treatment rather than buccal or fecal ones. CONCLUSIONS: The fecal microbiota had a strong effect on the host's immune indices, while the oral bacterial microbiota could help stratification for ulcerative colitis patients with oral ulcers. Additionally, the oral microbiota had the potential role in reflecting the treatment response of UC patients. Three oral bacteria genera (Fusobacterium, Oribacterium, and Campylobacter) might be involved in UC patients with oral ulcers lacking treatment responses, and monitoring oral microbiota may be meaningful in assessing the therapeutic response in UC patients.


Assuntos
Colite Ulcerativa , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Microbiota , Úlceras Orais , Humanos , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/microbiologia , Úlceras Orais/tratamento farmacológico , RNA Ribossômico 16S/genética , Microbioma Gastrointestinal/genética , Doenças Inflamatórias Intestinais/microbiologia , Bactérias/genética , Fezes/microbiologia , Mesalamina
7.
Front Microbiol ; 14: 1236904, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37675433

RESUMO

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction, repetitive behavior and language impairment, and its worldwide prevalence has been found to be increasing annually in recent years. Till now, ASD is uncurable as its pathogenesis remains unknown. However, studies on both animals and humans have demonstrated that fecal microbiota transplantation (FMT) may ameliorate the symptoms of ASD, as well as gastrointestinal symptoms. Nonetheless, there is still no agreement regarding the optimal dosage or duration of FMT treatment for individuals with ASD. Methods: This clinical study is a double-blind, randomized, interventional trial conducted at a single center. The aim is to investigate the safety and efficacy of a pediatric formulation of FMT for ASD. A total of 42 children between the ages of 3-9 with ASD will be randomly assigned in a 2:1 ratio to either an FMT treatment group (n = 28) or a placebo group (n = 14), forming cohort 1. Additionally, 30 healthy children of similar age and gender will be recruited as the control group (cohort 2). Cohort 1 will be assessed using a variety of scales, including the Autism Behavior Checklist, Childhood Autism Rating Scale, Social Responsiveness Scale, Gastrointestinal Symptom Rating Scale, Children's Sleep Habits Questionnaire, and Psychoeducational Profile (Third Edition). These assessments will evaluate the effectiveness of FMT in reducing core symptoms and comorbidities (such as gastrointestinal symptoms and sleep disturbances) in children with ASD. The study will use metagenomic and metabolomic sequencing to assess changes in the composition and structure of the intestinal flora and its metabolites in blood, urine, and feces following treatment. Furthermore, the study will evaluate the acceptability of the FMT formulation by participants' legal guardians and investigate differences in the intestinal flora and metabolism in the FMT group before and after treatment compared to 30 healthy children. Clinical trial registration: https://www.chictr.org.cn/, identifier ChiCTR2200058459.

8.
Opt Express ; 31(18): 28891-28899, 2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37710698

RESUMO

In this paper, the effects of optical power factors like laser power, the powers of the laser beams in the two arms of the optical system, and the power of the photodetector on laser-linewidth measurements are studied. From the experiments, it can be found that when the average optical input power for the photodetector is about 50% of its linear saturation power, the measured laser line width is a minimum. When the optical powers of the laser beams in the two arms are equal in short-delay self-homodyne system, the measured laser line width is narrowest. In the low output power range of the laser, its line width decreases with the increase in optical power. By comparing experiments, it can also be clear that the conventional measurement method is seriously affected by different noise types, which causes the measured line width to become wider and not change even if the laser linewidth changes. However, based on the short-delay coherent envelope method, the measured coherent envelope changes significantly when the laser line width changes slightly, and its corresponding laser-linewidth values are also clearly visible. It confirms the low noise and high resolution of the short-delay self-homodyne coherent-envelope laser-measurement method. The outcomes of this study can provide helpful information for precision ultra-narrow laser-linewidth measurements.

9.
Opt Express ; 31(13): 22189-22203, 2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-37381299

RESUMO

We propose an all-fiber reflective sensing scheme to simultaneously measure temperature and strain. A length of polarization-maintaining fiber serves as the sensing element, and a piece of hollow-core fiber assists with introducing Vernier effect. Both theoretical deductions and simulative studies have demonstrated the feasibility of the proposed Vernier sensor. Experimental results have shown that the sensor can deliver sensitivities of -88.73 nm/°C and 1.61 nm/µÎµ for temperature and strain, respectively. Further, Both theoretical analyses and experimental results have suggested the capability of simultaneous measurement for such a sensor. Significantly, the proposed Vernier sensor not only presents high sensitivities, but also exhibits a simple structure, compact size and light weight, as well as demonstrates ease of fabrication and hence high repeatability, thus holding great promise for widespread applications in daily life and industry world.

10.
Arch Med Sci ; 19(2): 401-410, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37034523

RESUMO

Introduction: Infant jaundice is a common condition which results from a high concentration of serum bilirubin. Phototherapy is a widely used treatment for bilirubin clearance. We analyzed the effect of phototherapy on intestinal flora and metabolism of newborns. The aim was to assess the benefit of treatment for hyperbilirubinemia with phototherapy. Material and methods: Fifty-three jaundiced infants hospitalized at our neonatal intensive care unit were treated with phototherapy. Of them, 29 were prescribed antibiotics during the hospitalization. Fecal samples were collected before and 24 h and 48 h after phototherapy. The bacterial species and relative abundance were identified with Macrogene sequencing. The bile acids in feces were identified using liquid chromatography-mass spectroscopy (LC-MS). Results: Differential microbial species/genera and secondary bile acids were found after phototherapy. There are significant differences in the changes of the microbial species/genera between infants who did not receive antibiotic treatment and those who were given antibiotic treatment. Secondary bile acids were also significantly altered. At the same time, the differential microbial species/genera and the differential secondary bile acids interacted with each other. Conclusions: This study identified several differential intestinal microbial species and secondary bile acids in fecal samples from infants with jaundice before and after phototherapy. Phototherapy can change the flora and its metabolism and its long-term impact needs further observation.

11.
Front Immunol ; 14: 1076772, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36999019

RESUMO

E-cigarette use has rapidly increased as an alternative means of nicotine delivery by heated aerosolization. Recent studies demonstrate nicotine-containing e-cigarette aerosols can have immunosuppressive and pro-inflammatory effects, but it remains unclear how e-cigarettes and the constituents of e-liquids may impact acute lung injury and the development of acute respiratory distress syndrome caused by viral pneumonia. Therefore, in these studies, mice were exposed one hour per day over nine consecutive days to aerosol generated by the clinically-relevant tank-style Aspire Nautilus aerosolizing e-liquid containing a mixture of vegetable glycerin and propylene glycol (VG/PG) with or without nicotine. Exposure to the nicotine-containing aerosol resulted in clinically-relevant levels of plasma cotinine, a nicotine-derived metabolite, and an increase in the pro-inflammatory cytokines IL-17A, CXCL1, and MCP-1 in the distal airspaces. Following the e-cigarette exposure, mice were intranasally inoculated with influenza A virus (H1N1 PR8 strain). Exposure to aerosols generated from VG/PG with and without nicotine caused greater influenza-induced production in the distal airspaces of the pro-inflammatory cytokines IFN-γ, TNFα, IL-1ß, IL-6, IL-17A, and MCP-1 at 7 days post inoculation (dpi). Compared to the aerosolized carrier VG/PG, in mice exposed to aerosolized nicotine there was a significantly lower amount of Mucin 5 subtype AC (MUC5AC) in the distal airspaces and significantly higher lung permeability to protein and viral load in lungs at 7 dpi with influenza. Additionally, nicotine caused relative downregulation of genes associated with ciliary function and fluid clearance and an increased expression of pro-inflammatory pathways at 7 dpi. These results show that (1) the e-liquid carrier VG/PG increases the pro-inflammatory immune responses to viral pneumonia and that (2) nicotine in an e-cigarette aerosol alters the transcriptomic response to pathogens, blunts host defense mechanisms, increases lung barrier permeability, and reduces viral clearance during influenza infection. In conclusion, acute exposure to aerosolized nicotine can impair clearance of viral infection and exacerbate lung injury, findings that have implications for the regulation of e-cigarette products.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Pneumonia Viral , Camundongos , Animais , Humanos , Nicotina/efeitos adversos , Interleucina-17/farmacologia , Aerossóis e Gotículas Respiratórios , Pulmão , Expressão Gênica
12.
Opt Express ; 30(25): 44827-44836, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36522897

RESUMO

Three-dimensional surface-enhanced Raman scattering (SERS) platform based on microstructure fibers has many advantages for rapid liquid detection due to its microfluidic channels and light guidance. The fiber mode field distribution determines the light-analyte interaction strength but has rarely been studied in SERS applications. In this paper, we numerically and experimentally investigate the mode field distribution in suspended-core fibers decorated with gold nanoparticles. The interaction between the core mode and surface mode is controlled by changing the density of gold nanoparticles on the inner surface. The avoided crossing wavelength shifts linearly to red with the decrease of the nanoparticle spacing. With an optimized nanoparticle spacing of 20 nm, the avoided crossing occurs near the laser wavelength of 633 nm, which greatly increases the power ratio in the liquid channels and hence improves the SERS performance. The detection limit for crystal violet was 10-9 M, and the enhancement factor was 108. The avoided crossing mechanism can be applied to all fiber SERS probes for sensitivity improvement.

13.
Front Pediatr ; 10: 1063587, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36507139

RESUMO

Background: Studies show that lung ultrasound (LUS) can accurately diagnose community-acquired pneumonia (CAP) and keep children away from radiation, however, it takes a long time and requires experienced doctors. Therefore, a robust, automatic and computer-based diagnosis of LUS is essential. Objective: To construct and analyze convolutional neural networks (CNNs) based on transfer learning (TL) to explore the feasibility of ultrasound image diagnosis and grading in CAP of children. Methods: 89 children expected to receive a diagnosis of CAP were prospectively enrolled. Clinical data were collected, a LUS images database was established comprising 916 LUS images, and the diagnostic values of LUS in CAP were analyzed. We employed pre-trained models (AlexNet, VGG 16, VGG 19, Inception v3, ResNet 18, ResNet 50, DenseNet 121 and DenseNet 201) to perform CAP diagnosis and grading on the LUS database and evaluated the performance of each model. Results: Among the 89 children, 24 were in the non-CAP group, and 65 were finally diagnosed with CAP, including 44 in the mild group and 21 in the severe group. LUS was highly consistent with clinical diagnosis, CXR and chest CT (kappa values = 0.943, 0.837, 0.835). Experimental results revealed that, after k-fold cross-validation, Inception v3 obtained the best diagnosis accuracy, PPV, sensitivity and AUC of 0.87 ± 0.02, 0.90 ± 0.03, 0.92 ± 0.04 and 0.82 ± 0.04, respectively, for our dataset out of all pre-trained models. As a result, best accuracy, PPV and specificity of 0.75 ± 0.03, 0.89 ± 0.05 and 0.80 ± 0.10 were achieved for severity classification in Inception v3. Conclusions: LUS is a reliable method for diagnosing CAP in children. Experiments showed that, after transfer learning, the CNN models successfully diagnosed and classified LUS of CAP in children; of these, the Inception v3 achieves the best performance and may serve as a tool for the further research and development of AI automatic diagnosis LUS system in clinical applications. Registration: www.chictr.org.cn ChiCTR2200057328.

14.
Materials (Basel) ; 15(20)2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36295435

RESUMO

In this paper, we demonstrate an active metamaterial manifesting electromagnetically induced transparency (EIT) effect in the microwave regime. The metamaterial unit cell consists of a double-cross structure, between which a varactor diode is integrated. The capacitance of the diode is controlled by a reversed electrical bias voltage supplied through two connected strip lines. The diode behaves as a radiative resonant mode and the strip lines as a non-radiative resonant mode. The two modes destructively interference with each other through conductive coupling, which leads to a transmission peak in EIT effect. Through electrical control of the diode capacitance, the transmission peak frequency is shifted from 7.4 GHz to 8.7 GHz, and the peak-to-dip ratio is tuned from 1.02 to 1.66, demonstrating a significant tunability.

15.
Front Pediatr ; 10: 878473, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36275061

RESUMO

Background: In clinical practice, oral probiotics are often given to children with hyperbilirubinaemia who receive phototherapy, but the exact mechanism of the action of the probiotics on hyperbilirubinaemia remains unclear. It is unclear how the effects of phototherapy on the probiotic flora in the neonatal gut, in particular. Materials and methods: Fifty newborns who needed phototherapy from June 2018 to June 2020 were selected as the study subjects, and five healthy newborns in the same period were used as controls to analyse the changes in probiotic bacteria in their faeces. Results: 1. In the intestinal tracts of newborns, Bifidobacterium is the main probiotic strain, with a small amount of Lactobacillus. There were probiotic species changes in the neonatal intestinal microbiota after phototherapy for 24 and 48 h. The amount of Bifidobacterium and Lactobacillus decreased significantly (P < 0.05). 2. A correlation analysis of probiotic species and bile acid metabolism indexes showed that Bifidobacterium was positively correlated with many metabolites (P < 0.05), such as chenodeoxycholic acid, hyodeoxycholic acid, cholic acid, allocholic acid, and ß-cholic acid. It was also negatively correlated with many metabolites (P < 0.05), such as glycocholic acid, sodium, sodium tudca, and chenodeoxycholic acid. Lactobacillus was negatively correlated with metabolites (P < 0.05) such as α-sodium cholate and ß-cholic acid. 3. A correlation analysis between the changes in probiotics and intestinal short-chain fatty acid metabolites after phototherapy showed that acetic acid, butyric acid, caproic acid, and propionic acid decreased and were significantly correlated with Bifidobacterium (P < 0.05). 4. After phototherapy, 17 metabolites changed significantly (P < 0.05). This correlated with many probiotics (P < 0.05). The significantly changed probiotics in this study showed a significant correlation with some intestinal metabolites (P < 0.05). Conclusion: It was found that phototherapy can significantly affect the intestinal probiotic flora and the metabolic indicators of newborns, which may be an important reason for the side effects of phototherapy, and also provides the theoretical basis for the provision of probiotics to newborns with jaundice.

16.
bioRxiv ; 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35982664

RESUMO

As SARS-CoV-2 continues to spread worldwide, tractable primary airway cell models that accurately recapitulate the cell-intrinsic response to arising viral variants are needed. Here we describe an adult stem cell-derived human airway organoid model overexpressing the ACE2 receptor that supports robust viral replication while maintaining 3D architecture and cellular diversity of the airway epithelium. ACE2-OE organoids were infected with SARS-CoV-2 variants and subjected to single-cell RNA-sequencing. NF-κB inhibitor alpha was consistently upregulated in infected epithelial cells, and its mRNA expression positively correlated with infection levels. Confocal microscopy showed more IκBα expression in infected than bystander cells, but found concurrent nuclear translocation of NF-κB that IκBα usually prevents. Overexpressing a nondegradable IκBα mutant reduced NF-κB translocation and increased viral infection. These data demonstrate the functionality of ACE2-OE organoids in SARS-CoV-2 research and identify an incomplete NF-κB feedback loop as a rheostat of viral infection that may promote inflammation and severe disease.

17.
Inorg Chem ; 61(28): 10756-10767, 2022 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-35794725

RESUMO

The electronic and nonlinear optical (NLO) properties of BN-substituted graphynes and the corresponding alkali-doped hybrid systems have been determined using density functional theory. When the carbon atoms in the graphyne are replaced by BN pairs, the highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) gap (Egap) increases to some extent, and the static first hyperpolarizabilities (ß0) of the novel systems hardly increase. However, when an alkali atom is introduced on the surface of BN-substituted graphyne, the doping effect can effectively modulate the electronic and NLO properties. Doping the alkali atom can significantly narrow the wide Egap of BN-substituted graphynes in the range of 1.03-2.03 eV. Furthermore, the doping effect brings considerable ß0 values to these alkali-doped systems, which are 52-3609 au for Li-doped systems and 3258-211 053 au for Na/K-doped ones. The result reveals that the ß0 values of alkali-doped complexes are influenced by the atomic number of alkali metals and the proportion of BN pairs. The nature of the excellent NLO responses of alkali-doped complexes can be understood by the low excitation energy of the crucial excited state and the analysis of the first hyperpolarizability density. Besides, these alkali-doped complexes have a deep-ultraviolet working region. Therefore, the combined effect of alkali metal doping and BN substitution can be an excellent strategy to design novel high-performance NLO materials based on graphyne.

18.
Am J Physiol Lung Cell Mol Physiol ; 323(2): L152-L164, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35670478

RESUMO

Electronic cigarettes (e-cigarettes) are designed to simulate combustible cigarette smoking and to aid in smoking cessation. Although the number of e-cigarette users has been increasing, the potential health impacts and biological effects of e-cigarettes are still not fully understood. Previous research has focused on the biological effects of e-cigarettes on lung cancer cell lines and distal airway epithelial cells; however, there have been few published studies on the effect of e-cigarettes on primary lung alveolar epithelial cells. The primary purpose of this study was to investigate the direct effect of e-cigarette aerosol on primary human lung alveolar epithelial type 2 (AT2) cells, both alone and in the presence of viral infection. The Melo-3 atomizer caused direct AT2 cell toxicity, whereas the more popular Juul pod's aerosol did not have a detectable cytotoxic effect on AT2 cells. Juul nicotine aerosol also did not increase short-term susceptibility to viral infection. However, 3 days of exposure upregulated genes central to the generation of reactive oxygen species, lipid peroxidation, and carcinogen metabolism and downregulated key innate immune system genes related to cytokine and chemokine signaling. These findings have implications for the potentially injurious impact of long-term use of popular low-power e-cigarette pods on the human alveolar epithelium. Gene expression data might be an important endpoint for evaluating the potential harmful effects of vaping devices that do not cause overt toxicity.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Vaping , Células Epiteliais Alveolares , Humanos , Nicotina/efeitos adversos , Aerossóis e Gotículas Respiratórios , Vaping/efeitos adversos
19.
Polymers (Basel) ; 14(11)2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35683826

RESUMO

This paper reports the manipulation of elastic instability of the viscoelastic fluid in a rhombus cross microchannel (RCM) structure. The bistable instability and unsteady instability of the flow is firstly demonstrated in a standard cross microchannel (SCM) for reference. We then keep the bi-stable instability over a much wider injection rate range in the RCM, which is attributed to the stabilizing effect of the rhombus structure. A semi-bistable instability was also established in the RCM at a high enough injection rate. In addition, the unsteady elastic instability is realized in the RCM through an asymmetric injection rate condition.

20.
Nature ; 607(7918): 351-355, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35584773

RESUMO

SARS-CoV-2 Delta and Omicron are globally relevant variants of concern. Although individuals infected with Delta are at risk of developing severe lung disease, infection with Omicron often causes milder symptoms, especially in vaccinated individuals1,2. The question arises of whether widespread Omicron infections could lead to future cross-variant protection, accelerating the end of the pandemic. Here we show that without vaccination, infection with Omicron induces a limited humoral immune response in mice and humans. Sera from mice overexpressing the human ACE2 receptor and infected with Omicron neutralize only Omicron, but not other variants of concern, whereas broader cross-variant neutralization was observed after WA1 and Delta infections. Unlike WA1 and Delta, Omicron replicates to low levels in the lungs and brains of infected animals, leading to mild disease with reduced expression of pro-inflammatory cytokines and diminished activation of lung-resident T cells. Sera from individuals who were unvaccinated and infected with Omicron show the same limited neutralization of only Omicron itself. By contrast, Omicron breakthrough infections induce overall higher neutralization titres against all variants of concern. Our results demonstrate that Omicron infection enhances pre-existing immunity elicited by vaccines but, on its own, may not confer broad protection against non-Omicron variants in unvaccinated individuals.


Assuntos
COVID-19 , Proteção Cruzada , SARS-CoV-2 , Vacinação , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/virologia , Vacinas contra COVID-19/administração & dosagem , Proteção Cruzada/imunologia , Citocinas , Humanos , Camundongos , SARS-CoV-2/classificação , SARS-CoV-2/imunologia , Vacinação/estatística & dados numéricos
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