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Ferroptosis plays a crucial role in the development of non-alcoholic fatty liver disease (NAFLD). In this study, we aimed to use a comprehensive bioinformatics approach and experimental validation to identify and verify potential ferroptosis-related genes in NAFLD. We downloaded the microarray datasets for screening differentially expressed genes (DEGs) and identified the intersection of these datasets with ferroptosis-related DEGs from the Ferroptosis database. Subsequently, ferroptosis-related DEGs were obtained using SVM analysis; the LASSO algorithm was then used to identify six marker genes. Furthermore, the CIBERSORT algorithm was used to estimate the proportion of different types of immune cells. Subsequently, we constructed drug regulatory networks and ceRNA regulatory networks. We identified six genes as marker genes for NAFLD, demonstrating their robust diagnostic abilities. Subsequent functional enrichment analysis results revealed that these marker genes were associated with multiple diseases and play a key role in NAFLD via the regulation of immune response and amino acid metabolism, among other pathways. The expression of hepatic EGR1, IL-6, SOCS1, and NR4A1 was significantly downregulated in the NAFLD model. Our findings provide new insights and molecular clues for understanding and treating NAFLD. Further studies are needed to assess the diagnostic potential of these markers for NAFLD.
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Biomarcadores , Biologia Computacional , Ferroptose , Hepatopatia Gordurosa não Alcoólica , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ferroptose/genética , Biomarcadores/metabolismo , Humanos , Animais , Camundongos , Perfilação da Expressão Gênica , Redes Reguladoras de GenesRESUMO
Protein post-translational modifications (PTMs) are crucial for cancer cells to adapt to hypoxia; however, the functional significance of lysine crotonylation (Kcr) in hypoxia remains unclear. Herein we report a quantitative proteomics analysis of global crotonylome under normoxia and hypoxia, and demonstrate 128 Kcr site alterations across 101 proteins in MDA-MB231 cells. Specifically, we observe a significant decrease in K131cr, K156cr and K220cr of phosphoglycerate kinase 1 (PGK1) upon hypoxia. Enoyl-CoA hydratase 1 (ECHS1) is upregulated and interacts with PGK1, leading to the downregulation of PGK1 Kcr under hypoxia. Abolishment of PGK1 Kcr promotes glycolysis and suppresses mitochondrial pyruvate metabolism by activating pyruvate dehydrogenase kinase 1 (PDHK1). A low PGK1 K131cr level is correlated with malignancy and poor prognosis of breast cancer. Our findings show that PGK1 Kcr is a signal in coordinating glycolysis and the tricarboxylic acid (TCA) cycle and may serve as a diagnostic indicator for breast cancer.
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Neoplasias da Mama , Ciclo do Ácido Cítrico , Glicólise , Fosfoglicerato Quinase , Fosfoglicerato Quinase/metabolismo , Fosfoglicerato Quinase/genética , Humanos , Glicólise/genética , Linhagem Celular Tumoral , Feminino , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Lisina/metabolismo , Processamento de Proteína Pós-Traducional , Animais , Carcinogênese/genética , Carcinogênese/metabolismo , Regulação para Baixo , Camundongos , Proteômica/métodos , Camundongos Nus , Regulação Neoplásica da Expressão Gênica , Mitocôndrias/metabolismo , Hipóxia Celular , Piruvato Desidrogenase Quinase de Transferência de Acetil/metabolismo , Piruvato Desidrogenase Quinase de Transferência de Acetil/genéticaRESUMO
Cross conjugation, though prevalent in many organic compounds, is typically considered less effective for electron delocalization compared to linear conjugation. Consequently, it is rarely used as the backbone structure for semiconducting conjugated polymers. In this study, we designed and synthesized a novel building block, TIDP, which features a central cyclic dipeptide with cross conjugation characteristics. Strong intramolecular hydrogen bonding interactions confer TIDP with a highly rigid and coplanar conformation. Importantly, theoretical calculations reveal that π electrons are well delocalized across the entire structure, despite its low aromaticity. Conjugated polymers incorporating TIDP exhibit high charge carrier mobilities, demonstrating the effective π electron delocalization of this innovative building block. Our findings show that with rational design, cross conjugation can achieve effective π electron delocalization, providing a valuable approach for developing high-performance conjugated polymers for organic electronic materials.
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ABSTRACT: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is highly prevalent worldwide and poses a significant threat to men's health, particularly affecting young men. However, the exact causes and mechanisms behind CP/CPPS remain unclear, leading to challenges in its treatment. In this research, a CP/CPPS rat model was established with complete Freund's adjuvant (CFA), and berberine hydrochloride was administered through daily gavage to assess its therapeutic effects. The alterations in the gut microbiome induced by CP/CPPS and berberine hydrochloride were investigated through 16S ribosomal RNA sequencing of cecum content and colonic epithelial cells. To investigate the impact of the gut microbiome on CP/CPPS, a pseudo germ-free rat model was established, and fecal microbiome transplantation (FMT) was performed on these rats. In all, berberine hydrochloride demonstrated effective reduction of inflammation and oxidative stress in the prostate, offering significant therapeutic advantages for CP/CPPS. Through analysis of the gut microbiome using 16S ribosome RNA sequencing, distinct differences were observed between CP/CPPS rats and control rats, and Clostridium butyricum was identified as a key bacteria. Pseudo germ-free rats that underwent FMT from CP/CPPS rats or rats treated with berberine hydrochloride displayed varying levels of inflammatory cytokine production, oxidative stress, and activity of associated signaling pathways. In conclusion, the therapeutic potential of berberine hydrochloride in addressing CP/CPPS is highly significant. The gut microbiome has emerged as a critical factor in the development of CP/CPPS and plays a pivotal role in mediating the therapeutic effects of berberine hydrochloride.
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This work pioneers to combine fast self-assembly of polyhedral oligomeric silsesquioxanes (POSS) nanocage-based giant surfactants with high etching contrast and directed self-assembly for reliable long-range lateral order to create well-aligned sub-10 nm line nanopatterns via reactive ion etching (RIE). Polystyrene-block-oligo(dimethylsiloxane) substituted POSS (PS-b-oDMS7POSS) with seven oligo(dimethylsiloxane) at the corners of the POSS nanocage and one polystyrene (PS) tail is designed and synthesized as a giant surfactant with self-assembly behaviors like block copolymer (BCP). In contrast to BCP, oDMS7POSS gives a volume-persistent "nanoatom" particle with higher mobility for fast self-assembly and higher segregation strength with PS for smaller feature size. By taking advantage of directed self-assembly using nano-trench fabricated by electron beam lithography, well-ordered nanostructured monolayer with well-aligned parallel oDMS7POSS cylinders can be formed by confined self-assembly within the nano-trench. With the optimization of the RIE treatment using O2 as an etchant, the high etching contrast from the oDMS7POSS and PS gives the formation of well-defined line nanopatterns with sub-10 nm critical dimension that can serve as a mask for pattern transfer in lithography. These results demonstrate a cost-effective approach for nanopatterning by utilizing a creatively designed giant surfactant with sub-10 nm feature size and excellent etching contrast for modern lithographic applications.
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BACKGROUND: The available evidence presented inconsistencies and inconclusive findings regarding the associations between co-existing asthma and mortality among COVID-19 patients. The objective of the current study is to investigate the relationship between asthma and severe outcomes after SARS-CoV-2 Omicron infection in an infection-naïve population. METHODS: A retrospective cohort study using propensity score matching was conducted. The COVID-19 patients requiring hospitalisation in Hong Kong from January 1, 2022, to November 13, 2022, an Omicron-predominated period, were identified. Severe clinical outcomes were defined as ICU admission and inpatient death after the first positive PCR results as well as a composite outcome of both. RESULTS: Of the 74,396 hospitalised COVID-19 patients admitted, 1,290 asthma patients and 18,641 non-asthma patients were included in the matched cohort. The rates of death and the composite outcome were 15·3% and 17·2%, respectively, among the non-asthma patients,12·2% and 13·6%, respectively, among the asthma patients, with adjusted hazard ratios equal to 0·775 (95% CI: 0·660-0·909) and 0·770 (95% CI: 0·662-0·895), respectively. The negative association was more apparent in the elderly and female groups. Asthma remained a factor that lowered the risk of disease severity even though the patients were not fully vaccinated with at least two doses. CONCLUSIONS: We used real-world data to demonstrate that asthma was not a risk factor for COVID-19 severity of the infections of Omicron variant, even though the patients were not fully vaccinated.
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Asma , COVID-19 , Hospitalização , SARS-CoV-2 , Índice de Gravidade de Doença , Humanos , COVID-19/epidemiologia , COVID-19/mortalidade , COVID-19/complicações , Feminino , Masculino , Estudos Retrospectivos , Asma/epidemiologia , Asma/complicações , Pessoa de Meia-Idade , Hong Kong/epidemiologia , Idoso , Adulto , Hospitalização/estatística & dados numéricos , Pontuação de Propensão , Fatores de RiscoRESUMO
BACKGROUND: The COVID-19 pandemic has led to decreased measles vaccination rates globally, exacerbating vaccine hesitancy. This study examines the relationship between COVID-19 vaccine acceptance and childhood measles vaccination among parents in Hong Kong. METHODS: A cross-sectional online survey was conducted in Hong Kong from March to September 2022. Parents were recruited via the Qualtrics panel, and a total of 588 parents were invited via email or social media account to participate in the survey. We used the adjusted Measles-containing Vaccine Hesitancy Scale for the assessment of parental vaccine hesitancy for children. A multiple linear regression analysis was conducted to examine the association between parental acceptance of the COVID-19 vaccine and their attitudes towards childhood measles vaccination. RESULTS: Of the 588 participants, parents who have been vaccinated against COVID-19 exhibited significantly less measles-containing vaccine hesitancy comparing to those unvaccinated (ß = -2.96, 95% confidence interval [CI]: -5.10 to -0.83, p = 0.007). Mothers exhibited more hesitancy compared to fathers (ß = 1.64, 95% CI: 0.60 to 2.68, p = 0.002). Parents with a higher self-rated health (ß = -2.20, 95% CI: -3.21 to -1.20, p < 0.001), or who have received advice from health professionals to offer measles, influenza, or COVID-19 vaccines for kids (ß = -2.41, 95% CI: -3.49 to -1.32, p < 0.001) had lower levels of hesitancy. CONCLUSION: COVID-19 vaccine status of parents was associated with reduced hesitancy towards measles vaccines for their children. Addressing vaccine hesitancy effectively requires targeted communication strategies, particularly focusing on those unvaccinated and leveraging the influence of healthcare professionals.
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BACKGROUND: Since the end of 2022, Azvudine was widely used to treat hospitalized coronavirus disease 2019 (COVID-19) patients in China. However, data on the real-world effectiveness of Azvudine against severe outcomes and post-COVID-19-conditions (PCC) among patients infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants was limited. This study evaluates the effectiveness of Azvudine in hospitalized COVID-19 patients during a SARS-CoV-2 Omicron BA.5 dominance period. METHODS: From 1 November 2022 to 1 July 2023, an SARS-CoV-2 Omicron BA.5 dominant period, we conducted a single-center retrospective cohort study based on hospitalized patients with laboratory-confirmed SARS-CoV-2 infection from a tertiary hospital in Shihezi, China. Patients treated with Azvudine and usual care were propensity-score matched (PSM) at a 1:1 ratio to a control group in which patients received usual care only, with matching based on covariates such as sex, age, ethnicity, number of preexisting conditions, antibiotic use at admission, and baseline complete blood cell count. The primary outcomes were all-cause death and short-term (60 days) PCC post discharge. The secondary outcomes included the initiation of invasive mechanical ventilation and PCC at long-term post discharge (120 days). Cox proportional hazards (PH) regression models were employed to estimate the hazard ratios (HR) of Azvudine treatment for both all-cause death and invasive mechanical ventilation, and logistic regression models were used to estimate the odds ratios (OR) for short-term and long-term PCC. Subgroup analyses were performed based on a part of the matched covariates. RESULTS: A total of 2,639 hospitalized patients with SARS-CoV-2 infection were initially identified, and 2,069 ineligible subjects were excluded from analyses. After matching, 297 Azvudine recipients and 297 matched controls were eligible for analyses. The incidence rate of all-cause death was relatively lower in the Azvudine group than in control group (0.007 per person, 95% confidence interval [CI]: 0.001, 0.024 vs 0.128, 95% CI: 0.092, 0.171), and the use of Azvudine was associated with a significantly lower risk of death (HR: 0.049, 95% CI: 0.012, 0.205). Subgroup analyses suggested protection of Azvudine against the risks of all-cause death among men, age over 65, patients without the preexisting conditions, and patients with antibiotics dispensed at admission. Statistical differences were not observed between the Azvudine group and the control group for the risks of invasive mechanical ventilation or short and long-term PCC. CONCLUSIONS: Our findings indicated that Azvudine was associated with lower risk of all-cause death among hospitalized patients with Omicron BA.5 infection in a real-world setting. Further investigation is needed to explore the effectiveness of Azvudine against the PCC after discharge.
This study aims to evaluate the real-world effectiveness of Azvudine among hospitalized COVID-19 patients during a SARS-CoV-2 Omicron BA.5 dominant epidemic phase. Cox proportional hazards (PH) regression models were employed to estimate the hazard ratios (HR) for all-cause death. We found that the use of Azvudine was associated with a significantly reduced risk of all-cause death among hospitalized patients with SARS-CoV-2 infection.
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There is a correlation between IBD and breast cancer according to previous observational studies. However, so far there is no evidence to support if there is a causal relationship between these 2 diseases. We acquired comprehensive Genome-Wide Association Study (GWAS) summary data on IBD (including ulcerative colitis [UC] and Crohn disease [CD]) as well as breast cancer of completely European descent from the IEU GWAS database. The estimation of bidirectional causality between IBD (including UC and CD) and breast cancer was achieved through the utilization of 2-sample Mendelian randomization (MR). The MR results were also assessed for any potential bias caused by heterogeneity and pleiotropy through sensitivity analyses. Our study found a bidirectional causal effect between IBD and breast cancer. Genetic susceptibility to IBD was associated with an increased risk of breast cancer (ORâ =â 1.053, 95% CI: 1.016-1.090, Pâ =â .004). Similarly, the presence of breast cancer may increase the risk of IBD (ORâ =â 1.111, 95% CI: 1.035-1.194, Pâ =â .004). Moreover, the bidirectional causal effect between IBD and breast cancer can be confirmed by another GWAS of IBD. Subtype analysis showed that CD was associated with breast cancer (ORâ =â 1.050, 95% CI: 1.020-1.080, Pâ <â .001), but not UC and breast cancer. There was a suggestive association between breast cancer and UC (ORâ =â 1.106, 95% CI: 1.011-1.209, Pâ =â .028), but not with CD. This study supports a bidirectional causal effect between IBD and breast cancer. There appear to be considerable differences in the specific associations of UC and CD with AD. Understanding that IBD including its specific subtypes and breast cancer constitute common risk factors can contribute to the clinical management of both diseases.
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Neoplasias da Mama , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Humanos , Análise da Randomização Mendeliana/métodos , Neoplasias da Mama/genética , Neoplasias da Mama/epidemiologia , Feminino , Doença de Crohn/genética , Doença de Crohn/epidemiologia , Doenças Inflamatórias Intestinais/genética , Colite Ulcerativa/genética , Colite Ulcerativa/epidemiologia , Fatores de Risco , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Trisulfide unit is widely found in natural products and has garnered attention due to the unique pharmacological and physiochemical properties. However, despite limited progress, widely applicable approaches for constructing unsymmetrical trisulfides have so far remain scarce. In this work, an easy-to-prepare, solid-state and scalable reagent, S-substituted sulphenylthiosulphate, has been developed for the divergent synthesis of unsymmetrical trisulfides. Alkyl electrophile substrates, including bromides, chlorides, iodides and tosylates, with diverse substituents are smoothly converted to the corresponding trisulfides with S-substituted sulphenylthiosulphates and thiourea as another sulfur source. Furthermore, the late-stage modification of drug molecules was successfully achieved through this method.
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Surfactin is widely used in the petroleum extraction, cosmetics, biopharmaceuticals and agriculture industries. It possesses antibacterial and antiviral activities and can reduce interfacial tension. Bacillus are commonly used as production chassis, but wild-type Bacillus subtilis 168 cannot synthesise surfactin. In this study, the phosphopantetheinyl transferase (PPTase) gene sfp* (with a T base removed) was overexpressed and enzyme activity was restored, enabling B. subtilis 168 to synthesise surfactin with a yield of 747.5 ± 6.5 mg/L. Knocking out ppsD and yvkC did not enhance surfactin synthesis. Overexpression of predicted surfactin transporter gene yfiS increased its titre to 1060.7 ± 89.4 mg/L, while overexpression of yerP, ycxA and ycxA-efp had little or negative effects on surfactin synthesis, suggesting YfiS is involved in surfactin efflux. By replacing the native promoter of the srfA operon encoding surfactin synthase with three promoters, surfactin synthesis was significantly reduced. However, knockout of the global transcriptional regulator gene codY enhanced the surfactin titre to 1601.8 ± 91.9 mg/L. The highest surfactin titre reached 3.89 ± 0.07 g/L, with the yield of 0.63 ± 0.02 g/g DCW, after 36 h of fed-batch fermentation in 5 L fermenter. This study provides a reference for further understanding surfactin synthesis and constructing microbial cell factories.
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The rapid development of ultrawideband (UWB) communication systems has resulted in increasing performance requirements for the antenna system. In addition to a wide bandwidth, fast propagation rates and compact dimensions, flexibility, wearability or portability are also desirable for UWB antennas, as are excellent notch characteristics. Although progress has been made in the development of flexible/wearable antennas desired notch properties are still rather limited. Moreover, most presently available flexible UWB antennas are fabricated using environmentally not attractive subtractive etching-based processes. The usage of facile additive sustainably inkjet printing processes also utilizing low temperature plasma-activated conductive inks is rarely reported. In addition, the currently used tri-notched flexible UWB antenna designs have a relatively large footprint, which poses difficulties when integrated into miniaturized and compact communication devices. In this work, a silver nano ink is used to fabricate the antenna via inkjet printing and an efficient plasma sintering procedure. For the targeted UWB applications miniaturized tri-notched flexible antenna is realized on a flexible polyethylene terephthalate (PET) substrate with a compact size of 17.6 mm × 16 mm × 0.12 mm. The antenna operates in the UWB frequency band (2.9-10.61 GHz), and can shield interferences from WiMAX (3.3-3.6 GHz), WLAN (5.150-5.825 GHz) and X-uplink (7.9-8.4 GHz) bands, as well as exhibits a certain of bendability. Three nested "C" slots of different sizes were adopted to achieve notch features. The simulation and test results demonstrate that the proposed antenna can generate signal radiation in the desired UWB frequency band while retaining the desired notch properties and having acceptable SAR values on-body, making it a viable candidate for usage in flexible or wearable communication transmission devices. The research provides a facile and highly efficient method for fabricating flexible/wearable UWB antennas, that is, the effective combination of inkjet printing processing, flexible substrates, low temperature-activated conductive ink and antenna structure design.
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BACKGROUND: As SARS-CoV-2 Omicron variants circulating globally since 2022, assessing the transmission characteristics, and the protection of vaccines against emerging Omicron variants among children and adolescents are needed for guiding the control and vaccination policies. METHODS: We conducted a retrospective cohort study for SARS-CoV-2 infections and close contacts aged <18 years from an outbreak seeded by Omicron BA.5 variants. The secondary attack rate (SAR) was calculated and the protective effects of two doses of inactivated vaccine (mainly Sinopharm /BBIBP-CorV) within a year versus one dose or two doses above a year after vaccination against the transmission and infection of Omicron BA.5 were estimated. RESULTS: A total of 3442 all-age close contacts of 122 confirmed SARS-CoV-2 infections aged 0-17 years were included. The SAR was higher in the household setting and for individuals who received a one-dose inactivated vaccine or those who received a two-dose for more than one year, with estimates of 28.5% (95% credible interval [CrI]: 21.1, 37.7) and 55.3% (95% CrI: 24.4, 84.8), respectively. The second dose of inactivated vaccine conferred substantial protection against all infection and transmission of Omicron BA.5 variants within a year. CONCLUSIONS: Our findings support the rollout of the second dose of inactivated vaccine for children and adolescents during the Omciron BA.5 predominant epidemic phase. Given the continuous emergence of SARS-CoV-2 variants, monitoring the transmission risk and corresponding vaccine effectiveness against SARS-CoV-2 variants among children and adolescents is important to inform control strategy.
Children and adolescents have reported suffering less severe outcomes from the SARS-CoV-2 Omicron variant. However, the risk of transmission and vaccine effectiveness among this population group is not well studied. Here, we used contact tracing data that was collected during an Omicron BA.5 outbreak from Urumqi, China, before the exit of "zero-COVID" measures, to evaluate the spread of SARS-CoV-2 infection among those age under 18 years, and the effectiveness of inactivated vaccine regimens. Our findings indicate there is a high rate of transmission among children and adolescents in a household setting and receiving two doses of inactivated COVID-19 vaccination within a year was more effective than a single dose or two doses given more than a year apart. These findings highlight the importance of tracking transmission and vaccine effectiveness of novel SARS-CoV-2 variants in younger populations to inform control strategies.
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AIMS: Non-alcoholic fatty liver disease (NAFLD) has risen as a significant global public health issue, for which vertical sleeve gastrectomy (VSG) has become an effective treatment method. The study sought to elucidate the processes through which PIM1 mitigates the advancement of NAFLD. The Pro-viral integration site for Moloney murine leukemia virus 1 (PIM1) functions as a serine/threonine kinase. Bioinformatics analysis revealed that reduced PIM1 expression in NAFLD. METHODS: To further prove the role of PIM1 in NAFLD, an in-depth in vivo experiment was performed, in which male C57BL/6 mice were randomly grouped to receive a normal or high-fat diet for 24 weeks. They were operated or delivered the loaded adeno-associated virus which the PIM1 was overexpressed (AAV-PIM1). In an in vitro experiment, AML12 cells were treated with palmitic acid to induce hepatic steatosis. KEY FINDINGS: The results revealed that the VSG surgery and virus delivery of mice alleviated oxidative stress, and apoptosis in vivo. For AML12 cells, the levels of oxidative stress, apoptosis, and lipid metabolism were reduced via PIM1 upregulation. Moreover, ML385 treatment resulted in the downregulation of the NRF2/HO-1/NQO1 signaling cascade, indicating that PIM1 mitigates NAFLD by targeting this pathway. SIGNIFICANCE: PIM1 alleviated mice liver oxidative stress and NAFLD induced by high-fat diet by regulating the NRF2/HO-1/NQO1 signaling Pathway.
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Heme Oxigenase-1 , Camundongos Endogâmicos C57BL , NAD(P)H Desidrogenase (Quinona) , Fator 2 Relacionado a NF-E2 , Hepatopatia Gordurosa não Alcoólica , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-pim-1 , Animais , Proteínas Proto-Oncogênicas c-pim-1/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Masculino , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , NAD(P)H Desidrogenase (Quinona)/metabolismo , NAD(P)H Desidrogenase (Quinona)/genética , Heme Oxigenase-1/metabolismo , Dieta Hiperlipídica/efeitos adversos , Fígado/metabolismo , Fígado/patologia , Transdução de Sinais , Apoptose , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genéticaRESUMO
BACKGROUND: While many investigations examined the association between environmental covariates and COVID-19 incidence, none have examined their relationship with superspreading, a characteristic describing very few individuals disproportionally infecting a large number of people. METHODS: Contact tracing data of all the laboratory-confirmed COVID-19 cases in Hong Kong from February 16, 2020 to April 30, 2021 were used to form the infection clusters for estimating the time-varying dispersion parameter (kt), a measure of superspreading potential. Generalized additive models with identity link function were used to examine the association between negative-log kt (larger means higher superspreading potential) and the environmental covariates, adjusted with mobility metrics that account for the effect of social distancing measures. RESULTS: A total of 6,645 clusters covering 11,717 cases were reported over the study period. After centering at the median temperature, a lower ambient temperature at 10th percentile (18.2 °C) was significantly associated with a lower estimate of negative-log kt (adjusted expected change: -0.239 [95 % CI: -0.431 to -0.048]). While a U-shaped relationship between relative humidity and negative-log kt was observed, an inverted U-shaped relationship with actual vapour pressure was found. A higher total rainfall was significantly associated with lower estimates of negative-log kt. CONCLUSIONS: This study demonstrated a link between meteorological factors and the superspreading potential of COVID-19. We speculated that cold weather and rainy days reduced the social activities of individuals minimizing the interaction with others and the risk of spreading the diseases in high-risk facilities or large clusters, while the extremities of relative humidity may favor the stability and survival of the SARS-CoV-2 virus.
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COVID-19 , SARS-CoV-2 , COVID-19/epidemiologia , COVID-19/transmissão , Humanos , Hong Kong/epidemiologia , Busca de Comunicante , Umidade , Conceitos Meteorológicos , Tempo (Meteorologia) , Temperatura , Feminino , Masculino , Adulto , Pessoa de Meia-IdadeRESUMO
The Dung beetle optimization (DBO) algorithm, devised by Jiankai Xue in 2022, is known for its strong optimization capabilities and fast convergence. However, it does have certain limitations, including insufficiently random population initialization, slow search speed, and inadequate global search capabilities. Drawing inspiration from the mathematical properties of the Sinh and Cosh functions, we proposed a new metaheuristic algorithm, Sinh-Cosh Dung Beetle Optimization (SCDBO). By leveraging the Sinh and Cosh functions to disrupt the initial distribution of DBO and balance the development of rollerball dung beetles, SCDBO enhances the search efficiency and global exploration capabilities of DBO through nonlinear enhancements. These improvements collectively enhance the performance of the dung beetle optimization algorithm, making it more adept at solving complex real-world problems. To evaluate the performance of the SCDBO algorithm, we compared it with seven typical algorithms using the CEC2017 test functions. Additionally, by successfully applying it to three engineering problems, robot arm design, pressure vessel problem, and unmanned aerial vehicle (UAV) path planning, we further demonstrate the superiority of the SCDBO algorithm.
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Postbiotics have been proposed as clinically viable alternatives to probiotics, addressing limitations and safety concerns associated with probiotic use. However, direct comparisons between the functional differences and health benefits of probiotics and postbiotics remain scarce. This study compared directly the desensitization effect of probiotics and postbiotics derived from Lactiplantibacillus plantarum strain DPUL-F232 in the whey protein-induced allergic rat model. The results demonstrate that administering both live and heat killed F232 significantly alleviated allergy symptoms, reduced intestinal inflammation, and decreased serum antibody and histamine levels in rats. Both forms of F232 were effective in regulating the Th1/Th2 balance, promoting the secretion of the regulatory cytokine IL-10, inhibiting mast cell degranulation and restoring the integrity of the intestinal barrier through the upregulation of tight junction proteins. Considering the enhanced stability and reduced safety concerns of postbiotics compared to probiotics, alongside their ability to regulate allergic reactions, we suggest that postbiotics may serve as viable substitutes for probiotics in managing food allergies and potentially other diseases.
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Hipersensibilidade Alimentar , Probióticos , Proteínas do Soro do Leite , Animais , Proteínas do Soro do Leite/farmacologia , Ratos , Probióticos/farmacologia , Lactobacillus plantarum , Ratos Sprague-Dawley , Mucosa Intestinal/imunologia , Masculino , Feminino , Temperatura Alta , HumanosRESUMO
BACKGROUND: Studies have established the short-term efficacy of nirmatrelvir-ritonavir in managing COVID-19, yet its effect on post-COVID-19 condition, especially in patients admitted to hospital, remains understudied. This study aimed to examine the effect of nirmatrelvir-ritonavir on post-COVID-19 condition among patients admitted to hospital in Hong Kong. METHODS: This retrospective cohort study used real-world, territory-wide inpatient records, vaccination records, and confirmed COVID-19 case data from the Hong Kong Hospital Authority and Department of Health, The Government of the Hong Kong Special Administrative Region. Patients aged 18 years and older who tested positive for SARS-CoV-2 between March 11, 2022, and Oct 10, 2023, and who were admitted to hospital with COVID-19 were included. The treatment group included patients prescribed nirmatrelvir-ritonavir within 5 days of symptom onset, excluding those prescribed molnupiravir within 21 days, and the control group had no exposure to either nirmatrelvir-ritonavir or molnupiravir. The outcomes were post-acute inpatient death and 13 sequelae (congestive heart failure, atrial fibrillation, coronary artery disease, deep vein thrombosis, chronic pulmonary disease, acute respiratory distress syndrome, interstitial lung disease, seizure, anxiety, post-traumatic stress disorder, end-stage renal disease, acute kidney injury, and pancreatitis). These outcomes were evaluated starting at 21 days after the positive RT-PCR date in each respective cohort constructed for the outcome. Standardised mortality ratio weights were applied to balance covariates, and Cox proportional hazards regression was used to investigate the relationship between nirmatrelvir-ritonavir and outcomes. FINDINGS: 136 973 patients were screened for inclusion, among whom 50 055 were eligible and included in the analysis (24 873 [49·7%] were female and 25 182 [50·3%] were male). 15 242 patients were prescribed nirmatrelvir-ritonavir during acute COVID-19 and 23 756 patients were included in the control group; 11 057 patients did not meet our definition for the exposed and unexposed groups. Patients were followed up for a median of 393 days (IQR 317-489). In the nirmatrelvir-ritonavir group compared with the control group, there was a significantly lower hazard of post-acute inpatient death (hazard ratio 0·62 [95% CI 0·57-0·68]; p<0·0001), congestive heart failure (0·70 [0·58-0·85]; p=0·0002), atrial fibrillation (0·63 [0·52-0·76]; p<0·0001), coronary artery disease (0·71 [0·59-0·85]; p=0·0002), chronic pulmonary disease (0·68 [0·54-0·86]; p=0·0011), acute respiratory distress syndrome (0·71 [0·58-0·86]; p=0·0007), interstitial lung disease (0·17 [0·04-0·75]; p=0·020), and end-stage renal disease (0·37 [0·18-0·74]; p=0·0049). There was no evidence indicating difference between the groups in deep vein thrombosis, seizure, anxiety, post-traumatic stress disorder, acute kidney injury, and pancreatitis. INTERPRETATION: This study showed extended benefits of nirmatrelvir-ritonavir for reducing the risk of post-acute inpatient death as well as cardiovascular and respiratory complications among patients admitted to hospital with COVID-19. Further research is essential to uncover the underlying mechanisms responsible for these observed negative associations and to devise effective strategies for preventing the onset of post-acute sequelae. FUNDING: Health and Medical Research Fund, Research Grants Council theme-based research schemes, and Research Grants Council Collaborative Research Fund.
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Improvement of indoor air quality is beneficial for human health. However, previous studies have not reached consistent conclusions regarding the effects of indoor air filtration on inflammation and oxidative stress. This study aims to determine the relationship between indoor air filtration and inflammation and oxidative stress biomarkers. We conducted an electronic search that evaluated the association of indoor air filtration with biomarkers of inflammation and oxidative stress in five databases (PubMed, Cochrane Library, EMBASE, Web of Science, and Scopus) from the beginning to April 23, 2023. Outcomes included the following markers: interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), malondialdehyde (MDA), 8-hydroxy-2deoxyguanosine (8-OHdG), and 8-iso-prostaglandinF2α (8-isoPGF2α). We extracted data from the included studies according to the system evaluation and the preferred reporting item for meta-analysis (PRISMA) guidelines and used the Cochrane risk of bias tool to assess bias risk. Our meta-analysis included 15 studies with 678 participants to assess the combined effect size. The meta-analysis demonstrated that indoor air filtration could have a marked reduction in IL-6 (SMD: -0.275, 95% CI: -0.545 to -0.005, p = 0.046) but had no significant effect on other markers of inflammation or oxidative stress. Subgroup analysis results demonstrated a significant reduction in 8-OHdG levels in the subgroup with < 1 day of duration (SMD: -0.916, 95% CI: -1.513 to -0.320; p = 0.003) and using filtrete air filter (SMD: -5.530, 95% CI: -5.962 to -5.099; p < 0.001). Our meta-analysis results depicted that indoor air filtration can significantly reduce levels of inflammation and oxidative stress markers. Considering the adverse effects of air pollution on human health, our study provides powerful evidence for applying indoor air filtration to heavy atmospheric pollution.
Assuntos
Poluição do Ar em Ambientes Fechados , Biomarcadores , Inflamação , Estresse Oxidativo , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Filtros de Ar , Filtração , Interleucina-6RESUMO
Objectives: To estimate the association between the transition to daylight saving time and the risks of all cause and cause specific mortality in the US. Design: Nationwide time series observational study based on weekly data. Setting: US state level mortality data from the National Center for Health Statistics, with death counts from 50 US states and the District of Columbia, from the start of 2015 to the end of 2019. Population: 13 912 837 reported deaths in the US. Main outcome measures: Weekly counts of mortality for any cause, and for Alzheimer's disease, dementia, circulatory diseases, malignant neoplasms, and respiratory diseases. Results: During the study period, 13 912 837 deaths were reported. The analysis found no evidence of an association between the transition to spring daylight saving time (when clocks are set forward by one hour on the second Sunday of March) and the risk of all cause mortality during the first eight weeks after the transition (rate ratio 1.003, 95% confidence interval 0.987 to 1.020). Autumn daylight saving time is defined in this study as the time when the clocks are set back by one hour (ie, return to standard time) on the first Sunday of November. Evidence indicating a substantial decrease in the risk of all cause mortality during the first eight weeks after the transition to autumn daylight saving time (0.974, 0.958 to 0.990). Overall, when considering the transition to both spring and autumn daylight saving time, no evidence of any effect of daylight saving time on all cause mortality was found (0.988, 0.972 to 1.005). These patterns of changes in mortality rates associated with transition to daylight saving time were consistent for Alzheimer's disease, dementia, circulatory diseases, malignant neoplasms, and respiratory diseases. The protective effect of the transition to autumn daylight saving time on the risk of mortality was more pronounced in elderly people aged ≥75 years, in the non-Hispanic white population, and in those residing in the eastern time zone. Conclusions: In this study, transition to daylight saving time was found to affect mortality patterns in the US, but an association with additional deaths overall was not found. These findings might inform the ongoing debate on the policy of shifting daylight saving time.