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1.
Nature ; 622(7984): 724-729, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37880438

RESUMEN

In quantum mechanical many-body systems, long-range and anisotropic interactions promote rich spatial structure and can lead to quantum frustration, giving rise to a wealth of complex, strongly correlated quantum phases1. Long-range interactions play an important role in nature; however, quantum simulations of lattice systems have largely not been able to realize such interactions. A wide range of efforts are underway to explore long-range interacting lattice systems using polar molecules2-5, Rydberg atoms2,6-8, optical cavities9-11 or magnetic atoms12-15. Here we realize novel quantum phases in a strongly correlated lattice system with long-range dipolar interactions using ultracold magnetic erbium atoms. As we tune the dipolar interaction to be the dominant energy scale in our system, we observe quantum phase transitions from a superfluid into dipolar quantum solids, which we directly detect using quantum gas microscopy with accordion lattices. Controlling the interaction anisotropy by orienting the dipoles enables us to realize a variety of stripe-ordered states. Furthermore, by transitioning non-adiabatically through the strongly correlated regime, we observe the emergence of a range of metastable stripe-ordered states. This work demonstrates that novel strongly correlated quantum phases can be realized using long-range dipolar interactions in optical lattices, opening the door to quantum simulations of a wide range of lattice models with long-range and anisotropic interactions.

2.
Nature ; 611(7936): 548-553, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36323787

RESUMEN

Real-time chemical sensing is crucial for applications in environmental and health monitoring1. Biosensors can detect a variety of molecules through genetic circuits that use these chemicals to trigger the synthesis of a coloured protein, thereby producing an optical signal2-4. However, the process of protein expression limits the speed of this sensing to approximately half an hour, and optical signals are often difficult to detect in situ5-8. Here we combine synthetic biology and materials engineering to develop biosensors that produce electrical readouts and have detection times of minutes. We programmed Escherichia coli to produce an electrical current in response to specific chemicals using a modular, eight-component, synthetic electron transport chain. As designed, this strain produced current following exposure to thiosulfate, an anion that causes microbial blooms, within 2 min. This amperometric sensor was then modified to detect an endocrine disruptor. The incorporation of a protein switch into the synthetic pathway and encapsulation of the bacteria with conductive nanomaterials enabled the detection of the endocrine disruptor in urban waterway samples within 3 min. Our results provide design rules to sense various chemicals with mass-transport-limited detection times and a new platform for miniature, low-power bioelectronic sensors that safeguard ecological and human health.


Asunto(s)
Técnicas Biosensibles , Conductividad Eléctrica , Contaminantes Ambientales , Escherichia coli , Humanos , Técnicas Biosensibles/métodos , Disruptores Endocrinos/análisis , Escherichia coli/química , Escherichia coli/metabolismo , Nanoestructuras/química , Factores de Tiempo , Contaminantes Ambientales/análisis , Biología Sintética , Transporte de Electrón , Tiosulfatos/análisis , Contaminantes del Agua/análisis
3.
J Virol ; 98(5): e0159623, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38587378

RESUMEN

Following acute herpes simplex virus type 2 (HSV-2) infection, the virus undergoes an asymptomatic latent infection of sensory neurons of dorsal root ganglia (DRG). Chemical and physical stress cause intermittent virus reactivation from latently infected DRG and recurrent virus shedding in the genital mucosal epithelium causing genital herpes in symptomatic patients. While T cells appear to play a role in controlling virus reactivation from DRG and reducing the severity of recurrent genital herpes, the mechanisms for recruiting these T cells into DRG and the vaginal mucosa (VM) remain to be fully elucidated. The present study investigates the effect of CXCL9, CXCL10, and CXCL11 T-cell-attracting chemokines on the frequency and function of DRG- and VM-resident CD4+ and CD8+ T cells and its effect on the frequency and severity of recurrent genital herpes in the recurrent herpes guinea pig model. HSV-2 latent-infected guinea pigs were immunized intramuscularly with the HSV-2 ribonucleotide reductase 2 (RR2) protein (Prime) and subsequently treated intravaginally with the neurotropic adeno-associated virus type 8 expressing CXCL9, CXCL10, or CXCL11 chemokines to recruit CD4+ and CD8+ T cells into the infected DRG and VM (Pull). Compared to the RR2 therapeutic vaccine alone, the RR2/CXCL11 prime/pull therapeutic vaccine significantly increased the frequencies of functional tissue-resident and effector memory CD4+ and CD8+ T cells in both DRG and VM tissues. This was associated with less virus in the healed genital mucosal epithelium and reduced frequency and severity of recurrent genital herpes. These findings confirm the role of local DRG- and VM-resident CD4+ and CD8+ T cells in reducing virus shedding at the vaginal site of infection and the severity of recurrent genital herpes and propose the novel prime-pull vaccine strategy to protect against recurrent genital herpes.IMPORTANCEThe present study investigates the novel prime/pull therapeutic vaccine strategy to protect against recurrent genital herpes using the latently infected guinea pig model. In this study, we used the strategy that involves immunization of herpes simplex virus type 2-infected guinea pigs using a recombinantly expressed herpes tegument protein-ribonucleotide reductase 2 (RR2; prime), followed by intravaginal treatment with the neurotropic adeno-associated virus type 8 expressing CXCL9, CXCL10, or CXCL11 T-cell-attracting chemokines to recruit T cells into the infected dorsal root ganglia (DRG) and vaginal mucosa (VM) (pull). We show that the RR2/CXCL11 prime-pull therapeutic vaccine strategy elicited a significant reduction in virus shedding in the vaginal mucosa and decreased the severity and frequency of recurrent genital herpes. This protection was associated with increased frequencies of functional tissue-resident (TRM cells) and effector (TEM cells) memory CD4+ and CD8+ T cells infiltrating latently infected DRG tissues and the healed regions of the vaginal mucosa. These findings shed light on the role of tissue-resident and effector memory CD4+ and CD8+ T cells in DRG tissues and the VM in protection against recurrent genital herpes and propose the prime-pull therapeutic vaccine strategy in combating genital herpes.


Asunto(s)
Quimiocina CXCL11 , Herpes Genital , Herpesvirus Humano 2 , Ribonucleótido Reductasas , Animales , Femenino , Cobayas , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Quimiocina CXCL11/inmunología , Quimiocina CXCL11/metabolismo , Modelos Animales de Enfermedad , Ganglios Espinales/inmunología , Ganglios Espinales/virología , Herpes Genital/inmunología , Herpes Genital/prevención & control , Herpesvirus Humano 2/inmunología , Células T de Memoria/inmunología , Ribonucleótido Reductasas/metabolismo , Vacunación , Vagina/virología , Vagina/inmunología
4.
Cereb Cortex ; 34(1)2024 01 14.
Artículo en Inglés | MEDLINE | ID: mdl-38031362

RESUMEN

Fractal patterns have been shown to change in resting- and task-state blood oxygen level-dependent signals in bipolar disorder patients. However, fractal characteristics of brain blood oxygen level-dependent signals when responding to external emotional stimuli in pediatric bipolar disorder remain unclear. Blood oxygen level-dependent signals of 20 PBD-I patients and 17 age- and sex-matched healthy controls were extracted while performing an emotional Go-Nogo task. Neural responses relevant to the task and Hurst exponent of the blood oxygen level-dependent signals were assessed. Correlations between clinical indices and Hurst exponent were estimated. Significantly increased activations were found in regions covering the frontal lobe, parietal lobe, temporal lobe, insula, and subcortical nuclei in PBD-I patients compared to healthy controls in contrast of emotional versus neutral distractors. PBD-I patients exhibited higher Hurst exponent in regions that involved in action control, such as superior frontal gyrus, inferior frontal gyrus, inferior temporal gyrus, and insula, with Hurst exponent of frontal orbital gyrus correlated with onset age. The present study exhibited overactivation, increased self-similarity and decreased complexity in cortical regions during emotional Go-Nogo task in patients relative to healthy controls, which provides evidence of an altered emotional modulation of cognitive control in pediatric bipolar disorder patients. Hurst exponent may be a fractal biomarker of neural activity in pediatric bipolar disorder.


Asunto(s)
Trastorno Bipolar , Humanos , Niño , Trastorno Bipolar/diagnóstico por imagen , Trastorno Bipolar/psicología , Encéfalo/diagnóstico por imagen , Emociones/fisiología , Lóbulo Frontal , Corteza Prefrontal , Mapeo Encefálico , Imagen por Resonancia Magnética
5.
J Transl Med ; 22(1): 6, 2024 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-38167440

RESUMEN

BACKGROUND: Tandem C2 domains, nuclear (TC2N) is a C2 domain-containing protein that belongs to the carboxyl-terminal type (C-type) tandem C2 protein family, and acts as an oncogenic driver in several cancers. Previously, we preliminarily reported that TC2N mediates the PI3K-Akt signaling pathway to inhibit tumor growth of breast cancer (BC) cells. Beyond that, its precise biological functions and detailed molecular mechanisms in BC development and progression are not fully understood. METHODS: Tumor tissues of 212 BC patients were subjected to tissue microarray and further assessed the associations of TC2N expression with pathological parameters and FASN expression. The protein levels of TC2N and FASN in cell lines and tumor specimens were monitored by qRT-PCR, WB, immunofluorescence and immunohistochemistry. In vitro cell assays, in vivo nude mice model was used to assess the effect of TC2N ectopic expression on tumor metastasis and stemness of breast cancer cells. The downstream signaling pathway or target molecule of TC2N was mined using a combination of transcriptomics, proteomics and lipidomics, and the underlying mechanism was explored by WB and co-IP assays. RESULTS: Here, we found that the expression of TC2N remarkedly silenced in metastatic and poorly differentiated tumors. Function-wide, TC2N strongly inhibits tumor metastasis and stem-like properties of BC via inhibition of fatty acid synthesis. Mechanism-wise, TC2N blocks neddylated PTEN-mediated FASN stabilization by a dual mechanism. The C2B domain is crucial for nuclear localization of TC2N, further consolidating the TRIM21-mediated ubiquitylation and degradation of FASN by competing with neddylated PTEN for binding to FASN in nucleus. On the other hand, cytoplasmic TC2N interacts with import proteins, thereby restraining nuclear import of PTEN to decrease neddylated PTEN level. CONCLUSIONS: Altogether, we demonstrate a previously unidentified role and mechanism of TC2N in regulation of lipid metabolism and PTEN neddylation, providing a potential therapeutic target for anti-cancer.


Asunto(s)
Neoplasias de la Mama , Animales , Ratones , Humanos , Femenino , Neoplasias de la Mama/patología , Ratones Desnudos , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal , Ácidos Grasos , Línea Celular Tumoral , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfohidrolasa PTEN/genética , Proliferación Celular , Regulación Neoplásica de la Expresión Génica
6.
BMC Microbiol ; 24(1): 141, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38658829

RESUMEN

BACKGROUND: Recent studies have more focused on gut microbial alteration in tuberculosis (TB) patients. However, no detailed study on gut fungi modification has been reported till now. So, current research explores the characteristics of gut microbiota (bacteria)- and mycobiota (fungi)-dysbiosis in TB patients and also assesses the correlation between the gut microbiome and serum cytokines. It may help to screen the potential diagnostic biomarker for TB. RESULTS: The results show that the alpha diversity of the gut microbiome (including bacteria and fungi) decreased and altered the gut microbiome composition of TB patients. The bacterial genera Bacteroides and Prevotella were significantly increased, and Blautia and Bifidobacterium decreased in the TB patients group. The fungi genus Saccharomyces was increased while decreased levels of Aspergillus in TB patients. It indicates that gut microbial equilibrium between bacteria and fungi has been altered in TB patients. The fungal-to-bacterial species ratio was significantly decreased, and the bacterial-fungal trans-kingdom interactions have been reduced in TB patients. A set model including Bacteroides, Blautia, Eubacterium_hallii_group, Apiotrichum, Penicillium, and Saccharomyces may provide a better TB diagnostics option than using single bacterial or fungi sets. Also, gut microbial dysbiosis has a strong correlation with the alteration of IL-17 and IFN-γ. CONCLUSIONS: Our results demonstrate that TB patients exhibit the gut bacterial and fungal dysbiosis. In the clinics, some gut microbes may be considered as potential biomarkers for auxiliary TB diagnosis.


Asunto(s)
Bacterias , Disbiosis , Hongos , Microbioma Gastrointestinal , Humanos , Disbiosis/microbiología , Hongos/clasificación , Hongos/aislamiento & purificación , Hongos/genética , Masculino , Femenino , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genética , Adulto , Persona de Mediana Edad , Tuberculosis/microbiología , Tuberculosis/complicaciones , Heces/microbiología , Citocinas/sangre , Interleucina-17/sangre
7.
Plant Physiol ; 193(2): 1695-1712, 2023 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-37364582

RESUMEN

NAC (NAM, ATAF1,2, and CUC2) transcription factors (TFs) play critical roles in controlling plant growth, development, and abiotic stress responses. However, few studies have examined NAC proteins related to drought stress tolerance in rose (Rosa chinensis). Here, we identified a drought- and abscisic acid (ABA)-induced NAC TF, RcNAC091, that localizes to the nucleus and has transcriptional activation activity. Virus-induced silencing of RcNAC091 resulted in decreased drought stress tolerance, and RcNAC091 overexpression had the opposite effect. Specifically, ABA mediated RcNAC091-regulated drought tolerance. A transcriptomic comparison showed altered expression of genes involved in ABA signaling and oxidase metabolism in RcNAC091-silenced plants. We further confirmed that RcNAC091 directly targets the promoter of RcWRKY71 in vivo and in vitro. Moreover, RcWRKY71-slienced rose plants were not sensitive to both ABA and drought stress, whereas RcWRKY71-overexpressing plants were hypersensitive to ABA, which resulted in drought-tolerant phenotypes. The expression of ABA biosynthesis- and signaling-related genes was impaired in RcWRKY71-slienced plants, suggesting that RcWRKY71 might facilitate the ABA-dependent pathway. Therefore, our results show that RcWRKY71 is transcriptionally activated by RcNAC091, which positively modulates ABA signaling and drought responses. The results of this study provide insights into the roles of TFs as functional links between RcNAC091 and RcWRKY71 in priming resistance; our findings also have implications for the approaches to enhance the drought resistance of roses.


Asunto(s)
Ácido Abscísico , Rosa , Ácido Abscísico/farmacología , Ácido Abscísico/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Rosa/genética , Rosa/metabolismo , Resistencia a la Sequía , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Plantas Modificadas Genéticamente/metabolismo , Sequías , Estrés Fisiológico/genética
8.
Invest New Drugs ; 42(3): 309-317, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38700579

RESUMEN

BACKGROUND: Platinum-based doublet chemotherapy is commonly used in the treatment of non-small cell lung cancer (NSCLC). A growing body of evidence indicates that incorporating antiangiogenic agents into platinum-based chemotherapy may enhance the survival outcomes for NSCLC patients. However, the optimal administration protocol for intravenous recombinant human endostatin (rh-endostatin), an antiangiogenic agent, remains uncertain at present. AIM: This study aims to investigate the efficacy and safety of 5-d continuous intravenous infusion of rh-endostatin in combination with chemotherapy for patients with advanced NSCLC. The predictive biomarkers for this treatment regimen were further probed. METHODS: This prospective, single-arm multicenter study enrolled a total of 48 patients with advanced NSCLC who were histologically or cytologically confirmed but had not received any prior treatment from January 2021 to December 2022. Prior to the chemotherapy, these patients received a continuous intravenous infusion of rh-endostatin (210 mg) over a period of 120 h, using an infusion pump. The chemotherapy regimen included a combination of platinum with either pemetrexed or paclitaxel, given in 21-day cycles. The primary endpoint of the study was median progression-free survival (mPFS), and the secondary endpoints included median overall survival (mOS), objective response rate (ORR), disease control rate (DCR), and assessment of adverse events (AEs). RESULTS: The mPFS was 6.5 months (95% confidence interval (CI): 3.8-9.1 m) while the mOS was 12.3 months (95% CI: 7.6-18.5 m). The ORR and DCR was 52.1% and 75.0%, respectively. Leukopenia (52.1%), anemia (33.3%), and thrombocytopenia (20.8%) were the most common adverse effects and these toxicities were deemed acceptable and manageable. In addition, a correlation was noted between elevated serum carcinoembryonic antigen (CEA) levels and decreased PFS and OS. CONCLUSIONS: The incorporation of a 5-day continuous intravenous infusion of rh-endostatin into platinum-based doublet chemotherapy has demonstrated both safety and efficacy in the treatment of advanced NSCLC. Furthermore, the baseline serum levels of CEA may potentially function as a predictor for the efficacy of rh-endostatin when combined with chemotherapy in NSCLC patients. CLINICALTRIALS: GOV: NCT05574998.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Pulmón de Células no Pequeñas , Endostatinas , Neoplasias Pulmonares , Paclitaxel , Pemetrexed , Proteínas Recombinantes , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Endostatinas/administración & dosificación , Endostatinas/efectos adversos , Endostatinas/uso terapéutico , Femenino , Masculino , Neoplasias Pulmonares/tratamiento farmacológico , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anciano , Infusiones Intravenosas , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Estudios Prospectivos , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Paclitaxel/uso terapéutico , Pemetrexed/administración & dosificación , Pemetrexed/efectos adversos , Pemetrexed/uso terapéutico , Adulto , Supervivencia sin Progresión
9.
J Exp Bot ; 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38706346

RESUMEN

Rose black spot disease, caused by Marssonina rosae (syn. Diplocarpon rosae), is one of the most widespread diseases of field-grown roses worldwide. Pathogens have been found to interfere with or stimulate plant immune response through the secreted effectors. However, the molecular mechanism involved in inhibition of rose immune response by M. rosae effectors remains poorly understood. In this study, we identified the effector MrSEP43, which played a pivotal role in promoting the virulence of M. rosae and enhancing rose susceptibility by reducing callose deposition, H2O2 accumulation, and the expression of defense genes in jasmonic acid signaling pathway. Through Y2H, BiFC, and LUC assays, MrSEP43 was proved to interact with the rose orphan protein RcBROG. RcBROG, which was a positive regulator of defense against M. rosae, enhanced rose resistance by increasing callose deposition, H2O2 accumulation, and expression of RcERF1 in the ethylene signaling pathway. Overall, our findings suggested that the virulence effector MrSEP43 from M. rosae specifically targeted the orphan protein RcBROG to suppress rose immune response to M. rosae. These results provided new insight into how M. rosae manipulated and successfully colonized rose leaves, and were essential for preventing the breakdown of resistance to rose black spot disease.

10.
Microb Pathog ; 190: 106632, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38537762

RESUMEN

With the widespread introduction of the Hib conjugate vaccine, Nontypeable Haemophilus influenzae (NTHi) has emerged as the predominant strain globally. NTHi presents a significant challenge as a causative agent of chronic clinical infections due to its high rates of drug resistance and biofilm formation. While current research on NTHi biofilms in children has primarily focused on upper respiratory diseases, investigations into lower respiratory sources remain limited. In this study, we collected 54 clinical strains of lower respiratory tract origin from children. Molecular information and drug resistance features were obtained through whole gene sequencing and the disk diffusion method, respectively. Additionally, an in vitro biofilm model was established. All clinical strains were identified as NTHi and demonstrated the ability to form biofilms in vitro. Based on scanning electron microscopy and crystal violet staining, the strains were categorized into weak and strong biofilm-forming groups. We explored the correlation between biofilm formation ability and drug resistance patterns, as well as clinical characteristics. Stronger biofilm formation was associated with a longer cough duration and a higher proportion of abnormal lung imaging findings. Frequent intake of ß-lactam antibiotics might be associated with strong biofilm formation. While a complementary relationship between biofilm-forming capacity and drug resistance may exist, further comprehensive studies are warranted. This study confirms the in vitro biofilm formation of clinical NTHi strains and establishes correlations with clinical characteristics, offering valuable insights for combating NTHi infections.


Asunto(s)
Antibacterianos , Biopelículas , Infecciones por Haemophilus , Haemophilus influenzae , Biopelículas/crecimiento & desarrollo , Humanos , Infecciones por Haemophilus/microbiología , Haemophilus influenzae/fisiología , Haemophilus influenzae/aislamiento & purificación , Haemophilus influenzae/genética , Haemophilus influenzae/efectos de los fármacos , Haemophilus influenzae/clasificación , Antibacterianos/farmacología , Preescolar , Femenino , Masculino , Niño , Lactante , Pruebas de Sensibilidad Microbiana , Infecciones del Sistema Respiratorio/microbiología , Infecciones del Sistema Respiratorio/virología , Microscopía Electrónica de Rastreo , Farmacorresistencia Bacteriana , Sistema Respiratorio/microbiología , Sistema Respiratorio/virología
11.
Cancer Cell Int ; 24(1): 188, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38811918

RESUMEN

BACKGROUND: Breast cancer is a serious threat to women's health with high morbidity and mortality. The development of more effective therapies for the treatment of breast cancer is strongly warranted. Growing evidence suggests that targeting glucose metabolism may be a promising cancer treatment strategy. We previously identified a new glyceraldehyde-3-phosphate dehydrogenase (GAPDH) inhibitor, DC-5163, which shows great potential in inhibiting tumor growth. Here, we evaluated the anticancer potential of DC-5163 in breast cancer cells. METHODS: The effects of DC-5163 on breast cancer cells were investigated in vitro and in vivo. Seahorse, glucose uptake, lactate production, and cellular ATP content assays were performed to examine the impact of DC-5163 on cellular glycolysis. Cell viability, colony-forming ability, cell cycle, and apoptosis were assessed by CCK8 assay, colony formation assay, flow cytometry, and immunoblotting respectively. The anticancer activity of DC-5163 in vivo was evaluated in a mouse breast cancer xenograft model. RESULTS: DC-5163 suppressed aerobic glycolysis and reduced energy supply of breast cancer cells, thereby inhibiting breast cancer cell growth, inducing cell cycle arrest in the G0/G1 phase, and increasing apoptosis. The therapeutic efficacy was assessed using a breast cancer xenograft mouse model. DC-5163 treatment markedly suppressed tumor growth in vivo without inducing evident systemic toxicity. Micro-PET/CT scans revealed a notable reduction in tumor 18F-FDG and 18F-FLT uptake in the DC-5163 treatment group compared to the DMSO control group. CONCLUSIONS: Our results suggest that DC-5163 is a promising GAPDH inhibitor for suppressing breast cancer growth without obvious side effects. 18F-FDG and 18F-FLT PET/CT can noninvasively assess the levels of glycolysis and proliferation in tumors following treatment with DC-5163.

12.
Virol J ; 21(1): 74, 2024 03 26.
Artículo en Inglés | MEDLINE | ID: mdl-38532424

RESUMEN

BACKGROUND: To investigate the efficacy of different doses of corticosteroids in treating severe coronavirus disease 2019 (COVID-19) pneumonia. METHODS: Between May 01, 2023, and June 20, 2023, 48 patients with severe COVID-19 pneumonia were treated at the Department of Respiratory and Critical Care Medicine of Jinan Fourth People's Hospital. The observation group (21 patients) received standard care and high-dose corticosteroids, (high-dose group). The control group (27 patients) received standard care and low-dose corticosteroids (low-dose group). We collected baseline data and recorded inflammatory marker levels after 3 days of treatment, body temperature recovery time, length of stay, and 28-day all-cause mortality. The results of outpatient follow-up were recorded after 1 month. RESULTS: There were no significant differences in 28-day mortality and length of stay. The number of days it took for body temperature to return to normal in the high-dose group was less than in the low-dose group. The high-dose group had significantly more reduced inflammatory factors (C-reactive protein (CRP), interleukin-6 (IL-6). A total of 20 discharged patients were given 8-16 mg of methylprednisolone, depending on chest computed tomography (CT) and clinical symptoms after 1 month; in all discharged patients using oral corticosteroids, CT features improved. CONCLUSION: High-dose corticosteroids had a significantly positive effect on the reduction of inflammatory factors and shortening body temperature recovery time. In the treatment of severe COVID-19 pneumonia, early administration of high-dose, short-course corticosteroids should be implemented.


Asunto(s)
COVID-19 , Neumonía , Humanos , SARS-CoV-2 , Corticoesteroides , Metilprednisolona
13.
Fish Shellfish Immunol ; 148: 109473, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38458502

RESUMEN

Japanese flounder (Paralichthys olivaceus) is an economically crucial marine species, but diseases like hemorrhagic septicemia caused by Edwardsiella tarda have resulted in significant economic losses. E. tarda infects various hosts, and its pathogenicity in fish is not fully understood. Lipopolysaccharides (LPS) are components of the outer membrane of Gram-negative bacteria and are representative of typical PAMP molecules that cause activation of the immune system. The PoIEC cell line is a newly established intestinal epithelial cell line from P. olivaceus. In order to investigate whether it can be used as an in vitro model for studying the pathogenesis of E. tarda and LPS stimulation, we conducted RNA-seq experiments for the PoIECs model of E. tarda infection and LPS stimulation. In this study, transcriptome sequencing was carried out in the PoIEC cell line after treatment with LPS and E. tarda. A total of 62.52G of high-quality data from transcriptome sequencing results were obtained in nine libraries, of which an average of 87.96% data could be aligned to the P. olivaceus genome. Data analysis showed that 283 and 414 differentially expressed genes (DEGs) in the LPS versus Control (LPS-vs-Con) and E. tarda versus Control groups (Et-vs-Con), respectively, of which 60 DEGs were shared in two comparation groups. The GO terms were predominantly enriched in the extracellular space, inflammatory response, and cytokine activity in the LPS-vs-Con group, whereas GO terms were predominantly enriched in nucleus and positive regulation of transcription by RNA polymerase II in the Et-vs-Con group. KEGG analysis revealed that three immune-related pathways were co-enriched in both comparison groups, including the Toll-like receptor signaling pathway, C-type lectin receptor signaling pathway, and Cytokine-cytokine receptor interaction. Five genes were randomly screened to confirm the validity and accuracy of the transcriptome data. These results suggest that PoIEC cell line can be an ideal in vitro model for studies of marine fish gut immunity and pathogenesis of Edwardsiellosis.


Asunto(s)
Infecciones por Enterobacteriaceae , Enfermedades de los Peces , Lenguado , Animales , Lenguado/genética , Lipopolisacáridos/farmacología , Perfilación de la Expresión Génica/veterinaria , Citocinas/genética , Edwardsiella tarda/fisiología , Inmunidad
14.
BJOG ; 131(3): 278-287, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37503769

RESUMEN

OBJECTIVE: To investigate the association between preconception maternal retinal arteriolar calibre and fetal growth. DESIGN, SETTING AND POPULATION: A hospital-based, prospective preconception cohort including 369 women with a singleton live birth. METHODS: We collected detailed information on sociodemographic status, pregnancy history and lifestyle, and performed retinal imaging at the preconception visit. MAIN OUTCOME MEASURES: We retrieved medical records documenting fetal growth biometrics (e.g., abdominal circumference [AC], head circumference [HC], femur length [FL]) at 11-13, 18-21, 24-28, and 32-34 weeks throughout pregnancy. We then computed the z scores for all fetal growth biometrics from 14 weeks of gestation where data were available, referencing the INTERGROWTH-21st fetal growth chart. We used a linear mixed model to estimate the association between maternal preconception retinal arteriolar calibre and fetal growth biometrics z scores throughout pregnancy, with random intercept accounting for repeated measures within individuals. We then performed a multivariable linear regression of maternal preconception retinal arteriolar calibre and z score changes for all fetal growth biometrics between 24-28 weeks and 32-34 weeks of gestation, after full adjustment. RESULTS: Maternal preconception generalised retinal arteriolar narrowing was consistently associated with a reduction in fetal AC z scores (-0.34; 95% CI -0.66 to -0.03) throughout pregnancy. In addition, women with preconception generalised retinal arteriolar narrowing tended to have significantly reduced z score changes in AC (-0.41; 95% CI -0.90 to -0.001) and fetal FL (-0.55; 95% CI -1.00 to -0.10) between 24-28 weeks and 32-34 weeks of gestation, respectively. CONCLUSIONS: Our findings suggest that women with narrower preconception retinal arterioles had smaller fetuses, evidenced by reductions in AC and FL z score throughout pregnancy.


Asunto(s)
Desarrollo Fetal , Feto , Embarazo , Femenino , Humanos , Estudios Prospectivos , Edad Gestacional , Biometría , Ultrasonografía Prenatal/métodos
15.
Nature ; 562(7725): 140-144, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30209391

RESUMEN

Extracellular electron transfer (EET) describes microbial bioelectrochemical processes in which electrons are transferred from the cytosol to the exterior of the cell1. Mineral-respiring bacteria use elaborate haem-based electron transfer mechanisms2-4 but the existence and mechanistic basis of other EETs remain largely unknown. Here we show that the food-borne pathogen Listeria monocytogenes uses a distinctive flavin-based EET mechanism to deliver electrons to iron or an electrode. By performing a forward genetic screen to identify L. monocytogenes mutants with diminished extracellular ferric iron reductase activity, we identified an eight-gene locus that is responsible for EET. This locus encodes a specialized NADH dehydrogenase that segregates EET from aerobic respiration by channelling electrons to a discrete membrane-localized quinone pool. Other proteins facilitate the assembly of an abundant extracellular flavoprotein that, in conjunction with free-molecule flavin shuttles, mediates electron transfer to extracellular acceptors. This system thus establishes a simple electron conduit that is compatible with the single-membrane structure of the Gram-positive cell. Activation of EET supports growth on non-fermentable carbon sources, and an EET mutant exhibited a competitive defect within the mouse gastrointestinal tract. Orthologues of the genes responsible for EET are present in hundreds of species across the Firmicutes phylum, including multiple pathogens and commensal members of the intestinal microbiota, and correlate with EET activity in assayed strains. These findings suggest a greater prevalence of EET-based growth capabilities and establish a previously underappreciated relevance for electrogenic bacteria across diverse environments, including host-associated microbial communities and infectious disease.


Asunto(s)
Transporte de Electrón , Flavinas/metabolismo , Bacterias Grampositivas/metabolismo , Aerobiosis , Animales , Benzoquinonas/metabolismo , Respiración de la Célula , Electrodos , Transporte de Electrón/genética , Electrones , Femenino , Firmicutes/enzimología , Firmicutes/genética , Firmicutes/metabolismo , Tracto Gastrointestinal/microbiología , Bacterias Grampositivas/enzimología , Bacterias Grampositivas/genética , Hierro/química , Listeria monocytogenes/enzimología , Listeria monocytogenes/genética , Listeria monocytogenes/metabolismo , Ratones , NADH Deshidrogenasa/metabolismo
16.
BMC Pediatr ; 24(1): 364, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38802810

RESUMEN

BACKGROUND: Randomized controlled trials (RCTs) are usually the basis of evidence-based medicine, but whether the results of RCTs can be correctly translated into clinical practice depends on the quality of the literature reported. In this study, we evaluated the general characteristics and quality of paediatric RCTs published in China to provide evidence for the reporting of paediatric RCTs and their application in clinical practice. METHODS: We conducted a cross-sectional observational study of paediatric RCTs published in paediatric journals in China between January 1, 1999, and December 30, 2022. All RCTs that included children (younger than 18 years old) were retrieved, and the general characteristics of the RCTs were extracted and analysed. The quality of the RCTs was assessed by the Cochrane quality assessment protocol. RESULTS: After screening 20 available paediatric journals, 3545 RCTs were included for analysis. The average annual growth rate of the number of published paediatric RCTs from 1999 to 2022 was 7.8% (P = 0.005, R2 = 0.311). Most of the studies were carried out in East China [1148 (32.4%]; the centres of the RCTs were mainly single-centre [3453 (97.4%], and the interventions were mainly medication [2442 (68.9%)]. Comparing RCTs published in 2017-2022 with RCTs published in 1999-2004, the quality of RCTs significantly improved in terms of random sequence generation, allocation concealment, blinding participants and personnel, incomplete outcome data and selective outcome reporting. RCTs published in multiple centres from the Chinese Science Citation Database were identified, and the approval of the ethics committee was of better quality for all the analysed risk of bias items. CONCLUSION: The number and quality of paediatric RCTs reported in China have improved in recent years, but the overall quality was relatively low. Special attention should be given to allocation concealment and blinding outcome assessment, and dropouts, adverse effects and sample size calculations should be reported. Promoting government policies, strengthening the standardization of journal publishing and advancing the registration of clinical trials are feasible measures.


Asunto(s)
Pediatría , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Transversales , China , Ensayos Clínicos Controlados Aleatorios como Asunto/normas , Humanos , Pediatría/normas , Niño , Publicaciones Periódicas como Asunto/normas
18.
J Med Internet Res ; 26: e46036, 2024 05 07.
Artículo en Inglés | MEDLINE | ID: mdl-38713909

RESUMEN

BACKGROUND: A plethora of weight management apps are available, but many individuals, especially those living with overweight and obesity, still struggle to achieve adequate weight loss. An emerging area in weight management is the support for one's self-regulation over momentary eating impulses. OBJECTIVE: This study aims to examine the feasibility and effectiveness of a novel artificial intelligence-assisted weight management app in improving eating behaviors in a Southeast Asian cohort. METHODS: A single-group pretest-posttest study was conducted. Participants completed the 1-week run-in period of a 12-week app-based weight management program called the Eating Trigger-Response Inhibition Program (eTRIP). This self-monitoring system was built upon 3 main components, namely, (1) chatbot-based check-ins on eating lapse triggers, (2) food-based computer vision image recognition (system built based on local food items), and (3) automated time-based nudges and meal stopwatch. At every mealtime, participants were prompted to take a picture of their food items, which were identified by a computer vision image recognition technology, thereby triggering a set of chatbot-initiated questions on eating triggers such as who the users were eating with. Paired 2-sided t tests were used to compare the differences in the psychobehavioral constructs before and after the 7-day program, including overeating habits, snacking habits, consideration of future consequences, self-regulation of eating behaviors, anxiety, depression, and physical activity. Qualitative feedback were analyzed by content analysis according to 4 steps, namely, decontextualization, recontextualization, categorization, and compilation. RESULTS: The mean age, self-reported BMI, and waist circumference of the participants were 31.25 (SD 9.98) years, 28.86 (SD 7.02) kg/m2, and 92.60 (SD 18.24) cm, respectively. There were significant improvements in all the 7 psychobehavioral constructs, except for anxiety. After adjusting for multiple comparisons, statistically significant improvements were found for overeating habits (mean -0.32, SD 1.16; P<.001), snacking habits (mean -0.22, SD 1.12; P<.002), self-regulation of eating behavior (mean 0.08, SD 0.49; P=.007), depression (mean -0.12, SD 0.74; P=.007), and physical activity (mean 1288.60, SD 3055.20 metabolic equivalent task-min/day; P<.001). Forty-one participants reported skipping at least 1 meal (ie, breakfast, lunch, or dinner), summing to 578 (67.1%) of the 862 meals skipped. Of the 230 participants, 80 (34.8%) provided textual feedback that indicated satisfactory user experience with eTRIP. Four themes emerged, namely, (1) becoming more mindful of self-monitoring, (2) personalized reminders with prompts and chatbot, (3) food logging with image recognition, and (4) engaging with a simple, easy, and appealing user interface. The attrition rate was 8.4% (21/251). CONCLUSIONS: eTRIP is a feasible and effective weight management program to be tested in a larger population for its effectiveness and sustainability as a personalized weight management program for people with overweight and obesity. TRIAL REGISTRATION: ClinicalTrials.gov NCT04833803; https://classic.clinicaltrials.gov/ct2/show/NCT04833803.


Asunto(s)
Inteligencia Artificial , Conducta Alimentaria , Aplicaciones Móviles , Humanos , Conducta Alimentaria/psicología , Adulto , Femenino , Masculino , Obesidad/psicología , Obesidad/terapia , Persona de Mediana Edad
19.
Artículo en Inglés | MEDLINE | ID: mdl-38647686

RESUMEN

PURPOSE: We performed this systematic review and meta-analysis to explore the impact of preoperative sarcopenia on postoperative complication risks after head and neck cancer (HNC) surgery. METHODS: We identified eligible studies by searching Ovid-MEDLINE, Ovid-Embase, EBM Reviews-Cochrane Central Register of Controlled Trials, Web of Science Core Collection, and Scopus. This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance. RESULTS: Twenty-one studies with a total of 3480 patients met our inclusion criteria. The presence of sarcopenia significantly increased the incidence of overall postoperative complications (OR = 1.72, 95% CI 1.23, 2.41; P = 0.002; I2 = 59%). Subgroup analyses showed a higher risk of postoperative complications in the populations in which sarcopenia was diagnosed with low L3-skeletal muscle index (L3-SMI) or low cross-sectional area of the rectus femoris, but not in the group that sarcopenia was diagnosed with low C3-SMI. Preoperative sarcopenia also substantially increased the risk of severe postoperative complications (OR = 2.26), pharyngocutaneous fistulas (OR = 2.15), free flap-related complications (OR = 1.63), and surgical site infections (OR = 1.84). We also found a tendency toward a higher incidence of wound complications and 30-day mortality in patients with sarcopenia. CONCLUSION: Preoperative sarcopenia is a negative prognostic indicator for postoperative complications in patients with HNC after surgery. To reduce the incidence of postoperative complications and improve poor prognosis, further attention needs to be paid to the evaluation and management of preoperative sarcopenia.

20.
J Environ Manage ; 351: 119864, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38109823

RESUMEN

It is well accepted that tidal wetland vegetation performs a significant amount of water filtration for wetlands. However, there is currently little information on how various wetland plants remove nitrogen (N) and phosphorus (P) and how they differ in their denitrification processes. This study compared and investigated the denitrification and phosphorus removal effects of three typical wetland plants in the Yangtze River estuary wetland (Phragmites australis, Spartina alterniflora, and Scirpus mariqueter), as well as their relevant mechanisms, using an experimental laboratory-scale horizontal subsurface flow constructed wetland (CW). The results showed that all treatment groups with plants significantly reduced N pollutants as compared to the control group without plants. In comparison to S. mariqueter (77.2-83.2%), S. alterniflora and P. australis had a similar total nitrogen (TN)removal effectiveness of nearly 95%. With a removal effectiveness of over 99% for ammonium nitrogen (NH4+-N), P. australis outperformed S. alterniflora (95.6-96.8%) and S. mariqueter (94.6-96.5%). The removal of nitrite nitrogen (NO2--N)and nitrate nitrogen (NO3--N)from wastewater was significantly enhanced by S. alterniflora compared to the other treatment groups. Across all treatment groups, the removal rate of PO43--P was greater than 95%. P. australis and S. alterniflora considerably enriched more 15N than S. mariqueter, according to the results of the 15N isotope labeling experiment. While the rhizosphere and bulk sediments of S. alterniflora were enriched with more simultaneous desulfurization-denitrification bacterial genera (such as Paracoccus, Sulfurovum, and Sulfurimonas), which have denitrification functions, the rhizosphere and bulk sediments of P. australis were enriched with more ammonia-oxidizing archaea and ammonia-oxidizing bacteria. As a result, compared to the other plants, P. australis and S. alterniflora demonstrate substantially more significant ability to remove NH4+-N and NO2--N/NO3--N from simulated domestic wastewater.


Asunto(s)
Nitrógeno , Humedales , Nitrógeno/análisis , Fósforo/análisis , Amoníaco , Dióxido de Nitrógeno , Aguas Residuales , Plantas , Poaceae , China
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