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1.
Plant Biotechnol J ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587024

RESUMO

The clade III subfamily of OsSWEETs includes transmembrane proteins necessary for susceptibility to bacterial blight (BB). These genes are targeted by the specific transcription activator-like effector (TALE) of Xanthomonas oryzae pv. oryzae and mediate sucrose efflux for bacterial proliferation. However, the mechanism through which OsSWEETs regulate rice immunity has not been fully elucidated. Here, we demonstrated that the cytosolic carboxyl terminus of OsSWEET11a/Xa13 is required for complementing susceptibility to PXO99 in IRBB13 (xa13/xa13). Interestingly, the C-terminus of ZmXa13, the maize homologue of OsSWEET11a/Xa13, could perfectly substitute for the C-terminus of OsSWEET11a/Xa13. Furthermore, OsSWEET11a/Xa13 interacted with the high-mobility group B1 (OsHMGB1) protein and the small heat shock-like protein OsHsp20L through the same regions in the C-terminus. Consistent with the physical interactions, knockdown or knockout of either OsHMGB1 or OsHsp20L caused an enhanced PXO99-resistant phenotype similar to that of OsSWEET11a/OsXa13. Surprisingly, the plants in which OsHMGB1 or OsHsp20L was repressed developed increased resistance to PXO86, PXO61 and YN24, which carry TALEs targeting OsSWEET14/Xa41 or OsSWEET11a/Xa13. Additionally, OsHsp20L can interact with all six members of clade III OsSWEETs, whereas OsHMGB1 can interact with five other members in addition to OsSWEET12. Overall, we revealed that OsHMGB1 and OsHsp20L mediate conserved BB susceptibility by interacting with clade III OsSWEETs, which are candidates for breeding broad-spectrum disease-resistant rice.

2.
Insect Mol Biol ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38767730

RESUMO

Bee venom serves as an essential defensive weapon for bees and also finds application as a medicinal drug. MicroRNAs (miRNAs) serve as critical regulators and have been demonstrated to perform a variety of biological functions. However, the presence of miRNAs in bee venom needs to be confirmed. Therefore, we conducted small RNA sequencing and identified 158 known miRNAs, 15 conserved miRNAs and 4 novel miRNAs. It is noteworthy that ame-miR-1-3p, the most abundant among them, accounted for over a quarter of all miRNA reads. To validate the function of ame-miR-1-3p, we screened 28 candidate target genes using transcriptome sequencing and three target gene prediction software (miRanda, PITA and TargetScan) for ame-miR-1-3p. Subsequently, we employed real-time quantitative reverse transcription PCR (qRT-PCR), Western blot and other technologies to confirm that ame-miR-1-3p inhibits the relative expression of antizyme inhibitor 1 (AZIN1) by targeting the 3' untranslated region (UTR) of AZIN1. This, in turn, caused ODC antizyme 1 (OAZ1) to bind to ornithine decarboxylase 1 (ODC1) and mark ODC1 for proteolytic destruction. The reduction in functional ODC1 ultimately resulted in a decrease in polyamine biosynthesis. Furthermore, we determined that ame-miR-1-3p accelerates cell death through the AZIN1/OAZ1-ODC1-polyamines pathway. Our studies demonstrate that ame-miR-1-3p diminishes cell viability and it may collaborate with sPLA2 to enhance the defence capabilities of honeybees (Apis mellifera L.). Collectively, these data further elucidate the defence mechanism of bee venom and expand the potential applications of bee venom in medical treatment.

3.
FASEB J ; 37(9): e23146, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37584664

RESUMO

Adipogenesis is tightly regulated by various factors, including genes and microRNAs. Excessive fat deposition is the key feature of obesity, which is a low-grade chronic inflammatory disease. Follistatin-like 1 (FSTL1) has been reported to be an important mediator involved in various inflammatory diseases. However, the underlying mechanism of FSTL1 in preadipocyte differentiation and inflammatory response is still unclear. The current study was designed to explore the biological function and potential mechanism of FSTL1 in mouse subcutaneous preadipocyte differentiation. We found that FSTL1 was highly expressed in the early stage of differentiation and subsequently decreased sharply, suggesting that FSTL1 played a possible role in adipogenesis. Meanwhile, the gain- and loss-of-function assays showed that FSTL1 was not only involved in the inflammatory response by inducing the expression of pro-inflammatory factors IL-1ß and CCL2 but also significantly attenuated preadipocyte differentiation, as evidenced by the reduction of lipid accumulation and the levels of adipogenic genes, including PPARγ and FABP4. In addition, the target gene prediction and luciferase reporter assay validated that miR-125a-3p targeted the 3' UTR region of FSTL1. These results demonstrated that miR-125a-3p negatively regulated the expression of FSTL1 at the mRNA and protein levels. Furthermore, overexpressing miR-125a-3p in preadipocytes dramatically accelerated adipogenic differentiation and downregulated the levels of IL-1ß and CCL2, which were in accordance with the knockdown of FSTL1. On the contrary, treatment with miR-125a-3p inhibitors attenuated adipogenesis but induced the expression of inflammatory genes. In summary, this study suggests a positive function of FSTL1 in adipocyte-induced inflammation and negatively regulates preadipocyte differentiation. Further studies demonstrated that miR-125a-3p could reverse the effect by targeting FSTL1, which might provide a better understanding of treating obesity-related inflammatory diseases.


Assuntos
Adipogenia , MicroRNAs , Animais , Camundongos , Adipócitos/metabolismo , Adipogenia/genética , MicroRNAs/metabolismo , Obesidade/genética , Obesidade/metabolismo , RNA Mensageiro/metabolismo
4.
Physiol Plant ; 176(4): e14415, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962818

RESUMO

The monotonicity of color type in naturally colored cottons (NCCs) has become the main limiting factor to their widespread use, simultaneously coexisting with poor fiber quality. The synchronous improvement of fiber quality and color become more urgent and crucial as the demand for sustainable development increases. The homologous gene of wild cotton Gossypium stocksii LAC15 in G. hirsutum, GhLAC15, was also dominantly expressed in the developing fibers of brown cotton XC20 from 5 DPA (day post anthesis) to 25 DPA, especially at the secondary cell wall thickening stage (20 DPA and 25 DPA). In XC20 plants with downregulated GhLAC15 (GhLAC15i), a remarkable reduction in proanthocyanidins (PAs) and lignin contents was observed. Some of the key genes in the phenylpropane and flavonoid biosynthesis pathway were down-regulated in GhLAC15i plants. Notably, the fiber length of GhLAC15i plants showed an obvious increase and the fiber color was lightened. Moreover, we found that the thickness of cotton fiber cell wall was decreased in GhLAC15i plants and the fiber surface became smoother compared to that of WT. Taken together, this study revealed that GhLAC15 played an important role in PAs and lignin biosynthesis in naturally colored cotton fibers. It might mediate fiber color and fiber quality by catalyzing PAs oxidation and lignin polymerization, ultimately regulating fiber colouration and development.


Assuntos
Fibra de Algodão , Regulação da Expressão Gênica de Plantas , Gossypium , Lacase , Lignina , Proteínas de Plantas , Gossypium/genética , Gossypium/metabolismo , Gossypium/enzimologia , Lacase/metabolismo , Lacase/genética , Lignina/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Parede Celular/metabolismo , Proantocianidinas/metabolismo , Cor , Pigmentação/genética
5.
Environ Sci Technol ; 58(8): 3755-3765, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38285506

RESUMO

Carbon dioxide removal (CDR) is necessary for reaching net zero emissions, with studies showing potential deployment at multi-GtCO2 scale by 2050. However, excessive reliance on future CDR entails serious risks, including delayed emissions cuts, lock-in of fossil infrastructure, and threats to sustainability from increased resource competition. This study highlights an alternative pathway─prioritizing near-term non-CDR mitigation and minimizing CDR dependence. We impose a 1 GtCO2 limit on global novel CDR deployment by 2050, forcing aggressive early emissions reductions compared to 8-22 GtCO2 in higher CDR scenarios. Our results reveal that this low CDR pathway significantly decreases fossil fuel use, greenhouse gas (GHG) emissions, and air pollutants compared to higher CDR pathways. Driving rapid energy transitions eases pressures on land (including food cropland), water, and fertilizer resources required for energy and negative emissions. However, these sustainability gains come with higher mitigation costs from greater near-term low/zero-carbon technology deployment for decarbonization. Overall, this work provides strong evidence for maximizing non-CDR strategies such as renewables, electrification, carbon neutral/negative fuels, and efficiency now rather than betting on uncertain future CDR scaling. Ambitious near-term mitigation in this decade is essential to prevent lock-in and offer the best chance of successful deep decarbonization. Our constrained CDR scenario offers a robust pathway to achieving net zero emissions with limited sustainability impacts.


Assuntos
Dióxido de Carbono , Gases de Efeito Estufa , Dióxido de Carbono/análise
6.
Nature ; 564(7734): 130-135, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30487606

RESUMO

Dysfunctional T cells in the tumour microenvironment have abnormally high expression of PD-1 and antibody inhibitors against PD-1 or its ligand (PD-L1) have become commonly used drugs to treat various types of cancer1-4. The clinical success of these inhibitors highlights the need to study the mechanisms by which PD-1 is regulated. Here we report a mechanism of PD-1 degradation and the importance of this mechanism in anti-tumour immunity in preclinical models. We show that surface PD-1 undergoes internalization, subsequent ubiquitination and proteasome degradation in activated T cells. FBXO38 is an E3 ligase of PD-1 that mediates Lys48-linked poly-ubiquitination and subsequent proteasome degradation. Conditional knockout of Fbxo38 in T cells did not affect T cell receptor and CD28 signalling, but led to faster tumour progression in mice owing to higher levels of PD-1 in tumour-infiltrating T cells. Anti-PD-1 therapy normalized the effect of FBXO38 deficiency on tumour growth in mice, which suggests that PD-1 is the primary target of FBXO38 in T cells. In human tumour tissues and a mouse cancer model, transcriptional levels of FBXO38 and Fbxo38, respectively, were downregulated in tumour-infiltrating T cells. However, IL-2 therapy rescued Fbxo38 transcription and therefore downregulated PD-1 levels in PD-1+ T cells in mice. These data indicate that FBXO38 regulates PD-1 expression and highlight an alternative method to block the PD-1 pathway.


Assuntos
Proteínas F-Box/genética , Neoplasias/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Linfócitos T/imunologia , Ubiquitinação , Animais , Proteínas F-Box/metabolismo , Feminino , Células HEK293 , Humanos , Interleucina-2/imunologia , Lisina/metabolismo , Masculino , Melanoma Experimental/imunologia , Camundongos , Receptor de Morte Celular Programada 1/química , Complexo de Endopeptidases do Proteassoma/metabolismo , Microambiente Tumoral
7.
BMC Public Health ; 24(1): 72, 2024 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172749

RESUMO

BACKGROUND: In ageing societies such as the United States, evaluating the incidence and survival rates of cancer in older adults is essential. This study aimed to analyse the incidence and survival rates of cancer in individuals aged 55 years or older in the United States. METHODS: This retrospective study (1975-2019) was conducted using combined registry data from the Surveillance, Epidemiology, and End Results database. Data from the 9, 12, and 17 Registries (Nov 2021 Sub) datasets were used. RESULTS: In 2019, the incidence of cancer in individuals older than 55 years and the overall population was 1322.8 and 382.1 per 100,000 population, respectively. From 2000 to 2019, the incidence of cancer in individuals older than 55 years showed a decreasing trend, whereas their five-year survival rates showed an increasing trend. The incidence of cancer in the 75-79 and 80-84 year age groups was the highest among all age groups. CONCLUSIONS: The incidence of colon cancer declined significantly, whereas that of intrahepatic bile duct cancer increased considerably. These trends may be due to increased screening for cancers with high incidence rates and improved control of the risk factors for cancer. Rapid development of targeted therapy and immunotherapy combined with early tumour detection may be an important reason for the improved survival rates.


Assuntos
Neoplasias do Colo , Idoso , Humanos , Neoplasias do Colo/mortalidade , Incidência , Sistema de Registros , Estudos Retrospectivos , Programa de SEER , Taxa de Sobrevida , Estados Unidos/epidemiologia
8.
BMC Pediatr ; 24(1): 234, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566022

RESUMO

BACKGROUND: The rebound of influenza A (H1N1) infection in post-COVID-19 era recently attracted enormous attention due the rapidly increased number of pediatric hospitalizations and the changed characteristics compared to classical H1N1 infection in pre-COVID-19 era. This study aimed to evaluate the clinical characteristics and severity of children hospitalized with H1N1 infection during post-COVID-19 period, and to construct a novel prediction model for severe H1N1 infection. METHODS: A total of 757 pediatric H1N1 inpatients from nine tertiary public hospitals in Yunnan and Shanghai, China, were retrospectively included, of which 431 patients diagnosed between February 2023 and July 2023 were divided into post-COVID-19 group, while the remaining 326 patients diagnosed between November 2018 and April 2019 were divided into pre-COVID-19 group. A 1:1 propensity-score matching (PSM) was adopted to balance demographic differences between pre- and post-COVID-19 groups, and then compared the severity across these two groups based on clinical and laboratory indicators. Additionally, a subgroup analysis in the original post-COVID-19 group (without PSM) was performed to investigate the independent risk factors for severe H1N1 infection in post-COIVD-19 era. Specifically, Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied to select candidate predictors, and logistic regression was used to further identify independent risk factors, thus establishing a prediction model. Receiver operating characteristic (ROC) curve and calibration curve were utilized to assess discriminative capability and accuracy of the model, while decision curve analysis (DCA) was used to determine the clinical usefulness of the model. RESULTS: After PSM, the post-COVID-19 group showed longer fever duration, higher fever peak, more frequent cough and seizures, as well as higher levels of C-reactive protein (CRP), interleukin 6 (IL-6), IL-10, creatine kinase-MB (CK-MB) and fibrinogen, higher mechanical ventilation rate, longer length of hospital stay (LOS), as well as higher proportion of severe H1N1 infection (all P < 0.05), compared to the pre-COVID-19 group. Moreover, age, BMI, fever duration, leucocyte count, lymphocyte proportion, proportion of CD3+ T cells, tumor necrosis factor α (TNF-α), and IL-10 were confirmed to be independently associated with severe H1N1 infection in post-COVID-19 era. A prediction model integrating these above eight variables was established, and this model had good discrimination, accuracy, and clinical practicability. CONCLUSIONS: Pediatric H1N1 infection during post-COVID-19 era showed a higher overall disease severity than the classical H1N1 infection in pre-COVID-19 period. Meanwhile, cough and seizures were more prominent in children with H1N1 infection during post-COVID-19 era. Clinicians should be aware of these changes in such patients in clinical work. Furthermore, a simple and practical prediction model was constructed and internally validated here, which showed a good performance for predicting severe H1N1 infection in post-COVID-19 era.


Assuntos
COVID-19 , Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Humanos , Criança , Interleucina-10 , Influenza Humana/complicações , Influenza Humana/diagnóstico , Estudos Retrospectivos , China/epidemiologia , Gravidade do Paciente , Convulsões , Tosse
9.
Altern Ther Health Med ; 30(1): 148-153, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37773664

RESUMO

Objective: There are few studies on the application effects of acknowledge introduce duration explanation thank you (AIDET) and Pendleton-based consultation modes on outpatient visits. Outpatients were included as the subjects to investigate the application effects of AIDET interaction mode and Pendleton general consultation mode in outpatients' visits, which provided the referable basis for outpatient management. Methods: In this research, a retrospective analysis was performed for 303 outpatients treated in the general outpatient clinic of our hospital between March 2021 and March 2022. According to different treatment methods, they were enrolled into groups A (101 cases), P (101 cases), and C (101 cases). The patients in Group A were treated with AIDET interaction mode, those in Group P were treated with Pendleton general consultation mode, and those in Group C were treated with traditional doctor-patient interaction mode. Self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were utilized to evaluate anxiety and depression among patients before and after treatment. What's more, the interaction effects on patients in the three groups after consultation were compared, and the cooperation degree of patients in the three groups during consultation and treatment were summarized. What's more, a simplified coping style questionnaire (SCSQ) was employed to evaluate patients' responses to doctors' advice, and the satisfaction among patients in different groups was statistically analyzed. Results: SAS and SDS scores for groups A and P after consultation were apparently inferior to those before consultation (P < .01) and those for group C (P < .01). The proportion of patients whose disease was completely summarized and accurately analyzed in Group A was notably superior to that in Group C (P < .001), and the proportion in Group P was superior to that in Group C (P < .05). The degree of cooperation in group A and P were higher than that in group C (P < .05).Positive and passive response scores for groups A and P differed from those for group C (P < .05). The satisfaction with outpatient visits in groups A and P were superior to those in group C (P < .05). Conclusion: AIDET and Pendleton consultation modes could relieve anxiety about medical visits and improve patients' cooperation and satisfaction with treatment. In particular, AIDET was more effective and had potential application values in outpatient treatment.


Assuntos
Pacientes Ambulatoriais , Satisfação do Paciente , Humanos , Estudos Retrospectivos , Inquéritos e Questionários , Encaminhamento e Consulta
10.
Artigo em Inglês | MEDLINE | ID: mdl-38687851

RESUMO

Objective: Necrotizing pneumonia is a rare and serious complication in pediatric patients, and its treatment often involves the complexity of choosing between surgical intervention and medical management. The disease is difficult to treat because of its devastating characteristics and high mortality rate, especially when considering the risks associated with surgery. The purpose of this report is to present two cases of necrotizing pneumonia in pediatric patients and demonstrate successful conservative management to provide additional insights for clinical decision-making. Case Report: We report two pediatric patients, aged 3 years 7 months and 7 years respectively, who presented with varying degrees of clinical symptoms, including persistent high fever, shortness of breath, and were confirmed to have necrotizing pneumonia after thorough diagnosis and underwent a period of intensive care. Weeks of treatment. Both patients received long-term antibiotic therapy, ventilator support, and analgesia. Conservative management including type of antibiotics, duration of treatment, specific parameters of respiratory support, and analgesic medications is detailed. Conclusion: Our case report highlights that necrotizing pneumonia can be successfully treated with conservative treatment, thus obviating the need for early surgical intervention. These findings are potentially important for guiding clinical practice, suggesting that conservative management can be an effective treatment strategy for necrotizing pneumonia in certain circumstances.

11.
Ecotoxicol Environ Saf ; 272: 116028, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38310824

RESUMO

Extensive application of lead (Pb) brought about environmental pollution and toxic reactions of organisms. Selenium (Se) has the effect of antagonizing Pb poisoning in humans and animals. However, it is still unclear how Pb causes brainstem toxicity. In the present study, we wanted to investigate whether Se can alleviate Pb toxicity in chicken brainstems by reducing apoptosis. One hundred and eighty chickens were randomly divided into four groups, namely the control group, the Se group, the Pb group, and the Se/Pb group. Morphological examination, ultrastructural observation, relative mRNA expressions of genes on heat shock proteins (HSPs); selenoproteins; inflammatory cytokines; and apoptosis-related factors were investigated. The results showed that Pb exposure led to tissue damage and apoptosis in chicken brainstems. Furthermore, an atypical expression of HSPs (HSP27, HSP40, HSP60, HSP70, and HSP90); selenoprotein family glutathione peroxidase (GPx) 1, GPx2, GPx3, and GPx4), thioredoxin reductases (Txnrd) (Txnrd1, Txnrd2, and Txnrd3), dio selenoprotein famliy (diodothyronine deiodinases (Dio)1, Dio2, and Dio3), as well as other selenoproteins (selenoprotein (Sel)T, SelK, SelS, SelH, SelM, SelU, SelI, SelO, Selpb, selenoprotein n1 (Sepn1), Sepp1, Sepx1, Sepw1, 15-kDa selenoprotein (Sep15), and selenophosphate synthetases 2 (SPS2)); inflammatory cytokines (Interleukin 2 (IL-2), IL-4, IL-6, IL-12ß, IL-17, and Interferon-γ (IFN-γ)); and apoptosis-related genes (B-cell lymphoma-2 (Bcl-2), tumor protein 53 (p53), Bcl-2 Associated X (Bax), Cytochrome c (Cyt c), and Caspase-3) were identified. An inflammatory reaction and apoptosis were induced in chicken brainstems after exposure to Pb. Se alleviated the abnormal expression of HSPs, selenoproteins, inflammatory cytokines, and apoptosis in brainstem tissues of chickens treated with Pb. The results indicated that HSPs, selenoproteins, inflammatory, and apoptosis were involved in Se-resisted Pb poisoning. Overall, Se had resistance effect against Pb poisoning, and can be act as an antidote for Pb poisoning in animals.


Assuntos
Selênio , Humanos , Animais , Selênio/farmacologia , Galinhas/metabolismo , Citocinas/genética , Chumbo , Selenoproteínas/genética , Selenoproteínas/metabolismo , Proteínas de Choque Térmico/genética , Proteínas Proto-Oncogênicas c-bcl-2
12.
Arthroscopy ; 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38735417

RESUMO

PURPOSE: To evaluate whether the modified suture-button Latarjet procedure with coracoacromial ligament (CAL) and pectoralis minor (PM) preservation could achieve excellent outcomes at the 2-year follow-up. METHODS: During January 2019 to January 2021, the data of patients who underwent modified suture-button Latarjet with CAL and PM preservation in our department were collected. The glenoid bone loss of these patients was greater than 20% or greater than 10% with high demands for exercise. Partial coracoid osteotomy was based on the results of a preoperative 3-dimensional computed tomography evaluation of the glenoid defect area and corresponding coracoid process morphology. The preoperative and postoperative clinical results were assessed. The minimal clinically important difference (MCID) was used to compare improvement in clinical outcomes. Graft-glenoid union and remodeling were assessed using postoperative 3-dimensional computed tomography, and magnetic resonance imaging was performed to confirm the integrity of the CAL and PM postoperatively. RESULTS: In total, 35 patients were included in this study; the mean follow-up time was 26.9 ± 1.9 months. No case of recurrent dislocation or sublaxity. Significant improvements were observed in mean visual analog scale (VAS) scores for pain during motion, American Shoulder and Elbow Surgeons (ASES) score, Rowe score, and Walch-Duplay score (P < .001). The percentage of patients achieving at least an MCID improvement in clinical outcomes was VAS 85.71%, ASES 97.14%, Rowe 100%, and Walch-Duplay 97.14%. Thirty-three patients (94.3% of all cases) were able to return to their preoperative sport levels, 34 grafts (97.1%) achieved bone union (1 soft union) in 6.3 ± 2.2 months, and the coracoid grafts restored 97.1 ± 4.0% of the perfect-fitting circle at the last follow-up. Postoperative computed tomography scan showed that 31 grafts (88.6%) were placed ideally in vertical view. In the axial view, 25 grafts (82.9%) were flushed to the glenoid, whereas 1 and 5 grafts were fixed medially and laterally, respectively. The CAL and PM were visualized postoperatively. No arthropathy was observed in any patient at the last follow-up. CONCLUSIONS: The modified suture-button Latarjet procedure with CAL and PM preservation obtained good clinical and radiological results without recurrence or complications. A substantial number of patients (>85%) achieved the MCID for the VAS, ASES, Rowe, and Walch-Duplay scores. In addition, the malpositioned graft (17.1%) did not cause arthropathy of the joints at 2-year follow-up. LEVEL OF EVIDENCE: Level IV, retrospective case series.

13.
Antimicrob Agents Chemother ; 67(7): e0026223, 2023 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-37358468

RESUMO

Nanoparticle-based antibiotic delivery systems are essential in combating antibiotic-resistant bacterial infections arising from acquired resistance and/or biofilm formation. Here, we report that the ceftazidime-decorated gold nanoparticles (CAZ_Au NPs) can effectively kill clinical ceftazidime-avibactam-resistant Enterobacteriaceae with various resistance mechanisms. Further study of underlying antibacterial mechanisms suggests that CAZ_Au NPs can damage the bacterial cell membrane and increase the level of intracellular reactive oxygen species. Moreover, CAZ_Au NPs show great potential in inhibiting biofilm formation and eradicating mature biofilms via crystal violet and scanning electron microscope assays. In addition, CAZ_Au NPs demonstrate excellent performance in improving the survival rate in the mouse model of abdominal infection. In addition, CAZ_Au NPs show no significant toxicity at bactericidal concentrations in the cell viability assay. Thus, this strategy provides a simple way to drastically improve the potency of ceftazidime as an antibiotic and its use in further biomedical applications.


Assuntos
Ceftazidima , Nanopartículas Metálicas , Animais , Camundongos , Ceftazidima/farmacologia , Enterobacteriaceae , Ouro , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Compostos Azabicíclicos/farmacologia , Combinação de Medicamentos
14.
Am J Gastroenterol ; 118(3): 465-474, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36002919

RESUMO

INTRODUCTION: Congenital hypertrophic pyloric stenosis (CHPS), the most common infantile disease requiring surgical intervention, is routinely treated with open or laparoscopic pyloromyotomy. Recently, gastric peroral endoscopic pyloromyotomy (G-POEM) has been used for adult gastroparesis. We aimed to evaluate the efficacy and safety of G-POEM in treating infantile CHPS. METHODS: We reviewed data from 21 G-POEM-treated patients at 3 tertiary children's endoscopic centers in China between January 2019 and December 2020. Clinical characteristics, procedure-related parameters, perioperative management, and follow-up outcomes were summarized. RESULTS: G-POEM was performed successfully in all patients. The median operative duration was 49 (14-150) minutes. The submucosal tunnels were successfully established along the greater curvature of the stomach in 19 cases, and 2 cases were switched to the lesser curvature because of difficulty. No perioperative major adverse events occurred. Minor adverse events included inconsequential mucosal injury in 5 cases and unsatisfactory closure of the mucosal incision in 1 case. Upper gastrointestinal contrast radiography in all patients showed smooth passage of the contrast agent through the pylorus on postoperative day 3. The growth curves of the patients reached normal levels 3 months after the procedure. No recurrent clinical symptoms occurred in any patient during the median follow-up period of 25.5 (14-36) months. DISCUSSION: G-POEM is feasible, safe, and effective for infants with CHPS, with satisfactory clinical responses over a short-term follow-up. Further multicenter studies should be performed to compare the long-term outcomes of this minimally invasive technique with open or laparoscopic pyloromyotomy.


Assuntos
Acalasia Esofágica , Gastroparesia , Estenose Pilórica Hipertrófica , Piloromiotomia , Adulto , Criança , Humanos , Lactente , Piloromiotomia/métodos , Estenose Pilórica Hipertrófica/cirurgia , Estenose Pilórica Hipertrófica/complicações , Acalasia Esofágica/cirurgia , Resultado do Tratamento , Esfíncter Esofágico Inferior , Piloro/cirurgia , Gastroparesia/diagnóstico
15.
Eur Radiol ; 33(6): 4280-4291, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36525088

RESUMO

OBJECTIVES: Differentiation between COVID-19 and community-acquired pneumonia (CAP) in computed tomography (CT) is a task that can be performed by human radiologists and artificial intelligence (AI). The present study aims to (1) develop an AI algorithm for differentiating COVID-19 from CAP and (2) evaluate its performance. (3) Evaluate the benefit of using the AI result as assistance for radiological diagnosis and the impact on relevant parameters such as accuracy of the diagnosis, diagnostic time, and confidence. METHODS: We included n = 1591 multicenter, multivendor chest CT scans and divided them into AI training and validation datasets to develop an AI algorithm (n = 991 CT scans; n = 462 COVID-19, and n = 529 CAP) from three centers in China. An independent Chinese and German test dataset of n = 600 CT scans from six centers (COVID-19 / CAP; n = 300 each) was used to test the performance of eight blinded radiologists and the AI algorithm. A subtest dataset (180 CT scans; n = 90 each) was used to evaluate the radiologists' performance without and with AI assistance to quantify changes in diagnostic accuracy, reporting time, and diagnostic confidence. RESULTS: The diagnostic accuracy of the AI algorithm in the Chinese-German test dataset was 76.5%. Without AI assistance, the eight radiologists' diagnostic accuracy was 79.1% and increased with AI assistance to 81.5%, going along with significantly shorter decision times and higher confidence scores. CONCLUSION: This large multicenter study demonstrates that AI assistance in CT-based differentiation of COVID-19 and CAP increases radiological performance with higher accuracy and specificity, faster diagnostic time, and improved diagnostic confidence. KEY POINTS: • AI can help radiologists to get higher diagnostic accuracy, make faster decisions, and improve diagnostic confidence. • The China-German multicenter study demonstrates the advantages of a human-machine interaction using AI in clinical radiology for diagnostic differentiation between COVID-19 and CAP in CT scans.


Assuntos
COVID-19 , Infecções Comunitárias Adquiridas , Aprendizado Profundo , Pneumonia , Humanos , Inteligência Artificial , SARS-CoV-2 , Tomografia Computadorizada por Raios X/métodos , Teste para COVID-19
16.
Soft Matter ; 19(30): 5781-5794, 2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37469310

RESUMO

This study aims to experimentally and theoretically investigate the roles of a threaded nozzle and yield stress in the coaxial air blast atomization of a gelled jet by means of rheological tests and high-speed flow visualization techniques. Similar to the breakup types of Newtonian fluids, a gelled jet will gradually exhibit an oscillation mode, membrane-type breakup, fiber-type breakup and a superpulsating submode as the airflow velocity increases. The transition conditions for each type are determined and plotted in the dimensionless map of We-Oh. For the jet spray angle, the maximum occurs when We = 600 and is clearly enlarged by the gas-side thread in the nozzle. The numerical results of the linear stability analysis indicate that a smaller dominant unstable growth rate is acquired by swelling the yield stress, while the higher dominant unstable growth rate and truncated wavenumber appear as the rotational airflow is acquired through the gas-side threaded nozzle.

17.
Fish Shellfish Immunol ; 139: 108866, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37277049

RESUMO

Pyroptosis is a newly discovered programmed cell death pathway that plays an essential role in the host's defense against pathogenic infections. This process is orchestrated by inflammasomes, which are intricate multiprotein complexes that orchestrate the activation of caspase and instigate the liberation of proinflammatory cytokines. Additionally, gasdermin family proteins execute their role by forming pores in the cell membrane, ultimately leading to cell lysis. In recent years, pyroptosis has emerged as a promising target for disease management in fish, particularly in the context of infectious diseases. In this review, we provide an overview of the current understanding regarding the role of pyroptosis in fish, focusing on its involvement in host-pathogen interactions and its potential as a therapeutic target. We also highlighted the latest advancements in the field development of pyroptosis inhibitors and their potential applications in fish disease management. Subsequently, we deliberate on the obstacles and future prospects for pyroptosis research in fish, emphasizing the necessity of conducting more comprehensive investigations to unravel the intricate regulatory mechanisms governing this process across diverse fish species and environmental contexts. Finally, this review will also highlight the current limitations and future perspectives of pyroptosis research in aquaculture.


Assuntos
Apoptose , Piroptose , Animais , Inflamassomos , Caspases/metabolismo , Gerenciamento Clínico
18.
Fish Shellfish Immunol ; 139: 108885, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37290612

RESUMO

Liver fibrosis is a pathological process whereby the liver is subjected to various acute and chronic injuries, resulting in the activation of hepatic stellate cells (HSCs), an imbalance of extracellular matrix generation and degradation, and deposition in the liver. This review article summarizes the current understanding of liver fibrosis in fish research. Liver fibrosis is a common pathological condition that occurs in fish raised in aquaculture. It is often associated with poor water quality, stressful conditions, and the presence of pathogens. The review describes the pathophysiology of liver fibrosis in fish, including the roles of various cells and molecules involved in the development and progression of the disease. The review also covers the various methods used to diagnose and assess the severity of liver fibrosis in fish, including histological analysis, biochemical markers, and imaging techniques. In addition, the article discusses the current treatment options for liver fibrosis in fish, including dietary interventions, pharmaceuticals, and probiotics. This review highlights the need for more in-depth research in this area to better understand the mechanisms by which liver fibrosis in fish occurs and to develop effective prevention and treatment strategies. Finally, improved management practices and the development of new treatments will be critical to the sustainability of aquaculture and the health of farmed fish.


Assuntos
Transdução de Sinais , Drogas Veterinárias , Animais , Transdução de Sinais/fisiologia , Drogas Veterinárias/metabolismo , Cirrose Hepática/veterinária , Cirrose Hepática/patologia , Fígado/metabolismo , Matriz Extracelular , Fibrose
19.
Methods ; 198: 3-10, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34562584

RESUMO

The coronavirus disease 2019 (COVID-19) has outbreak since early December 2019, and COVID-19 has caused over 100 million cases and 2 million deaths around the world. After one year of the COVID-19 outbreak, there is no certain and approve medicine against it. Drug repositioning has become one line of scientific research that is being pursued to develop an effective drug. However, due to the lack of COVID-19 data, there is still no specific drug repositioning targeting the COVID-19. In this paper, we propose a framework for COVID-19 drug repositioning. This framework has several advantages that can be exploited: one is that a local graph aggregating representation is used across a heterogeneous network to address the data sparsity problem; another is the multi-hop neighbors of the heterogeneous graph are aggregated to recall as many COVID-19 potential drugs as possible. Our experimental results show that our COVDR framework performs significantly better than baseline methods, and the docking simulation verifies that our three potential drugs have the ability to against COVID-19 disease.


Assuntos
COVID-19 , Preparações Farmacêuticas , Antivirais , Reposicionamento de Medicamentos , Humanos , Simulação de Acoplamento Molecular , SARS-CoV-2
20.
Mol Biol Rep ; 50(6): 4865-4873, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37052804

RESUMO

BACKGROUND: The naturally colored brown cotton fiber is the most widely used environmentally friendly textile material, which primarily contains proanthocyanidins and their derivatives. Many structural genes in the flavonoid synthesis pathway are known to improve the genetic resources of naturally colored cotton. Among them, DFR is a crucial late enzyme to synthesis both anthocyanins and proanthocyanidins in the plant flavonoid pathway. METHODS: The protein sequences of GhDFRs were analyzed using bioinformatic tools. The expression levels of GhDFRs in various tissues and organs of upland cotton Zongxu1 (ZX1), were analyzed by quantitative real-time PCR, and the expression pattern of GhDFR1 during fiber development of white cotton and brown cotton was analyzed further. The function of GhDFR1 in NCC ZX1 was preliminarily analyzed by virus induced gene silencing (VIGS) technology. RESULTS: Bioinformatic analysis revealed that GhDFRs sequences in upland cotton genome were extremely conserved. Furthermore, evolutionary tree analysis revealed that the functions of GhDFR1 and GhDFR2, and GhDFR3 and GhDFR4, presented different and shared some similarities. Our study showed GhDFR1 and GhDFR2 were specifically expressed in fibers, while GhDFR3 and GhDFR4 were specifically expressed in petals. GhDFR1 was exclusively expressed in brown cotton fiber at various stages of development and progressively increased with the growth of fiber, but the trend of expression in white cotton was quite the opposite. We silenced GhDFR1 expression in brown cotton fiber using VIGS technology, and observed the VIGS-interference plants. After reducing the expression level of GhDFR1, the period for significant GhDFR1 expression in the developing fibers changed, reducing the content of anthocyanins, and lightening the color of mature cotton fibers. CONCLUSION: GhDFR1 was preferentially expressed in brown cotton during fiber development. The timing of GhDFR1 expression for flavonoid synthesis altered, resulting in anthocyanin contents reduced and the fiber color of the GhDFR1i lines lightened. These findings showed the role of GhDFR1 in fiber coloration of NCC and provided a new candidate for NCC genetic improvement.


Assuntos
Flavonoides , Proantocianidinas , Flavonoides/genética , Antocianinas/metabolismo , Proantocianidinas/metabolismo , Proteínas de Plantas/metabolismo , Fibra de Algodão , Clonagem Molecular , Gossypium/genética , Gossypium/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Perfilação da Expressão Gênica/métodos
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