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1.
J Colloid Interface Sci ; 678(Pt B): 221-232, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39243722

RESUMO

Constructing amorphous/crystalline heterophase structure with high porosity is a promising strategy to effectively tailor the physicochemical properties of electrode materials and further improve the electrochemical performance of supercapacitors. Here, the porous C-doped NiO (C-NiO) with amorphous/crystalline heterophase grown on NF was prepared using NF as Ni source via a self-sacrificial template method. Calcining the self-sacrificial NiC2O4 template at a suitable temperature (400 °C) was beneficial to the formation of porous heterophase structure with abundant cavities and cracks, resulting in high electrical conductivity and rich ion/electron-transport channels. The density functional theory (DFT) calculations further verified that in-situ C-doping could modulate the electronic structure and enhance the OH- adsorption capability. The unique porous amorphous/crystalline heterophase structure greatly accelerated electrons/ions transfer and Faradaic reaction kinetic, which effectively improved the charge storage. The C-NiO calcined at 400 °C (C-NiO(400)) displayed a markedly enhanced specific charge, outstanding rate property and excellent cycling stability. Furthermore, the hybrid supercapacitor assembled by C-NiO(400) and active carbon achieved a high energy density of 49.0 Wh kg-1 at 800 W kg-1 and excellent cycle stability (90.9 % retention at 5 A/g after 10 000 cycles). This work provided a new strategy for designing amorphous/crystalline heterophase electrode materials in high-performance energy storage.

2.
Front Oncol ; 14: 1435256, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39252952

RESUMO

Purpose: To explore the plasma proteomic changes of rabbit lung VX2 tumors treated by microwave ablation, and to explore the molecular pathway mechanisms that may be involved. Methods: New Zealand white rabbits were inoculated with VX2 tumor cell suspension in the right lower lung and treated with microwave ablation after 2-3 weeks of tumor formation. Blood was collected at 5 time points (TP1~TP5) before and after ablation by cardiac blood sampling and pre-treated before proteomic analysis. The plasma proteome was analyzed by Data-Independent Acquisition (DIA). Results: Different molecular pathways were activated at different time points:(i) TP1vsTP2: more proteins were down-regulated and enrichment analysis showed that the proteasome pathway was activated. The abnormal protein folding process involved in this pathway is closely related to the process of tumor development. (ii) TP2vsTP3: more proteins were up-regulated although the number of differentially differentiated proteins was lower and enrichment analysis showed that the phagosome pathway was activated. After microwave ablation inactivates tumor cells, it activates the phagosomal pathway for immune clearance of necrotic tumor tissue. (iii) TP3vsTP4: more down-regulated proteins, enrichment analysis showed that cysteine and methionine metabolism pathway was activated. Decreased metabolism of these amino acids suggests that cancer progression may be blocked after microwave ablation therapy. (iv) TP4vsTP5: the number of differential proteins was less and more down-regulated proteins, enrichment analysis showed that glutathione metabolism and metabolism of xenobiotics by cytochrome P450 pathway were activated. The down-regulated proteins in this pathway may suggest that microwave ablation may have reduced resistance to certain chemotherapeutic agents following. Conclusions: In the process of lung cancer treatment by microwave ablation, the changes of proteins on the possible molecular pathways at each time point are related to lung cancer, and not only involve some simple inflammatory reactions, and some of the proteins released by destroying the tumor cells can be used as possible drug binding sites and reduce drug resistance.

3.
Data Brief ; 57: 110930, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39328962

RESUMO

Pythium species are distributed globally, with certain members playing significant roles as plant and animal pathogens. Pythium cedri Chen 4 has been identified as a pathogenic isolate responsible for causing root rot on Cedrus deodara. Here, a comprehensive genome-wide sequence of P. cedri strain Chen 4 utilizing the Illumina NovaSeq sequencing platform and a Pacific Biosciences Sequel sequencing platform is presented. The genome of P. cedri strain Chen 4 was assembled into 150 contigs containing a combined size of 41.25 Mb, N50 value of 1,717,859 bp and N90 value of 431,829 bp. Genome annotation revealed 14,077 protein-encoding genes and 364 of the 1016 predicted proteins were putative effectors. The present work enriches the genetic resources of P. cedri for studying its evolution and can contribute to a better understanding of P. cedri-host interaction.

4.
BMC Infect Dis ; 24(1): 988, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39289626

RESUMO

BACKGROUND: Corynebacterium striatum (C. striatum), a common skin and mucosal colonizer, is increasingly considered as an opportunistic pathogen causing bloodstream infections (BSIs). This study aims to investigate the clinical features and outcomes of C. striatum-BSI. METHODS: We included hospitalized cases with C. striatum-positive blood cultures from January 2014 to June 2022 and classified them into C. striatum-BSI group and contamination group; Clinical characteristics, treatments, and outcomes were compared between the C. striatum-BSI group and contamination group, Methicillin-resistant Staphylococcus aureus (MRSA)-BSI and Methicillin-resistant Staphylococcus epidermidis (MRSE)-BSI. RESULTS: Fifty-three patients with positive C. striatum blood cultures were identified. Among them, 25 patients were classified as C. striatum-BSI, with 21 as contamination cases. And 62 cases of MRSA-BSI and 44 cases of MRSE-BSI were identified. Compared to the contaminated group, the C. striatum-BSI group had a shorter time to positivity of blood cultures (27.0 h vs. 42.5 h, P = 0.011). C. striatum-BSI group had a longer time to positivity (27 h) when compared to both the MRSA (20 h) and MRSE groups (19 h) (p < 0.05). Appropriate therapy within 24 h of BSI onset was significantly lower in the C. striatum group (28%) compared to the MRSA (64.5%) and MRSE (65.9%) groups (p < 0.005). The 28-day mortality was higher in the C. striatum group (52.0%) compared to the MRSA (25.8%) and MRSE (18.2%) groups.  CONCLUSIONS: Given the distinct characteristics of C. striatum-BSI, including a longer time to positivity than other Gram-positive bacteria and higher mortality rates, we suggest prescribing early appropriate antibiotics if C. striatum-BSI is suspected.


Assuntos
Bacteriemia , Infecções por Corynebacterium , Corynebacterium , Staphylococcus aureus Resistente à Meticilina , Humanos , Corynebacterium/isolamento & purificação , Corynebacterium/classificação , Corynebacterium/genética , Masculino , Feminino , Pessoa de Meia-Idade , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções por Corynebacterium/microbiologia , Infecções por Corynebacterium/tratamento farmacológico , Bacteriemia/microbiologia , Bacteriemia/tratamento farmacológico , Bacteriemia/mortalidade , Idoso , Staphylococcus epidermidis/isolamento & purificação , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/mortalidade , Infecções Estafilocócicas/tratamento farmacológico , Adulto , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Estudos Retrospectivos , Idoso de 80 Anos ou mais
5.
BMC Infect Dis ; 24(1): 1015, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39304817

RESUMO

BACKGROUND: Serum (1,3)-ß-D-glucan (BDG) detection for diagnosis of Pneumocystis jirovecii pneumonia (PJP) in non-human immunodeficiency virus (HIV) immunocompromised patients lacks intensive care unit (ICU)-specific data. We aimed to assess its performance and determine the optimal cutoff for PJP in ICU population. METHODS: This retrospective study included critically ill non-HIV immunocompromised patients admitted to a medical ICU with suspected pneumonia, undergoing simultaneous microbiological testing for P. jirovecii on lower respiratory tract specimens and serum BDG. Confounders affecting BDG positivity were explored by multivariable logistic regression. Optimal cut-offs were derived from Youden's index for the entire cohort and subgroups stratified by confounders. Diagnostic performance of serum BDG was estimated at different cutoffs. RESULTS: Of 400 patients included, 42% were diagnosed with PJP and 58.3% had positive serum BDG. Serum BDG's area under the receiver operating characteristic curve was 0.90 (0.87-0.93). At manufacturer's 150 pg/ml cut-off, serum BDG had high sensitivity and negative predictive value (94%), but low specificity and positive predictive value (67%). Confounders associated with a positive serum BDG in PJP diagnosis included IVIG infusion within 3 days (odds ratio [OR] 9.24; 95% confidence interval [CI] 4.09-20.88, p < 0.001), other invasive fungal infections (OR 4.46; 95% CI 2.10-9.49, p < 0.001) and gram-negative bacteremia (OR 29.02; 95% CI 9.03-93.23, p < 0.001). The application of optimal BDG cut-off values determined by Youden's index (252 pg/ml, 390 pg/ml, and 202 pg/ml) specific for all patients and subgroups with or without confounders improved the specificity (79%, 74%, and 88%) and corresponding PPV (75%, 65%, and 85%), while maintaining reasonable sensitivity and NPV. CONCLUSIONS: Tailoring serum BDG cutoff specific to PJP and incorporating consideration of confounders could enhance serum BDG's diagnostic performance in the ICU settings.


Assuntos
Unidades de Terapia Intensiva , Pneumocystis carinii , Pneumonia por Pneumocystis , beta-Glucanas , Humanos , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/sangue , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , beta-Glucanas/sangue , Pneumocystis carinii/isolamento & purificação , Idoso , Hospedeiro Imunocomprometido , Proteoglicanas , Curva ROC , Sensibilidade e Especificidade , Estado Terminal , Adulto
6.
J Am Dent Assoc ; 155(9): 765-773, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39101860

RESUMO

BACKGROUND: The aim of this study was to assess factors associated with higher odds of undergoing repeat general anesthesia (GA2) for dental treatments. METHODS: The authors studied children up to age 48 months of age enrolled in Medicaid who underwent dental treatment under first general anesthesia (GA1). The authors used a case-control design to compare children who had a GA2 within 48 months of GA1 (case patients) with those who did not (control patients). RESULTS: In total, 60 case patients were age and sex matched to 120 control patients. Mean (SD) age at GA1 was 38 (5.2) months for case participants and 40 (4.7) months for control participants (P = .08). Higher caries involvement of maxillary incisors (P = .04), and lower caries involvment of canines (P = .003), first molars (P = .012), and second molars (P < .001) at GA1 was associated with higher odds of occurrence of GA2. There was a significant inverse association between full-coverage restoration on canines (P = .003), first molars (P = .001), and second molars (P = .002) at GA1 and occurrence of GA2. There was a significant direct association between the use of composites or sealants on second molars in GA1 and occurrence of GA2 (P = .02). The number of extractions at GA1 was not associated significantly with the occurrence of GA2. CONCLUSIONS: The use of full-coverage restorations on primary molars and canines under general anesthesia (GA) was associated with lower odds of occurrence of GA2. Resin restorations and sealants on primary second molars were associated with higher odds of occurrence repeat GA. The findings support preferential use of full-coverage restorations for young children undergoing dental GA. PRACTICAL IMPLICATIONS: Full-coverage restorations should be considered strongly for young children undergoing GA for dental treatments to reduce the risk of requiring GA2.


Assuntos
Anestesia Dentária , Anestesia Geral , Cárie Dentária , Restauração Dentária Permanente , Humanos , Estudos de Casos e Controles , Anestesia Geral/estatística & dados numéricos , Masculino , Feminino , Pré-Escolar , Restauração Dentária Permanente/métodos , Restauração Dentária Permanente/estatística & dados numéricos , Anestesia Dentária/métodos , Lactente , Dente Decíduo , Dente Molar , Dente Canino , Estados Unidos , Medicaid , Incisivo , Assistência Odontológica para Crianças/métodos , Fatores de Risco , Resinas Compostas/uso terapêutico
8.
Pediatr Dent ; 46(4): 253-257, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39123322

RESUMO

Purpose: The purpose of this study was to explore the perceived value of clinical photographs for traumatic dental injuries (TDIs). Methods: A survey was sent to members of the American Academy of Pediatric Dentistry (AAPD). The survey collected respondents' responses to case-based questions with and without photographs, and opinions about the value of photography for TDI. Results: A total of 496 respondents (5.8 percent response) completed the survey. Overall, no significant difference in correct answers was observed between cases with and without a photograph (P=0.09). The majority of respondents (82.2 percent) agreed that photographs should be taken for the management of TDIs, with 88.7 percent stating that the photographs aided in the diagnosis of TDIs. The majority of respondents acknowledged the time-saving (80.9 percent) and legal importance (77.0 percent) of photographs. Conclusion: Photographs should be taken in the management of traumatic dental injuries when possible for history and documentation purposes.


Assuntos
Fotografia Dentária , Traumatismos Dentários , Humanos , Traumatismos Dentários/terapia , Criança , Atitude do Pessoal de Saúde , Odontopediatria , Fotografação , Documentação
9.
J Dent Child (Chic) ; 91(2): 60-72, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-39123336

RESUMO

Purpose: To identify pandemic-related behavioral and attitudinal changes in caregivers. Methods: A 38-question cross-sectional survey was developed and distributed to English-speaking caregivers accompanying children for dental care in a hospital dental clinic. The questionnaire surveyed caregiver beliefs and behaviors regarding COVID19, whether the pandemic altered their use of medical and dental care or at-home health habits, as well as their attitudes toward medical and dental teams. Results: The 594 respondents varied in age, marital status, education and income level. Trust was high regarding medical and dental teams, government public health management and mask policies for children. However, those respondents who did not think children should be required to wear masks at school if the health department recommended it and respondents who did not think that government agencies would protect them if another pandemic happened were less likely to change perceptions on dental care, preventive dentistry, sugar intake and toothbrushing (P<0.05). No other strong and consistent relationships were found. Conclusions: In a safety-net dental clinic population, over half of caregivers changed dental behaviors and attitudes following the pandemic. Caregivers cynical of mask mandates and governmental pandemic management were not in the group to change their dental attitudes and behaviors. No other consistent pattern of demographic variables offered a clear profile of group beliefs and behaviors, suggesting the necessity of inquiring individuals and families about their oral health perceptions and behaviors.


Assuntos
COVID-19 , Cuidadores , Humanos , COVID-19/prevenção & controle , Estudos Transversais , Masculino , Feminino , Cuidadores/psicologia , Adulto , Inquéritos e Questionários , Pessoa de Meia-Idade , Conhecimentos, Atitudes e Prática em Saúde , Criança , SARS-CoV-2 , Máscaras , Assistência Odontológica para Crianças/psicologia , Adulto Jovem , Adolescente , Comportamentos Relacionados com a Saúde , Pandemias
10.
Chemistry ; : e202402487, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39177474

RESUMO

A base promoted oxidative [4+2] annulation of pyrrole-2-carbaldehyde derivatives with o-hydroxyphenyl propargylamines for the synthesis of highly substituted indolizines has been developed. Using DBN as base, a broad range of 5,6,7-trisubstituted indolizines have been prepared in good to excellent yields under mild conditions, and many useful functional groups can be tolerated.

11.
Langmuir ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39017586

RESUMO

Silicone rubber has broad applications in the field of industrial engineering due to its stable physical and chemical properties. However, the superhydrophobic properties, of silicone rubber, especially large deformation superhydrophobic properties, were not satisfactory for many harsh application environments and complex engineering structures. Here, we report the preparation of superhydrophobic tensile designable silicone rubber composites by a mixed deposition process that included powder deposition and smoke deposition. The infrared test showed that the deposited powder from silicone rubber combustion was mainly composed of SiO2 and short chain siloxane. The mixed deposited surface with a rich micro-nanostructure, which was the key to the formation of superhydrophobic properties. The water contact angle (WCA) and sliding angle (SA) of coating surface could reach 157.6° and 5° ± 1°, respectively, and the tensile designability of superhydrophobic surface is closely related to the prestretched process. In addition, bounce tests, high temperature tests, and solvent resistance tests showed the application potential of modified silicone rubber composites in the field of engineering.

12.
ANZ J Surg ; 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39051445

RESUMO

BACKGROUND: Isolated splenic abscesses are rare, but increasingly reported with newer organisms and changes in mechanisms involved. We conducted a comparative review of publications from 1900-1977, 1977-1986, 1987-1995, and 1996-2022. METHODS: A systematic search in Embase and PubMed resulted in 522 publications (1111 cases). Data was tabulated, analysed, and compared. RESULTS: Patient demographics and symptoms remain unchanged although more Asian patients were reported. Metastatic infections remain the main cause, but COVID-19-linked and iatrogenic causes post bariatric surgery and splenic artery embolization are increasingly reported. Aerobic organisms remain the commonest (68%), with a variety of exotic organisms reported. Splenectomy remains the definitive treatment, although antibiotics only and percutaneous aspiration/catheter-drainage are increasingly used with reasonable outcomes, with salvage splenectomy for therapeutic failures not having significantly higher mortality than upfront splenectomy. CONCLUSIONS: Isolated splenic abscesses continue to be uncommon, with diagnosis requiring a high degree of suspicion. Non-surgical options for treatment can sometimes be definitive.

13.
Adv Respir Med ; 92(4): 263-277, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39051188

RESUMO

A common life-threatening hereditary disease, Cystic Fibrosis (CF), affects primarily Caucasian infants. High sweat-salt levels are observed as a result of a single autosomal mutation in chromosome 7 that affects the critical function of the cystic fibrosis transmembrane regulator (CFTR). For establishing tailored treatment strategies, it is important to understand the broad range of CFTR mutations and their impacts on disease pathophysiology. This study thoroughly investigates the six main classes of classification of CFTR mutations based on their functional effects. Each class is distinguished by distinct molecular flaws, such as poor protein synthesis, misfolding, gating defects, conduction defects, and decreased CFTR expression at the apical membrane. Furthermore, this paper focuses on the emerging field of CFTR modulators, which intend to restore CFTR function or mitigate its consequences. These modulators, which are characterized by the mode of action and targeted mutation class, have the potential to provide personalized therapy regimens in CF patients. This review provides valuable insights into the genetic basis of CF pathology, and highlights the potential for precision medicine methods in CF therapy by thoroughly investigating CFTR mutation classification and related modulators.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística , Fibrose Cística , Mutação , Humanos , Fibrose Cística/genética , Fibrose Cística/terapia , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Medicina de Precisão/métodos
14.
Org Lett ; 26(27): 5625-5629, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38953484

RESUMO

A palladium-catalyzed cascade carbonylation reaction of 2-bromo-N-(2-iodophenyl)benzamides with benzylidenecyclopropanes for the synthesis of fused isoindolinone derivatives has been developed. A broad range of 6/5/6/6 tetracyclic isoindolinone products were efficiently prepared in moderate to good yields with diverse substitution. Two carbonyl groups were incorporated into the substrates in a single step with the formation of four carbon-carbon bonds and two carbon-heteroatom bonds.

16.
Biomolecules ; 14(6)2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38927096

RESUMO

The relationship between type 2 diabetes mellitus (T2DM) and colorectal cancer (CRC) has long been extensively recognized, but their crosstalk mechanisms based on gene regulation remain elusive. In our study, for the first time, bulk RNA-seq and single-cell RNA-seq data were used to explore the shared molecular mechanisms between T2DM and CRC. Moreover, Connectivity Map and molecular docking were employed to determine potential drugs targeting the candidate targets. Eight genes (EVPL, TACSTD2, SOX4, ETV4, LY6E, MLXIPL, ENTPD3, UGP2) were identified as characteristic comorbidity genes for T2DM and CRC, with EVPL and ENTPD3 further identified as core comorbidity genes. Our results demonstrated that upregulation of EVPL and downregulation of ENTPD3 were intrinsic molecular features throughout T2DM and CRC and were significantly associated with immune responses, immune processes, and abnormal immune landscapes in both diseases. Single-cell analysis highlighted a cancer-associated fibroblast (CAF) subset that specifically expressed ENTPD3 in CRC, which exhibited high heterogeneity and unique tumor-suppressive features that were completely different from classical cancer-promoting CAFs. Furthermore, ENTPD3+ CAFs could notably predict immunotherapy response in CRC, holding promise to be an immunotherapy biomarker at the single-cell level. Finally, we identified that droperidol may be a novel drug simultaneously targeting EVPL and ENTPD3. In conclusion, previous studies have often focused solely on metabolic alterations common to T2DM and CRC. Our study establishes EVPL and ENTPD3 as characteristic molecules and immune biomarkers of comorbidity in T2DM and CRC patients, and emphasizes the importance of considering immunological mechanisms in the co-development of T2DM and CRC.


Assuntos
Neoplasias Colorretais , Diabetes Mellitus Tipo 2 , Análise de Célula Única , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Comorbidade , Regulação Neoplásica da Expressão Gênica , Simulação de Acoplamento Molecular , Masculino
17.
BMC Med Imaging ; 24(1): 154, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902660

RESUMO

BACKGROUND: Acute pancreatitis is one of the most common diseases requiring emergency surgery. Rapid and accurate recognition of acute pancreatitis can help improve clinical outcomes. This study aimed to develop a deep learning-powered diagnostic model for acute pancreatitis. MATERIALS AND METHODS: In this investigation, we enrolled a cohort of 190 patients with acute pancreatitis who were admitted to Sichuan Provincial People's Hospital between January 2020 and December 2021. Abdominal computed tomography (CT) scans were obtained from both patients with acute pancreatitis and healthy individuals. Our model was constructed using two modules: (1) the acute pancreatitis classifier module; (2) the pancreatitis lesion segmentation module. Each model's performance was assessed based on precision, recall rate, F1-score, Area Under the Curve (AUC), loss rate, frequency-weighted accuracy (fwavacc), and Mean Intersection over Union (MIOU). RESULTS: Upon admission, significant variations were observed between patients with mild and severe acute pancreatitis in inflammatory indexes, liver, and kidney function indicators, as well as coagulation parameters. The acute pancreatitis classifier module exhibited commendable diagnostic efficacy, showing an impressive AUC of 0.993 (95%CI: 0.978-0.999) in the test set (comprising healthy examination patients vs. those with acute pancreatitis, P < 0.001) and an AUC of 0.850 (95%CI: 0.790-0.898) in the external validation set (healthy examination patients vs. patients with acute pancreatitis, P < 0.001). Furthermore, the acute pancreatitis lesion segmentation module demonstrated exceptional performance in the validation set. For pancreas segmentation, peripancreatic inflammatory exudation, peripancreatic effusion, and peripancreatic abscess necrosis, the MIOU values were 86.02 (84.52, 87.20), 61.81 (56.25, 64.83), 57.73 (49.90, 68.23), and 66.36 (55.08, 72.12), respectively. These findings underscore the robustness and reliability of the developed models in accurately characterizing and assessing acute pancreatitis. CONCLUSION: The diagnostic model for acute pancreatitis, driven by deep learning, exhibits excellent efficacy in accurately evaluating the severity of the condition. TRIAL REGISTRATION: This is a retrospective study.


Assuntos
Aprendizado Profundo , Pancreatite , Tomografia Computadorizada por Raios X , Humanos , Pancreatite/diagnóstico por imagem , Masculino , Feminino , Tomografia Computadorizada por Raios X/métodos , Pessoa de Meia-Idade , Adulto , Doença Aguda , Idoso , Estudos Retrospectivos
18.
J Org Chem ; 89(12): 9001-9010, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38842478

RESUMO

2,3-Allenamides are an important class of unsaturated group-substituted carbonyl compounds. A palladium-catalyzed aminocarbonylation of propargyl acetates with amines for the synthesized tri-/tetrasubstituted 2,3-allenamides has been developed. A broad range of tri-/tetrasubstituted 2,3-allenamides have been prepared from propargyl acetates in good to excellent yields. The reaction featured mild reaction conditions and good functional group tolerance. The applicability of this methodology was further highlighted by the late-stage modification of several natural products and pharmaceuticals.

19.
Int J Biol Macromol ; 274(Pt 2): 133463, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38944094

RESUMO

The membrane-associated RING-CH 8 protein (MARCH8), a member of the E3 ubiquitin ligase family, has broad-spectrum antiviral activity. However, some viruses hijack MARCH8 to promote virus replication, highlighting its dual role in the viral lifecycle. Most studies on MARCH8 have focused on RNA viruses, leaving its role in DNA viruses largely unexplored. Pseudorabies virus (PRV) is a large DNA virus that poses a potential threat to humans. In this study, we found that MARCH8 inhibited PRV replication at the cell-to-cell fusion stage. Interestingly, our findings proved that MARCH8 blocks gB cleavage by recruiting furin but this activity does not inhibit viral infection in vitro. Furthermore, we confirmed that MARCH8 inhibits cell-to-cell fusion independent of its E3 ubiquitin ligase activity but dependent on the interaction with the cell-to-cell fusion complex (gB, gD, gH, and gL). Finally, we discovered that the distribution of the cell-to-cell fusion complex is significantly altered and trapped within the trans-Golgi network. Overall, our results indicate that human MARCH8 acts as a potent antiviral host factor against PRV via trapping the cell-to-cell fusion complex in the trans-Golgi network.


Assuntos
Fusão Celular , Herpesvirus Suídeo 1 , Ubiquitina-Proteína Ligases , Replicação Viral , Rede trans-Golgi , Animais , Humanos , Linhagem Celular , Herpesvirus Suídeo 1/fisiologia , Rede trans-Golgi/metabolismo , Rede trans-Golgi/virologia , Ubiquitina-Proteína Ligases/metabolismo
20.
Vet Microbiol ; 295: 110164, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38936155

RESUMO

The membrane-associated RING-CH (MARCH) family of proteins are members of the E3 ubiquitin ligase family and are essential for a variety of biological functions. Currently, MARCH proteins are discovered to execute antiviral functions by directly triggering viral protein degradation or blocking the furin cleavage of viral class I fusion proteins. Here, we report a novel antiviral mechanism of MARCH1 and MARCH2 (MARCH1/2) in the replication of Pseudorabies virus (PRV), a member of the Herpesviridae family. We discovered MARCH1/2 restrict PRV replication at the cell-to-cell fusion step. Furthermore, MARCH1/2 block gB cleavage, and this is dependent on their E3 ligase activity. Interestingly, the blocking of gB cleavage by MARCH1/2 does not contribute to their antiviral activity in vitro. We discovered that MARCH1/2 are associated with the cell-to-cell fusion complex of gB, gD, gH, and gL and trap these viral proteins in the trans-Golgi network (TGN) rather than degrading them. Overall, we conclude that MARCH1/2 inhibit PRV by trapping the viral cell-to-cell fusion complex in TGN.


Assuntos
Herpesvirus Suídeo 1 , Ubiquitina-Proteína Ligases , Replicação Viral , Rede trans-Golgi , Herpesvirus Suídeo 1/fisiologia , Animais , Rede trans-Golgi/virologia , Rede trans-Golgi/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Fusão Celular , Suínos , Linhagem Celular , Humanos , Proteínas Virais/metabolismo , Proteínas Virais/genética , Células HEK293 , Pseudorraiva/virologia
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