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2.
Comp Immunol Microbiol Infect Dis ; 109: 102179, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38636297

RESUMO

porcine reproductive and respiratory syndrome (PRRS), caused by porcine reproductive and respiratory syndrome virus (PRRSV) infection, is an important swine infectious disease that causes substantial losses worldwide each year. PRRSV is a positive-sense single-stranded RNA virus that is highly susceptible to mutation and recombination, making vaccine and drug research for the disease extremely difficult. In this study, the binding of PRRSV nsp2 to HSP71 protein was detected by using the IP/MS technique. And the inhibitory effect of HSP71 on nsp2 antagonistic activity was validated by measuring NF-kB luciferase reporter. According to stress from inhibitory effects, the amino acid variation profile of PRRSV nsp2 under HSP71 stress was further analyzed using second-generation sequencing. Surprisingly, the results indicated that HSP71 pressure limits the random mutations of PRRSV nsp2 and maintains the dominant PRRSV strain within the population. Mutant strain showed weaker antagonistic activity and replication capability in cell. These results imply the binding of HSP71 with PRRSV nsp2 may lead to maintain the stability of highly virulent strains of PRRSV.

3.
Vet Sci ; 11(3)2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38535872

RESUMO

Caprine arthritis encephalitis is an infectious disease caused by the caprine arthritis encephalitis virus that infects goats, sheep, and other small ruminants. An outbreak of CAEV could be extremely harmful to the goat farming industry and could cause severe economic losses. We designed specific primers and probes for the gag gene and established a TaqMan real-time quantitative polymerase chain reaction assay. This method's correlation coefficient (R2) was >0.999, and the sensitivity of the assay to the plasmid-carried partial gag gene was approximately 10 copies/µL, 1000 times higher than that of conventional PCR. No specific fluorescence was detected for other sheep viruses. Using this method, we tested 776 asymptomatic sheep blood samples and 4 neurodegenerative sheep brain samples from six farms in eastern China, and the positivity rate was 0.77% (6/780). The gag gene was partially sequenced in the three positive samples and compared with the sequences from other representative strains in GenBank. The results revealed that all three strains belonged to the B1 subtype and were most closely related to the strains from Shanxi and Gansu, previously isolated in China, with their homology ranging from 97.7% to 98.9%. These results suggest that the designed RT-qPCR assay can be used to detect subclinical CAEV in sheep and that the virus is still present in eastern China.

4.
Vector Borne Zoonotic Dis ; 24(4): 245-248, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38441490

RESUMO

Japanese encephalitis virus is mainly prevalent in the tropical and subtropical regions of Asia and Oceania. Through immunoprecipitation-mass spectrometry analysis using monoclonal antibodies targeting JEV E protein, we found that mosquito Histone 2A protein could bind to JEV particles. The binding of H2A and JEV was detected in the salivary gland and supernatant of mosquito cells. Furthermore, RNA interference experiments in vitro and in vivo confirmed that H2A protein promotes JEV infection in mosquitoes. In summary, we found that mosquito H2A is a factor that supports JEV infection and can potentially facilitate cross-species transmission of JEV.


Assuntos
Culex , Culicidae , Vírus da Encefalite Japonesa (Espécie) , Encefalite Japonesa , Animais , Vírus da Encefalite Japonesa (Espécie)/genética , Histonas , Encefalite Japonesa/veterinária , Mosquitos Vetores
5.
ACS Appl Mater Interfaces ; 16(12): 15133-15142, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38488729

RESUMO

Dynamic control of ultralong organic room-temperature phosphorescence (UORTP) is a charming target. Herein, we report a stimuli-responsive phosphorescence unit 7H-indolo[2,3-c]quinoline (NBCz) and its derivatives (PCBNBCz, FSO2NBCz, and N2BCzSO2NBCz) that show photo- and oxygen- synergistically induced afterglow activation and afterglow color change in the PMMA film. PCBNBCz and FSO2NBCz feature a donor-acceptor (D-A) structure, and N2BCzSO2NBCz features acceptor-bridged two different phosphorescence units (NBCz and N2BCz). The photoactivated UORTP of PCBNBCz and FSO2NBCz arises from the photoinduced consumption of oxygen in the PMMA film. It is clear that the phosphorescence unit NBCz contributes to subsequent photoinduced UORTP color change because the NBCz-doped PMMA film shows the same UORTP color change process. ESR and HRMS measurements confirmed that oxidation of NBCz occurs at the nitrogen atom of the quinoline ring via photogenerated superoxide radicals, which results in the UORTP color change. TDDFT calculations proved that after oxidation of NBCz, the T1 energy level declines significantly. Furthermore, photocontrolled selective expression of phosphorescence units is achieved in the case of N2BCzSO2NBCz. After further UV irradiation, oxidation of NBCz happened, and the oxidized form N2BCzSO2NBCz-O emitted the intrinsic orange UORTP of NBCz-O selectively and screened the intrinsic yellowish-green UORTP of N2BCz. Finally, multilevel photolithography can be demonstrated based on the photoactivated UORTP and the photoinduced UORTP color change. This work may give a deep insight into organic phosphorescence and pave a simple way for the development of stimulus-responsive smart UORTP materials.

6.
Nat Commun ; 15(1): 1512, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38374204

RESUMO

This was a single-arm, multicenter phase 2 clinical trial (ChiCTR1900021726) involving advanced squamous non-small cell lung cancer (sq-NSCLC) patients undergoing 2 cycles of nab-paclitaxel/carboplatin and sintilimab (anti-PD-1), followed by sintilimab maintenance therapy. The median progression-free survival (PFS) was 11.4 months (95% CI: 6.7-18.1), which met the pre-specified primary endpoint. Secondary endpoints included objective response rate reaching 70.5% and a disease control rate of 93.2%, with a median duration of response of 13.6 months [95% CI: 7.0-not evaluable (NE)]. The median overall survival was 27.2 months (95% CI: 20.2-NE) with treatment-related adverse events grades ≥3 occurring in 10.9% of patients. Predefined exploratory endpoints comprised relationships between biomarkers and treatment efficacy, and the association between circulating tumor DNA (ctDNA) dynamics and PFS. Biomarker analysis revealed that the breast cancer gene 2, BMP/Retinoic Acid Inducible Neural Specific 3, F-box/WD repeat-containing protein 7, tyrosine-protein kinase KIT and retinoblastoma 1 abnormalities led to shorter PFS, while ctDNA negative at baseline or clearance at 2 cycles of treatment was associated with longer PFS (18.1 vs. 4.3 months). Taken together, sintilimab in combination with 2 cycles of nab-paclitaxel/carboplatin treatment produced encouraging PFS and better tolerability as first-line treatment for advanced sq-NSCLC.


Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/uso terapêutico , Carboplatina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética
7.
Food Chem ; 444: 138695, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38346362

RESUMO

Neonicotinoids (NEOs) are the most widely used insecticides globally. They can contaminate or migrate into foodstuffs and exert severe neonic toxicity on humans. Therefore, lots of feasible analytical methods were developed to assure food safety. Nevertheless, there is a lack of evaluation that the impacts of food attributes on the accurate determination of NEOs. This review aims to provide a comprehensive overview of sample preparation methods regarding 6 categories of plant-derived foodstuffs. Currently, QuEChERS as the common strategy can effectively extract NEOs from plant-derived foodstuffs. Various enrichment technologies were developed for trace levels of NEOs in processed foodstuffs, and multifarious novel sorbents provided more possibility for removing complex matrices to lower matrix effects. Additionally, detection methods based on liquid chromatography were summarized and discussed in this review. Finally, some limitations were summarized and new directions were proposed for better advancement.


Assuntos
Inseticidas , Humanos , Inseticidas/análise , Neonicotinoides/análise , Cromatografia Líquida , Alimentos , Inocuidade dos Alimentos
8.
ACS Macro Lett ; 13(3): 308-314, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38373339

RESUMO

As molecular design and the structure-property relationships of photochemical molecules established in the literature serve as a convenient reference for mechanophore exploration, many typical mechanophores suffer undesired responses to UV light or even sunlight in bulk polymers. We developed a strategy of a poly(methyl acrylate)/polyurethane (PMA/PU) interpenetrating polymer network (IPN) to suppress the photochromic property of the mechanophore and promote its mechanochromic property. A widely used rhodamine mechanophore (Rh-2OH) was first incorporated into polyurethane (P1). Then P1 was swollen in methyl acrylate and photopolymerized to prepare a PMA2.8/PU IPN (P2). Different from photo/force-responsive P1, P2 selectively responded to force because the low free volume in IPN greatly hinders photoisomerization of the rhodamine spirolactam, suggesting that a simple IPN strategy successfully resolves the giant problem of nonselective response to photo/force for photochromic mechanophores. Moreover, PMA/PU IPN enhanced the mechanical property, resulting in a higher mechanochemical activation ratio than PU, and the prestretching effect of PMA/PU IPN promoted the force sensitivity of rhodamine mechanophores significantly. We believe that the strategy can be applied to other mechanophores, promoting their application in more complicated environments.

9.
Viruses ; 16(2)2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38400034

RESUMO

Japanese encephalitis virus (JEV) causes acute encephalitis in humans and is of major public health concern in most Asian regions. Dogs are suitable sentinels for assessing the risk of JEV infection in humans. A neutralization test (NT) or an enzyme-linked immunosorbent assay (ELISA) is used for the serological detection of JEV in dogs; however, these tests have several limitations, and, thus, a more convenient and reliable alternative test is needed. In this study, a colloidal gold immunochromatographic strip (ICS), using a purified recombinant EDIII protein, was established for the serological survey of JEV infection in dogs. The results show that the ICSs could specifically detect JEV antibodies within 10 min without cross-reactions with antibodies against other canine viruses. The test strips could detect anti-JEV in serum with dilution up to 640 times, showing high sensitivity. The coincidence rate with the NT test was higher than 96.6%. Among 586 serum samples from dogs in Shanghai examined using the ICS test, 179 (29.98%) were found to be positive for JEV antibodies, and the high seropositivity of JEV in dogs in China was significantly correlated with the season and living environment. In summary, we developed an accurate and economical ICS for the rapid detection of anti-JEV in dog serum samples with great potential for the surveillance of JEV in dogs.


Assuntos
Vírus da Encefalite Japonesa (Espécie) , Encefalite Japonesa , Cães , Animais , Humanos , Coloide de Ouro , China/epidemiologia , Encefalite Japonesa/diagnóstico , Encefalite Japonesa/veterinária , Encefalite Japonesa/epidemiologia , Ensaio de Imunoadsorção Enzimática/métodos , Anticorpos Antivirais , Proteínas Recombinantes
10.
Micromachines (Basel) ; 15(2)2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38398955

RESUMO

This paper characterizes the sensitivity of a time domain MEMS accelerometer. The sensitivity is defined by the increment in the measured time interval per gravitational acceleration. Two sensitivities exist, and they can be enhanced by decreasing the amplitude and frequency. The sensitivity with minor nonlinearity is chosen to evaluate the time domain sensor. The experimental results of the developed accelerometer demonstrate that the sensitivities span from -68.91 µs/g to -124.96 µs/g and the 1σ noises span from 8.59 mg to 6.2 mg (amplitude of 626 nm: -68.91 µs/g and 10.21 mg; amplitude of 455 nm: -94.51 µs/g and 7.76 mg; amplitude of 342 nm: -124.96 µs/g and 6.23 mg), which indicates the bigger the amplitude, the smaller the sensitivity and the bigger the 1σ noise. The adjustable sensitivity provides a theoretical foundation for range self-adaption, and all the results can be extended to other time domain inertial sensors, e.g., a gyroscope or an inclinometer.

11.
Gene ; 901: 148162, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38224924

RESUMO

Circular RNAs (circRNAs) are a class of stable non-coding RNAs that have emerged as key regulators in human diseases including cancer. This study investigates the role of circRNA_0102913 (circ_0102913) in malignant behavior of colorectal cancer (CRC) cells and the underpinning mechanisms. By analyzing CRC-related GSE197991, GSE159669, and GSE223001 datasets, we obtained circ_0102913 as an aberrantly upregulated circRNA in CRC. Increased circ_0102913 expression was detected in CRC tissues and cells. By querying multiple bioinformatics systems (circBank, Circular RNA Interactome, TargetScan, miRDIP, miRwalk, and miRDB), we identified microRNA-571 (miR-571) as a target of circ_0102913 and Rac family small GTPase 2 (RAC2) mRNA as a target of miR-571. Biotinylated-RNA pull-down and/or luciferase assays showed that circ_0102913 bound to miR-571 to restore the expression of RAC2 mRNA. Circ_0102913 silencing or miR-571 overexpression repressed proliferation, migration and invasion, and in vivo tumorigenesis abilities of CRC cells. However, the malignant properties of cells were restored by RAC2 overexpression. The increased circ_0102913 expression in CRC cells was attributed to increased 5-methylcytosine (m5C) modification levels. Silencing of NOP2/Sun RNA methyltransferase 5 reduced the m5C level and therefore reduced stability and expression of circ_0102913 expression in CRC cells. In conclusion, this study demonstrates that m5C-mediated upregulation of circ_0102913 augments malignant properties of CRC cells through a miR-571/RAC2 axis.


Assuntos
Ataxina-3 , Neoplasias Colorretais , MicroRNAs , RNA Circular , Humanos , 5-Metilcitosina , Proliferação de Células , Neoplasias Colorretais/genética , MicroRNAs/genética , RNA Circular/metabolismo , RNA Mensageiro , Regulação para Cima , Ataxina-3/genética
12.
Thorac Cancer ; 15(5): 419-426, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38219795

RESUMO

Immune checkpoint inhibitor (ICI) rechallenge in non-small cell lung cancer (NSCLC) is a promising therapeutic strategy. The situation for ICI rechallenge can be divided into three categories: adverse events (AEs); resistance to ICIs, and rechallenge becomes compulsive because of tumor relapse while the patients had completed a 2 year course of immunotherapy. However, these categories are still controversial and should be explored further. Through voting at the 6th Straits Summit Forum on Lung Cancer, in this study we summarize the consensus of 147 experts in ICI rechallenges. A total of 97.74% experts agreed to rechallenge; 48.87% experts rechallenge with the original drug, and the others rechallenge with a different drug; 40.3% agreed to rechallenge directly after progression; 88.06% experts agreed to ICI rechallenge with a combination regimen; and factors such as previous performance status score, PD-1 expression, and age should also be considered. Understanding the the clinical studies in ICI rechallenge could bring us one step closer to understanding the consensus. In patients with advanced NSCLC who have suffered recurrent or distant metastasis after immunotherapy, the option of rechallenge with ICIs is a promising treatment option.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Consenso , Imunoterapia
14.
Front Microbiol ; 14: 1302101, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38045034

RESUMO

Japanese encephalitis (JE) is a zoonotic ailment from the Japanese encephalitis virus (JEV). JEV belongs to the flavivirus genus and is categorized into a solitary serotype consisting of five genetically diverse genotypes (I, II, III, IV, and V). The JEV genotype III (GIII) was the prevailing strain responsible for multiple outbreaks in countries endemic to JEV until 1990. In recent years, significant improvements have occurred in the epidemiology of JE, encompassing the geographical expansion of the epidemic zone and the displacement of prevailing genotypes. The dominant genotype of the JEV has undergone a progressive shift from GIII to GI due to variations in its adaptability within avian populations. From 2021 to 2022, Australia encountered an epidemic of viral encephalitis resulting from infection with the GIV JEV pathogen. The current human viral encephalitis caused by GIV JEV is the initial outbreak since its initial discovery in Indonesia during the late 1970s. Furthermore, following a time frame of 50 years, the detection and isolation of GV JEV have been reported in Culex mosquitoes across China and South Korea. Evidence suggests that the prevalence of GIV and GV JEV epidemic regions may be on the rise, posing a significant threat to public safety and the sustainable growth of animal husbandry. The global approach to preventing and managing JE predominantly revolves around utilizing the GIII strain vaccine for vaccination purposes. Nevertheless, research has demonstrated that the antibodies generated by the GIII strain vaccine exhibit limited capacity to neutralize the GI and GV strains. Consequently, these antibodies cannot protect against JEV challenge caused by animal GI and GV strains. The limited cross-protective and neutralizing effects observed between various genotypes may be attributed to the low homology of the E protein with other genotypes. In addition, due to the GIV JEV outbreak in Australia, further experiments are needed to evaluate the protective efficiency of the current GIII based JE vaccine against GIV JEV. The alteration of the prevailing genotype of JEV and the subsequent enlargement of the geographical extent of the epidemic have presented novel obstacles in JE prevention and control. This paper examines the emerging features of the JE epidemic in recent years and the associated problems concerning prevention and control.

15.
bioRxiv ; 2023 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-38105993

RESUMO

Japanese Encephalitis Virus (JEV) NS2B-NS3 is a protein complex composed of NS3 proteases and a NS2B cofactor. The N-terminal protease domain (180 residues) of NS3 (NS3(pro)) interacts directly with a central 40-amino acid hydrophilic domain of NS2B (NS2B(H)) to form an active serine protease. In this study, the recombinant NS2B(H)-NS3(pro) proteases were prepared in E. coli and used to compare the enzymatic activity between genotype I (GI) and III (GIII) NS2B-NS3 proteases. The GI NS2B(H)-NS3(pro) was able to cleave the sites at internal C, NS2A/NS2B, NS2B/NS3 and NS3/NS4A junctions that were identical to the sites proteolytically processed by GIII NS2B(H)-NS3(pro). Analysis of the enzymatic activity of recombinant NS2B(H)-NS3(pro) proteases using a model of fluorogenic peptide substrate revealed that the proteolytical processing activity of GIII NS2B(H)-NS3(pro) was significantly higher than that of GI NS2B(H)-NS3(pro). There were eight amino acid variations between GI and GIII NS2B(H)-NS3(pro), which may be responsible for the difference in enzymatic activities between GI and GIII proteases. Therefore, recombinant mutants were generated by exchanging NS2B(H) and NS3(pro) domains between GI and GIII NS2B(H)-NS3(pro) and subjected to protease activity analysis. Substitution of NS2B(H) significantly altered the protease activities, as compared to the parental NS2B(H)-NS3(pro), suggesting that NS2B(H) played an essential role in regulation of NS3(pro) protease activity. To further identify the amino acids responsible for the difference in protease activities, multiple substitution mutants including the individual and combined mutations at the variant residue 55 and 65 of NS2B(H) were generated and subjected to protease activity analysis. Replacement of NS2B-55 and NS2B-65 of GI to GIII significantly increased the enzymatic activity of GI NS2B(H)-NS3(pro) protease, whereas mutation of NS2B-55 and NS2B-65 of GIII to GI remarkably reduced the enzymatic activity of GIII NS2B(H)-NS3(pro) protease. Overall, these data demonstrated that NS2B-55 and NS2B-65 variations in hydrophilic domain of NS2B co-contributed to the difference in NS2B(H)-NS3(pro) protease activities between GI and GIII. These observations gain an insight into the role of NS2B in regulation of NS3 protease activities, which is useful for understanding the replication of JEV GI and GIII viruses.

16.
ACS Appl Mater Interfaces ; 15(47): 54732-54742, 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-37964465

RESUMO

We successfully tune ultralong organic room-temperature phosphorescence (UORTP) by a simple strategy of precisely modifying nitrogen atoms on Phosphorescence Units, and colorful ultralong phosphorescence can be achieved. We for the first time investigate the structure-function relationship between phosphorescence properties and molecular structures of Phosphorescence Units. With BCz and BCz-1 as comparison, eight new Phosphorescence Units were synthesized by introducing one or two nitrogen atoms to the naphthalene moiety. For all the 10 Phosphorescence Units, their room-temperature ultralong phosphorescence in the PMMA film should be assigned to monomer phosphorescence from intrinsic T1 decay. For Phosphorescence Units series I (BCz, NBCz-1, NBCz-2, NBCz-3, NBCz-4, NBCz-5, and NBCz-6), introducing one nitrogen atom to the naphthalene moiety can significantly affect the phosphorescence properties of Phosphorescence Units, and the effect is quite complicated. For modification on the inner ring, the T1 energy level of NBCz-1 decreases, and the red shift of UORTP occurs while the T1 energy level of NBCz-2 increases and the blue shift of UORTP happens. For modification on the outer ring, no phosphorescence color change is observed for NBCz-3 and NBCz-4, but their phosphorescence lifetimes vary notably due to different intersystem crossing efficiencies; as the modification site approaches the central five-member ring, the T1 energy levels of NBCz-5 and NBCz-6 decrease, and their UORTP red shifts dramatically. For Phosphorescence Units series II (BCz, 2NBCz, BCz-1, and 2NBCz-1), introducing two nitrogen atoms to the outer six-member ring reduces energy level of T1 excitons and leads to incredible red shift of UORTP for BCz and 2NBCz while surprisingly energy levels of T1 excitons rise and UORTP blue shifts for BCz-1 and 2NBCz-1. Under the condition of proper modification sites, it is true that the more the additional nitrogen atoms, the more red-shifted the ultralong phosphorescence. This study may expand our knowledge of organic phosphorescence and lay the foundation for its future applications.

17.
Thorac Cancer ; 14(34): 3421-3429, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37963454

RESUMO

Immune checkpoint inhibitors (PD-1/PD-L1 and CTLA-4 blockade) have revolutionized the treatment landscape in non-small cell lung cancer (NSCLC). Secondary resistance to immunotherapy (IO), which poses a substantial challenge in clinical settings, occurs in several initial responders. Currently, new treatment approaches have been extensively evaluated in investigational studies for these patients to tackle this difficult problem; however, the lack of consistency in clinical definition, uniform criteria for enrollment in clinical trials, and interpretation of results remain significant hurdles to progress. Thus, our expert panel comprehensively synthesized data from current studies to propose a practical clinical definition of secondary resistance to immunotherapy in NSCLC in metastatic and neoadjuvant settings. In addition to patients who received IO alone (including IO-IO combinations), we also generated a definition for patients treated with chemotherapy plus IO. This consensus aimed to provide guidance for clinical trial design and facilitate future discussions with investigators. It should be noted that additional updates in this consensus are required when new data is available.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Imunoterapia/métodos , Terapia Neoadjuvante , Antígeno B7-H1
18.
Front Oncol ; 13: 1248790, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37799470

RESUMO

Purpose-Immunotherapy has revolutionized cancer therapy, becoming the standard of care for various malignancy treatments. Human immunodeficiency virus (HIV) patients, however, are an underserved group with limited access to clinical trials and cancer therapy. This study was to evaluate the safety and efficacy of programmed cell death 1 (PD - 1) inhibitors in patients with advanced cancer and HIV/acquired immunodeficiency syndrome (AIDS). Methods and Materials-We performed a prospective, open-label, nonrandomized, phase 1 single center study. Patients with advanced cancer and HIV/AIDS received the treatment of PD - 1 inhibitors (camrelizumab, 200 mg, administered intravenously every 3 weeks), along with combination antiretroviral therapy (cART) for HIV. Results-Sixteen participants (12 men and 4 women; median age, 46.5 (29 - 78) years) were enrolled; 1 had non - Hodgkin lymphoma (NHL), and 15 had non - AIDS - defining cancers. Safety was observed over 130 cycles of treatment with camrelizumab. Most treatment-emergent adverse events at least possibly attributed to camrelizumab were grade 1 or 2, including reactive cutaneous capillary endothelial proliferation (RCCEP) (9 participants), hearing loss (1 participant), hypophysitis (1 participant). 3 participants experienced hemorrhage due to poor performance status. HIV was controlled in all participants. Best tumor responses included 3 complete response, 5 partial response, 2 stable disease, and 6 progressive disease. The 2 years progression-free survival (PFS) was 67.0% (95% CI: -0.05, 0.00) and overall survival (OS) was 55.3% (95% CI: -0.05, 0.01) for the 16 patients who had received camrelizumab. Conclusions-This study demonstrates that camrelizumab treatment in patients with advanced cancers and HIV/AIDS was feasible and the clinical outcomes were acceptable.

19.
Viruses ; 15(9)2023 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-37766229

RESUMO

Japanese encephalitis (JE), found in pigs, is a serious mosquito-borne zoonotic infectious disease caused by the Japanese encephalitis virus (JEV). JEV is maintained in an enzootic cycle between mosquitoes and amplifying vertebrate hosts, mainly pigs and wading birds. It is transmitted to humans through the bite of an infected mosquito, allowing the pathogen to spread and cause disease epidemics. However, there is little research on JEV genotype variation in mosquitoes and pigs in Fujian province. Previous studies have shown that the main epidemic strain of JEV in Fujian Province is genotype III. In this study, a survey of mosquito species diversity in pig farms and molecular evolutionary analyses of JEV were conducted in Fujian, China, in the summer of 2019. A total of 19,177 mosquitoes were collected at four sites by UV trap. Four genera were identified, of which the Culex tritaeniorhynchus was the most common mosquito species, accounting for 76.4% of the total (14,651/19,177). Anopheles sinensi (19.25%, 3691/19,177) was the second largest species. High mosquito infection rateswere an important factor in the outbreak. The captured mosquito samples were milled and screened with JEV-specific primers. Five viruses were isolated, FJ1901, FJ1902, FJ1903, FJ1904, and FJ1905. Genetic affinity was determined by analyzing the envelope (E) gene variants. The results showed that they are JEV gene type I and most closely related to the strains SH-53 and SD0810. In this study, it was found through genetic evolution analysis that the main epidemic strain of JE in pig farms changed from gene type III to gene type I. Compared with the SH-53 and SD0810 strains, we found no change in key sites related to antigenic activity and neurovirulence of JEV in Fujian JEV and pig mosquito strains, respectively. The results of the study provide basic data for analyzing the genotypic shift of JEV in Fujian Province and support the prevention and control of JEV.

20.
Anal Chem ; 95(40): 14944-14953, 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37772797

RESUMO

The selective recognition of dopamine (DA) over other neurotransmitter analogues is difficult due to the similar molecular structure and chemical reactivity. In this study, substitution-regulated chemical reactivity of the sensing substrate is utilized to explore a novel DA detection probe with satisfying selectivity. As a case study, 3,5-dihydroxybenzoic acid (DHBA, carboxy-substituted resorcinol)-based probes have been explored for selective and ratiometric DA sensing. The carboxy substitution benefits the stabilization of the carbanion intermediate and the azamonardine product, which enhances the reaction kinetics and thermodynamics and subsequently facilitates selective DA recognition over other analogues and interferents. By exploring DHBA emission as the internal reference, ratiometric fluorescence variation is realized, which contributes to sensitive DA analysis. With the combination of logic gate and fluorometric analysis, DA detection in both low and high concentrations can be readily achieved. In addition, the DA analysis in biological samples and the enzymatic transformation of DA analogues in cerebrospinal fluid samples are achieved by the proposed DHBA probe.

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