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1.
Emerg Microbes Infect ; : 2356149, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38747061

RESUMO

Lassa virus (LASV), a risk-group 4 pathogen, must be handled in biosafety level-4 (BSL-4) conditions, thereby limiting its research and antiviral development. Here, we developed a novel LASV reverse genetics system which, to our knowledge, is the first to study the complete LASV life cycle under BSL-2 conditions. Viral particles can be produced efficiently when LASV minigenomic RNA harboring minimal viral cis-elements and reporter genes is transfected into a helper cell line stably expressing viral NP, GP, Z and L proteins. The resulting defective virions, named LASVmg, can propagate only in the helper cell line, providing a BSL-2 model to study the complete LASV life cycle. Using this model, we found that a previously reported cellular receptor α-dystroglycan is dispensable for LASVmg infection. Furthermore, we showed that ribavirin can inhibit LASVmg infection by inducing viral mutations. This new BSL-2 system should facilitate studying the LASV life cycle and screening antivirals.

2.
Int J Biol Sci ; 20(7): 2476-2490, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38725863

RESUMO

Peristaltic movements in gut are essential to propel ingested materials through the gastrointestinal tract. Intestinal resident macrophages play an important role in this physiological function through protecting enteric neurons. However, it is incompletely clear how individuals maintain the homeostasis of gut motility. Here we found that NLRP3 is a critical factor in controlling loss of muscularis resident macrophages (MMs), and demonstrate that MMs are involved in the homeostasis of excitatory neurons such as choline acetyltransferase (ChAT)+ and vesicular glutamate transporter 2 (VGLUT2)+ but not inhibitory neuronal nitric oxide synthase (nNOS)+ neurons. NLRP3 knockout (KO) mice had enhanced gut motility and increased neurons, especially excitatory ChAT+ and VGLUT2+ neurons. Single cell analyses showed that there had increased resident macrophages, especially MMs in NLRP3 KO mice. The MM proportion in the resident macrophages was markedly higher than those in wild-type (WT) or caspase 1/11 KO mice. Deletion of the MMs and transplantation of the NLRP3 KO bone marrow cells showed that survival of the gut excitatory ChAT+ and VGLUT2+ neurons was dependent on the MMs. Gut microbiota metabolites ß-hydroxybutyrate (BHB) could promote gut motility through protecting MMs from pyroptosis. Thus, our data suggest that MMs regulated by NLRP3 maintain the homeostasis of excitatory neurons.


Assuntos
Homeostase , Macrófagos , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR , Neurônios , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Camundongos , Macrófagos/metabolismo , Neurônios/metabolismo , Camundongos Endogâmicos C57BL , Masculino , Colina O-Acetiltransferase/metabolismo , Colina O-Acetiltransferase/genética , Motilidade Gastrointestinal/fisiologia , Microbioma Gastrointestinal/fisiologia
3.
Adv Mater ; : e2403038, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724029

RESUMO

Perovskite solar cells (PSCs) are developed rapidly in efficiency and stability in recent years, which can compete with silicon solar cells. However, an important obstacle to the commercialization of PSCs is the toxicity of lead ions (Pb2+) from water-soluble perovskites. The entry of free Pb2+ into organisms can cause severe harm to humans, such as blood lead poisoning, organ failure, etc. Therefore, this work reports a "lead isolation-capture" dual detoxification strategy with calcium disodium edetate (EDTA Na-Ca), which can inhibit lead leakage from PSCs under extreme conditions. More importantly, leaked lead exists in a nontoxic aggregation state chelated by EDTA. For the first time, in vivo experiments are conducted in mice to systematically prove that this material has a significant inhibitory effect on the toxicity of perovskites. In addition, this strategy can further enhance device performance, enabling the optimized devices to achieve an impressive power conversion efficiency (PCE) of 25.19%. This innovative strategy is a major breakthrough in the research on the prevention of lead toxicity in PSCs.

4.
Reprod Biol ; 24(2): 100881, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38772286

RESUMO

Infertility poses a global health and social challenge, affecting approximately 15% of couples at childbearing age, with half of the cases attributed to male factors, wherein genetic factors exert a substantial role. In our prior investigation, we identified loss-of-function variants within the gene encoding glutamine-rich protein 2 (QRICH2) in two consanguineous families, leading to various morphological abnormalities in sperm flagella and male infertility. Moreover, our observations in Qrich2 knockout mice revealed a pronounced reduction in spermatozoa count. However, the underlying mechanism remains elusive, prompting further investigation in the current study. By conducting experiments such as Hematoxylin-eosin (HE) staining, immunofluorescence staining, flow cytometry, and single sperm metabolism analysis on the testes and spermatozoa of Qrich2 knockout mice, we found a strong antioxidant capacity mediated by QRICH2 both in vivo and in vitro. Qrich2 knockout led to elevated levels of ROS, consequently inducing DNA damage in spermatids, which in turn triggered increased autophagy and apoptosis, ultimately causing a significant decrease in spermatozoa count. Incubation with the N-terminal purified protein of QRICH2 exhibited potent strong antioxidant activity at the cell and spermatozoa levels in vitro, thereby enhancing spermatozoa viability and motility. Therefore, QRICH2 plays a crucial role in safeguarding spermatids from excessive ROS-induced damage by augmenting antioxidant capacity, thereby promoting spermatozoa survival and improving motility. Furthermore, the N-terminal purified protein of QRICH2 shows promise as an additive for protecting spermatozoa during preservation and cryopreservation.

5.
Angew Chem Int Ed Engl ; : e202407733, 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38735859

RESUMO

The variability of CO2 hydrogenation reaction demands new potential strategies to regulate the fine structure of the catalysts for optimizing the reaction pathways. Herein, we report a dual-site strategy to boost the catalytic efficiency of CO2-to-methanol (MA) conversion. A new descriptor, τ, was initially established for screening the promising candidates with low-temperature activation capability of CO2, and sequentially a high-performance catalyst was fabricated centred with oxophilic Mo single atoms, who was further decorated with Pt nanoparticles. In CO2 hydrogenation, the obtained dual-site catalysts possess a remarkably-improved MA generation rate (0.27 mmol gcat.-1 h-1). For comparison, the singe-site Mo and Pt-based catalysts can only produce ethanol (EA) and formate acid (FA) at a relatively low reaction rate (0.11 mmol gcat.-1 h-1 for EA and 0.034 mmol gcat.-1 h-1 for FA), respectively. Mechanism studies indicate that the introduction of Pt species could create an active hydrogen-rich environment, leading to the alterations of the adsorption configuration and conversion pathways of the *OCH2 intermediates on Mo sites. As a result, the catalytic selectivity was successfully switched.

6.
Theranostics ; 14(7): 2757-2776, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38773982

RESUMO

Background: Cancer cells are capable of evading clearance by macrophages through overexpression of anti-phagocytic surface proteins known as "don't eat me" signals. Monoclonal antibodies that antagonize the "don't-eat-me" signaling in macrophages and tumor cells by targeting phagocytic checkpoints have shown therapeutic promises in several cancer types. However, studies on the responses to these drugs have revealed the existence of other unknown "don't eat me" signals. Moreover, identification of key molecules and interactions regulating macrophage phagocytosis is required for tumor therapy. Methods: CRISPR screen was used to identify genes that impede macrophage phagocytosis. To explore the function of Vtn and C1qbp in phagocytosis, knockdown and subsequent functional experiments were conducted. Flow cytometry were performed to explore the phagocytosis rate, polarization of macrophage, and immune microenvironment of mouse tumor. To explore the underlying molecular mechanisms, RNA sequencing, immunoprecipitation, mass spectrometry, and immunofluorescence were conducted. Then, in vivo experiments in mouse models were conducted to explore the probability of Vtn knockdown combined with anti-CD47 therapy in breast cancer. Single-cell sequencing data from the Gene Expression Omnibus from The Cancer Genome Atlas database were analyzed. Results: We performed a genome-wide CRISPR screen to identify genes that impede macrophage phagocytosis, followed by analysis of cell-to-cell interaction databases. We identified a ligand-receptor pair of Vitronectin (Vtn) and complement C1Q binding protein (C1qbp) in tumor cells or macrophages, respectively. We demonstrated tumor cell-secreted Vtn interacts with C1qbp localized on the cell surface of tumor-associated macrophages, inhibiting phagocytosis of tumor cells and shifting macrophages towards the M2-like subtype in the tumor microenvironment. Mechanistically, the Vtn-C1qbp axis facilitated FcγRIIIA/CD16-induced Shp1 recruitment, which reduced the phosphorylation of Syk. Furthermore, the combination of Vtn knockdown and anti-CD47 antibody effectively enhanced phagocytosis and infiltration of macrophages, resulting in a reduction of tumor growth in vivo. Conclusions: This work has revealed that the Vtn-C1qbp axis is a new anti-phagocytic signal in tumors, and targeting Vtn and its interaction with C1qbp may sensitize cancer to immunotherapy, providing a new molecular target for the treatment of triple-negative breast cancer.


Assuntos
Antígeno CD47 , Macrófagos , Fagocitose , Animais , Camundongos , Humanos , Macrófagos/metabolismo , Macrófagos/imunologia , Antígeno CD47/metabolismo , Antígeno CD47/genética , Feminino , Linhagem Celular Tumoral , Microambiente Tumoral/imunologia , Microambiente Tumoral/efeitos dos fármacos , Comunicação Celular , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/imunologia , Neoplasias da Mama/genética , Transdução de Sinais/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Proteínas de Transporte , Proteínas Mitocondriais
7.
J Alzheimers Dis ; 99(2): 739-752, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38701142

RESUMO

Background: Early detection of Alzheimer's disease (AD) is a key component for the success of the recently approved lecanemab and aducanumab. Patients with neuroinflammation-related conditions are associated with a higher risk for developing AD. Objective: Investigate the incidence of AD among patients with neuroinflammation-related conditions including epilepsy, hemorrhage stroke, multiple sclerosis (MS), and traumatic brain injury (TBI). Methods: We used Optum's de-identified Clinformatics Data Mart Database (CDM). We derived covariate-matched cohorts including patients with neuroinflammation-related conditions and controls without the corresponding condition. The matched cohorts were: 1) patients with epilepsy and controls (N = 67,825 matched pairs); 2) patients with hemorrhage stroke and controls (N = 81,510 matched pairs); 3) patients with MS and controls (N = 9,853 matched pairs); and 4) patients TBI and controls (N = 104,637 matched pairs). We used the Cox model to investigate the associations between neuroinflammation-related conditions and AD. Results: We identified that epilepsy, hemorrhage stroke, and TBI were associated with increased risks of AD in both males and females (hazard ratios [HRs]≥1.74, p < 0.001), as well as in gender- and race-conscious subpopulations (HRs≥1.64, p < 0.001). We identified that MS was associated with increased risks of AD in both males and females (HRs≥1.47, p≤0.004), while gender- and race-conscious subgroup analysis shown mixed associations. Conclusions: Patients with epilepsy, hemorrhage stroke, MS, and/or TBI are associated with a higher risk of developing AD. More attention on cognitive status should be given to older patients with these conditions.


Assuntos
Doença de Alzheimer , Epilepsia , Humanos , Masculino , Doença de Alzheimer/epidemiologia , Feminino , Estados Unidos/epidemiologia , Idoso , Pessoa de Meia-Idade , Epilepsia/epidemiologia , Esclerose Múltipla/epidemiologia , Lesões Encefálicas Traumáticas/epidemiologia , Lesões Encefálicas Traumáticas/complicações , Doenças Neuroinflamatórias/epidemiologia , Incidência , Acidente Vascular Cerebral Hemorrágico/epidemiologia , Adulto , Idoso de 80 Anos ou mais , Estudos de Coortes , Bases de Dados Factuais , Revisão da Utilização de Seguros
8.
BMC Health Serv Res ; 24(1): 562, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693514

RESUMO

BACKGROUND: This study aimed to examine the reporting quality of existing economic evaluations for negotiated glucose-lowering drugs (GLDs) included in China National Reimbursement Drug List (NRDL) using the Consolidated Health Economic Evaluation Reporting Standards 2013 (CHEERS 2013). METHODS: We performed a systematic literature research through 7 databases to identify published economic evaluations for GLDs included in the China NRDL up to March 2021. Reporting quality of identified studies was assessed by two independent reviewers based on the CHEERS checklist. The Kruskal-Wallis test and Mann-Whitney U test were performed to examine the association between reporting quality and characteristics of the identified studies. RESULTS: We have identified 24 studies, which evaluated six GLDs types. The average score rate of the included studies was 77.41% (SD:13.23%, Range 47.62%-91.67%). Among all the required reporting items, characterizing heterogeneity (score rate = 4.17%) was the least satisfied item. Among six parts of CHEERS, results part scored least at 0.55 (score rate = 54.79%) because of the incompleteness of characterizing uncertainty. Results from the Kruskal-Wallis test and Mann-Whitney U test showed that model choice, journal type, type of economic evaluations, and study perspective were associated with the reporting quality of the studies. CONCLUSIONS: There remains room to improve the reporting quality of economic evaluations for GLDs in NRDL. Checklists such as CHEERS should be widely used to improve the reporting quality of economic researches in China.


Assuntos
Hipoglicemiantes , China , Humanos , Hipoglicemiantes/economia , Hipoglicemiantes/uso terapêutico , Análise Custo-Benefício , Mecanismo de Reembolso/normas , Negociação
9.
Nat Biomed Eng ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714892

RESUMO

Messenger RNA vaccines lack specificity for dendritic cells (DCs)-the most effective cells at antigen presentation. Here we report the design and performance of a DC-targeting virus-like particle pseudotyped with an engineered Sindbis-virus glycoprotein that recognizes a surface protein on DCs, and packaging mRNA encoding for the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or for the glycoproteins B and D of herpes simplex virus 1. Injection of the DC-targeting SARS-CoV-2 mRNA vaccine in the footpad of mice led to substantially higher and durable antigen-specific immunoglobulin-G titres and cellular immune responses than untargeted virus-like particles and lipid-nanoparticle formulations. The vaccines also protected the mice from infection with SARS-CoV-2 or with herpes simplex virus 1. Virus-like particles with preferential uptake by DCs may facilitate the development of potent prophylactic and therapeutic vaccines.

10.
Heliyon ; 10(9): e29911, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38707428

RESUMO

Introduction: Unilateral pulmonary edema (UPE), a life-threatening complication of cardiac surgery, often occurs after prolonged cardiopulmonary bypass and lung collapse, especially in minimally-invasive cardiac surgery (MICS). The present study reported a young patient with severe UPE after the surgery as well as corresponding clinical treatments. In addition to the supportive treatment of extracorporeal membrane oxygenation (ECMO), monitoring changes in cardiopulmonary function and early clinical interventions are crucial. Conclusion: By weighing the beneficial and detrimental effects of the treatment, it calls for early diagnosis and new therapeutic strategies for the complication.

11.
J Dairy Sci ; 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38762108

RESUMO

Udder conformation is directly related to milk yield, cow health, workability, and welfare. Automatic milking systems (AMS, also known as milking robots) have become popular worldwide, and the number of dairy farms adopting these systems have increased considerably over the past years. In each milking visit, AMS record the location of the 4 teats as Cartesian coordinates in a xyz plan, which can then be used to derive udder conformation traits. AMS generate a large amount of per milking visit data for individual cows, which contribute to an accurate assessment of important traits such as udder conformation without the addition of human classifier errors (in subjective scoring systems). Therefore, the primary objectives of this study were to estimate genomic-based genetic parameters for udder conformation traits derived from AMS records in North American Holstein cattle and to assess the genetic correlation between the derived traits for evaluating the feasibility of multi-trait genomic selection for breeding cows that are more suitable for milking in AMS. The Cartesian teat coordinates measured during each milking visit were collected by 36 milking robots in 4,480 Holstein cows from 2017 to 2021, resulting in 5,317,488 records. A total of 4,118 of these Holstein cows were also genotyped for 57,600 single nucleotide polymorphisms. Five udder conformation traits were derived: udder balance (UB, mm), udder depth (UD, mm), front teat distance (FTD, mm), rear teat distance (RTD, mm), and distance front-rear (DFR, mm). In addition, 2 traits directly related to cow productivity in the system were added to the study: daily milk yield (DY) and milk electroconductivity (EC; as an indicator of mastitis). Variance components and genetic parameters for UB, UD, FTD, RTD, DFR, DY, and EC were estimated based on repeatability animal models. The estimates of heritability (±standard error, SE) for UB, UD, FTD, RTD, DFR, DY, and EC were 0.41 ± 0.02, 0.79 ± 0.01, 0.53 ± 0.02, 0.40 ± 0.02, 0.65 ± 0.02, 0.20 ± 0.02, and 0.46 ± 0.02, respectively. The repeatability estimates (±SE) for UB, UD, FTD, RTD, and DFR were 0.82 ± 0.01, 0.93 ± 0.01, 0.87 ± 0.01, 0.83 ± 0.01, and 0.88 ± 0.01, respectively. The strongest genetic correlations were observed between the FTD and RTD (0.54 ± 0.03), UD and DFR (-0.47 ± 0.03), DFR and FTD (0.32 ± 0.03), and UD and FTD (-0.31 ± 0.03). These results suggest that udder conformation traits derived from Cartesian coordinates from AMS are moderately to highly heritable. Furthermore, the moderate genetic correlations between these traits should be considered when developing selection sub-indexes. The most relevant genetic correlations between traits related to cow milk productivity and udder conformation traits were between UD and EC (-0.25 ± 0.03) and between DFR and DY (0.30 ± 0.04), in which both genetic correlations are favorable. These findings will contribute to the design of genomic selection schemes for improving udder conformation in North American Holstein cattle, especially in precision dairy farms.

12.
Angew Chem Int Ed Engl ; : e202316755, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38739420

RESUMO

The hydrazine oxidation-assisted H2 evolution method promises low-input and input-free hydrogen production. However, developing high-performance catalysts for hydrazine oxidation (HzOR) and hydrogen evolution (HER) is challenging. Here, we introduce a bifunctional electrocatalyst α-MoC/N-C/RuNSA, merging ruthenium (Ru) nanoclusters (NCs) and single atoms (SA) into cubic α-MoC nanoparticles-decorated N-doped carbon (α-MoC/N-C) nanowires, through electrodeposition. The composite showcases exceptional activity for both HzOR and HER, requiring -80 mV and -9 mV respectively to reach 10 mA cm-2. Theoretical and experimental insights confirm the importance of two Ru species for bifunctionality: NCs enhance the conductivity, and its coexistence with SA balances the H adsorption for HER and facilitates the initial dehydrogenation during the HzOR. In the overall hydrazine splitting (OHzS) system, α-MoC/N-C/RuNSA excels as both anode and cathode materials, achieving 10 mA cm-2 at just 64 mV. The zinc hydrazine (Zn-Hz) battery assembled with α-MoC/N-C/RuNSA cathode and Zn foil anode can exhibit 96% energy efficiency, as well as temporary separation of hydrogen gas during the discharge process. Therefore, integrating Zn-Hz with OHzS system enables self-powered H2 evolution, even in hydrazine sewage. Overall, the amalgamation of NCs with SA achieves diverse catalytic activities for yielding multifold hydrogen gas through advanced cell-integrated-electrolyzer system.

15.
J Intensive Care Med ; : 8850666241253800, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38748542

RESUMO

Objectives: To investigate the relationship between sublingual microcirculation and the prognosis of sepsis. Data sources: The PubMed, Web of Science, Embase, and China National Knowledge Infrastructure (CNKI) databases were searched to identify studies published from January 2003 to November 2023. Study selection: Clinical studies examining sublingual microcirculation and the prognosis of sepsis were included. Data extraction: Sublingual microcirculation indices included the microvascular blood index (MFI), total vascular density (TVD), perfusion vascular density (PVD), perfusion vascular vessel (PPV), and heterogeneity index (HI). Prognostic outcomes included mortality and severity. Funnel plots and Egger's test were used to detect publication bias. The ability of the small vessel PPV (PPVs) to predict sepsis-related mortality was analyzed based on the summary receiver operating characteristic (SROC) curve, pooled sensitivity, and pooled specificity. Data synthesis: Twenty-five studies involving 1750 subjects were included. The TVD (95% CI 0.11-0.39), PVD (95% CI 0.42-0.88), PPV (95% CI 6.63-13.83), and MFI (95% CI 0.13-0.6) of the survival group were greater than those of the nonsurvival group. The HI in the survival group was lower than that in the nonsurvival group (95% CI -0.49 to -0.03). The TVD (95% CI 0.41-0.83), PVD (95% CI 0.83-1.17), PPV (95% CI 14.49-24.9), and MFI (95% CI 0.25-0.66) of the nonsevere group were greater than those of the severe group. Subgroup analysis revealed no significant difference in TVD between the survival group and the nonsurvival group in the small vessel subgroup. The area under the SROC curve (AUC) was 0.88. Conclusions: Sublingual microcirculation was worse among patients who died and patients with severe sepsis than among patients who survived and patients with nonsevere sepsis. PPV has a good predictive value for the mortality of sepsis patients. This study was recorded in PROSPERO (registration number: CRD42023486349).

16.
World J Clin Oncol ; 15(3): 456-463, 2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38576599

RESUMO

BACKGROUND: SMARCA4 is a component of chromatin remodeling of SWItch/sucrose-nonfermenting (SWI/SNF) complexes and plays an essential role in oncogenesis. SMARCA4-deficient malignancies arising from the gastrointestinal tract are rare and have a poor prognosis. There is no standard treatment for advanced and undifferentiated SMARCA4-deficient duodenal malignancies. Programmed death 1 (PD-1) antibodies, known as immune checkpoint inhibitor antibodies, potentially play a role in treating gastrointestinal tract malignancies. CASE SUMMARY: We present two patients with SMARCA4 deficiency and TP53 gene mutation in advanced undifferentiated carcinomas of the duodenum. For both patients, SMARCA4 deficiency was confirmed by immunohistochemical staining for the BRG1 protein, while TP53 gene mutations were observed via next-generation sequencing. Both patients were administered chemotherapy in combination with an anti-PD-1 antibody. The two patients exhibited completely different responses to treatment and had different prognoses. Case 1 experienced rapid progression after PD-1 infusion and chemotherapy, case 2 experienced a remarkable response after treatment, and the progression-free survival was more than 6 months. CONCLUSION: This study described our clinical and pathological observations of SMARCA4-deficient advanced undifferentiated carcinoma of the duodenum. PD-1 combined with chemotherapy showed a certain efficacy in select patients, providing options for treating these highly malignant tumors. Patients with liver metastases had a worse prognosis than did those with only lymph node metastasis.

17.
RSC Adv ; 14(16): 10953-10961, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38577433

RESUMO

Purine nucleoside ester is one of the derivatives of purine nucleoside, which has antiviral and anticancer activities. In this work, a continuous flow synthesis of purine nucleoside esters catalyzed by lipase TL IM from Thermomyces lanuginosus was successfully achieved. Various parameters including solvent, reaction temperature, reaction time/flow rate and substrate ratio were investigated. The best yields were obtained with a continuous flow microreactor for 35 min at 50 °C with the substrate ratio of 1 : 5 (nucleosides to vinyl esters) in the solvent of tert-amyl alcohol. 12 products were efficiently synthesized with yields of 78-93%. Here we reported for the first time the use of lipase TL IM from Thermomyces lanuginosus in the synthesis of purine nucleoside esters. The significant advantages of this methodology are a green solvent and mild conditions, a simple work-up procedure and the highly reusable biocatalyst. This research provides a new technique for rapid synthesis of anticancer and antiviral nucleoside drugs and is helpful for further screening of drug activity.

18.
World J Hepatol ; 16(3): 465-476, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38577526

RESUMO

BACKGROUND: Although hepatitis B virus infection is the leading cause of chronic liver injury globally, nonalcoholic fatty liver disease (NAFLD) is gradually gaining attention as another major chronic liver disease. The number of patients having chronic hepatitis B (CHB) with concomitant hepatic steatosis has increased. AIM: To analyze the effect of NAFLD on the response to antiviral treatment in patients with CHB. METHODS: Relevant English studies were systematically searched across PubMed, EMBASE, Web of Science, and Cochrane Library until October 2023. Studies in which the treatment outcomes were compared between patients with CHB only and those with CHB and hepatic steatosis were included. RESULTS: Of the 2502 retrieved studies, 11 articles were finally included. Biochemical response until 48 wk (OR = 0.87, 95%CI: 0.50-1.53, P = 0.000) and 96 wk (OR = 0.35, 95%CI: 0.24-0.53, P = 0.24) and virological response until 96 wk (OR = 0.80, 95%CI: 0.43-1.49, P = 0.097) were lower in patients with hepatic steatosis than in patients with CHB alone. CONCLUSION: Hepatic steatosis lowers the biochemical response to antiviral treatment in patients with CHB.

19.
Pediatr Transplant ; 28(3): e14743, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38566336

RESUMO

BACKGROUND: There are scant data on the effect of rituximab on EBV DNA levels and prevention of post-transplant lymphoproliferative disorder (PTLD) in pediatric kidney transplant recipients with EBV DNAemia. METHODS: Kidney transplant recipients with EBV DNAemia treated with rituximab to prevent PTLD between 7/1999 and 7/2019 at five pediatric centers were included. Those with confirmed PTLD at the onset of rituximab were excluded. Primary outcomes included percentage change in EBV DNAemia and occurrence of PTLD post rituximab. RESULTS: Twenty-six pediatric kidney transplant recipients were included. Median age at transplant was 4 years (IQR 2.1-10.3). EBV DNA load monitoring by qPCR was performed at 1-3 month intervals. EBV DNAemia onset occurred at a median of 73 days post-transplant (IQR 52-307), followed by DNAemia peak at a median of 268 days (IQR 112-536). Rituximab was administered at a median of 9 days post peak (IQR 0-118). Rituximab regimens varied; median dose 375 mg/m2 (IQR 375-439) weekly for 1-4 doses per course. Following rituximab, EBV DNA load decreased to <10% of baseline at 120 days in 20/26 patients; however, only 30% achieved complete resolution at last follow-up (median 2094 days post-transplant [IQR 1538-3463]). Two (7%) developed PTLD at 915 and 1713 days post rituximab. All recipients had functioning grafts. One death occurred in a child with PTLD following remission due to unrelated reasons. CONCLUSIONS: In the largest pediatric kidney transplant recipient case series with EBV DNAemia given rituximab to prevent PTLD, rituximab achieved a short-term reduction in DNA load; however, recurrent DNAemia is common.


Assuntos
Infecções por Vírus Epstein-Barr , Transplante de Rim , Transtornos Linfoproliferativos , Nefrologia , Humanos , Criança , Pré-Escolar , Rituximab/uso terapêutico , Herpesvirus Humano 4/genética , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/prevenção & controle , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Transplante de Rim/efeitos adversos , DNA Viral , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/prevenção & controle , Transtornos Linfoproliferativos/tratamento farmacológico , Transplantados , Carga Viral
20.
Artigo em Inglês | MEDLINE | ID: mdl-38570724

RESUMO

PURPOSE: This study analyzes the relationship between human papillomavirus (HPV) infection, vaginal microecology, and cervical lesions to provide a basis for the prevention and treatment of cervical cancer (CC) in the Xinjiang region. METHODS: Real-time quantitative PCR was used for HPV genotyping and viral load. The Gram staining and dry biochemical enzyme kit were utilized to diagnose vaginal secretions. The χ2 test and Logistic regression analysis were used for statistical analysis. RESULTS: The HPV infection rate among women in the Xinjiang region was 30.29%, of which the single HPV infection accounts for 77%. HPV16 and HPV52 were the main infection types. There was significant differences in the HPV infection rate and infection types among the Han, Uighur, Hui, and Kazakh ethnic groups. The viral load of HPV16 and HPV52 increases with the upgrade of cervical lesions. There were significant differences in vaginal microecology evaluation indicators H2O2, SNA, LE, GUS, trichomonas, clue cells, and lactobacilli among different ethnic groups. HPV negative patients with varying grades of cervical lesions exhibit a notable variance in H2O2 and LE, which is statistically significant. Single HPV infection and high viral load HPV significantly increase the risk of CC. CONCLUSIONS: This study indicates that HPV infection and vaginal microecology differ among ethnic groups, which have a strong correlation with the progression of CC, offering guidance on CC screening and interventions in the Xinjiang area.

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