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1.
Biotechnol Bioeng ; 119(3): 743-761, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34936091

RESUMO

For drug products manufactured in mammalian cells, safety assurance practices are needed during production to assure that the final medicinal product is safe from the potential risk of viral contamination. Virus filters provide viral retention for a range of viruses through robust, largely size-based retention mechanism. Therefore, a virus filtration step is commonly utilized in a well-designed recombinant therapeutic protein purification process and is a key component in an overall strategy to minimize the risks of adventitious and endogenous viral particles during the manufacturing of biotechnology products. This study summarizes the history of virus filtration, currently available virus filters and prefilters, and virus filtration integrity test methods and study models. There is also discussion of current understanding and gaps with an eye toward future trends and emerging filtration technologies.


Assuntos
Vírus , Animais , Biotecnologia/métodos , Contaminação de Medicamentos/prevenção & controle , Filtração , Mamíferos , Vírion
2.
Vet Med Sci ; 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35920114

RESUMO

OBJECTIVE: Delayed cardiac tamponade, a life-threatening complication of pericardial effusion in humans, has rarely been described in large animal models. We report here a pig with cardiac tamponade that developed 29 days after cardiac surgery. STUDY DESIGN: Case report. ANIMALS: One 45-kg domestic pig. METHODS: Open-chest surgery was performed on a pig to induce chronic heart failure. At 15 days after surgery, the pig's breathing appeared laboured; induced heart failure was considered the cause. Routine heart failure medications were administered. RESULTS: On day 28, the pig's status deteriorated. On day 29, echocardiography performed just before the pig's death showed a large pericardial effusion, mainly in the lateral and anterior walls of the right heart, with several fibre exudation bands. The right heart was severely compressed with an extremely small right ventricle. An emergency sternotomy was unsuccessful. Pathologic examination showed a severely thickened, fibrous pericardium. The pericardial sac was distended (up to 4.5 cm) and was full of dark brown, soft, friable material. Epicardial haemorrhage with a fresh, organised thrombus was noted in the pericardium. CONCLUSION: Delayed tamponade occurring at least 15 days after open-chest surgery is easy to misdiagnose or overlook in large animal models where attention is often focused on primary pathological model changes. To decrease mortality in animal models, researchers should be aware of potential complications and use the same level of follow-up monitoring of large animals as in clinical care.

3.
Chem Commun (Camb) ; 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35912868

RESUMO

Fungal bifunctional terpene synthases (BFTSs) reportedly associate with a series of new skeletons of di/sesterterpenes. However, the molecular mechanisms underlying the variabilities in the ring system of BFTS-catalyzed products are not well understood. In this study, we identified a key site, S89/L89, that controls the conversion between bicyclic and polycyclic terpene skeletons catalyzed by two BFTSs, BsPS and FoFS. Our analysis revealed that a mutation on site 89 in the BFTSs alters the carbocation transportation pathway and redirects the competing reactions for previously unreported terpenes.

4.
Chem Commun (Camb) ; 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35913073

RESUMO

Sulfonyl fluorides are emerging as key structural motifs in organic synthesis, medicinal chemistry, and materials science. Herein we report two efficient and complementary methods for direct decarboxylative fluorosulfonylation of carboxylic acids by the merging of copper catalysis with different N-centered HAT regents. A wide range of structurally diverse sulfonyl fluorides was readily accessed from primary, secondary, and tertiary carboxylic acids in a single step under mild conditions.

5.
Sci Total Environ ; : 157860, 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35934025

RESUMO

BACKGROUND: Short-term exposure to ambient air pollution has been linked to an increased risk of mortality from a variety of causes, but its effects on mortality from dementia remain largely unknown. OBJECTIVES: To investigate the association between short-term exposure to ambient air pollution and dementia mortality, and quantitatively assess the excess mortality. METHODS: In this time-stratified case-crossover study, 47,108 dementia deaths were identified in Jiangsu province, China during 2015-2019. Exposure to particulate matter with an aerodynamic diameter ≤ 2.5 µm (PM2.5), PM10, sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) was assessed by extracting daily concentrations from a validated grid dataset based on each subject's residential address. Conditional logistic regression models were applied for exposure-response analyses. RESULTS: There were 47,108 case days and 159,852 control days during the study period. Each 10 µg/m3 increase of lag 04-day exposure to PM2.5, PM10, and NO2 was significantly associated with a 1.43 % (95 % CI: 0.77, 2.09 %), 1.06 % (0.59, 1.54 %), and 2.80 % (1.51, 4.10 %) increase in odds of dementia mortality, corresponding to an excess mortality of 4.87 %, 5.50 %, and 6.43 %, respectively. We estimated that reducing ambient air pollutant exposures to the WHO air quality guidelines would avoid up to 4.17 % of the dementia deaths, while the ambient air quality standards in China would only help avoid up to 0.39 %. CONCLUSIONS: This study provides consistent evidence that short-term exposure to PM2.5, PM10, and NO2 is associated with increased risk of dementia mortality, which can be translated to a considerable excess mortality. Our findings highlight a potential approach to prevent deaths from dementia by reducing individual exposures to ambient air pollution, especially in areas with high levels of ambient air pollution.

6.
Comput Math Methods Med ; 2022: 9547166, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35936378

RESUMO

Objective: This study is aimed at analyzing the factors affecting the recurrence patterns and recurrence-free survival (RFS) of high-grade gliomas (HGG). Methods: Eligible patients admitted to the Affiliated Hospital of Xuzhou Medical University were selected. Subsequently, the effects of some clinical data including age, gender, WHO pathological grades, tumor site, tumor size, clinical treatments, and peritumoral edema (PTE) area and molecular markers (Ki-67, MGMT, IDH-1, and p53) on HGG patients' recurrence patterns and RFS were analyzed. Results: A total number of 77 patients were enrolled into this study. After analyzing all the cases, it was determined that tumor size and tumor site had a significant influence on the recurrent patterns of HGG, and PTE was an independent predict factor of recurrence patterns. Specifically, when the PTE was mild (<1 cm), the recurrence pattern tended to be local; in contrast, HGG was more likely to progress to marginal recurrence and distant recurrence. Furthermore, age and PTE were significantly associated with RFS; the median RFS of the population with PTE < 1 cm (23.60 months) was obviously longer than the population with PTE ≥ 1 cm (5.00 months). Conclusions: PTE is an independent predictor of recurrence patterns and RFS for HGG. Therefore, preoperative identification of PTE in HGG patients is crucially important, which is helpful to accurately estimate the recurrence pattern and RFS.


Assuntos
Neoplasias Encefálicas , Glioma , Neoplasias Encefálicas/patologia , Edema , Glioma/patologia , Humanos
7.
Front Oncol ; 12: 880305, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35936720

RESUMO

Chondrosarcoma is a malignant bone tumor with a low incidence rate. Accurate risk evaluation is crucial for chondrosarcoma treatment. Due to the limited reliability of existing predictive models, we intended to develop a credible predictor for clinical chondrosarcoma based on the Surveillance, Epidemiology, and End Results data and four Chinese medical institutes. Three algorithms (Best Subset Regression, Univariate and Cox regression, and Least Absolute Shrinkage and Selector Operator) were used for the joint training. A nomogram predictor including eight variables-age, sex, grade, T, N, M, surgery, and chemotherapy-is constructed. The predictor provides good performance in discrimination and calibration, with area under the curve ≥0.8 in the receiver operating characteristic curves of both internal and external validations. The predictor especially had very good clinical utility in terms of net benefit to patients at the 3- and 5-year points in both North America and China. A convenient web calculator based on the prediction model is available at https://drwenle029.shinyapps.io/CHSSapp, which is free and open to all clinicians.

8.
Ann Surg Oncol ; 2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-35933542

RESUMO

BACKGROUND: The present study was conducted to evaluate the clinical, pathological response, and prognosis characteristics of human epidermal growth factor receptor 2 (HER2)-low breast cancer in the neoadjuvant chemotherapy setting. METHODS: Patients with HER2-negative breast cancer who received neoadjuvant chemotherapy from January 2017 to December 2019 were retrospectively analyzed. HER2-negative breast cancer was divided into two groups: HER2-zero (defined as immunohistochemistry [IHC] 0) and HER2-low (defined as IHC 1+, or IHC 2+ and fluorescence in-situ hybridization-negative. RESULTS: Overall, 314 patients with HER2-negative breast cancer were analyzed. The proportion of HER2-low patients with hormone receptor (HR)-positive disease was higher than in triple-negative breast cancer (TNBC; 75.3% vs. 63.2%, p = 0.032). In HR-positive breast cancer, HER2-low tumors presented less nodal involvement (p = 0.023) and earlier clinical stage (p = 0.015) compared with HER2-zero tumors; however, in TNBC, HER2-low patients had a later clinical stage (p = 0.028). With the pathological complete response (pCR) defined as ypTis/0ypN0, there was no difference in pCR rates among the entire cohort, HR-positive disease, and TNBC. However, with the pCR defined as ypT0ypN0, the pCR rate in HER2-low breast cancer was significantly lower than HER2-zero breast cancer in the entire cohort (24.3% vs. 36.4%, p = 0.032) and the HR-positive subgroup (18.7% vs. 32.1%, p = 0.035), but not for TNBC. Multivariate analysis demonstrated that HER2 status (low vs. zero) was an independent predictive factor for pCR (p = 0.013) in HR-positive breast cancer. There were no statistically significant differences in 3-year disease-free survival and overall survival between HER2-low and HER2-zero breast cancer among the entire cohort, HR-positive disease, and TNBC. CONCLUSIONS: HER2-low breast cancer exhibits specific clinical features and different response to treatment associated with HR status in the neoadjuvant chemotherapy setting.

9.
Adv Mater ; : e2204458, 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35950226

RESUMO

Phase instability (especially phase transition) is one of the major obstacles to the wide application of formamidinium (FA)-dominated perovskite solar cells (PSCs). An in-depth investigation on relevant phase transition kinetics is urgently needed to explore more effective phase stabilization strategies. Herein for the first time, we monitored the reversible phase transition process of FA1- x Csx PbI3 perovskite between photoactive phase (α phase) and non-photoactive phase (δ phase) under humidity, as well as the reversible healing of the degraded devices. Moreover, through in-situ atomic force microscope (AFM) characterization, the kinetic transition between α and δ phase was revealed to be the "nucleation-growth transition" process. Density functional theory (DFT) calculation was employed to analyze the thermodynamic origin of phase transition, where the driving force for α-to-δ transition was associated with configurational enthalpy, while the δ-to-α transition was dominated by the temperature-related vibrational entropy. The α phase of FA1- x Csx PbI3 could be finally stabilized at elevated temperature (e.g., 60°C) under high humidity due to the increased nucleation barrier, and the resulting non-encapsulated PSCs retained over 90% of their initial efficiency after aging at 60°C and 60% relative humidity (RH) for 1000 hours. Our finding provided a deepened understanding on the phase transition process of FA1- x Csx PbI3 from both thermodynamics and kinetics points of view, which also presented an effective means to stabilize the α phase of FA-dominated perovskites and devices for practical applications. This article is protected by copyright. All rights reserved.

10.
Aging (Albany NY) ; 14(undefined)2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35951361

RESUMO

The E3 ligase SIAH1 is deregulated in human cancers and correlated with poor prognosis, but its contributions to chemoresistance in epithelial ovarian cancer (EOC) are not evident. Herein we found that SIAH1 was decreased in EOC tumour tissues and cell lines and negatively correlated with the RPS3 levels. SIAH1 overexpression suppressed tumour cell growth, colony formation, invasion, metastasis, and cisplatin resistance in vivo and in vitro. SIAH1 promoted RPS3 ubiquitination and degradation using the RING-finger domain, and these steps were required for RPS3 localization to the cytoplasm, which led to subsequent NF-κB inactivation and thereby conferred chemosensitivity. Moreover, ectopic expression of RPS3 or depletion of RPS3 ubiquitination mediated by SIAH1 via the K214R mutant significantly impaired cisplatin-induced tumour suppression in cells stably expressing SIAH1. Together, our findings reveal a tumour suppressor function of SIAH1 and provide evidence showing that the SIAH1-RPS3-NF-κB axis may act as an appealing strategy for tackling treatment resistance in EOC.

11.
Eye Vis (Lond) ; 9(1): 30, 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35941698

RESUMO

BACKGROUND: To explore the changes in blood supply and structure around the optic nerve head (ONH) in thyroid-associated ophthalmopathy (TAO) patients with suspected dysthyroid optic neuropathy (DON). METHODS: TAO patients [19 with DON; 24 non-DON (NDON); 20 with equivocal DON (EDON)], and 34 control subjects were examined. Optical coherence tomography angiography (OCTA) was used to obtain peripapillary retinal nerve fiber layer (p-RNFL) and vessel density parameters, including the ONH whole image vessel density (ONH-wiVD) and the radial peripapillary capillary vessel density (RPC-VD) in early DON. RESULTS: Although there were no differences in p-RNFL thickness among the groups, there were differences in the ONH-wiVD of each grid section and the RPC-VD in all areas (P < 0.01). Compared with healthy controls, the EDON eyes had significantly lower RPC-VDs in all aeras (P < 0.05).The peripapillary region was further divided into eight sectors, and the RPC-VD in the temporal upper, superior temporal, and temporal lower sectors in the EDON group were significantly lower than in the controls. The visual impairment was closely related to the loss of peripapillary capillary vessel density. Univariate correlation analysis showed that the ONH-wiVD and RPC-VD of the TAO groups were negatively correlated with the intraocular pressure (r = - 0.296, P = 0.006; r = - 0.258, P = 0.016 respectively). CONCLUSIONS: EDON patients had significantly lower ONH-wiVD and RPC-VD than control subjects, and the temporal and upper VDs were more likely to be affected in the early stage of TAO. The combined use of spectral domain optical coherence tomography and OCTA technologies offer a new method for early diagnosis of suspected DON patients.

12.
Int J Surg ; : 106781, 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35963576

RESUMO

BACKGROUND: Due to the high technical requirements of laparoscopic radical gastrectomy (LRG), establishing an effective training system to promote clinical technology and operation specifications is necessary. We aimed to evaluate the effect of a national advanced training program for LRG (ATP-LRG). MATERIALS AND METHODS: The contents of the training include the following: 1) detailed technique descriptions; 2) prevention and solving of intraoperative complications; 3) live surgery performance; 4) theory and practice of clinical research; 5) comments on trainees' videos; and 6) questions, answers, and discussions. This retrospective before and after study surveyed 875 trainees from January 2015 to October 2020. Endpoints were general surgical skills (GSS), laparoscopic gastrectomy acceptance (LGA), and clinical research possibilities (CRP). The analysis took place in December 2021. RESULTS: The response rate was 70.5% (617/875). ATP-LRG reportedly had a positive impact on the LRG practice of 99.5% (614/617) of trainees. Their GSS (before vs. after: 16.5 ±â€¯3.7 vs. 20.3 ±â€¯3.1, P < 0.001), LGA (4.2 ±â€¯0.9 vs. 4.6 ±â€¯0.7, P < 0.001), and CRP (2.6 ±â€¯1.2 vs. 3.2 ±â€¯1.1, P < 0.001) significantly improved. The improvement in GSS for those with professional titles of associate chief surgeons and below was significantly higher than that for chief surgeons (4.0 ±â€¯3.0 vs 3.3 ±â€¯2.4, P = 0.017), while those of LGA and CRP were not. The annual number of operations before training was negatively correlated with improvement in GSS (P < 0.001, Pearson's correlation coefficient: 0.14). Multivariate logistic regression showed that those with professional titles of associate chief surgeons and below (odds ratio [OR]: 1.719, 95% confidence interval [CI]: 1.038-2.846, P = 0.035), and with annual number of operations before training being <60, (OR: 5.257, 95% CI: 2.573-10.742, P < 0.001) were most prone to high-GSS improvement. CONCLUSION: The nationwide ATP-LRG facilitates the improvement of trainees' GSS, LGA, and CRP levels. Surgeons with lower professional titles and fewer performed operations are most likely to improve their GSS through training.

13.
BMC Anesthesiol ; 22(1): 244, 2022 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-35918638

RESUMO

BACKGROUND: The analgesic effects of erector spinae plane block in general anesthesia for cesarean section and recovery from puerperae remain unclear. METHODS: Sixty patients with contraindications for spinal anesthesia who required general anesthesia for cesarean section were enrolled and randomly divided into the erector spinal plane block (ESPB) combined with the general anesthesia group (group E) and general anesthesia group (group G). Group E received bilateral ESPB (20 ml of 0.25% ropivacaine on each side) under ultrasound guidance 30 min before general anesthesia. The primary outcomes were the number of patient-controlled intravenous analgesia (PCIA) boluses, and Bruggemann comfort scale (BCS) scores at 2 h, 6 h, 12 h, and 24 h after operation. The second outcome was intraoperative anesthesia dosage, fetal delivery time, puerperae emergence time, visual analog scale (VAS) at 2 h, 6 h, 12 h, and 24 h after operation, and incidence of nausea and vomiting. Heart rate (HR) and mean arterial pressure (MAP) were recorded 10 min before the start of anesthesia (T0), at the induction of anesthesia (T1), at skin incision (T2), and fetal delivery (T3), and immediately after surgery (T4). RESULTS: The number of PCIA boluses was lower in group E than in group G (P < 0.001). The BCS score increased at 2 h and 6 h after the operation in group E (P < 0.05), while the VAS score significantly decreased in group E at the same time (P < 0.05). Compared with group G, the doses of propofol and remifentanil were significantly decreased in group E (P < 0.001), the emergence time of puerperae was shortened (P = 0.003), and the incidence of nausea and vomiting was significantly decreased (P = 0.014). CONCLUSION: Ultrasound-guided ESPB applied to general anesthesia for a cesarean section can significantly reduce the required dose of general anesthetic drugs, shorten the recovery time of the puerperae, and improve postoperative analgesia. TRIAL REGISTRATION: www. CLINICALTRIALS: gov under the number ChiCTR2200056337 (04-02-2022).


Assuntos
Bloqueio Nervoso , Analgésicos/uso terapêutico , Anestesia Geral/efeitos adversos , Cesárea/efeitos adversos , Feminino , Humanos , Náusea/complicações , Bloqueio Nervoso/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Gravidez , Ultrassonografia de Intervenção , Vômito
14.
Front Oncol ; 12: 892171, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35924169

RESUMO

Purpose: The aim of this study was to propose and evaluate a novel three-dimensional (3D) V-Net and two-dimensional (2D) U-Net mixed (VUMix-Net) architecture for a fully automatic and accurate gross tumor volume (GTV) in esophageal cancer (EC)-delineated contours. Methods: We collected the computed tomography (CT) scans of 215 EC patients. 3D V-Net, 2D U-Net, and VUMix-Net were developed and further applied simultaneously to delineate GTVs. The Dice similarity coefficient (DSC) and 95th-percentile Hausdorff distance (95HD) were used as quantitative metrics to evaluate the performance of the three models in ECs from different segments. The CT data of 20 patients were randomly selected as the ground truth (GT) masks, and the corresponding delineation results were generated by artificial intelligence (AI). Score differences between the two groups (GT versus AI) and the evaluation consistency were compared. Results: In all patients, there was a significant difference in the 2D DSCs from U-Net, V-Net, and VUMix-Net (p=0.01). In addition, VUMix-Net showed achieved better 3D-DSC and 95HD values. There was a significant difference among the 3D-DSC (mean ± STD) and 95HD values for upper-, middle-, and lower-segment EC (p<0.001), and the middle EC values were the best. In middle-segment EC, VUMix-Net achieved the highest 2D-DSC values (p<0.001) and lowest 95HD values (p=0.044). Conclusion: The new model (VUMix-Net) showed certain advantages in delineating the GTVs of EC. Additionally, it can generate the GTVs of EC that meet clinical requirements and have the same quality as human-generated contours. The system demonstrated the best performance for the ECs of the middle segment.

15.
Front Microbiol ; 13: 929202, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910614

RESUMO

In contrast to dog-associated human rabies cases decline year by year due to the rabies vaccination coverage rates increase in China, ferret badger (FB, Melogale moschata)-associated human rabies cases emerged in the 1990s, and are now an increasingly recognized problem in southeast China. To investigate epidemiology, temporal evolution dynamics, transmission characterization, and pathogenicity of FB-associated rabies viruses (RABVs), from 2008 to 2018, we collected 3,622 FB brain samples in Jiangxi and Zhejiang Province, and detected 112 RABV isolates. Four FB-related lineages were identified by phylogenetic analysis (lineages A-D), the estimated Times to Most Recent Common Ancestor were 1941, 1990, 1937, and 1997 for lineages A-D, respectively. Furthermore, although no FB-associated human rabies case has been reported there apart from Wuyuan area, FB-RABV isolates are mainly distributed in Jiangxi Province. Pathogenicity of FB-RABVs was assessed using peripheral inoculation in mice and in beagles with masseter muscles, mortality-rates ranging from 20 to 100% in mice and 0 to 20% in beagles in the groups infected with the various isolates. Screening of sera from humans with FB bites and no post-exposure prophylaxis to rabies revealed that five of nine were positive for neutralizing antibodies of RABV. All the results above indicated that FB-RABV variants caused a lesser pathogenicity in mice, beagles, and even humans. Vaccination in mice suggests that inactivated vaccine or recombinant subunit vaccine products can be used to control FB-associated rabies, however, oral vaccines for stray dogs and wildlife need to be developed and licensed in China urgently.

16.
Ecotoxicol Environ Saf ; 242: 113931, 2022 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-35914398

RESUMO

AIMS: To study the association between short-term exposure to air pollutants and mortality of Chronic Ischemic Heart Disease (CIHD). METHODS: Using a case-crossover design, we investigated 148,443 CIHD deaths from 2015 to 2020 in Jiangsu Province, China. Exposure to six ambient pollutants, including PM10, PM2.5, NO2, CO, SO2, and O3, was assessed by extracting daily concentrations from validated 10 km × 10 km pollutant grids at each subject's residential address. A conditional logistic regression approach was used to explore the exposure-response relationship with adjustment for temperature and relative humidity. We calculated the Population Attributable Fractions (PAFs) and the attributable deaths number of CIHD. RESULTS: An increase of 10 µg/m3 in PM10 and PM2.5 exposure was associated with a 1.16% (95% CI: 0.85-1.48%) and 1.80% (1.36-2.24%) increase in CIHD mortality, respectively. A threshold value of 123 µg/m3 was identified for the association between O3 exposure and CIHD mortality. Controlling for PM2.5, each increase of 10 µg/m3 in O3 (>threshold) was statistically significantly associated with a 0.94% (0.19-1.71%) increase in CIHD mortality, however there was no association between NO2, SO2, CO exposure and CIHD mortality. Reducing PM2.5, PM10 and O3 to the WHO air quality guidelines would prevent 6.16% (95% CI: 4.70-7.58%), 4.30% (3.18-5.43%) and 1.29% (0.48-4.20%) of CIHD deaths, respectively. During the warm season, mortality and PAFs of CIHD associated with PM2.5, PM10, and O3 were significantly higher. CONCLUSIONS: Short-term exposure to ambient PM2.5, PM10, and O3 might trigger deaths from CIHD. These findings indicate that the premature deaths of CIHD patients can be alleviated by reducing exposure to polluted air.

17.
Front Cell Infect Microbiol ; 12: 956311, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35959378

RESUMO

Tuberculosis caused by Mycobacterium tuberculosis (MTB) is an ancient chronic infectious disease and is still the leading cause of death worldwide due to a single infectious disease. MTB can achieve immune escape by interacting with host cells through its special cell structure and secreting a variety of effector proteins. Innate immunity-related pattern recognition receptors (PPR receptors) play a key role in the regulation of signaling pathways. In this review, we focus on the latest research progress on related signal transduction molecules in the interaction between MTB and the host. In addition, we provide new research ideas for the development of new anti-tuberculosis drug targets and lead compounds and provide an overview of information useful for approaching future tuberculosis host-oriented treatment research approaches and strategies, which has crucial scientific guiding significance and research value.

18.
Plant Pathol J ; 38(4): 287-295, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35953048

RESUMO

Citrus tristeza virus (CTV) is efficiently transmitted in a semi-persistent manner by the brown citrus aphid (Toxoptera citricida (Kirkaldy)). Currently, the most sensitive method for detecting plant viruses in insect vectors is reverse-transcription quantitative polymerase chain reaction (RT-qPCR). In this study, the elongation factor-1 alpha (EF-1α) gene and acidic p0 ribosomal protein (RPAP0) gene were confirmed to be suitable reference genes for RT-qPCR normalization in viruliferous T. citricida aphids using the geNorm, NormFinder, and BestKeeper tools. Then the relative CTV titer in aphids (T. citricida) at different post-acquisition feeding times on healthy plants was quantified by RT-qPCR using EF-1α and RPAP0 as reference genes. The relative CTV titer retained in the aphids gradually decreased with increasing feeding time. During the first 0.5 h of feeding time on healthy plants, the remaining CTV titer in aphids showed about 80% rapid loss for the highly transmissible isolate CT11A and 40% loss for the poorly transmissible isolate CTLJ. The relative CTV titer in aphids during more than 12 h post-acquisition times for CT11A was significantly lower than at the other feeding times, which is similar to the trend found for CTLJ. To our knowledge, this is the first report about the relative titer variation of CTV remaining in T. citricida at different post-acquisition feeding times on healthy plants.

19.
Int Urol Nephrol ; 2022 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-35960478

RESUMO

BACKGROUND: Acute kidney injury (AKI) is a severe complication of sepsis, and is strongly correlated with MicroRNAs (miRNAs). However, the mechanism of miR-22 on sepsis-induced AKI is not clearly understood. The study aimed to explore the role and mechanism of miR-22 on AKI. METHODS: The AKI models were established by cecal ligation and puncture (CLP) surgery in SD rats and lipopolysaccharide (LPS) induction in HBZY-1 cells. In AKI rats, the content of serum creatinine (SCr) and blood urea nitrogen (BUN) were detected. Kidney tissues were pathologically examined by H&E and PAS staining. The LPS-induced HBZY-1 cells were transfected with mimics miR-22, si-HMGB1, or oe-HMGB1. miR-22 and HMGB1 expression was detected in vivo and in vitro. In transfected cells, HMGB1/TLR4/NF-κB pathway-related protein expressions were measured by Western blot. The relationship between miR-22 and HMGB1 was assessed by a dual-luciferase gene report. Inflammatory cytokine levels in serum and cells were assessed by ELISA. RESULTS: In AKI rats, kidney injury was observed, accompanied by the down-regulated miR-122 expression and up-regulated HMBG1 expression. The dual-luciferase report found miR-22-3p could targetly regulate HMBG1. Furthermore, both in vitro and in vivo experiments revealed that the releases of inflammatory cytokine were increased after AKI modeling, but the situation was reversed by mimics miR-22 or si-HMGB1 in vitro. In HBZY-1 cells, mimics miR-22 could suppress LPS-induced overexpression of HMGB1/TLR4/NF-κB signaling pathway-related proteins. However, the oe-HMGB1 addition reversed the effect of mimics miR-22. CONCLUSION: miR-22 can inhibit the inflammatory response, target the HMGB1, and inhibit the HMGB1/TLR4/NF-kB pathway, to attenuate the sepsis-induced AKI, which indicates that miR-22 may serve as a potential treatment target in sepsis-induced AKI.

20.
Artigo em Inglês | MEDLINE | ID: mdl-35802237

RESUMO

Monascus species are the producers of Monascus azaphilone pigments (MonAzPs) and lipid-lowering component Monacolin K, which have been widely used as food colorant and health products. In this study, silent information regulator 2 (Sir2) homolog (MrSir2) was characterized, and its impacts on the development and MonAzPs production of Monascus ruber were evaluated. Enzyme activity test in vitro showed that MrSir2 was an NAD+-dependent histone deacetylase. Compared to WT, Δmrsir2 strain accumulated more acetylated lysine residues of histone H3 subunit during its vegetative growth phase, and it exhibited accelerated mycelial aging, more spores, increased resistance to oxidative stress, and more MonAzPs production. RNA-Seq-based transcriptome analysis revealed that MrSir2 mainly regulated the gene expression in macromolecular metabolism such as carbohydrates, proteins, and nucleotides, as well as genes encoding cell wall synthesis and cell membrane component, indicating that MrSir2 probably facilitates the metabolic transition from the primary growth phase to the mycelial aging. Taken together, MrSir2 mainly targets H3 subunit at the vegetative growth phase and affects the development of M. ruber and MonAzPs production.

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