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1.
J Ethnopharmacol ; 301: 115773, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36191660

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Panacis Quinquefolii Radix (PQR) is often illegally sulfur fumigated to extend shelf life and improve appearance, but existing regulations of detecting SO2 residues do not accurately identify desulfurized sulfur-fumigated PQR (SF-PQR). Although sulfur-containing derivatives (SCDs) have been reported in some sulfur-fumigated herbs, there is a lack of research on the generation mechanisms and toxicity of SCDs. Our previous study reported the nephrotoxicity of SF-PQR, and there is an urgent necessity to illuminate the mechanism of toxicity as well as its association with SCDs. AIM OF THE STUDY: To investigate the transformation pattern of chemical components and SCDs in SF-PQR, and to disclose the linkage between SCDs and SF-PQR nephrotoxicity. MATERIALS AND METHODS: The extracts of PQR (before and after SF) were detected by the UPLC-LTQ-Orbitrap-MS method, and SCDs were screened as quality markers (Q-markers). The composition of sulfur combustion products was examined by ion chromatography to exploit the conversion mechanism of SCDs. After administration of PQR extracts to mice for two weeks, serum was collected for GC-MS-based untargeted metabolomics study to mine for differential metabolites. The upstream genes were traced by network analysis to probe toxicity targets. Molecular docking was used to uncover the interactions between SCDs and the targets. RESULTS: Thirty-three compounds were identified and 11 SCDs of saponins were screened, including four SO3 sulfonation products and five H2SO3 sulfonation products. Metabolomics study showed significant alterations in serum biochemistry of SF-PQR group, with substantial increases in fumarate and 2-heptanone content, and induced disturbances in glycerolipid metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis in mice. Network analysis revealed that the key toxicity targets were DECR1, PLA2G1B, and CAT. Molecular docking indicated that SCDs had stable interaction forces with the above three toxicity targets. CONCLUSION: SF-PQR caused kidney damage by affecting glycerolipid metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis. Eleven SCDs were potential nephrotoxic substances and Q-markers for identifying SF-PQR. This study is the first to systematically elucidate the mechanism of SF-PQR-related nephrotoxicity, providing a robust basis for the construction of new quality control standards and a global prohibition of sulfur fumigation.


Assuntos
Medicamentos de Ervas Chinesas , Triptofano , Camundongos , Animais , Cromatografia Líquida de Alta Pressão/métodos , Simulação de Acoplamento Molecular , Fumigação , Enxofre/toxicidade , Enxofre/química , Metabolômica , Medicamentos de Ervas Chinesas/química , Tirosina , Fenilalanina
2.
Anal Biochem ; 660: 114961, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36341769

RESUMO

Imaging capillary isoelectric focusing (icIEF) technology has been becoming the gold criteria of monitoring monoclonal antibody (mAb) charge heterogeneity that is one of the major product-related variants in recombinant biopharmaceuticals, since the first commercial instrument developed twenty years ago. However, the protein identification in icIEF separation is just based on isoelectric point (pI) measurement of protein. Although high resolution mass spectrometry (HRMS) is currently the most powerful means of qualitative protein analysis, traditional icIEF cannot compatibly be used in conjunction with MS due to the use of less volatile reagents. In addition, protein heterogeneity characterization in depth such as peptide mapping by high performance liquid chromatography (HPLC) requires the focused protein bands to be collected as fractions after the icIEF separation, which is a great challenge in biopharmaceutical discovery. In this work, pembrolizumab was employed as targeting mAb (a highly selective anti-PD-1 humanized mAb), an integrated icIEF platform was developed including analytical profiling, MS coupling and fraction collections for charged variant preparation. Multiple operation modes can be rapidly and flexibly switched just by changing customized capillary separation cartridges without more configurations. Main component, four acidic variants (A1-A4) and three basic variants (B1-B3) were baseline separated then directly detected by icIEF-HRMS online coupling for rapid screening of intact protein heterogeneity where reliable and accurate molecular weight of protein charged variants were obtained. Next, by installing preparative capillary separation cartridge, fractions of major charge variants (A2-3 and B1-2) and main component were collected for following LC-MS peptide mapping characterization. The whole workflow of icIEF-based MS strategy for protein heterogeneity is straight forward, reliable and accurate, which provides a comprehensive and revolutionary technology for protein drug quality control (QC) monitoring, MS coupling for fingerprinting intact protein and HPLC-MS peptide mapping in depth.


Assuntos
Anticorpos Monoclonais , Produtos Biológicos , Focalização Isoelétrica , Espectrometria de Massas , Mapeamento de Peptídeos , Controle de Qualidade
3.
Nucleic Acids Res ; 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36318246

RESUMO

CRAMdb (a database for composition and roles of animal microbiome) is a comprehensive resource of curated and consistently annotated metagenomes for non-human animals. It focuses on the composition and roles of the microbiome in various animal species. The main goal of the CRAMdb is to facilitate the reuse of animal metagenomic data, and enable cross-host and cross-phenotype comparisons. To this end, we consistently annotated microbiomes (including 16S, 18S, ITS and metagenomics sequencing data) of 516 animals from 475 projects spanning 43 phenotype pairs to construct the database that is equipped with 9430 bacteria, 278 archaea, 2216 fungi and 458 viruses. CRAMdb provides two main contents: microbiome composition data, illustrating the landscape of the microbiota (bacteria, archaea, fungi, and viruses) in various animal species, and microbiome association data, revealing the relationships between the microbiota and various phenotypes across different animal species. More importantly, users can quickly compare the composition of the microbiota of interest cross-host or body site and the associated taxa that differ between phenotype pairs cross-host or cross-phenotype. CRAMdb is freely available at (http://www.ehbio.com/CRAMdb).

4.
Brain Sci ; 12(11)2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-36421912

RESUMO

OBJECTIVE: The aim of this study was to investigate the efficacy and safety of deep-brain stimulation (DBS) in the treatment of patients with Parkinson's disease aged 75 years and older. METHODS: From March 2013 to June 2021, 27 patients with Parkinson's disease (≥75 years old) who underwent DBS surgery at the First Medical Center of the PLA General Hospital were selected. The Unified Parkinson's Disease Rating Scale Part 3 (UPDRS-III), 39-item Parkinson's Disease Questionnaire (PDQ-39), and Barthel Index for Activities of Daily Living (BI) scores were used to evaluate motor function and quality of life before surgery and during on and off periods of DBS at 1 year post operation and at the final follow-up. A series of non-motor scales were used to evaluate sleep, cognition, and mood, and the levodopa equivalent daily dose (LEDD) was also assessed. Adverse events related to surgery were noted. RESULTS: The average follow-up time was 55.08 (21-108) months. Symptoms were significantly improved at 1 year post operation. The median UPDRS-III score decreased from 35 points (baseline) to 19 points (improvement of 45.7%) in the stimulation-on period at 1 year post operation (t = 19.230, p < 0.001) and to 32 points (improvement of 8.6%) at the final follow-up (t = 3.456, p = 0.002). In the stimulation-off period, the median score of UPDRS-III increased from 35 points to 39 points (deterioration of -11.4%) at 1 year post operation (Z = -4.030, p < 0.001) and 45 points (deterioration of -28.6%) at the final follow-up (Z = -4.207, p < 0.001). The PDQ-39 overall scores decreased from 88 points (baseline) to 55 points (improvement of 37.5%) in the stimulation-on period at 1 year post operation (t = 11.390, p < 0.001) and 81 points (improvement of 8.0%) at the final follow-up (t = 2.142, p = 0.044). In the stimulation-off period, the median PDQ-39 score increased from 88 points to 99 points (deterioration of -12.5%) at the final follow-up (Z = -2.801, p = 0.005). The ADL-Barthel Index score increased from 25 points (baseline) to 75 points (improvement of 66.7%) at 1 year post operation (Z = -4.205, p < 0.001) and to 35 points (improvement of 28.6%) at the final follow-up (Z = -4.034, p < 0.001). In the stimulation-off period, BI scores decreased from 25 points to 15 points (deterioration of -40%) at 1 year post operation (Z = -3.225, p = 0.01) and to 15 points (deterioration of -40%) at the final follow-up (Z = -3.959, p = 0.001). Sleep, cognition, and mood were slightly improved at 1 year post operation (p < 0.05), and LEDD was reduced from 650 mg (baseline) to 280 mg and 325 mg at 1 year post operation and the final follow-up, respectively (p < 0.05). One patient had a cortical hemorrhage in the puncture tract on day 2 after surgery, five patients had hallucinations in the acute stage after surgery, and one patient had an exposed left-brain electrode lead at 4 months post operation; there were no infections or death. CONCLUSION: DBS showed efficacy and safety in treating older patients (≥75 years old) with Parkinson's disease. Motor function, quality of life, activities of daily living, LEDD, and sleep all showed long-term improvements with DBS; short-term improvements in emotional and cognitive function were also noted.

5.
Front Plant Sci ; 13: 986678, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36426160

RESUMO

The formation of leaf color largely depends on the components of pigment accumulation in plastids, which are involved in chloroplast development and division. Here, we isolated and characterized the rice albino leaf 4 (al4) mutant, which exhibited an albino phenotype and eventually died at the three-leaf stage. The chloroplasts in al4 mutant were severely damaged and unable to form intact thylakoid structure. Further analysis revealed that the candidate gene encodes 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase (IspE), which participates in the methylerythritol phosphate (MEP) pathway of isoprenoid biosynthesis. We further demonstrated that the mutation at the exon-intron junction site cause alternative splicing factors fail to distinguish the origin of the GT-AG intron, leading to exon skipping and producing a truncated OsIspE in the al4 mutant. Notably, disruption of OsIspE led to the reduced expression of chloroplast-associated genes, including chloroplast biosynthetic and translation related genes and photosynthetic associated nuclear genes (PhANGs). In summary, these findings reveal that OsIspE plays a crucial role in chloroplast biogenesis and provides novel insights into the function of CMK during chloroplast development in rice.

6.
Front Psychol ; 13: 996905, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389479

RESUMO

Micro-expressions (MEs) can reflect an individual's subjective emotions and true mental state, and they are widely used in the fields of mental health, justice, law enforcement, intelligence, and security. However, one of the major challenges of working with MEs is that their neural mechanism is not entirely understood. To the best of our knowledge, the present study is the first to use electroencephalography (EEG) to investigate the reorganizations of functional brain networks involved in MEs. We aimed to reveal the underlying neural mechanisms that can provide electrophysiological indicators for ME recognition. A real-time supervision and emotional expression suppression experimental paradigm was designed to collect video and EEG data of MEs and no expressions (NEs) of 70 participants expressing positive emotions. Based on the graph theory, we analyzed the efficiency of functional brain network at the scalp level on both macro and micro scales. The results revealed that in the presence of MEs compared with NEs, the participants exhibited higher global efficiency and nodal efficiency in the frontal, occipital, and temporal regions. Additionally, using the random forest algorithm to select a subset of functional connectivity features as input, the support vector machine classifier achieved a classification accuracy for MEs and NEs of 0.81, with an area under the curve of 0.85. This finding demonstrates the possibility of using EEG to recognize MEs, with a wide range of application scenarios, such as persons wearing face masks or patients with expression disorders.

7.
ACS Sens ; 7(11): 3450-3460, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36342111

RESUMO

Two-dimensional (2D) magnetic materials are the key to the development of the new generation in spintronics technology and engineering multifunctional devices. Herein, the electronic, spin-resolved transmission, and gas sensing properties of the 2D g-C4N3/MoS2 van der Waals (vdW) heterostructure have been investigated by using density functional theory with non-equilibrium Green's function method. First, the g-C4N3/MoS2 vdW heterostructure demonstrates ferromagnetic half-metallicity and superior adsorption capacity for gas molecules. The spin-dependent electronic transport of the g-C4N3/MoS2-based nanodevice is obviously regulated by parallel or anti-parallel spin configuration in electrodes, leading to perfect single-spin conduction behavior with a nearly 100% spin filtering efficiency, a negative differential resistance effect, and other interesting electrical transport phenomena. Moreover, g-C4N3/MoS2 exhibits directional dependency and strong transport anisotropic behavior under bias windows, indicating that the electric current propagates more easily through the vertical direction than the horizontal direction. The physical mechanisms are revealed and analyzed by presenting the bias-dependent transmission spectra in combination with the projected local device density of states. Finally, the g-C4N3/MoS2-based gas sensor is more sensitive to CO, NO, NO2, and NH3 molecules with the chemisorption type. The strong chemical adsorption leads to the formation of electrons on the local scattering center and ultimately affects the transport properties, resulting in the maximum gas sensitivity reaching 6.45 for NO at the bias of 0.8 V. This work not only reveals that the g-C4N3/MoS2 vdW heterostructure with high anisotropy, perfect spin filtering, and outstanding gas sensitivity is a promising 2D material but also provides an insight into the further application in futuristic electronic nanodevices.

8.
Front Pharmacol ; 13: 1021653, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36408253

RESUMO

Objective: This network meta-analysis aimed to explore the effect of different drugs on mortality and neurological improvement in patients with traumatic brain injury (TBI), and to clarify which drug might be used as a more promising intervention for treating such patients by ranking. Methods: We conducted a comprehensive search from PubMed, Medline, Embase, and Cochrane Library databases from the establishment of the database to 31 January 2022. Data were extracted from the included studies, and the quality was assessed using the Cochrane risk-of-bias tool. The primary outcome measure was mortality in patients with TBI. The secondary outcome measures were the proportion of favorable outcomes and the occurrence of drug treatment-related side effects in patients with TBI in each drug treatment group. Statistical analyses were performed using Stata v16.0 and RevMan v5.3.0. Results: We included 30 randomized controlled trials that included 13 interventions (TXA, EPO, progesterone, progesterone + vitamin D, atorvastatin, beta-blocker therapy, Bradycor, Enoxaparin, Tracoprodi, dexanabinol, selenium, simvastatin, and placebo). The analysis revealed that these drugs significantly reduced mortality in patients with TBI and increased the proportion of patients with favorable outcomes after TBI compared with placebo. In terms of mortality after drug treatment, the order from the lowest to the highest was progesterone + vitamin D, beta-blocker therapy, EPO, simvastatin, Enoxaparin, Bradycor, Tracoprodi, selenium, atorvastatin, TXA, progesterone, dexanabinol, and placebo. In terms of the proportion of patients with favorable outcomes after drug treatment, the order from the highest to the lowest was as follows: Enoxaparin, progesterone + vitamin D, atorvastatin, simvastatin, Bradycor, EPO, beta-blocker therapy, progesterone, Tracoprodi, TXA, selenium, dexanabinol, and placebo. In addition, based on the classification of Glasgow Outcome Scale (GOS) scores after each drug treatment, this study also analyzed the three aspects of good recovery, moderate disability, and severe disability. It involved 10 interventions and revealed that compared with placebo treatment, a higher proportion of patients had a good recovery and moderate disability after treatment with progesterone + vitamin D, Bradycor, EPO, and progesterone. Meanwhile, the proportion of patients with a severe disability after treatment with progesterone + vitamin D and Bradycor was also low. Conclusion: The analysis of this study revealed that in patients with TBI, TXA, EPO, progesterone, progesterone + vitamin D, atorvastatin, beta-blocker therapy, Bradycor, Enoxaparin, Tracoprodi, dexanabinol, selenium, and simvastatin all reduced mortality and increased the proportion of patients with favorable outcomes in such patients compared with placebo. Among these, the progesterone + vitamin D had not only a higher proportion of patients with good recovery and moderate disability but also a lower proportion of patients with severe disability and mortality. However, whether this intervention can be used for clinical promotion still needs further exploration.

9.
Cell Death Dis ; 13(11): 943, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36351894

RESUMO

Glioblastoma (GBM) is the most common and aggressive primary brain tumor, but the mechanisms underlying tumor growth and progression remain unclear. The protein arginine methyltransferases (PRMTs) regulate a variety of biological processes, however, their roles in GBM growth and progression are not fully understood. In this study, our functional analysis of gene expression networks revealed that among the PRMT family expression of PRMT3 was most significantly enriched in both GBM and low-grade gliomas. Higher PRMT3 expression predicted poorer overall survival rate in patients with gliomas. Knockdown of PRMT3 markedly reduced the proliferation and migration of GBM cell lines and patient-derived glioblastoma stem cells (GSC) in cell culture, while its over-expression increased the proliferative capacity of GSC cells by promoting cell cycle progression. Consistently, stable PRMT3 knockdown strongly inhibited tumor growth in xenograft mouse models, along with a significant decrease in cell proliferation as well as an increase in apoptosis. We further found that PRMT3 reprogrammed metabolic pathways to promote GSC growth via increasing glycolysis and its critical transcriptional regulator HIF1α. In addition, pharmacological inhibition of PRMT3 with a PRMT3-specific inhibitor SGC707 impaired the growth of GBM cells. Thus, our study demonstrates that PRMT3 promotes GBM progression by enhancing HIF1A-mediated glycolysis and metabolic rewiring, presenting a point of metabolic vulnerability for therapeutic targeting in malignant gliomas.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Camundongos , Animais , Glioblastoma/genética , Glioblastoma/patologia , Proteína-Arginina N-Metiltransferases/genética , Proteína-Arginina N-Metiltransferases/metabolismo , Glicólise/genética , Proliferação de Células/genética , Apoptose/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
10.
Hum Cell ; 2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-36403174

RESUMO

Breast cancer is the most prevalent cancer, and it is accompanied by high heterogeneity. N6-methyladenosine (m6A) modification significantly contributes to breast cancer tumorigenesis and progression. However, how m6A-related genes affect the clinical outcomes and tumor immune microenvironment (TIME) of breast cancer is largely unknown. Our study developed an m6A-related gene signature on the basis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The m6A-related gene signature was constructed using univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses. Breast cancer patients were classified into low- and high-risk groups depending on the median risk score. The reliability and efficiency of the signature were validated using Kaplan-Meier analysis, receiver operating characteristic (ROC) curves, and principal component analysis (PCA). The risk score was validated as an independent indicator associated with overall survival, and a nomogram model was created to estimate the overall survival of patients with breast cancer. Functional annotation suggested that the risk score had a strong relationship with immune-related pathways. Different proportions of immune cell infiltration between the two groups were evaluated using various algorithms. The high-risk group had higher immune checkpoint expression levels. We discovered that one of the 6 prognostic genes, TMEM71, was downregulated in breast cancer tissues. In vitro experiments indicated that overexpression of TMEM71 suppressed breast cancer cell proliferation and migration. In conclusion, the m6A-related gene signature may be a sensitive biomarker for overall survival prediction and guide the individualized treatment for breast cancer patients.

11.
Int J Mol Sci ; 23(21)2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36362268

RESUMO

Diterpene alkaloids (DAs) are characteristic compounds in Aconitum, which are classified into four skeletal types: C18, C19, C20, and bisditerpenoid alkaloids. C20-DAs are thought to be the precursor of the other types. Their biosynthetic pathway, however, is largely unclear. Herein, we combine metabolomics and transcriptomics to unveil the methyl jasmonate (MJ) inducible biosynthesis of DAs in the sterile seedling of A. gymnandrum, the only species in the Subgenus Gymnaconitum (Stapf) Rapaics. Target metabolomics based on root and aerial portions identified 51 C19-DAs and 15 C20-DAs, with 40 inducible compounds. The highest content of C20-DA atisine was selected for further network analysis. PacBio Isoform sequencing integrated with RNA sequencing not only provided the full-length transcriptome but also their response to induction, revealing 1994 genes that exhibited up-regulated expression. Further, 38 genes involved in terpenoid biosynthesis were identified, including 7 diterpene synthases. In addition to the expected function of the four diterpene synthases, AgCPS5 was identified to be a new ent-8,13-CPP synthase in Aconitum and could also combine with AgKSL1 to form the C20-DAs precursor ent-atiserene. Combined with multiple network analyses, six CYP450 and seven 2-ODD genes predicted to be involved in the biosynthesis of atisine were also identified. This study not only sheds light on diterpene synthase evolution in Aconitum but also provides a rich dataset of full-length transcriptomes, systemic metabolomes, and gene expression profiles, setting the groundwork for further investigation of the C20-DAs biosynthesis pathway.


Assuntos
Aconitum , Alcaloides , Diterpenos , Aconitum/genética , Aconitum/metabolismo , Transcriptoma , Alcaloides/metabolismo , Diterpenos/metabolismo , Vias Biossintéticas/genética
12.
ACS Appl Mater Interfaces ; 14(47): 53150-53164, 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36394639

RESUMO

Membrane capacitive deionization (MCDI) has emerged as a promising electric-field-driven technology for brackish water desalination and specific salt or charged ion separation. The use of carbon-based or pseudocapacitive materials alone for MCDI usually suffers from the drawbacks of low desalination capacity and poor cycling stability due to their limited accessible adsorption sites and obstructed charge-carrier diffusion pathways. Therefore, developing a hybrid electrode material with multiple charge storage mechanisms and continuous electron/ion transport pathways that can synergistically improve its specific capacitance and cycling durability has currently become one of the most critical technical demands. Herein, we developed a novel hierarchically architectured hybrid electrode by first spinning MXene into polyacrylonitrile (PAN)-based carbon nanofibers (MCNFs) to obtain a highly conductive carbon nanocomposite framework. The excellent spatial support structure can effectively prevent the dense packing of Cl-- and DBS--doped polypyrrole (PPy) molecular chains during the following electrodeposition process, which not only ensures the efficient transport of electrons in the continuous hybrid carbon nanofibrous skeleton but also provides abundant accessible sites for ion adsorption and insertion. The obtained self-supporting membrane electrodes (MCNF@PPy+Cl- and MCNF@PPy+DBS-) have the advantages of outstanding specific capacitance (318.4 and 153.9 F/g, respectively), low charge transfer resistance (10.0 and 5.3 Ω, respectively), and excellent cycling performance (78% and 90% capacitance retention ratios, respectively, after 250 electrochemical cycles). Furthermore, the asymmetrical membrane electrodes showed a superior desalination capacity of 91.2 mg g-1 in 500 mg/L NaCl aqueous solution and obvious divalent ion (Ca2+, Mg2+) selective adsorption properties in high-salt water from the cooling towers of thermal power plants.

13.
J Pharm Biomed Anal ; 224: 115178, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36435084

RESUMO

Since the first commercial imaged capillary isoelectric focusing (icIEF) instrument was developed twenty years ago, the technology has become the gold standard of quality and manufacturing process control in the biopharmaceutical industry. This is owing to its high-resolution and high-throughput characterization of protein charge heterogeneity. In addition to a charge variant profiling, mass spectrometry (MS) analyses are also desirable to obtain an in-tact molecular weight (MW) and further identification of these charged species. While offline fractionation technologies including isoelectric focusing (IEF) and free flow electrophoresis (FFE) followed by liquid chromatography (LC)-mass spectrometry (MS) coupling have been employed for this purpose, there have been much fewer reported applications of icIEF-based MS connection and fraction collection. Factors that have impeded the development of these icIEF applications include difficulties with a direct connection to the MS interface as well as high background signal of carrier ampholytes and incompatible coated capillary cartridges. In this work, we developed a robust and flexible icIEF-MS platform which overcomes these challenges to achieve both the rapid icIEF separation and high-resolution MS (HRMS) identification of protein charged variants simultaneously. We demonstrate how this methodology proves highly-sensitive and highly reliable for the characterization of commercial monoclonal antibodies (mAbs) and antibody-drug-conjugates (ADCs). The whole workflow of icIEF-MS for protein heterogeneity is straight forward and accurate and can be performed within 45 min. Furthermore, the developed icIEF-MS configuration can flexibly switch to icIEF-based fraction collection model allowing the user to perform additional in-depth characterization such as peptide mapping by high performance liquid chromatography (HPLC) tandem mass spectrometry (LC-MS/MS).

14.
Waste Manag ; 156: 33-43, 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36436406

RESUMO

The SN-containing inhibitors are effective for suppressing the formation of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in the post-combustion zone of municipal solid waste incineration systems, but the industrial application of the SN-containing inhibitors is restricted by the high cost and the generation of corrosive by-products (e.g., SOx). To develop cost-effective and environmentally friendly inhibitors, a new inhibition system consisting of P-based compounds (i.e., NH4H2PO4 (ADP) and KH2PO4 (PDP)) and a chlorine-deactivation material (CaO) was proposed in this study. Also, the performance of this inhibition system in terms of suppressing PCDD/Fs formation was evaluated in an experimental system which simulated PCDD/Fs generation in the post-combustion zone. Generally, the formation of PCDD/Fs was effectively suppressed by over 95 % by the mixed inhibitors (ADP/CaO and PDP/CaO) and the individual inhibitor of ADP. Based on the observation on PCDD/F-fingerprints and the chemical speciation of Cl and Cu, the mechanisms of inhibitors were identified as: (i) passivating metal catalyst by converting the speciation of Cu from chlorides and Cu2+ with high reactivities to phosphates, oxides, and Cu+ with low reactivities, and (ii) deactivating Cl by CaO to prevent the formation of organic Cl which was critical for PCDD/Fs formation. In addition, both mechanisms were supported by (i) the better performance of inhibitors on suppressing the PCDD/F-congeners formed via de novo pathway than congeners synthesized from chlorophenols and (ii) lower degrees of chlorination of PCDD/Fs for reaction systems with CaO involved than other systems.

15.
Front Immunol ; 13: 1039862, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36439151

RESUMO

Purpose: The systemic immune-inflammation index (SII) has been considered a novel prognostic biomarker in several types of lymphoma. Our aims were to determine the best statistical relationship between pretreatment SII and survival and to combination of SII and the Memorial Sloan Kettering Cancer Center model (MSKCC) to derive the best prognostic mode in primary central nervous system lymphoma (PCNSL). Methods: Pretreatment SII and clinical data in 174 newly diagnosed PCNSL patients were included from two retrospective discovery cohorts (n = 128) and one prospective validation cohort (n = 46). A generalized additive model, Kaplan-Meier curve, and Cox analysis were performed. The high risk versus low risk of SII-MSKCC for the PCNSL cutoff point (0-1 vs. 2-4) was determined by the minimum P-value approach. Results: The SII showed a U-shaped relationship with the risk of overall survival (OS; P = 0.006). The patients with low SII or high SII had poorer OS and progression-free survival (PFS) than those with median SII. For PFS and OS, SII-MSKCC was a better predictor than MSKCC alone. The area under the receiver operating characteristic curve of the SII-MSKCC score was 0.84 for OS and 0.78 for PFS in the discovery cohorts. The predictive value of the SII-MSKCC score (OS, 0.88; PFS, 0.95) was verified through the validation cohort. Multivariable Cox analysis and Kaplan-Meier curve showed excellent performance for SII-MSKCC, with significant separation of two groups and better performance than MSKCC alone. Conclusions: We propose a new prognostic model using SII, age, and Karnofsky score that outperforms MSKCC alone and enables individualized estimates of patient outcome.


Assuntos
Linfoma , Neutrófilos , Humanos , Prognóstico , Neutrófilos/patologia , Estudos Retrospectivos , Inflamação/patologia , Linfoma/diagnóstico , Linfoma/patologia , Sistema Nervoso Central/patologia
16.
Plant Physiol ; 2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36250906

RESUMO

Fruit ripening is a complicated process that is accompanied by the formation of fruit quality. It is not only regulated at the transcriptional level via transcription factors or DNA methylation but also fine-tuned after transcription occurs. Here, we review recent advances in our understanding of key regulatory mechanisms of fleshy fruit ripening after transcription. We mainly highlight the typical mechanisms by which fruit ripening is controlled, namely, alternative splicing, mRNA m6A methylation, and non-coding RNAs at the post-transcriptional level; regulation of translation efficiency and uORF-mediated translational repression at the translational level; and histone modifications, protein phosphorylation, and protein ubiquitination at the post-translational level. Taken together, these post-transcriptional regulatory mechanisms, along with transcriptional regulation, constitute the molecular framework of fruit ripening. We also critically discuss the potential usage of some mechanisms to improve fruit traits.

17.
Medicine (Baltimore) ; 101(39): e30687, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36181060

RESUMO

The aim of this study is to clarify the association between lymphovascular invasion (LVI) and/or perineural invasion (PNI) and the clinical characteristics and prognostic importance of rectal cancer, to provide a basis for early adjuvant treatment of rectal cancer. We retrospectively analyzed patients diagnosed with rectal cancer. This study involved rectal cancer tissue samples were obtained by surgical methods. Data on histological form, tumor classification, tumor size, gross growth pattern, blood and lymphatic vessel invasion, and PNI of the slice by HE staining were obtained from pathological examination. Immunohistochemical analysis of tissue samples was performed to determine p53 and EGFR expressions. There were 330 rectal cancer patients included in the study. LVI and/or PNI can be used as a high-risk factor for the prognosis of rectal cancer, predict prognostic survival, and guide adjuvant therapy. The detection rates of LVI and PNI were 32.1% and 16.1%. Differentiation grade, Union for International Cancer Control staging, tumor-lymph node-metastasis staging are significantly related to LVI or PNI. Multivariate logistic regression analysis shows that poor differentiation and N ≥ 1 can be used as independent risk factors and predictive factors for LVI. At the same time, poor differentiation and T > 3 is an independent risk factor for PNI. Only poor differentiation is the risk factor for poor prognosis in Cox risk regression analysis. In addition, the simultaneous occurrence of LVI and PNI is an independent prognostic factor.


Assuntos
Neoplasias Retais , Proteína Supressora de Tumor p53 , Receptores ErbB , Humanos , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Neoplasias Retais/patologia , Estudos Retrospectivos
18.
Neurosci Lett ; 790: 136897, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36195299

RESUMO

The inhibition hypothesis advocated by Ekman (1985) states when an emotion is concealed or masked, the true emotion is manifested as a micro-expression (ME) which is a fleeting expression lasting for 40 to 500 ms. However, research about the inhibition hypothesis of ME from the perspective of electrophysiology is lacking. Here, we report the electrophysiological evidence obtained from an electroencephalography (EEG) data analysis method. Specifically, we designed an ME elicitation paradigm to collect data of MEs of positive emotions and EEG from 70 subjects, and proposed a method based on tensor component analysis (TCA) combined with the Physarum network (PN) algorithm to characterize the spatial, temporal, and spectral signatures of dynamic EEG data of MEs. The proposed TCA-PN methods revealed two pathways involving dorsal and ventral streams in functional brain networks of MEs, which reflected the inhibition processing and emotion arousal of MEs. The results provide evidence for the inhibition hypothesis from an electrophysiological standpoint, which allows us to better understand the neural mechanism of MEs.


Assuntos
Mapeamento Encefálico , Physarum , Humanos , Mapeamento Encefálico/métodos , Eletroencefalografia/métodos , Encéfalo/fisiologia , Algoritmos
19.
Ann Hematol ; 101(12): 2611-2616, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36220881

RESUMO

Hetrombopag is the only CFDA-approved thrombopoietin (TPO) receptor agonist for severe aplastic anemia (SAA) in China. Its chemical structure has an iron chelation domain. To explore the iron chelation effect of hetrombopag, we performed a post hoc analysis of the phase II clinical trial (NCT03557099). Thirty-five immunosuppressive therapy (IST)-refractory SAA patients were enrolled in the study, and the longitudinal changes of serum ferritin (SF) were assessed. At 18 weeks post-hetrombopag initiation, 51.4% of patients showed decreased SF levels by a median of 49.0 (18.1-95.5) % from baseline (median ΔSF decrease value, 917.2 ng/ml, range from 104.0 to 7030.0 ng/ml). A decrease in SF was found in 75.0% of hematologic responders and 31.6% of non-responders. Among the 24 patients with iron overload, 12 had decreased SF levels by up to 51% of the baseline. Patients with normal SF levels also showed decreased SF levels, and iron deficiency occurred in two patients. In conclusion, hetrombopag showed a powerful and rapid iron chelation effect.


Assuntos
Anemia Aplástica , Pirazolonas , Humanos , Anemia Aplástica/tratamento farmacológico , Pirazolonas/uso terapêutico , Hidrazonas/uso terapêutico , Trombopoetina/uso terapêutico , Quelantes de Ferro/uso terapêutico
20.
Theriogenology ; 194: 75-82, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36209547

RESUMO

Theca cells (TCs) are regulated by various factors during ovarian development. However, the role of follicular fluid exosomes in ovarian TCs has not yet been reported. In the present study, we explored the effects of follicular fluid exosomes on porcine ovarian TCs. TCs were treated with follicular fluid exosomes in vitro, and the differential gene expression profiles of TCs in the exosome and control groups were obtained via transcriptome sequencing. Differentially expressed genes were identified and found to be associated with antioxidative stress, proliferation, and steroid hormone synthesis of TCs. In addition, exosomes were found to increase antioxidative stress, proliferation, and steroid synthesis, as revealed by a higher mRNA and protein expression of GPX1, CCND1, PCNA, CYP11A1, and HSD3B1 and lower mRNA and protein expression of TNFR1 and BAX. In conclusion, we demonstrated that exosomes are essential components in regulating the physiological function of TCs.


Assuntos
Exossomos , Células Tecais , Feminino , Suínos , Animais , Células Tecais/fisiologia , Líquido Folicular/metabolismo , Exossomos/metabolismo , RNA Mensageiro/metabolismo , Esteroides , Proliferação de Células , Estresse Oxidativo , Células da Granulosa/metabolismo
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