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1.
Brief Bioinform ; 25(1)2023 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-38055840

RESUMO

As a kind of small molecule protein that can fight against various microorganisms in nature, antimicrobial peptides (AMPs) play an indispensable role in maintaining the health of organisms and fortifying defenses against diseases. Nevertheless, experimental approaches for AMP identification still demand substantial allocation of human resources and material inputs. Alternatively, computing approaches can assist researchers effectively and promptly predict AMPs. In this study, we present a novel AMP predictor called iAMP-Attenpred. As far as we know, this is the first work that not only employs the popular BERT model in the field of natural language processing (NLP) for AMPs feature encoding, but also utilizes the idea of combining multiple models to discover AMPs. Firstly, we treat each amino acid from preprocessed AMPs and non-AMP sequences as a word, and then input it into BERT pre-training model for feature extraction. Moreover, the features obtained from BERT method are fed to a composite model composed of one-dimensional CNN, BiLSTM and attention mechanism for better discriminating features. Finally, a flatten layer and various fully connected layers are utilized for the final classification of AMPs. Experimental results reveal that, compared with the existing predictors, our iAMP-Attenpred predictor achieves better performance indicators, such as accuracy, precision and so on. This further demonstrates that using the BERT approach to capture effective feature information of peptide sequences and combining multiple deep learning models are effective and meaningful for predicting AMPs.


Assuntos
Aminoácidos , Peptídeos Antimicrobianos , Humanos , Sequência de Aminoácidos , Processamento de Linguagem Natural , Pesquisadores
2.
Cancer ; 130(8): 1246-1256, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-37941429

RESUMO

BACKGROUND: Marginal zone lymphomas (MZLs) comprise a diverse group of indolent lymphoproliferative disorders; however, some patients develop histologic transformation (HT) with rapid progression to aggressive lymphoma. METHODS: Forty-three MZLs with HT (HT-MZLs), 535 MZLs, and 174 de novo diffuse large B-cell lymphomas (DLBCLs) without rearrangements of MYC, BCL2, and BCL6 were collected. Among these, 22 HT-MZLs, 39 MZLs, and 174 DLBCLs were subjected to 148-gene targeted exome sequencing. The clinicopathologic features of patients who had HT-MZL and their genetic alterations were compared with those of patients who had MZLs and DLBCLs. RESULTS: All 43 HT-MZLs corresponded to DLBCLs. No HT-MZLs harbored BCL2 and MYC and/or BCL6 rearrangements. Bone marrow involvement and higher levels of lactate dehydrogenase were significantly more common in HT-MZLs than in MZLs. Furthermore, upregulated BCL6, MUM1, C-MYC, and Ki-67 expression was observed more frequently in HT-MZLs than in MZLs. TBL1XR1 was the most frequently altered gene (63.6%) in HT-MZLs, followed by CCND3 (31.8%), CARD11, ID3, and TP53 (22.7%). A trend toward worse progression-free survival in patients with TBL1XR1 mutations was observed. Compared with MZLs and non-germinal center B-cell (GCB) type DLBCLs, significantly higher frequencies of TBL1XR1 and ID3 mutations were identified in HT-MZLs. PIM1 mutations frequently occurred in DLBCLs and were significantly associated with TBL1XR1 mutations but were mutated less in HT-MZLs that had TBL1XR1 mutations. CONCLUSIONS: The current findings reveal the clinicopathologic and genetic features of HT-MZLs, suggesting that these tumors might constitute a group distinct from MZL and de novo non-GCB type DLBCL. TBL1XR1 mutations may be considered a predictor of HT in MZL.


Assuntos
Linfoma de Zona Marginal Tipo Células B , Linfoma Difuso de Grandes Células B , Humanos , Linfoma de Zona Marginal Tipo Células B/genética , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Intervalo Livre de Progressão , Proteínas Proto-Oncogênicas c-bcl-2/genética
3.
Appl Opt ; 63(3): 668-675, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38294378

RESUMO

Hollow corner-cube retroreflectors (HCCRs) are an essential reflection component of next-generation lunar laser-ranging technology. The verticality among the three reflectors, known as the right-angle error, is a critical parameter that affects the emission performance, and thus, should be correctly measured and calibrated. However, conventional methods measure the three right-angle errors separately, which can induce error superposition during the measurement process. A one-time measurement method was developed for the three right-angle errors of the HCCR using a single autocollimator (AC). The method establishes a mathematical relationship between the right-angle error of the HCCR and the angle offset of the reflected beam, and it considers the observation coordinates of the AC simultaneously to perform the coordinate transformation of the relationship parameters. The corresponding measurement equation was derived to extract the three-plane right-angle error of the HCCR using the measured readings of a single AC. In addition, a HCCR was designed to freely adjust the angle of the two reflective surfaces and used to simulate the different states of the three right-angle errors in practice. The measurement results show that the root-mean-square error of the proposed method in all right-angle error states is smaller than 16 ' ' .

4.
J Cell Biochem ; 124(4): 557-572, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36842167

RESUMO

Gastric cancer (GC) with pulmonary metastasis is one of the deadliest diseases in the world; however, the underlying pathological mechanisms and potential therapeutic targets remain to be elucidated. As exosomes play indispensable roles in the formation of premetastatic niches (PMN) and cancer metastasis. Therefore, investigating the underlying mechanisms of exosome-mediated pulmonary metastasis of GC may shed new light on identifying novel therapeutic targets for GC treatment. GC-derived exosomes were isolated from the conditioned medium of mouse forestomach carcinoma (MFC) cell line. The effects of MFC-derived exosomes on pulmonary macrophage polarization were analyzed by reverse- transcription polymerase chain reaction and flow cytometry. Expression of PD-L1 and other proteins was evaluated by Western blot. Exosomal microRNAs (miRNAs) were analyzed by microarray. GC-derived exosomes (GC-exo) accumulated in high numbers in the lungs and were ingested by macrophages. The extracellular-signal-regulated kinase (ERK) signaling pathway was activated by GC-exo, inducing macrophage immunosuppressive-phenotype differentiation and increased PD-L1 expression. miRNA-sequencing identified 130 enriched miRNAs in GC-exo. Among the enriched miRNAs, miR-92a-3p plays a major role in activating ERK signaling via inhibition of PTEN expression. In addition, inhibiting ERK signaling with PD98059 significantly reduced the expression of PD-L1 in macrophages and, therefore, reversed the immunosuppressive PMN and inhibited the colonization of GC cells in the lungs. This study identified a novel mechanism of GC-exo mediated PD-L1 expression in lung macrophages that facilitates lung PMN formation and GC pulmonary metastasis, which also provided a potential therapeutic target for GC with pulmonary metastasis treatment.


Assuntos
Exossomos , Neoplasias Pulmonares , MicroRNAs , Neoplasias Gástricas , Animais , Camundongos , Neoplasias Gástricas/patologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Exossomos/metabolismo , Linhagem Celular Tumoral , MicroRNAs/genética , MicroRNAs/metabolismo , Macrófagos/metabolismo , Neoplasias Pulmonares/metabolismo
5.
Acta Pharmacol Sin ; 40(4): 460-467, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29946167

RESUMO

Metabotropic glutamate receptor 2 (mGlu2) belongs to the group-II metabotropic glutamate (mGlu) receptors and is a neurotransmitter G protein-coupled receptor. The group-II mGlu receptors are promising antipsychotic targets, but the specific role of mGlu2 signaling remains unclear. Receptor tyrosine kinases (RTKs) are also believed to participate in brain pathogenesis. To investigate whether there is any communication between mGlu2 and RTKs, we generated a CHO-mGlu2 cell line that stably expresses mGlu2 and showed that activation of mGlu2 by LY379268, a group II mGlu agonist, was able to transactivate insulin-like growth factor 1 receptor (IGF-1R). We further determined that the Gi/o protein, Gßγ subunits, phospholipase C, and focal adhesion kinase (FAK) were involved in the IGF-1R transactivation signaling axis, which further induced the phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2) and cAMP response element-binding protein. In primary mouse cortical neurons, similar signaling pathways were observed when mGlu2 were stimulated by LY487379, an mGlu2 positive allosteric modulator. Transactivation of IGF-1R through FAK in response to mGlu2 should provide a better understanding of the association of mGlu2 with brain disease.


Assuntos
Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Receptor IGF Tipo 1/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Aminoácidos/farmacologia , Animais , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Células CHO , Células Cultivadas , Cricetulus , Humanos , Camundongos , Fosforilação , Receptores de Glutamato Metabotrópico/agonistas
6.
Wei Sheng Wu Xue Bao ; 57(4): 513-25, 2017 Apr 04.
Artigo em Zh | MEDLINE | ID: mdl-29756735

RESUMO

Objective: To study the effect of amphipathic helix characteristics of FtsZ (236-245) domain on FtsZ assembly and interaction of FtsZ with FtsA in Escherichia coli strains. Methods: We constructed FtsZ and its mutant's plasmids by molecular clone and site-directed mutagenesis, and purified targeted proteins using affinity chromatography. QN23-QN29 strains were constructed by linear DNA homologous recombination and P1 transduction. We observed cellular localization patterns of FtsZ and its mutants in E. coli by living cell imaging experiments, examined membrane binding properties of FtsZ mutants by membrane proteins isolation and Western blot analysis, and analyzed interaction of FtsZ/FtsZ* with FtsA by Co-immunoprecipitation and far Western blot. Native gel separation and in vitro polymerization experiments were done to check effects of FtsZ point mutation on FtsZ assembly. Results: Yfp-labeled FtsZE237A/K and FtsZE241A/K mutant proteins failed to localize in E. coli strains, assemble into functional Z-ring structure, and had decreased function of FtsZ (wt). In vitro experiments showed that E237A/K and E241A/K mutations of FtsZ decreased the polymerization efficiency of FtsZ monomer, weakened FtsZ*-FtsA interaction and changed membrane binding properties of FtsZ. Conclusion: FtsZ E237 and E241 are critical amino acids that affect the amphipathic helix characteristics of FtsZ (236-245) domain, FtsZ assembly and FtsZ-FtsA interaction in E. coli strains.


Assuntos
Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Proteínas do Citoesqueleto/química , Proteínas do Citoesqueleto/metabolismo , Escherichia coli/metabolismo , Motivos de Aminoácidos , Proteínas de Bactérias/genética , Proteínas do Citoesqueleto/genética , Escherichia coli/química , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Mutagênese Sítio-Dirigida , Mutação , Ligação Proteica , Domínios Proteicos
7.
Wei Sheng Wu Xue Bao ; 56(2): 264-74, 2016 Feb 04.
Artigo em Zh | MEDLINE | ID: mdl-27373074

RESUMO

OBJECTIVE: To explore effects of FtsZ mutants FtsZ(E75A), FtsZ(R78G) and FtsZ(D82A) on FtsZ self-assembly and interaction of FtsZ with MreB in Escherichia coli strains. METHODS) We constructed FtsZ and its mutant's plasmids by molecular clone and site-directed mutagenesis methods, and purified targeted proteins by affinity chromatography. QN6(ftsZ::yfp-cat), QN7(tsZ::yfp-cat), QN8(ftsZ(R78G)::yfp-cat) and QN9 (ftsZ(D82A):.:yfp-cat) strains were constructed by linear DNA homologous recombination. We observed cellular localization pattern of FtsZ and its mutants in E. coli by living cell imaging experiments, examined interaction of FtsZ/FtsZ*-FtsZ* and FtsZ/FtsZ*-MreB by Coimmunoprecipitation and bacteria two hybrid, and analyzed assembly characteristics of FtsZ mutants by Light scattering. RESULTS) The Yfp-labeled FtsZ(E75A), FtsZ(R78G) and FtsZ(D82A) mutant proteins failed to assemble into functional Z-ring structure and localize correctly in E. coli strains. Interaction of FtsZ with its mutants, or FtsZ*-FtsZ* and FtsZ*-MreB interaction were weakened or completely disappeared. In addition, in vitro experiments show that E75A, R78G and D82A mutations decreased the polymerization efficiency of FtsZ monomer. CONCLUSION: FtsZ E75, R78 and D82 are critical amino acids in the assembly, function of FtsZ protein and FtsZ-MreB interaction in E. coli strains.


Assuntos
Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Proteínas do Citoesqueleto/química , Proteínas do Citoesqueleto/metabolismo , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Motivos de Aminoácidos , Proteínas de Bactérias/genética , Proteínas do Citoesqueleto/genética , Escherichia coli/química , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Mutação de Sentido Incorreto , Ligação Proteica
8.
Gene ; 911: 148346, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38452877

RESUMO

Noncoding RNAs (ncRNAs) have gained significant attention in recent years due to their crucial roles in various biological processes. However, our understanding of the expression and functions of ncRNAs in Cyclina sinensis, an economically important marine bivalve, remains limited. This study aimed to address this knowledge gap by systematically identifying ncRNAs in the mantles of C. sinensis with purple and white shells. Through our analysis, we identified a differential expression of 1244 mRNAs, 196 lncRNAs, 49 circRNAs, and 23 miRNAs between purple- and white-shell clams. Functional enrichment analysis revealed the involvement of these differentially expressed ncRNAs in biomineralization and pigmentation processes. To gain further insights into the regulatory mechanisms underlying shell color formation, we established competitive endogenous RNA (ceRNA) networks. These networks allowed us to identify targeted differentially expressed miRNAs (DEMis) and genes associated with shell color formation. Based on the ceRNA networks, we obtained an up-down-up lncRNA-miRNA-mRNA network consisting of 13 upregulated lncRNAs and a circRNA-miRNA-mRNA network comprising three upregulated circRNAs (novel_circ_0004787, novel_circ_0001165, novel_circ_0000245). Through these networks, we identified and selected an upregulated novel gene (evm.TU.Hic_asm_7.988) and a downregulated sponge miRNA (hru-miR-1985) as potential contributors to shell color regulation. In summary, the present investigation offers a comprehensive analysis of ncRNA catalogs expressed in the clam mantle of C. sinensis. The findings enhance our comprehension of the molecular mechanisms governing shell coloration and offer new perspectives for selective breeding of C. sinensis in the future.


Assuntos
Bivalves , MicroRNAs , RNA Longo não Codificante , Animais , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Endógeno Competitivo , RNA Circular/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Redes Reguladoras de Genes , MicroRNAs/genética , MicroRNAs/metabolismo , Bivalves/genética , Bivalves/metabolismo
9.
Front Public Health ; 12: 1230139, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38384888

RESUMO

Objective: This study aimed to evaluate the impact of nonpharmaceutical interventions (NPIs) taken to combat COVID-19 on the prevalence of respiratory viruses (RVs) of acute respiratory infections (ARIs) in Shanghai. Methods: Samples from ARI patients were collected and screened for 17 respiratory viral pathogens using TagMan low density microfluidic chip technology in Shanghai from January 2019 to December 2020. Pathogen data were analyzed to assess changes in acute respiratory infections between 2019 and 2020. Results: A total of 2,744 patients were enrolled, including 1,710 and 1,034 in 2019 and 2020, respectively. The total detection rate of RVs decreased by 149.74% in 2020. However, detection rates for human respiratory syncytial virus B (RSVB), human coronavirus 229E (HCoV229E), human coronavirus NL63 (HCoVNL63), and human parainfluenza virus 3 (HPIV3) increased by 91.89, 58.33, 44.68 and 24.29%, in 2020. The increased positive rates of RSVB, HPIV3, resulted in more outpatients in 2020 than in 2019. IFV detection rates declined dramatically across gender, age groups, and seasons in 2020. Conclusion: NPIs taken to eliminate COVID-19 had an impact on the prevalence of respiratory viral pathogens, especially the IFVs in the early phases of the pandemic. Partial respiratory viruses resurged with the lifting of NPIs, leading to an increase in ARIs infection.


Assuntos
COVID-19 , Infecções Respiratórias , Humanos , Pandemias , COVID-19/epidemiologia , Prevalência , China/epidemiologia , Infecções Respiratórias/epidemiologia
10.
Food Chem X ; 22: 101375, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38633737

RESUMO

Comparative nutritional analysis of Porphyra yezoensis strains "Jianghai No. 1" and "Sutong No.1" revealed significant differences in crude protein, crude fat, crude fiber, crude ash, and total sugar. Both strains contained 16 amino acids, with alanine as the highest and histidine the lowest content. Methionine was determined to be the first limiting amino acid for both strains in both amino acid score and chemical score assessment. They also featured 24 fatty acids, differing notably in four saturated fatty acids and five unsaturated fatty acids. All 12 mineral elements were present, notably differing in sodium, magnesium, potassium, calcium, iron, and zinc. The "Jianghai No. 1" strain stands out with its nutrient-rich profile, featuring high protein content, low fat, and abundant minerals, which could potentially command higher market prices and generate greater economic benefits due to its superior nutritional, and set a strong foundation for its future large-scale promotion and cultivation.

11.
Protein Cell ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38721690

RESUMO

One of the basic questions in the ageing field is whether there is fundamental difference between the ageing of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-ageing Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at early age was observed, indicating its involvement in normal ageing of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal ageing. AAV-delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan (Stern 2017). These findings demonstrate the complexity of ageing in mammals, and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.

12.
Cell Res ; 34(7): 504-521, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38811766

RESUMO

Bidirectional transcription of mammalian mitochondrial DNA generates overlapping transcripts that are capable of forming double-stranded RNA (dsRNA) structures. Release of mitochondrial dsRNA into the cytosol activates the dsRNA-sensing immune signaling, which is a defense mechanism against microbial and viral attack and possibly cancer, but could cause autoimmune diseases when unchecked. A better understanding of the process is vital in therapeutic application of this defense mechanism and treatment of cognate human diseases. In addition to exporting dsRNAs, mitochondria also export and import a variety of non-coding RNAs. However, little is known about how these RNAs are transported across mitochondrial membranes. Here we provide direct evidence showing that adenine nucleotide translocase-2 (ANT2) functions as a mammalian RNA translocon in the mitochondrial inner membrane, independent of its ADP/ATP translocase activity. We also show that mitochondrial dsRNA efflux through ANT2 triggers innate immunity. Inhibiting this process alleviates inflammation in vivo, providing a potential therapeutic approach for treating autoimmune diseases.


Assuntos
Translocador 2 do Nucleotídeo Adenina , Mitocôndrias , Membranas Mitocondriais , RNA de Cadeia Dupla , Animais , Translocador 2 do Nucleotídeo Adenina/metabolismo , Translocador 2 do Nucleotídeo Adenina/genética , Humanos , RNA de Cadeia Dupla/metabolismo , Mitocôndrias/metabolismo , Membranas Mitocondriais/metabolismo , Camundongos , Imunidade Inata , Transporte de RNA , Células HEK293 , Camundongos Endogâmicos C57BL
13.
Semin Hematol ; 60(3): 173-177, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37563073

RESUMO

Natural killer (NK)/T-cell lymphomas (NK/TCL) and peripheral T-cell lymphomas (PTCL) are aggressive hematological malignancies. With the development of next-generation sequencing, circulating tumor DNA (ctDNA) can be detected by several techniques with clinical implications. So far, the effect of ctDNA in pretreatment prognosis prediction, longitudinal monitoring of treatment response and surveillance of long-term remission or relapse in NK/TCL and PTCL has been reported in several researches.


Assuntos
DNA Tumoral Circulante , Linfoma de Células T Periférico , Humanos , Linfoma de Células T Periférico/genética , Linfoma de Células T Periférico/tratamento farmacológico , Linfoma de Células T Periférico/patologia , DNA Tumoral Circulante/genética , Recidiva Local de Neoplasia/tratamento farmacológico , Prognóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
14.
Front Immunol ; 14: 1188058, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37457725

RESUMO

Unstable hemoglobinopathies are a rare, heterogeneous group of diseases that disrupt the stability of hemoglobin (Hb), leading to chronic hemolysis and anemia. Patients with severe phenotypes often require regular blood transfusions and iron chelation therapy. Although rare, studies have reported that hematopoietic stem cell transplantation (HSCT) seems to be an available curative approach in transfusion-dependent patients with unstable hemoglobinopathies. Here, we describe successful haploidentical HSCT for the treatment of an unstable Hb variant, Hb Bristol-Alesha, in a 6-year-old boy with severe anemia since early childhood. Two years after transplantation, he had a nearly normal hemoglobin level without evidence of hemolysis. DNA analysis showed complete chimerism of the donor cell origin, confirming full engraftment with normal erythropoiesis.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Hemoglobinopatias , Masculino , Pré-Escolar , Humanos , Hemólise , Hemoglobinopatias/genética , Hemoglobinopatias/terapia , Transfusão de Sangue
15.
Int J Surg ; 109(6): 1753-1768, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37132038

RESUMO

BACKGROUND: Available evidence shows that the incidence of toxicities associated with cancer immunotherapy, such as programmed cell death 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1)-related toxicities, is estimated to be between 0.3 and 1.3%. OBJECTIVE: This systematic review aimed to investigate cancer patients' susceptibility to toxicities associated with PD-1/PD-L1 inhibitors and establish a clinically relevant landscape of side effects of PD-1/PD-L1 inhibitors. DATA SOURCES: Relevant publications from PubMed, Embase, Cochrane Library, Web of Science, and China National Knowledge Infrastructure (CNKI) between 2014 and 2019. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: We searched randomized controlled trials (RCTs) reporting treatment-related toxicities associated with PD-1 and PD-L1 inhibitors in the treatment of cancers. The primary endpoint was to assess the difference in the incidences of toxicities between cancer patients who did and did not receive PD-1/PD-L1 inhibitors. A total of 29 RCTs, incorporating 8576 patients, met the eligibility criteria. STUDY APPRAISAL AND SYNTHESIS METHODS: We calculated the pooled relative risks and corresponding 95% CIs using a random-effects model and assessed the heterogeneity between different groups. The subgroup analyses were conducted based on cancer type, toxicity grade (severity), system and organ, treatment regimens in the intervention arm and the control arm, PD-1/PD-L1 inhibitor drug type, and cancer type. RESULTS: A total of 11 categories (e.g. endocrine toxicity), and 39 toxicity types (e.g. hyperthyroidism) were identified. For toxicities at any grade, those treated with PD-1/PD-L1 inhibitors were at lower risks for gastrointestinal toxicity, hematologic toxicity, and treatment event leading to discontinuation; and were at higher risks for respiratory toxicity (all P <0.05). Those treated with PD-1/PD-L1 inhibitors were at lower risks for fatigue, asthenia, and peripheral edema and were at higher risks for pyrexia, cough, dyspnea, pneumonitis, and pruritus. LIMITATIONS: The present research is a meta-analysis at the study level rather than at the patient level; insights on risk factors associated with the development of toxicities cannot be found in our study. There was a possible overlap in Common Terminology Criteria for Adverse Events (CTCAE) definitions which prevents understanding the true rates of specific toxicities. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: For most toxicity types based on system and organ, the incidence proportions for patients in the intervention arm were lower than those in the control arm, which suggested the general safety of PD-1/PD-L1 inhibitors against conventional chemotherapy and cytotoxic t-lymphocyte-associated protein 4 (CTLA-4) inhibitors. Future research should focus on taking effective targeted measures to decrease the risks of different toxicities for different patient populations. SYSTEMATIC REVIEW REGISTRATION NUMBER: We registered the research protocol with PROSPERO (registration number CRD42019135113).


Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Receptor de Morte Celular Programada 1 , Neoplasias/tratamento farmacológico , Risco , Incidência
16.
ACS Omega ; 7(35): 31448-31465, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36092627

RESUMO

In response to the frequent occurrence of coal spontaneous combustion accidents, this paper proposes to use glutathione (GSH) as an inhibitor to inhibit the coal oxidation at low temperature. Based on the gas production of oxidation, thermogravimetric analysis, electron spin resonance, and in situ Fourier infrared transform spectroscopy experiments, it is known that GSH has a good inhibiting effect on lignite, long-flame coal, and fatty coal. The optimal action temperature of GSH is 60-150 °C, which can effectively slow down the weight loss and exothermic process and reduce the gas production of CO and CO2. Compared with the raw coal, the GSH-treated coal samples possess higher crossing point temperature and lower reactive group content. Subsequently, quantum chemical calculations are performed using density functional theory. The results demonstrate that the inhibiting mechanism of GSH is inerting the reactive radicals in coal and converting them into more stable compounds. Meanwhile, the activation energy of the reaction between GSH and each reactive radical is small, and all of them can occur at room temperature and pressure. This study lays the groundwork for future development of inhibitors.

17.
Contrast Media Mol Imaging ; 2022: 5787981, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35601568

RESUMO

Functional analysis of immune subtypes in hepatocellular carcinoma has attracted much attention due to its advantages in solving some optimization problems. At present, the research on the immune subtype of hepatocellular carcinoma is still in its infancy, and the high stability of its system still has problems. Based on fuzzy logic and evolutionary algorithms, this paper constructs a Mate analysis of the optimization problem of immune subtypes and dynamic optimization problems of hepatocellular carcinoma. The model conducts in-depth analysis and research on the biological immune subtype system, solving the problems of reliable information processing and body defense. Tested with existing test functions, very competitive results were achieved. The simulation results show that the improved algorithm based on data statistics has global search ability, the solution accuracy reaches 0.931, and the stability reaches 88.1%.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Algoritmos , Simulação por Computador , Lógica Fuzzy , Humanos
18.
ACS Omega ; 7(22): 18552-18568, 2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35694513

RESUMO

In order to cut off the chain reaction in the process of coal oxidation at low temperature (COLT), butylated hydroxytoluene (BHT) was used as an inhibitor to explore its inhibition effect and mechanism. In this paper, in situ Fourier transform infrared spectroscopy, electron paramagnetic resonance, and gas production of COLT experiments were conducted to compare the inhibited coal sample (BHT-Coal) with the raw coal. The results showed that BHT can effectively inhibit the formation of active free radicals, reduce the content of active alkoxy, carbonyl, and hydroxyl groups, increase the production temperature of CO, CO2, and C2H4, and reduce the concentration. The crossing point temperature increased from 132.3 to 157.4 °C, indicating that BHT can reduce the spontaneous combustion tendency of the raw coal. To explore the inhibition mechanism of BHT on COLT, five typical active free-radical models were established, and their active sites, active bonds, and thermodynamic parameters were calculated according to the density functional theory. The results showed that the highly active H atoms of the phenolic hydroxyl group in BHT can combine with active free radicals to generate stable compounds, and the activation energy of each reaction is small, which can occur under normal temperature and pressure. The inhibition mechanism of BHT is to reduce the concentration of the free radicals, so as to weaken the chain reaction strength during the COLT. This study provides a reference for the development and utilization of inhibitors.

19.
Cancer Cell ; 40(2): 131-133, 2022 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-35167823

RESUMO

Two recent reports in the New England Journal of Medicine highlight the successful application of novel targeted therapies to improve the clinical outcomes of diffuse large B-cell lymphoma (DLBCL). These findings encourage us to pursue further mechanism-based therapeutic uses to make DLBCL curable in the era of precision medicine.


Assuntos
Linfoma Difuso de Grandes Células B , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Terapia de Alvo Molecular , Medicina de Precisão
20.
J Food Biochem ; 46(6): e13850, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34227128

RESUMO

Ophiopogonis Radix can be divided into Zhemaidong (ZMD) and Chuanmaidong (CMD). The main planting areas of ZMD are Cixi City and Sanmen county. The quality and price of Ophiopogonis Radix from different producing areas are different. In this study, the headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) method is used to rapidly identify ZMD and CMD. The method is also used to identify ZMD from Cixi and Sanmen by analyzing volatile organic compounds (VOCs). A total of 58 VOCs was obtained from ZMD samples with more abundant signals of which 41 were identified. The peak intensities of all VOCs in ZMD and CMD, Cixi and Sanmen data were averaged and then those VOCs whose peak intensities were distributed outside of mean ± 2 standard deviation (µ ± 2σ) were selected as characteristic markers. We selected 14 characteristic markers to establish the characteristic fingerprint of ZMD and CMD, among the 14 VOCs, ZMD contained more eucalyptus oil compounds than CMD, CMD contained more volatile aldehydes than ZMD. We selected 12 characteristic markers for the establishment of the characteristic fingerprint of ZMD from Cixi and Sanmen. The principal component analysis (PCA) results indicated that both ZMD and CMD or ZMD from Cixi and Sanmen could be effectively divided. The ZMD and CMD as well as ZMD from Cixi and Sanmen were evaluated by partial least squares regression-discriminants analysis (PLS-DA) resulting to be excellent chemical descriptors for sample discrimination. One hundred percent classification rates for both PLS-DA calibration and prediction models were obtained. These results provided a reference for the traceability of species and origin and market standard of Ophiopogonis Radix. PRACTICAL APPLICATIONS: Ophiopogonis Radix can be divided into Zhejiang Ophiopogonis Radix (ZMD) and Sichuan Ophiopogonis Radix (CMD). As far as ZMD is concerned, its producing areas mainly include the traditional planting areas (Cixi City) and new growth areas (Sanmen county). In this paper, the HS-GC-IMS method was adopted to analyze VOCs in Ophiopogonis Radix from different producing areas and then we screen out the respective characteristic VOCs of ZMD and CMD as well as ZMD from Cixi and Sanmen. These characteristic VOCs can effectively identify ZMD and CMD as well as ZMD from Cixi City and Sanmen country to provide a scientific basis for the origin identification of Ophiopogonis Radix.


Assuntos
Medicamentos de Ervas Chinesas , Compostos Orgânicos Voláteis , Cromatografia Gasosa-Espectrometria de Massas/métodos , Espectrometria de Mobilidade Iônica , Raízes de Plantas/química , Compostos Orgânicos Voláteis/análise
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