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1.
Ann Palliat Med ; 10(9): 10091-10094, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34628928

RESUMO

Emphysematous splenic infection is a rare disease. In this case, a 33-year-old woman presented to the emergency department with a 10-day history of left-upper-quadrant abdominal pain and intermittent fever. She positively denied any previous history of illness or trauma. On admission to the hospital, her white-cell count, neutrophil percentage, C-reactive protein level, blood glucose, and urine glucose were higher than normal. Computed tomography (CT) revealed gas-fluid levels and infection in the spleen. After multidisciplinary consultation and discussions, the patient was diagnosed with emphysema spleen infection and diabetes, and the infection was most likely related to the diabetes. The patient was treated with antibiotics, hypoglycemic therapy, and transabdominal spleen infection puncture and drainage. Finally, the patient's infection and blood sugar were controlled, and the drainage fluid was unobstructed. To the best of our knowledge, emphysematous spleen infection has only been reported once previously in a super obese female patient in 2007. Interestingly, the patient in the present case was also an obese and diabetic middle-aged woman. Similar to other documented emphysematous infection cases, the disease onset of our patient was indistinct and insidious. Due to advances in imaging tools and knowledge of emphysematous nephritis, the patient was successfully diagnosed and treated in time.


Assuntos
Diabetes Mellitus , Enfisema , Adulto , Antibacterianos/uso terapêutico , Drenagem , Enfisema/tratamento farmacológico , Enfisema/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
2.
Biomed Res Int ; 2021: 3047437, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631878

RESUMO

Our aim was to explore the effects of dietary and behavior interventions on lipometabolism caused by an unhealthy high-fat diet and the best method to rebuild lipid homeostasis of this lifestyle. Apart from normal diet rats, 34 rats were fed with high-fat emulsion for 4 weeks and then intervened for another 4 weeks. Eight of them were classified into high-fat control group, and 9 were sorted into high-fat diet with rice vinegar group. Meanwhile, 10 were put into high-fat diet in swimming group, and 7 were just for refeeding normal diet group. Then, the data of body weight was recorded and analyzed. Indexes of serum samples were tested by kits. AMPKα, HNF1α, and CTRP6 in pancreas, liver, cardiac, and epididymis adipose tissues were detected by western blot. According to our experiments, swimming and refeeding groups reflected a better regulation on lipid homeostasis mainly by upregulating the expression of pancreas AMPKα. To be more specific, the refeeding rats showed lower T-CHO (P < 0.001) and LDL-C (P < 0.05), but higher weight gain (P < 0.001), insulin level (P < 0.01), and pancreas AMPKα (P < 0.01) than high-fat control rats. Compared with rats intervened by swimming or rice vinegar, they showed higher weight gain (P < 0.001), insulin level (P < 0.01), and HNF1α, but lower of CTRP6. In summary, refeeding diet functioned better in regulating the lipometabolic level after high-fat diet. Whatever approach mentioned above we adopted to intervene, the best policy to keep the balance of lipid homeostasis is to maintain a healthy diet.

3.
Nat Methods ; 18(10): 1181-1191, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34594031

RESUMO

Cytokines are critical for intercellular communication in human health and disease, but the investigation of cytokine signaling activity has remained challenging due to the short half-lives of cytokines and the complexity/redundancy of cytokine functions. To address these challenges, we developed the Cytokine Signaling Analyzer (CytoSig; https://cytosig.ccr.cancer.gov/ ), providing both a database of target genes modulated by cytokines and a predictive model of cytokine signaling cascades from transcriptomic profiles. We collected 20,591 transcriptome profiles for human cytokine, chemokine and growth factor responses. This atlas of transcriptional patterns induced by cytokines enabled the reliable prediction of signaling activities in distinct cell populations in infectious diseases, chronic inflammation and cancer using bulk and single-cell transcriptomic data. CytoSig revealed previously unidentified roles of many cytokines, such as BMP6 as an anti-inflammatory factor, and identified candidate therapeutic targets in human inflammatory diseases, such as CXCL8 for severe coronavirus disease 2019.


Assuntos
COVID-19/imunologia , Citocinas/metabolismo , Bases de Dados de Proteínas , SARS-CoV-2 , COVID-19/metabolismo , Citocinas/genética , Regulação da Expressão Gênica/imunologia , Regulação da Expressão Gênica/fisiologia , Humanos , Transdução de Sinais/fisiologia
4.
Nat Commun ; 12(1): 5988, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645796

RESUMO

The behaviors and skills of models in many geosciences (e.g., hydrology and ecosystem sciences) strongly depend on spatially-varying parameters that need calibration. A well-calibrated model can reasonably propagate information from observations to unobserved variables via model physics, but traditional calibration is highly inefficient and results in non-unique solutions. Here we propose a novel differentiable parameter learning (dPL) framework that efficiently learns a global mapping between inputs (and optionally responses) and parameters. Crucially, dPL exhibits beneficial scaling curves not previously demonstrated to geoscientists: as training data increases, dPL achieves better performance, more physical coherence, and better generalizability (across space and uncalibrated variables), all with orders-of-magnitude lower computational cost. We demonstrate examples that learned from soil moisture and streamflow, where dPL drastically outperformed existing evolutionary and regionalization methods, or required only ~12.5% of the training data to achieve similar performance. The generic scheme promotes the integration of deep learning and process-based models, without mandating reimplementation.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34651221

RESUMO

PURPOSE: The aim of this study was to explore the association of cardiac fibroblast activation with clinical parameters and cardiovascular magnetic resonance (CMR) imaging parameters in patients with chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Thirteen CTEPH patients were prospectively enrolled. All of the patients underwent cardiac 68Gallium-labelled fibroblast activation protein inhibitor (68 Ga-FAPI-04)-positron emission tomography/computed tomography (PET/CT), right heart catheterisation, and echocardiography, and 11 of them additionally underwent CMR. Thirteen control subjects were selected to establish the normal range of cardiac 68 Ga-FAPI-04 uptake. Cardiac 68 Ga-FAPI-04 uptake higher than that in the blood pool was defined as abnormal. The global and segmental maximum standardised uptake values (SUVmax) of the right ventricle (RV) were measured and further expressed as target-to-background ratio (TBRRV) with left ventricular lateral wall activity as background. Late gadolinium enhancement (LGE) was visually evaluated, and native-T1 times, enhanced-T1 times, and extracellular volume (ECV) were quantitatively measured. RESULTS: Ten CTEPH patients (77%) had abnormal 68 Ga-FAPI-04 uptake in RV, mainly located in the free wall, which was significantly higher than that in controls (TBRRV: 2.4 ± 0.9 vs 1.0 ± 0.1, P < 0.001). The TBRRV correlated positively with the thickness of RV wall (r = 0.815, P = 0.001) and inversely with RV fraction area change (RVFAC) (r = - 0.804, P = 0.001) and tricuspid annular plane systolic excursion (TAPSE) (r = - 0.678, P = 0.011). No correlation was found between 68 Ga-FAPI-04 activity and CMR imaging parameters. CONCLUSION: Fibroblast activation in CTEPH, measured by 68 Ga-FAPI-04 imaging, is mainly localised in the RV free wall. Enhanced fibroblast activation reflects the thickening of the RV wall and decreased RV contractile function.

6.
Curr Med Sci ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34542828

RESUMO

OBJECTIVE: Autosomal dominant polycystic kidney disease (ADPKD) is mainly caused by the pathogenic mutation of PKD1 or PKD2 gene and usually affects bilateral kidneys. Synonymous mutations are generally assumed to be neutral as they do not alter amino acids. Herein, we described an extremely rare ADPKD child caused by a heterozygous synonymous mutation of PKD2 gene accompanied by massive proteinuria and congenital solitary kidney. METHODS: Clinical characteristics of the patients were summarized. Whole-exome sequencing was performed to screen the disease-causing gene mutation, and reverse transcription polymerase chain reaction (RT-PCR) and Sanger sequencing were applied to analyze the impact of the identified mutation on gene transcription and splicing. RESULTS: Polycystic changes were found in the solitary kidney of a girl initially presented with nephrotic-range proteinuria. Thereafter her mother and 2 other family members were diagnosed to be ADPKD. Whole-exome sequencing of the proband identified a heterozygous synonymous mutation (c.1716G>A, p.Lys572=) located in the splicing site of exon 7 in PKD2 gene, which was co-segregated with the PKD phenotype in the family. RT-PCR and direct sequencing of amplified products revealed that this heterozygous synonymous mutation led to exon7 skipping in PKD2 gene. CONCLUSION: We reported an extremely rare child case of ADPKD2 in combination with solitary kidney and nephrotic-range proteinuria, and firstly confirmed the pathogenicity of a heterozygous synonymous mutation (c.1716G>A) in PKD2 gene. The results indicate that synonymous mutations should not be excluded from disease-causing if they are located in splicing site of an exon.

7.
BMC Neurol ; 21(1): 360, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34530762

RESUMO

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) can increase cardiovascular risk. However, the association between LDL-C change and functional outcomes in acute ischemic stroke (AIS) patients who underwent reperfusion therapy remains unclear. METHODS: Patients who received reperfusion therapy were consecutively enrolled. LDL-C measurement was conducted at the emergency department immediately after admission and during hospitalization. The change of LDL-C level (ΔLDL-C) was calculated by subtracting the lowest LDL-C among all measurements during hospitalization from the admission LDL-C. Poor functional outcome was defined as modified Rankin Scale (mRS) > 2 at 90 days. RESULTS: A total of 432 patients were enrolled (mean age 69.2 ± 13.5 years, 54.6 % males). The mean LDL-C level at admission was 2.55 ± 0.93 mmol/L. The median ΔLDL-C level was 0.43 mmol/L (IQR 0.08-0.94 mmol/L). A total of 263 (60.9 %) patients had poor functional outcomes at 90 days. There was no significant association between admission LDL-C level and functional outcome (OR 0.99, 95 % CI 0.77-1.27, p = 0.904). ΔLDL-C level was positively associated with poor functional outcome (OR 1.80, 95 % CI 1,12-2.91, p = 0.016). When patients were divided into tertiles according to ΔLDL-C, those in the upper tertile (T3, 0.80-3.98 mmol/L) were positively associated with poor functional outcomes compared to patients in the lower tertile (T1, -0.91-0.13 mmol/L) (OR 2.56, 95 % CI 1.22-5.36, p = 0.013). The risk of poor functional outcome increased significantly with ΔLDL-C tertile (P-trend = 0.010). CONCLUSIONS: In AIS patients who underwent reperfusion therapy, the decrease in LDL-C level during hospitalization was significantly associated with poor functional outcomes at 90 days.

8.
JMIR Med Inform ; 9(9): e18471, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34581670

RESUMO

The capabilities of natural language processing (NLP) methods have expanded significantly in recent years, and progress has been particularly driven by advances in data science and machine learning. However, NLP is still largely underused in patient-oriented clinical research and care (POCRC). A key reason behind this is that clinical NLP methods are typically developed, optimized, and evaluated with narrowly focused data sets and tasks (eg, those for the detection of specific symptoms in free texts). Such research and development (R&D) approaches may be described as problem oriented, and the developed systems perform specialized tasks well. As standalone systems, however, they generally do not comprehensively meet the needs of POCRC. Thus, there is often a gap between the capabilities of clinical NLP methods and the needs of patient-facing medical experts. We believe that to increase the practical use of biomedical NLP, future R&D efforts need to be broadened to a new research paradigm-one that explicitly incorporates characteristics that are crucial for POCRC. We present our viewpoint about 4 such interrelated characteristics that can increase NLP systems' suitability for POCRC (3 that represent NLP system properties and 1 associated with the R&D process)-(1) interpretability (the ability to explain system decisions), (2) patient centeredness (the capability to characterize diverse patients), (3) customizability (the flexibility for adapting to distinct settings, problems, and cohorts), and (4) multitask evaluation (the validation of system performance based on multiple tasks involving heterogeneous data sets). By using the NLP task of clinical concept detection as an example, we detail these characteristics and discuss how they may result in the increased uptake of NLP systems for POCRC.

9.
Virchows Arch ; 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34562173

RESUMO

Glutaminase 1 (GLS) is a therapeutic target for breast cancer; although GLS inhibitors have been developed, only a few subjects responded well to the therapy. Considering that the expression of histone H3 lysine 27 trimethylation (H3K27me3) and menopausal status was closely linked to GLS, we examined the effects of H3K27me3 and menopausal status on GLS to breast cancer prognosis. Data for 962 women diagnosed with primary invasive breast cancer were analyzed. H3K27me3 and GLS expression in tumors were evaluated with tissue microarrays by immunohistochemistry. Hazard ratios (HRs) and their 95% confidence intervals (CIs) for overall survival and progression-free survival were estimated using Cox regression models. Statistical interaction was assessed on multiplicative scale. There was a beneficial prognostic effect of GLS expression on overall survival for those with low H3K27me3 level (HR = 0.50, 95% CI: 0.20-1.28) but an adverse prognostic effect for those with high H3K27me3 level (HR = 3.90, 95% CI: 1.29-11.78) among premenopausal women, and the statistical interaction was significant (Pinteraction = 0.003). Similar pattern was further observed for progression-free survival (HR = 0.44, 95% CI: 0.20-0.95 for low H3K27me3 level, HR = 1.35, 95% CI: 0.74-2.48 for high H3K27me3 level, Pinteraction = 0.024). The statistical interaction did not occur among postmenopausal women. Our study showed that the prognostic effects of GLS on breast cancer correlated to the expression level of H3K27me3 and menopausal status, which would help optimize the medication strategies of GLS inhibitors.

10.
Surg Endosc ; 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34586491

RESUMO

BACKGROUND: Photodocumentation during endoscopy procedures is one of the indicators for endoscopy performance quality; however, this indicator is difficult to measure and audit in the endoscopy unit. Emerging artificial intelligence technology may solve this problem, which requires a large amount of material for model development. We developed a deep learning-based endoscopic anatomy classification system through convolutional neural networks with an accelerated data preparation approach. PATIENTS AND METHODS: We retrospectively collected 8,041 images from esophagogastroduodenoscopy (EGD) procedures and labeled them using two experts for nine anatomical locations of the upper gastrointestinal tract. A base model for EGD image multiclass classification was first developed, and an additional 6,091 images were enrolled and classified by the base model. A total of 5,963 images were manually confirmed and added to develop the subsequent enhanced model. Additional internal and external endoscopy image datasets were used to test the model performance. RESULTS: The base model achieved total accuracy of 96.29%. For the enhanced model, the total accuracy was 96.64%. The overall accuracy improved with the enhanced model compared with the base model for the internal test dataset without narrowband images (93.05% vs. 91.25%, p < 0.01) or with narrowband images (92.74% vs. 90.46%, p < 0.01). The total accuracy was 92.56% of the enhanced model on the external test dataset. CONCLUSIONS: We constructed a deep learning-based model with an accelerated approach that can be used for quality control in endoscopy units. The model was also validated with both internal and external datasets with high accuracy.

11.
Oncol Rep ; 46(5)2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34523691

RESUMO

Cholangiocarcinoma (CCA) is a highly aggressive malignant tumor with an extremely poor prognosis. Minichromosome maintenance 8 homologous recombination repair factor (MCM8) is a helicase involved in the elongation step of DNA replication and tumorigenesis. In the present study, the clinical significance and biological function of MCM8 in CCA were investigated. The expression levels of MCM8 in CCA and paracancerous tissues were analyzed using immunohistochemical staining. The potential mechanisms underlying MCM8 and the biological effects of MCM8 in CCA cells were explored using in vitro assays and in vivo mouse xenograft models. The high expression levels of MCM8 in CCA has important clinical significance in predicting disease progression. Knockdown of MCM8 decreased proliferation, promoted apoptosis and suppressed migration of CCA cells. MCM8 knockdown also suppressed tumor growth in vivo. Mechanistically, MCM8 knockdown led to the abnormal downregulation of survivin, XIAP, HSP27, IGF­1sR, sTNF­R1, sTNF­R2, TNF­α and TNF­ß. Furthermore, downregulation of MCM8 expression inhibited the PI3K/Akt signaling pathway and induced the MAPK9 signaling pathway. MCM8 promoted the malignant progression of CCA, indicating that inhibition of MCM8 may have the potential to serve as a novel molecular targeted therapy.

12.
J Cell Mol Med ; 25(20): 9796-9804, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34545676

RESUMO

This study aimed to explore the possibility of miR-423-5p modified adipose-derived stem cell (ADSCs) therapy on streptozotocin (STZ)-induced diabetes mellitus erectile dysfunction (DMED) rats. MiR-423-5p was knocked down in ADSCs. ADSCs, NC-miR-ADSCs and miR-ADSCs were co-cultured with human umbilical vein endothelial cells (HUVECs). Normal and high glucose media were supplemented. The supernatant and HUVECs were collected for assessment of eNOS and VEGFa expression, cell proliferation, and apoptosis. HUVECs co-cultured with ADSCs or miR-ADSCs exhibited higher eNOS and VEGFa protein expression levels compared to DM groups. MiR-ADSCs enhanced HUVEC proliferation compared to the ADSCs and NC-miR-ADSCs. Lower apoptotic rates were observed when HUVECs were co-cultured with miR-ADSCs, compared to ADSCs and NC-miR-ADSCs. Fifteen male Sprague-Dawley (SD) rats aged 12 weeks were induced to develop diabetes mellitus by intraperitoneal injection with STZ, and five healthy SD rats were used as normal controls. Eight weeks after developing diabetes, the rats received ADSCs and miR-ADSCs via injection into the corpora cavernosa, whereas normal controls and DM controls were injected with saline. Erectile function and histological assessment of penile tissues were performed 8 weeks after injection. The ICP/MAP indicated that erectile function was impaired in the DM rats compared with the normal group. Injection of ADSCs and miR-ADSCs improved erectile function significantly and was associated with the overexpression of eNOS and VEGFa. MiR-423-5p knockdown in ADSCs ameliorated high glucose-mediated damage to HUVECs and improved erectile function in DM rats by inducing eNOS and VEGFa overexpression, indicating that miR-423-5p may be a potential target in the treatment of DMED.

13.
Cell Mol Neurobiol ; 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34460038

RESUMO

It is unclear how Toll-like receptor (TLR) 4 signaling affects protein succinylation in the brain after intracerebral hemorrhage (ICH). Here, we constructed a mouse ICH model to investigate the changes in ICH-associated brain protein succinylation, following a treatment with a TLR4 antagonist, TAK242, using a high-resolution mass spectrometry-based, quantitative succinyllysine proteomics approach. We characterized the prevalence of approximately 6700 succinylation events and quantified approximately 3500 sites, highlighting 139 succinyllysine site changes in 40 pathways. Further analysis showed that TAK242 treatment induced an increase of 29 succinyllysine sites on 28 succinylated proteins and a reduction of 24 succinyllysine sites on 23 succinylated proteins in the ICH brains. TAK242 treatment induced both protein hypersuccinylations and hyposuccinylations, which were mainly located in the mitochondria and cytoplasm. GO analysis showed that TAK242 treatment-induced changes in the ICH-associated succinylated proteins were mostly located in synapses, membranes and vesicles, and enriched in many cellular functions/compartments, such as metabolism, synapse, and myelin. KEGG analysis showed that TAK242-induced hyposuccinylation was mainly linked to fatty acid metabolism, including elongation and degradation. Moreover, a combined analysis of the succinylproteomic data with previously published transcriptome data revealed that most of the differentially succinylated proteins induced by TAK242 treatment were mainly distributed throughout neurons, astrocytes, and endothelial cells, and the mRNAs of seven and three succinylated proteins were highly expressed in neurons and astrocytes, respectively. In conclusion, we revealed that several TLR4 signaling pathways affect the succinylation processes and pathways in mouse ICH brains, providing new insights on the ICH pathophysiological processes. Data are available via ProteomeXchange with identifier PXD025622.

14.
J Affect Disord ; 294: 908-915, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34375219

RESUMO

OBJECTIVE: This study aimed to assess the clinical phenomenology and characteristics of prodromal symptoms in Chinese patients with bipolar disorder (BPD) prior to their index mood episode. METHODS: Semi-structured interviews [Bipolar Prodrome Symptom Scale-Retrospective (BPSS-R)] were administered to patients within 3 years of BPD (I and II) onset. RESULTS: 120 stable inpatients and outpatients were included (65% males, mean age: 26.5±10.0 years). Feeling extremely energetic (61.8%), overly cheerful (49.1%), racing thoughts (48.2%), overly talkative (47.3%), and decreased need for sleep (43.6%) most frequently preceded the first (hypo)manic episode, whereas depressed mood (78.5%), tiredness (53.9%), reduction of enjoyment (52.3%), trouble concentrating (49.2%) and insomnia (47.7%) often occurred prior to the index depressive episode. The prevalence of anxiety or nervousness (p = 0.009), social isolation (p = 0.004), and losing temper (p < 0.001) differed significantly depending on the different episodes. Prior to any depressive episode, insomnia (p = 0.035) lasted significantly longer and sleeping too much (p = 0.033) was more severe, whereas oppositionality (p < 0.001), hallucinations (p = 0.024) and psychosis index score (p = 0.044) were more severe before any (hypo) manic episode. Furthermore, depressed mood (p = 0.006) was more frequent prior to depression, while anxiety or nervousness (p = 0.018), oppositionality (p = 0.001), and psychosis index score (p = 0.009) were more frequent before any (hypo) manic episode. CONCLUSIONS: Characteristic affective and psychotic symptoms, including depressed mood and subthreshold hypo (manic) symptoms occurred in the prodromal phase. The pre-depression prodromal symptoms lasted longer than the pre-(hypo) mania prodromal symptoms. Our findings indicated that identifying prodromal symptoms of BPD may be beneficial for early diagnosis and intervention before the development of full episodes.

15.
Viruses ; 13(8)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34452441

RESUMO

The small brown planthopper, Laodelphax striatellus (Fallén), is an important agricultural pest that causes significant losses by sucking and transmitting multiple plant viruses, such as rice black-streaked dwarf virus (RBSDV). Insecticides are commonly used to control planthoppers and cause the induction or overexpression of cytochrome P450 monooxygenases (P450s) from the CYP3 and CYP4 clades after insecticide application. However, little is known about the roles of insecticides and P450s in the regulation of viral replication in insects. In this study, RBSDV-infected L. striatellus were injected with imidacloprid, deltamethrin, pymetrozine, and buprofezin, respectively. The insecticide treatments caused a significant decrease in RBSDV abundance in L. striatellus. Treatment of piperonyl butoxide (PBO), an effective inhibitor of P450s, significantly increased the RBSDV abundance in L. striatellus. Fourteen P450 candidate genes in the CYP3 clade and 21 in the CYP4 clade were systematically identified in L. striatellus, and their expression patterns were analyzed under RBSDV infection, in different tissues, and at different developmental stages. Among the thirty-five P450 genes, the expression level of CYP6CW1 was the highest, while CYP6AY3 was the lowest after RBSDV infection. Knockdown of CYP6CW1 and CYP6AY3 significantly increased the virus abundance and promoted virus replication in L. striatellus. Overall, our data reveal that CYP6CW1 and CYP6AY3 play a critical role in the regulation of virus replication in L.striatellus.

16.
J Immunol Res ; 2021: 5516399, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34458377

RESUMO

Purpose: This study is aimed at immunologically characterizing sentinel lymph nodes (SNs) in colorectal cancer (CRC) patients and identifying changes in immunological phenotype and function of SNs isolated from the tumor immunosuppressive microenvironment. Methods: A total of 53 pairs of matched SNs and non-SNs (NSNs) were collected by using a lymph node tracer dye. Flow cytometry was performed to detect the immunophenotype of T cells as well as the expression of activation and inhibitory markers. Differential expression and distribution of characteristic immune cell markers were analyzed by multiplex immunohistochemistry (mIHC). Transcriptomics analysis was conducted to compare the differences in the expression of immune-related genes among lymph nodes. The ex vivo culture of lymph nodes was carried out to examine changes in immunological phenotypes and functions. Results: Compared with NSNs, SNs harbored a significantly higher percentage of regulatory T cells (Tregs) but a lower proportion of MoMDSCs. As indicated in the mIHC assays, Tregs, T follicular helper (Tfh) cells, and M2 macrophages were mainly distributed in cortical areas, germinal centers, and subcapsular sinus areas, respectively, while significantly higher numbers of Tregs and Tfh cells were detected in SNs as compared to NSNs. Moreover, GSEA revealed that T cell activation genes and CD8+ T cell exhaustion-related genes are enriched in SNs and NSNs, respectively. The ex vivo culture led to an increase in the proportion of CD4+ cells, while activating T cells in SNs. In addition, SNs displayed a higher increase in the expression of cytokines IFN-γ, TNF-α, and sFas than NSNs. Conclusion: SNs are shown to be in an immune active state in vivo, while highly expressing inhibitory cytokines and suppressive markers. The ex vivo culture enhanced antitumor immunological function of SN-T cells, providing a starting material for adoptive cell therapy for CRC.

17.
J Phys Chem Lett ; : 8513-8520, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34463512

RESUMO

Fundamental understanding of the nature of active sites in real-life water gas shift (WGS) catalysts that can convert CO and H2O into CO2 and H2 is crucial to engineer related catalysts performing under ambient conditions. Herein, we identified that the WGS reaction can be, in principle, catalyzed by rhodium-manganese oxide clusters Rh2MnO1,2- in the gas phase at room temperature. This is the first example of the construction of such a potential catalysis in cluster science because it is challenging to discover clusters that can abstract the oxygen from H2O and then supply the anchored oxygen to oxidize CO. The WGS reaction was characterized by mass spectrometry, photoelectron spectroscopy, and quantum-chemical calculations. The coordinated oxygen in Rh2MnO1,2- is paramount for the generation of an electron-rich Mn+-Rh- bond that is critical to capture and reduce H2O and giving rise to a polarized Rh+-Rh- bond that functions as the real redox center to drive the WGS reaction.

18.
Org Lett ; 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34463519

RESUMO

A novel palladium-catalyzed divergent decarboxylative cyclization of 2-iodobiphenyls and α-oxocarboxylic acids utilizing the atmosphere as a controlled switch is reported. Under the protection of a nitrogen atmosphere, tribenzotropones are synthesized by a [4 + 3] decarboxylative cyclization. Employing a palladium/O2 system enables a [4 + 2] decarboxylative cyclization to assemble triphenylenes. Notably, preliminary mechanistic studies indicate that the formation of triphenylenes involves a double decarboxylation.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34343095

RESUMO

A hallmark impairment in a hemiparetic stroke is a loss of independent joint control resulting in abnormal co-activation of shoulder abductor and elbow flexor muscles in their paretic arm, clinically known as the flexion synergy. The flexion synergy appears while generating shoulder abduction (SABD) torques as lifting the paretic arm. This likely be caused by an increased reliance on contralesional indirect motor pathways following damage to direct corticospinal projections. The assessment of functional connectivity between brain and muscle signals, i.e., brain-muscle connectivity (BMC), may provide insight into such changes to the usage of motor pathways. Our previous model simulation shows that multi-synaptic connections along the indirect motor pathway can generate nonlinear connectivity. We hypothesize that increased usage of indirect motor pathways (as increasing SABD load) will lead to an increase of nonlinear BMC. To test this hypothesis, we measured brain activity, muscle activity from shoulder abductors when stroke participants generate 20% and 40% of maximum SABD torque with their paretic arm. We computed both linear and nonlinear BMC between EEG and EMG. We found dominant nonlinear BMC at contralesional/ipsilateral hemisphere for stroke, whose magnitude increased with the SABD load. These results supported our hypothesis and indicated that nonlinear BMC could provide a quantitative indicator for determining the usage of indirect motor pathways following a hemiparetic stroke.


Assuntos
Acidente Vascular Cerebral , Vias Eferentes , Eletromiografia , Humanos , Movimento , Paresia/etiologia , Amplitude de Movimento Articular , Ombro , Acidente Vascular Cerebral/complicações
20.
Oncol Rep ; 46(4)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34396427

RESUMO

The presence of cancer stem cells (CSCs) is a major cause of therapeutic failure in a variety of cancer types, including colorectal cancer (CRC). However, the underlying mechanisms that regulate the self­renewal of colorectal cancer stem cells (CRCSCs) remain unclear. Our previous study utilized CRCSCs and their parent cells; through gene microarray screening and bioinformatics analysis, we hypothesized that microRNA (miR)­8063 may bind to, and regulate the expression of, heterogeneous nuclear ribonucleoprotein AB (hnRNPAB) to facilitate the regulation of CRCSC self­renewal. The aim of the present study was to confirm this conjecture through relevant experiments. The results indicated that compared with that in parent cells, miR­8063 expression was significantly downregulated in CRCSCs, while hnRNPAB expression was increased. Furthermore, hnRNPAB was identified as a direct target of miR­8063 using a dual­Luciferase assay. Overexpression of hnRNPAB promoted the acquisition of CSC characteristics in CRC cells (increased colony formation ability, enhanced tumorigenicity, and upregulated expression of CSC markers), as well as the upregulation of key proteins (Wnt3a, Wnt5a and ß­catenin) in the Wnt/ß­catenin signaling pathway. Similarly, after silencing miR­8063 in CRC cells, the characteristics of CSC were altered, and the expression of hnRNPAB protein was promoted. However, post overexpression of miR­8063 in CRCSCs, the self­renewal ability of CSCs was weakened with the downregulation of hnRNPAB protein, Wnt3a, Wnt5a and ß­catenin. These results suggest that as a tumor suppressor, miR­8063 is involved in regulating the self­renewal of CRCSCs, where loss of miR­8063 expression weakens its inhibition on hnRNPAB, which leads to the activation of Wnt/ß­catenin signaling to promote the self­renewal of CRCSCs.

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