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1.
J Immunother Cancer ; 9(2)2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33589528

RESUMO

BACKGROUND: Chemokine (C-X-C motif) ligand 13 (CXCL13) was known as a selective chemotaxis for B cells, a product of follicular helper CD4+T cells (TFH) and a contributor to tertiary lymphoid structures (TLS). Although secretion and function of CXCL13 produced by TFH have been deeply explored, the immune function and prognostic significance of CXCL13 secreted by CD8+T cells still remain unrevealed. This study aims to investigate the clinical merit of CXCL13+CD8+T cells in clear cell renal cell carcinoma (ccRCC). METHODS: We analyzed prognostic value and immune contexture that associated with CXCL13+CD8+T cells infiltration level in a total of 755 patients from Zhongshan Hospital cohort (n=223) and The Cancer Genome Atlas cohort (n=532). In vitro analyses were conducted on 42 samples of resected tumor tissue from Zhongshan Hospital in order to detect the immune status of CXCL13+CD8+T cells and total CD8+T cells. Immunohistochemistry (IHC) and flow cytometry were applied to characterize immune cells and portray the tumor microenvironment (TME) in ccRCC. RESULTS: Intratumoral CXCL13+CD8+T cells abundance was associated with inferior overall survival and disease-free survival. CXCL13+CD8+T cells possessed higher level of immune checkpoints like programmed cell-death protein 1 (PD-1), T-cell immunoglobulin mucin 3 (Tim-3), T cell immunoreceptor with Ig and ITIM domains (TIGIT) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), higher Ki-67 expression and lower tumor necrosis factor α (TNF-α), interferon γ (IFN-γ) expression. Total CD8+T cells in high-level CXCL13+CD8+T cells infiltration subgroup exhibited elevated exhausted markers (PD-1, Tim-3, TIGIT) and descended activated markers (TNF-α, IFN-γ) without quantity variance. Furthermore, the abundance of intratumoral CXCL13+CD8+T cell was correlated with immunoevasive TME accompanied by increased T helper 2 cells, tumor-associated macrophages, Foxp3+ regulatory T cells, TLS and decreased natural killer cells, GZMB+ cells. CONCLUSIONS: Intratumoral CXCL13+CD8+T cells infiltration indicated inferior clinical outcome in patients with ccRCC. CXCL13+CD8+T cells possessed increased exhausted markers, decreased effector molecules and better proliferation ability. CXCL13+CD8+T cells abundance impaired total CD8+T cells' immune function. Intratumoral CXCL13+CD8+T cells abundance was associated with immunoevasive contexture. The abundance of CXCL13+CD8+T cells was an independent prognosticator and a potential immunotherapeutic target marker for ccRCC treatment.

2.
J Am Chem Soc ; 2020 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-33373209

RESUMO

Photocatalysis provides an intriguing approach for the conversion of methane to multicarbon (C2+) compounds under mild conditions; however, with methyl radicals as the sole reaction intermediate, the current C2+ products are dominated by ethane, with a negligible selectivity toward ethylene, which, as a key chemical feedstock, possesses higher added value than ethane. Herein, we report a direct photocatalytic methane-to-ethylene conversion pathway involving the formation and dehydrogenation of alkoxy (i.e., methoxy and ethoxy) intermediates over a Pd-modified ZnO-Au hybrid catalyst. On the basis of various in situ characterizations, it is revealed that the Pd-induced dehydrogenation capability of the catalyst holds the key to turning on the pathway. During the reaction, methane molecules are first dissociated into methoxy on the surface of ZnO under the assistance of Pd. Then these methoxy intermediates are further dehydrogenated and coupled with methyl radical into ethoxy, which can be subsequently converted into ethylene through dehydrogenation. As a result, the optimized ZnO-AuPd hybrid with atomically dispersed Pd sites in the Au lattice achieves a methane conversion of 536.0 µmol g-1 with a C2+ compound selectivity of 96.0% (39.7% C2H4 and 54.9% C2H6 in total produced C2+ compounds) after 8 h of light irradiation. This work provides fresh insight into the methane conversion pathway under mild conditions and highlights the significance of dehydrogenation for enhanced photocatalytic activity and unsaturated hydrocarbon product selectivity.

3.
J Stroke Cerebrovasc Dis ; 30(1): 105447, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33188953

RESUMO

BACKGROUND: Hand motor function is often severely affected in patients with hemorrhagic stroke. The present study aimed to investigate the feasibility of predicting hand function recovery after hypertensive intracerebral hemorrhage using diffusion tensor imaging (DTI). METHODS: A total of 75 patients with hypertensive intracerebral hemorrhage were prospectively included. DTI of the corticospinal tract (CST) connecting the hand knob area of the precentral gyrus and the cerebral peduncle was performed at around 3 weeks after stroke. Integrity of the CST was evaluated as no disruption, partial disruption, and complete disruption. Hand function was compared by the Brunnstrom recovery stage of hand (BRS-H) at post-stroke 3 weeks and 3 months. RESULTS: Degrees of integrity of the corticospinal cord was negatively correlated with the BRS-H at both post-stroke 3 weeks (r = -0.77, p < 0.01) and 3 months (r = -0.75, p < 0.01). Patients with intact CST or completely disrupted CST shown by DTI did not show significant improvement in the BRS-H at post-stroke 3 months. However, those with partially disrupted CST showed significant improvement in the BRS-H at post-stroke 3 months compared to 3 weeks (3.79 ± 1.36 vs 2.53 ± 1.58, p = 0.012). CONCLUSIONS: DTI can be used to visualize the damage to the hand fibers of the CST. Patients with partially disrupted CST may benefit most from rehabilitation therapy for hand function recovery after hypertensive intracerebral hemorrhage.

4.
Oncoimmunology ; 9(1): 1838141, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33178496

RESUMO

Objectives: Tumor necrosis receptor super family (TNFRSF) plays an important role in regulating the function of CD8+ T cells. In this study, we explored the clinical significance and immune profile of TNFRSF9+ CD8+ T cells in clear cell renal cell carcinoma (ccRCC). Methods: The infiltration of immune cells was determined by immunohistochemistry in ZS cohort from our hospital and their prognostic value was further determined by Cox regression. Functional status of CD8+ T cells in ccRCC was determined by flow cytometry in 29 fresh tumor samples. In silico analysis on a TCGA cohort and other datasets was performed to further demonstrate our findings. Results: High TNFRSF9+ CD8+ T cells infiltration was associated with inferior overall survival in ZS cohort (p = .0016) and TCGA-KIRC cohort (p = .018). TNFRSF9+ CD8+ T cells expressed higher exhaustion markers (PD-1, TIM-3, CTLA-4, and TIGIT), and effector markers (IFN-γ, GZMB, CD107a, and Ki-67), than their TNFRSF9 negative counterparts. In silico analysis indicated the expression of TNFRSF9 was significantly correlated with IFNG, GZMK, MKI-67, PDCD1, HAVCR2, TIGIT, and CTLA-4 in CD8+ T cells. However, higher TNFRSF9 signature was correlated with larger tumor size shrinkage (p = .003) and better progression-free survival (p = .012) in patients treated with nivolumab but not everolimus. Conclusion: TNFRSF9+ CD8+ T cells, which possessed both exhaustion and effector phenotype, were identified as an adverse prognosticator in ccRCC. These cells enrichment was associated with better immunotherapy response which indicated these cells potentially be crucial in immunotherapy.

5.
Bioconjug Chem ; 31(10): 2404-2412, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33001643

RESUMO

Development of nanoplatforms for targeted anticancer drug delivery for effective tumor therapy still remains challenging in the development of nanomedicine. Here, we present a facile method to formulate a LAPONITE (LAP) nanodisk-based nanosystem for anticancer drug doxorubicin (DOX) delivery to folic acid (FA) receptor-overexpressing tumors. In the current work, aminated LAP nanodisks were first prepared through silanization, then functionalized with polyethylene glycol-linked FA (PEG-FA) via 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) chemistry, and finally employed to physically encapsulate DOX. The formed functional LAP nanodisks (for short, LM-PEG-FA) possess a high DOX loading efficiency (88.6 ± 1.2%) and present a pH-dependent release feature with a quicker DOX release under acidic pH conditions (pH 5.0) than under physiological pH conditions (pH 7.4). In vitro flow cytometry, confocal microscopic observation, and cell viability assay show that the LM-PEG-FA/DOX complexes can be specifically taken up by FAR-overexpressing human ovarian cancer cells (SK-OV-3 cells) and present a specific cancer cell therapeutic effect. Further tumor treatment results reveal that the LM-PEG-FA/DOX complexes can exert a specific therapeutic efficacy to a xenografted SK-OV-3 tumor model in vivo when compared with nontargeted LM-mPEG/DOX complexes. Therefore, the developed LM-PEG-FA nanodisks could be employed as a potential platform for targeted cancer chemotherapy.

6.
Spine (Phila Pa 1976) ; 45(20): E1296-E1301, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32796464

RESUMO

STUDY DESIGN: A scanning electron microscopic study performed on three cadaveric specimens focused on the human suboccipital region, specifically, myodural bridge (MDB). OBJECTIVE: This study showed the connection form of the MDB among the suboccipital muscles, the posterior atlanto-occipital membrane (PAOM) and the spinal dura mater (SDM), and provided an ultrastructural morphological basis for the functional studies of the MDB. SUMMARY OF BACKGROUND DATA: Since the myodural bridge was first discovered by Hack, researches on its morphology and functions had been progressing continuously. However, at present, research results about MDB were still limited to the gross anatomical and histological level. There was no research report showing the MDB's ultrastructural morphology and its ultrastructural connection forms between PAOM and SDM. METHODS: A scanning electron microscope (SEM) was used to observe the connection of myodural bridge fibers with PAOM and SDM in atlanto-occipital and atlanto-axial interspaces, and the connection forms were analyzed. RESULTS: Under the SEM, it was observed that there were clear direct connections between the suboccipital muscles and the PAOM and SDM in the atlanto-occipital and atlanto-axial spaces. These connections were myodural bridge. The fibers of the myodural bridge merged into the spinal dura mater and gradually became a superficial layer of the spinal dura mater. CONCLUSION: MDB fibers merged into the SDM and became part of the SDM in the atlanto-occipital and atlanto-axial space. MDB could transfer tension and pulling force to the SDM effectively, during the contraction or relaxation of the suboccipital muscles. LEVEL OF EVIDENCE: N/A.

7.
J Immunother Cancer ; 8(2)2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32817209

RESUMO

BACKGROUND: T-cell immunoglobulin and ITIM domain (TIGIT) is identified as a novel checkpoint receptor that can facilitate immune escape via mediating T-cell exhaustion in tumors. However, the clinical significance and immune contexture correlation of intratumoral TIGIT+ CD8+ T-cells remain to be further explored in muscle-invasive bladder cancer (MIBC). METHODS: 259 patients with MIBC from two clinical centers (Zhongshan Hospital, n=141; Shanghai Cancer Center, n=118) were analyzed to evaluate the prognostic value and immune contexture association of TIGIT+ CD8+ T-cells through immunohistochemistry. Fresh tumor tissue samples from 26 patients with MIBC were examined to discover the phenotype of this CD8 subpopulation by flow cytometry. RESULTS: High infiltration of intratumoral TIGIT+ CD8+ T-cells predicted poor overall survival (OS) and recurrence-free survival (RFS) in MIBC. For patients with stage II MIBC with low infiltration of TIGIT+ CD8+ cells, adjuvant chemotherapy (ACT) could significantly prolong their OS and RFS. Intratumoral TIGIT+ CD8+ T-cell abundance was correlated with impaired CD8+ T-cell cytotoxicity and exhibited production of immunosuppressive cytokine IL-10. Further analysis of tumor-infiltrating immune cell landscape revealed TIGIT+ CD8+ T-cells were associated with suppressive immune contexture, including Th2 cells, regulatory T-cells, mast cells and neutrophils. CONCLUSION: Intratumoral TIGIT+ CD8+ T-cell abundance could serve as an independent prognosticator for clinical outcome and a predictive biomarker for inferior ACT responsiveness. Intratumoral TIGIT+ CD8+ T-cell abundance correlated with dampened CD8+ T-cell antitumor immunity and immunosuppressive contexture abundance, highlighting a tumor-promoting role of TIGIT+ CD8+ T-cells.

8.
Brief Bioinform ; 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32383445

RESUMO

RNA-sequencing enables accurate and low-cost transcriptome-wide detection. However, expression estimates vary as reference genomes and gene annotations are updated, confounding existing expression-based prognostic signatures. Herein, prognostic 9-gene pair signature (GPS) was applied to 197 patients with stage I lung adenocarcinoma derived from previous and latest data from The Cancer Genome Atlas (TCGA) processed with different reference genomes and annotations. For 9-GPS, 6.6% of patients exhibited discordant risk classifications between the two TCGA versions. Similar results were observed for other prognostic signatures, including IRGPI, 15-gene and ORACLE. We found that conflicting annotations for gene length and overlap were the major cause of their discordant risk classification. Therefore, we constructed a prognostic 40-GPS based on stable genes across GENCODE v20-v30 and validated it using public data of 471 stage I samples (log-rank P < 0.0010). Risk classification was still stable in RNA-sequencing data processed with the newest GENCODE v32 versus GENCODE v20-v30. Specifically, 40-GPS could predict survival for 30 stage I samples with formalin-fixed paraffin-embedded tissues (log-rank P = 0.0177). In conclusion, this method overcomes the vulnerability of existing prognostic signatures due to reference genome and annotation updates. 40-GPS may offer individualized clinical applications due to its prognostic accuracy and classification stability.

9.
BMC Genomics ; 21(1): 283, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32252627

RESUMO

BACKGROUND: Histological grade (HG) is commonly adopted as a prognostic factor for ER-positive breast cancer patients. However, HG evaluation methods, such as the pathological Nottingham grading system, are highly subjective with only 50-85% inter-observer agreements. Specifically, the subjectivity in the pathological assignment of the intermediate grade (HG2) breast cancers, comprising of about half of breast cancer cases, results in uncertain disease outcomes prediction. Here, we developed a qualitative transcriptional signature, based on within-sample relative expression orderings (REOs) of gene pairs, to define HG1 and HG3 and reclassify pathologically-determined HG2 (denoted as pHG2) breast cancer patients. RESULTS: From the gene pairs with significantly stable REOs in pathologically-determined HG1 (denoted as pHG1) samples and reversely stable REOs in pathologically-determined HG3 (denoted as pHG3) samples, concordantly identified from seven datasets, we extracted a signature which could determine the HG state of samples through evaluating whether the within-sample REOs match with the patterns of the pHG1 REOs or pHG3 REOs. A sample was classified into the HG3 group if at least a half of the REOs of the 10 gene pairs signature within this sample voted for HG3; otherwise, HG1. Using four datasets including samples of early stage (I-II) ER-positive breast cancer patients who accepted surgery only, we validated that this signature was able to reclassify pHG2 patients into HG1 and HG3 groups with significantly different survival time. For the original pHG1 and pHG3 patients, the signature could also more accurately and objectively stratify them into distinct prognostic groups. And the up-regulated and down down-regulated genes in HG1 compared with HG3 involved in cell proliferation and extracellular signal transduction pathways respectively. By comparing with existing signatures, 10-GPS was with prognostic significance and was more aligned with survival of patients especially for pHG2 samples. CONCLUSIONS: The transcriptional qualitative signature can provide an objective assessment of HG states of ER-positive breast cancer patients, especially for reclassifying patients with pHG2, to assist decision making on clinical therapy.

10.
ACS Appl Mater Interfaces ; 12(10): 12317-12327, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32115937

RESUMO

Peripheral nerve injury is a common serious disease, and the electrical conductivity of nerve scaffolds is of special significance for nerve regeneration. Here, a highly conductive silk knitted composite scaffold was prepared by utilizing hydrogen bonding and electrostatic adsorption between silk amino, graphene (RGO), and polyaniline (PANI). Compared to traditional in situ polymerization of aniline (ANI), the surface of the RGO/PANI/silk conductive knitted scaffold prepared by two-step electrostatic self-assembly had more uniform PANI particles and lower resistance; when GO was 1 g/L and ANI was 0.4, 0.6, or 0.8 mol/L, the RGO/PANI/silk scaffold had better electrical properties when the conductivity was between 0.62 × 10-3 and 1.72 × 10-3 S/cm. The scaffolds had good conductive stability under different physical stresses and good mechanical properties, wherein ultimately the strength, elongation at break, and Young's modulus ranges were 28.07-34.97 MPa, 105.91-109.85%, and 10.2-12.48 MPa, respectively, and so they provided good support. Conductive scaffolds had ordered loops, fiber structure, and large pore sizes between 40 and 70 µm. In summary, RGO/PANI/silk scaffold with good conductivity, pore size distribution, mechanical properties, thermal properties had potential applications in the field of peripheral nerve regeneration.


Assuntos
Nanoestruturas/química , Seda/química , Tecidos Suporte/química , Compostos de Anilina/química , Condutividade Elétrica , Grafite/química , Teste de Materiais , Propriedades de Superfície , Engenharia Tecidual
12.
Oncol Lett ; 19(4): 2621-2628, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32218812

RESUMO

Maspin has been identified as a tumor suppressor gene in breast cancer, but the underlying regulatory mechanisms remain unclear. In the present study, maspin pcDNA was transfected into MCF-7 cells. microRNA (miR) microarray and reverse transcription-quantitative polymerase chain reaction was used for analysis; the results demonstrated that maspin may inhibit miR-10b, miR-21 and miR-451 expression in MCF-7 cells. In addition, maspin increased the expression of certain miR-21 target genes (phosphatase and tensin homolog, programmed cell death 4 and B-cell lymphoma-2), miR-10b target gene (Homeobox D10; HOXD10) and miR-451 target gene (multidrug resistance protein 1). Furthermore, the results of the present study revealed that decreased expression of miR-21 suppressed the invasion and proliferation of MCF-7 cells. Therefore, in the present study, it was hypothesized that as a tumor-suppressor gene, the potential molecular mechanism of maspin include down-regulating the expression of miR-21 and increasing the expression of specific miR-21 target genes.

13.
Clin Neurol Neurosurg ; 192: 105706, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32058199

RESUMO

OBJECTIVES: Incidence rate of basal ganglia infarction (BGI) after mild head trauma was reported higher in children with basal ganglia calcification (BGC). We would like to review patients with BGC showed in head CT scan to see the incidence rate of stroke in these patients and the correlation of variables in these cases. PATIENTS AND METHODS: CT imaging data of cases with diagnosis of mild traumatic brain injury (mTBI) in a large tertiary pediatric center between Mar. 2014 and Mar. 2019 was retrospectively reviewed. Cases with findings of punctate calcification in the region of basal ganglion in CT scan were included. Correlation of variables of these cases (age, side and volume of basal ganglion calcification) with the diagnosis of BGI was the focus of this study. RESULTS: 37 patients (26 males, 9 females, median age: 3.88±3.54) were included in this study. 17 cases (45.9 %) were diagnosed of BGI and were admitted into the department of neurosurgery. Altogether 63 sides of BGC were categorized into two groups based on whether BGI happened and ROC curve was drawn. ROC curve showed when the cut-off point was 6.55 mm3, the sensitivity was 88.9 % and the specificity was 87.5 %; the area under curve was 0.849 (p<0.01). All the cases were divided into two groups according to whether basal ganglia infarction occurred or not. Mann-Whitney U test showed significant difference between these two groups in age (p=0.01). ROC curve of how age affect BGI after mTBI were drawn. The cut-off point was 3.25 years, and the sensitivity was 65.0 % and the specificity was 88.2 %; the area under curve was 0.746 (p=0.01). All patients received conservative treatment and recovered. CONCLUSION: Incidence rate is higher in children with BGC after mild head injury than that of other children. Larger BGC volume indicates higher risk of developing infarction after minor head injury. Older children with BGC are less-likely getting BGI after mTBI.

14.
J Transl Med ; 18(1): 25, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31937321

RESUMO

BACKGROUND: Immune checkpoint inhibitors are effective in some cases of lung adenocarcinoma (LUAD). Whole-exome sequencing has revealed that the tumour mutation burden (TMB) is associated with clinical benefits among patients from immune checkpoint inhibitors. Several commercial mutation panels have been developed for estimating the TMB regardless of the cancer type. However, different cancer types have different mutational landscapes; hence, this study aimed to develop a small cancer-type-specific mutation panel for high-accuracy estimation of the TMB of LUAD patients. METHODS: We developed a small cancer-type-specific mutation panel based on coding sequences (CDSs) rather than genes, for LUAD patients. Using somatic CDSs mutation data from 486 LUAD patients in The Cancer Genome Atlas (TCGA) database, we pre-selected a set of CDSs with mutation states significantly correlated with the TMB, from which we selected a CDS mutation panel with a panel-score most significantly correlated with the TMB, using a genetic algorithm. RESULTS: A mutation panel containing 106 CDSs of 100 genes with only 0.34 Mb was developed, whose length was much shorter than current commercial mutation panels of 0.80-0.92 Mb. The correlation of this panel with the TMB was validated in two independent LUAD datasets with progression-free survival data for patients treated with nivolumab plus ipilimumab and pembrolizumab immunotherapies, respectively. In both test datasets, survival analyses revealed that patients with a high TMB predicted via the 106-CDS mutation panel with a cut-point of 6.20 mutations per megabase, median panel score in the training dataset, had a significantly longer progression-free survival than those with a low predicted TMB (log-rank p = 0.0018, HR = 3.35, 95% CI 1.51-7.42; log-rank p = 0.0020, HR = 5.06, 95% CI 1.63-15.69). This small panel better predicted the efficacy of immunotherapy than current commercial mutation panels. CONCLUSIONS: The small-CDS mutation panel of only 0.34 Mb is superior to current commercial mutation panels and can better predict the efficacy of immunotherapy for LUAD patients, and its low cost and time-intensiveness make it more suitable for clinical applications.

16.
Childs Nerv Syst ; 36(9): 1935-1943, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31502037

RESUMO

PURPOSE: Our aim was to test whether the newly modified rhizotomy protocol which could be effectively used to guide single-level approach selective dorsal rhizotomy (SL-SDR) to treat spastic hemiplegic cases by mainly releasing those spastic muscles (target muscles) marked pre-operatively in their lower limbs was still applicable in spastic quadriplegic or diplegic cerebral palsy (CP) cases in pediatric population. METHODS: In the current study, we retrospectively conducted a cohort review of cases younger than 14 years of age diagnosed with spastic quadriplegic or diplegic CP who undergone our modified protocol-guided SL-SDR in the Department of Neurosurgery, Children's Hospital of Shanghai since July 2016 to November 2017 with at least 12 months post-op intensive rehabilitation program (pre-op GMFCS level-based). Clinical data including demographics, intra-operative EMG responses interpretation, and relevant assessment of included cases were taken from the database. Inclusion and exclusion criteria were set for the selection of patients in the current study. Muscle tone (modified Ashworth scale) and strength of those spastic muscles (muscle strength grading scale), range of motion (ROM) of those joints involved, the level of Gross Motor Function Classification System (GMFCS), and Gross Motor Function Measure 66 items (GMFM-66) score of those cases were our focus. RESULTS: A total of 86 eligible cases were included in our study (62 boys). Among these patients, 61.6% were quadriplegic. Pre-operatively, almost 2/3 of our cases were with GMFCS levels II and III. Mean age at the time of surgery in these cases was 6.2 (3.5-12) years. Pre-op assessment marked 582 target muscles in these patients. Numbers of nerve rootlets tested during SDR procedure were between 52 and 84 across our cases, with a mean of 66.5 ± 6.7/case. Among those tested (5721 in 86 cases), 47.9% (2740) were identified as lower limb-related sensory rootlets. Our protocol successfully differentiated sensory rootlets which were considered to be associated with spasticity of target muscles across all our 86 cases (ranged from 3 to 21). Based on our protocol, 871 dorsal nerve rootlets were sectioned 50%, and 78 were cut 75%. Muscle tone of those target muscles reduced significantly right after SL-SDR procedure (3 weeks post- vs. pre-op, 1.7 ± 0.5 vs. 2.6 ± 0.7). After an intensive rehabilitation program for 19.9 ± 6.0 months, muscle tone continued to decrease to 1.4 ± 0.5. With the reduction of muscle tone, strength of those target muscles in our cases improved dramatically with statistical significance achieved (3.9 ± 1.0 at the time of last follow-up vs. 3.3 ± 0.8 pre-op), and as well as ROM. Increase in GMFCS level and GMFM-66 score was observed at the time of last follow-up with a mean of 0.4 ± 0.6 and 6.1 ± 3.2, respectively, when compared with that at pre-op. In 81 cases with their pre-op GMFCS levels II to V, 27 (33.3%) presented improvement with regard to GMFCS level upgrade, among which 4 (4.9%) even upgraded over 2 levels. Better results with regard to upgrading in level of GMFCS were observed in cases with pre-op levels II and III when compared with those with levels IV and V (24/57 vs. 3/24). Upgrading percentage in cases younger than 6 years at surgery was significantly greater than in those older (23/56 vs. 4/25). Cases with their pre-op GMFM-66 score ≥ 50 had greater score increase of GMFM-66 when compared with those less (7.1 ± 3.4 vs. 5.1 ± 2.8). In the meanwhile, better score improvement was revealed in cases when SDR performed at younger age (6.9 ± 3.3 in case ≤ 6 years vs. 4.7 ± 2.7 in case > 6 years). No permanent surgery-related complications were recorded in the current study. CONCLUSION: SL-SDR when guided by our newly modified rhizotomy protocol was still feasible to treat pediatric CP cases with spastic quadriplegia and diplegia. Cases in this condition could benefit from such a procedure when followed by our intensive rehabilitation program with regard to their motor function.

17.
Biochem Biophys Res Commun ; 522(1): 26-32, 2020 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-31735338

RESUMO

Early secreted antigenic target 6-kDa protein (ESAT6) is an essential virulence factor of Mycobacterium tuberculosis (MTb). However, ESAT6 helped fighting MTb infection according to vaccine studies. It's unclear whether ESAT6 confers protection via enhancing the innate immunity of macrophages, which are the first-line defense against MTb. We profiled the global transcriptional changes and characterized the innate immunity of THP-1 macrophages treated with ESAT6. We found ESAT6 promoted the phagocytosis ability, enhanced reactive oxygen species (ROS) generation and accelerated glucose metabolism in macrophages. Meanwhile, ESAT6 induced a distinctive phenotype of macrophages with a concurrence of pro-inflammatory and anti-inflammatory cytokines and chemokines. ESAT6 increased the expression of HIF1α mRNA and protein. Interfering HIF1α with siRNA defected the capacity of phagocytosis and ROS generation as well as glucose metabolism. Thus, ESAT6 enhanced the protective innate immunity of macrophages partially via HIF1α. This study provided clues for developing therapies against tuberculosis by targeting ESAT6.


Assuntos
Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/imunologia , Imunidade Inata , Macrófagos/imunologia , Glucose/metabolismo , Humanos , Inflamação , Monócitos/microbiologia , Mycobacterium tuberculosis/metabolismo , Fagocitose , Fenótipo , RNA Interferente Pequeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Células THP-1
18.
Chemosphere ; 240: 124883, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31726606

RESUMO

A coupled algal-osmosis membrane treatment system was studied for recovering potable-quality water from municipal primary effluent. The core components of the system included a mixotrophic algal process for removal of biochemical oxygen demand (BOD) and nutrients, followed by a hybrid forward osmosis (FO)-reverse osmosis (RO) system for separation of biomass from the algal effluent and production of potable-quality water. Field experiments demonstrated consistent performance of the algal system to meet surface discharge standards for BOD and nutrients within a fed-batch processing time of 2-3 days. The hybrid FO-RO system reached water productivity of 1.57 L/m2-h in FO using seawater as draw solution; and permeate flux of 3.50 L/m2-h in brackish water RO (BWRO) and 2.07 L/m2-h in seawater RO (SWRO) at 2068 KPa. The coupled algal-membrane system achieved complete removal of ammonia, fluoride, and phosphate; over 90% removal of calcium, sulfate, and organic carbon; and 86-89% removal of potassium and magnesium. Broadband characterization using high resolution mass spectrometry revealed extensive removal of organic compounds, particularly wastewater surfactants upon algal treatment. This study demonstrated long-term performance of the FO system at water recovery of 90% and with membrane cleaning by NaOH solution.


Assuntos
Reatores Biológicos/microbiologia , Água Potável/análise , Membranas Artificiais , Rodófitas/crescimento & desenvolvimento , Purificação da Água/métodos , Filtração/métodos , Compostos Orgânicos/análise , Osmose , Águas Salinas/química , Água do Mar/química , Águas Residuárias/química , Poluentes Químicos da Água/análise
19.
Childs Nerv Syst ; 36(9): 1925-1933, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31686140

RESUMO

OBJECTIVE: Selective dorsal rhizotomy via a single-level approach (SL-SDR) to treat spasticity 100% relies on the interpretation of results from the intra-operative neuroelectrophysiological monitoring. The current study is to investigate the role EMG interpretation plays during SL-SDR procedure with regard to the selection of nerve rootlets for partially sectioning in pediatric cases with spastic cerebral palsy (CP). METHODS: A retrospective study was conducted in pediatric patients with spastic CP undergone our modified rhizotomy protocol-guided SL-SDR from May 2016 to Mar. 2019 in our hospital. Our study focused on intra-operative EMG interpretation and its correlation with pre-op evaluation results, and dorsal rootlet selection difference when data of our intra-operative EMG recordings interpreted using different rhizotomy protocols. RESULTS: Clinical and intra-operative neuroelectrophysiological monitoring data of a total of 318 consecutive cases were reviewed, which include 231 boys and 87 girls with 32 hemiplegias, 161 diplegias, and 125 quadriplegias. Age at the time of SL-SDR in those cases was between 3.0-14.0 (5.9 ± 1.9) years. The number of targeted muscle ranged from 2 to 8 over these cases (the muscle in lower limbs with its pre-op muscle tone ≥ 2 grade, Modified Ashworth scale). Among 21,728 nerve rootlets tested (68.3 ± 8.2/case), 6272 (28.9%) were identified sphincter related by our intra-operative neuromonitoring. In the rest of 15,456 (48.6 ± 7.6/case) nerve rootlets which neuromonitoring suggested associated with lower limbs, 11,009 were taken as the dorsal ones (34.6 ± 7.4/case). A total of 3370 (10.6 ± 4.7/case) rootlets matched our rhizotomy criteria with 3061 (9.6 ± 4.1/case) sectioned 50% and 309 (1.0 ± 1.0/case) cut 75%. The rhizotomy ratio (partially transected nerve rootlets/all dorsal rootlets associated with lower limbs in a particular case) was 15.8%, 22.3%, 33.4%, 41.8%, and 45.7% across cases with their pro-op GMFCS level from I to V, respectively. Rootlets required 75% cut had a tendency to increase as well in our cases with their pro-op GMFCS level from I to V, which comprising 1.5%, 4.8%, 8.5%, 14.1%, and 15.2% of all rootlets transected, respectively. The muscle tone of 2068 targeted muscles in these cases at the time of 3 weeks after the SL-SDR was revealed a significant decrease when compared to pre-op (1.7 ± 0.5 vs. 2.7 ± 0.6). Further investigation to compare our rootlet selection with the one guided by the traditional rhizotomy criteria using our intro-operative EMG recordings in 318 cases, revealed that the overlap ratio had a tendency to increase in cases when their pre-op GMFCS level increased (39.5%, 41.3%, 52.2%, 54.1%, and 62.8% in cases with levels I-V, respectively). While our modified rhizotomy protocol successfully identified 2-23 rootlets for sectioning in all of our 318 cases, the traditional rhizotomy protocol failed to distinguish any for cutting in about 20% of cases with their pre-op GMFCS levels I and II. CONCLUSIONS: The rhizotomy criteria fully rely on the EMG interpretation making intra-operative neuroelectrophysiological monitoring crucial when SDR is performed via a single-level approach. Our modified rhizotomy protocol is feasible, safe, and effective to guide SL-SDR to treat all types of spastic CP cases by decreasing muscle tone in particular spastic muscle groups in their lower limbs. Data of EMG responses during SL-SDR procedure and as well as the clinical outcomes based on their interpretation could help clinicians to further understand how neuronal circuits work in the spinal cord of these patients.

20.
Photochem Photobiol Sci ; 18(12): 2921-2930, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31691716

RESUMO

Boron nitride (BN) nanosheets are promising support materials for catalysts. A series of TiO2-BN enabled electrospun nanofibers were synthesized for the photocatalytic treatment of ibuprofen and secondary wastewater effluent under visible light. X-ray photoelectron spectroscopy confirmed the existence of B-O-Ti bonds between the BN nanosheets and TiO2 nanofibers, resulting in energy rearrangement, narrowed band gaps, and enhanced light utilization efficiency of the TiO2-BN nanocomposites in the visible light spectrum. Transient photocurrent measurements revealed that the BN enhanced the transport of photogenerated holes from the bulk TiO2 nanofibers to its surface, resulting in more efficient separation and less recombination of the charge carriers. A kinetic study of ibuprofen degradation indicated the enhanced photocatalytic performance of TiO2-BN catalysts with a higher BN content in the nanocomposites. The kinetic rate constant of the TiO2-10% BN catalysts was 10 times higher than that of the pure TiO2 nanofibers. The degradation of organic contaminants in wastewater followed the same trend as ibuprofen and improved with increasing BN content. The stability of the TiO2-BN nanocomposites as an effective solar photocatalyst was demonstrated by multiple cycles of wastewater treatment. The results proved that TiO2-BN is an appealing photocatalyst under visible light.


Assuntos
Compostos de Boro/química , Luz , Nanofibras/química , Preparações Farmacêuticas/química , Titânio/química , Eliminação de Resíduos Líquidos/métodos , Catálise , Ibuprofeno/química , Oxirredução , Poluentes Químicos da Água/química
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