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1.
Signal Transduct Target Ther ; 6(1): 342, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34531370

RESUMO

While some individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) present mild-to-severe disease, many SARS-CoV-2-infected individuals are asymptomatic. We sought to identify the distinction of immune response between asymptomatic and moderate patients. We performed single-cell transcriptome and T-cell/B-cell receptor (TCR/BCR) sequencing in 37 longitudinal collected peripheral blood mononuclear cell samples from asymptomatic, moderate, and severe patients with healthy controls. Asymptomatic patients displayed increased CD56briCD16- natural killer (NK) cells and upregulation of interferon-gamma in effector CD4+ and CD8+ T cells and NK cells. They showed more robust TCR clonal expansion, especially in effector CD4+ T cells, but lack strong BCR clonal expansion compared to moderate patients. Moreover, asymptomatic patients have lower interferon-stimulated genes (ISGs) expression in general but large interpatient variability, whereas moderate patients showed various magnitude and temporal dynamics of the ISGs expression across multiple cell populations but lower than a patient with severe disease. Our data provide evidence of different immune signatures to SARS-CoV-2 in asymptomatic infections.


Assuntos
COVID-19 , Portador Sadio/imunologia , Linfócitos/imunologia , SARS-CoV-2/imunologia , Análise de Célula Única , Transcriptoma/imunologia , Adolescente , Adulto , COVID-19/genética , COVID-19/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos B/genética , Receptores de Antígenos de Linfócitos B/imunologia , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , SARS-CoV-2/genética
2.
Protein Expr Purif ; 189: 105973, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34560256

RESUMO

The novel anti-PD-L1/TGFBR2-ECD fusion protein (BR102) comprises an anti-PD-L1 antibody (HS636) which is fused at the C terminus of the heavy chain to a TGF-ß1 receptor Ⅱ ectodomain (TGFBR2-ECD), and which can sequester the PD-1/PD-L1 pathway and TGF-ß bioactivity in the immunosuppressive tumor microenvironment. In the expression of TGFBR2-ECD wild-type fused protein (BR102-WT), a 50 kDa clipped species was confirmed to be induced by proteolytic cleavage at a "QKS" site located in the N-terminus of the ectodomain, which resulted in the formation of IgG-like clipping. The matrix metalloproteinase-9 was determined to be associated with BR102-WT digestion. In addition, it was observed that the N-glycosylation modifications of the fusion protein were tightly involved in regulating proteolytic activity and the levels of cleavage could be significantly suppressed by MMP-inhibitors. To avoid proteolytic degradation, eliminating protease-sensitive amino acid motifs and introducing potential glycosylation were performed. Three sensitive motifs were mutated, and the levels of clipping were strongly restrained. The mutant candidates exhibited similar binding affinities to hPD-L1 and hTGF-ß1 as well as highly purified BR102-WT2. Furthermore, the mutants displayed more significant proteolytic resistance than that of BR102-WT2 in the lysate incubation reaction and the plasma stability test. Moreover, the bifunctional candidate Mu3 showed an additive antitumor effect in MC38/hPD-L1 bearing models as compared to that of with anti-PD-L1 antibody alone. In conclusion, in this study, the protease-sensitive features of BR102-WT were well characterized and efficient optimization was performed. The candidate BR102-Mutants exhibited advanced druggability in drug stability and displayed desirable antitumor activity.

3.
Acta Pharmacol Sin ; 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34462564

RESUMO

N6-methyladenosine (m6A) is the most abundant posttranscriptional methylation modification that occurs in mRNA and modulates the fine-tuning of various biological processes in mammalian development and human diseases. In this study we investigated the role of m6A modification in the osteogenesis of mesenchymal stem cells (MSCs), and the possible mechanisms by which m6A modification regulated the processes of osteoporosis and bone necrosis. We performed systematic analysis of the differential gene signatures in patients with osteoporosis and bone necrosis and conducted m6A-RNA immunoprecipitation (m6A-RIP) sequencing to identify the potential regulatory genes involved in osteogenesis. We showed that fat mass and obesity (FTO), a primary m6A demethylase, was significantly downregulated in patients with osteoporosis and osteonecrosis. During the differentiation of human MSCs into osteoblasts, FTO was markedly upregulated. Both depletion of FTO and application of the FTO inhibitor FB23 or FB23-2 impaired osteogenic differentiation of human MSCs. Knockout of FTO in mice resulted in decreased bone mineral density and impaired bone formation. PPARG, a biomarker for osteoporosis, was identified as a critical downstream target of FTO. We further revealed that FTO mediated m6A demethylation in the 3'UTR of PPARG mRNA, and reduced PPARG mRNA stability in an YTHDF1-dependent manner. Overexpression of PPARG alleviated FTO-mediated osteogenic differentiation of MSCs, whereas knockdown of PPARG promoted FTO-induced expression of the osteoblast biomarkers ALPL and OPN during osteogenic differentiation. Taken together, this study demonstrates the functional significance of the FTO-PPARG axis in promoting the osteogenesis of human MSCs and sheds light on the role of m6A modification in mediating osteoporosis and osteonecrosis.

4.
Medicine (Baltimore) ; 100(22): e26247, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087913

RESUMO

RATIONALE: Open total dislocation of ankle joint is rare and often caused by high-energy injury. The present study describes a patient with open total lateral dislocation of ankle joint without fractures and obtained a satisfactory clinical result following early debridement and irrigation, one-stage repairment of ligaments, and plaster external fixation. PATIENT CONCERNS: The patient, a 45-year-old male, complained of right foot pain with bleeding and limited motion. Physical examination showed a 15-cm open wound at the medial ankle region, with soft tissues impaired and ankle bones exposed. The 3 dimensional reconstruction computed tomography (CT) examination showed an open total dislocation of ankle joint without concomitant fractures. DIAGNOSES: open total lateral dislocation of ankle joint without fractures. INTERVENTIONS: Early modern wound care including thorough debridement and irrigation on the wound was performed to remove contaminated soft tissues. Subsequently, the dislocated ankle joint was reduced by hand and the medial and lateral collateral ligaments were repaired using wire anchors. OUTCOMES: The medial wound healed at 2 weeks after surgery, and several common complications such as infection and skin necrosis did not occur. The last follow-up showed a good range of metatarsal flexion and extension of the injured foot, and obvious signs of traumatic arthritis were not observed. According to Kaikkonen ankle function score, the patient was assessed with 90 points. LESSONS: For open total dislocation of ankle joint, early treatment should focus on debridement and irrigation, reduction and fixation of the dislocated ankle, protection of the weak soft tissues, and stable external fixation to promote wound healing and reduce the incidence of related complications.


Assuntos
Articulação do Tornozelo/patologia , Desbridamento/métodos , Luxações Articulares/cirurgia , Irrigação Terapêutica/métodos , Assistência ao Convalescente , Articulação do Tornozelo/diagnóstico por imagem , Humanos , Imageamento Tridimensional/instrumentação , Luxações Articulares/diagnóstico , Ligamentos Laterais do Tornozelo/lesões , Ligamentos Laterais do Tornozelo/cirurgia , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular/fisiologia , Lesões dos Tecidos Moles/patologia , Lesões dos Tecidos Moles/cirurgia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Ferimentos e Lesões/patologia , Ferimentos e Lesões/cirurgia
5.
Cytokine ; 142: 155500, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33810947

RESUMO

We quantified the serum levels of 34 cytokines/chemokines in 30 patients with SARS-CoV-2 infection. Elevated levels of IP-10 and IL-7 were detected in the acute and convalescent stages of the infection and were highly associated with disease severity.


Assuntos
COVID-19/sangue , Quimiocina CXCL10/sangue , Interleucina-7/sangue , SARS-CoV-2/metabolismo , Índice de Gravidade de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
6.
Aesthet Surg J ; 41(7): NP748-NP757, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-33621335

RESUMO

BACKGROUND: Results regarding immediate prosthetic breast reconstruction after postmastectomy radiation therapy (PMRT) have been inconsistent. OBJECTIVES: The authors aimed to assess the efficacy and safety of PMRT before immediate prosthetic breast reconstruction for patients with breast cancer. METHODS: Electronic databases (PubMed, EmBase, and the Cochrane Library) were systematically searched to identify eligible studies from their inception until March 2020. The pooled odds ratio (OR) with 95% confidence intervals (CIs) was applied as an effect estimate and calculated using the random-effects model. RESULTS: Nineteen studies including a total of 6757 patients were selected for final meta-analysis. The pooled OR showed that PMRT was associated with a higher incidence of reconstruction failure (OR = 2.57; 95% CI =1.55-4.26; P < 0.001), capsular contracture (OR = 5.99; 95% CI = 3.12-11.47; P < 0.001), and overall complications (OR = 2.52; 95% CI = 1.68-3.79; P < 0.001). It was also associated with a lower incidence of patient satisfaction (OR = 0.29; 95% CI = 0.16-0.52; P < 0.001) and good aesthetic results (OR = 0.25; 95% CI = 0.12-0.52; P < 0.001) compared with those who did not undergo PMRT. These significant associations could be affected by study design, mean age, stage of immediate breast reconstruction, follow-up, and study quality. CONCLUSIONS: Although PMRT is the standard adjuvant therapy for mastectomy patients treated with immediate implant-based breast reconstruction, PMRT for patients undergoing immediate implant-based breast reconstruction has been associated with high risks of reconstruction failure, capsular contracture, and overall complications as well as low incidences of patient satisfaction and good aesthetic results.


Assuntos
Neoplasias da Mama , Mamoplastia , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mamoplastia/efeitos adversos , Mastectomia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Radioterapia Adjuvante/efeitos adversos
7.
Aesthetic Plast Surg ; 45(4): 1469-1475, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33420512

RESUMO

BACKGROUND: Breast ptosis is a deformity commonly found in patients seeking breast augmentation. Current mastopexy techniques rely on incisions on the breast to correct ptosis; nonetheless, they leave extensive scars. Having to opt for a visibly scarred breast over a ptotic breast can be a difficult choice. OBJECTIVES: We sought an innovative internal suture mastopexy for hypomastia of mild breast ptosis. METHODS: A procedure that left a tiny scar on the nipple-areolar complex was introduced. This method was safe and efficient when combining mastopexy with augmentation. RESULTS: Overall, 53 patients underwent this operation in the Plastic and Cosmetic Department of Guangdong Second Provincial General Hospital from January 1, 2013, to June 30, 2017, with a mean follow-up of 38 ± 16 months. The pre-operation and post-operation SN-N lines (the distance from the sternal notch to the nipple) were 21.8 ± 1.2 cm and 20.7 ± 1.0 cm, respectively; the difference was statistically significant (P<0.05). The patients and surgeon expressed satisfaction with the procedure. CONCLUSION: Based on the results of the present study, which included more than 50 patients, we believe that internal suture mastopexy can be used as an effective alternative hypomastia in patients with mild breast ptosis. LEVEL OF EVIDENCE IV: IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. .


Assuntos
Mamoplastia , Estudos de Coortes , Estética , Humanos , Mamilos/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
8.
Artigo em Inglês | MEDLINE | ID: mdl-33360415

RESUMO

Charge variants are the most commonly observed sources of heterogeneity in the routine manufacturing of monoclonal antibodies. To gain further insight into the structural foundation of charge heterogeneity and its influence on biological functions, an infliximab biosimilar HS626 from a biopharmaceutical facility was isolated by semipreparative cation exchange chromatography (CEX) to obtain fractions of acidic and basic charge variants and determine the main species. It was assessed again by CEX to ensure purities. Through a series of structural and physicochemical characterizations, we concluded that the acidic variants were caused by fragments, Met oxidation, Asn deamidation, higher levels of sialylation and galactosylation of N-linked glycans, and less high mannose. The basic variants resulted mainly from aggregates, fragments, and Met oxidation. Through further analysis of antigen binding affinity, cell death inhibitory activity, ADCC, and CDC, as well as FcRn, FcγRIIIa, and C1q affinity, we demonstrated that the charge heterogeneity did not affect biological functions. This research enhances the understanding of charge variants, which are usually effective components that should not be intentionally reduced unless biological functions are affected.


Assuntos
Medicamentos Biossimilares , Infliximab , Sequência de Aminoácidos , Animais , Medicamentos Biossimilares/análise , Medicamentos Biossimilares/química , Medicamentos Biossimilares/isolamento & purificação , Células CHO , Linhagem Celular , Cromatografia por Troca Iônica/métodos , Cricetinae , Cricetulus , Glicosilação , Infliximab/análise , Infliximab/química , Infliximab/isolamento & purificação , Camundongos
9.
Int J Ophthalmol ; 13(6): 902-906, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32566500

RESUMO

AIM: To study the imaging characteristics of lacrimal punctum lesion with optical coherence tomography (OCT), and provide imaging basis for the diagnosis and treatment of lacrimal punctum diseases. METHODS: A total of 25 patients (28 eyes) with epiphora and lacrimal puncta lesions were enrolled. Lacrimal puncta lesions included: punctum membrane obstruction in 7 cases (9 eyes), punctum agenesis in 1 case (1 eye), a mass protruded from the punctum in 1 case (1 eye), slit puncta in 1 case (1 eye), peri-puncta mass in 2 cases (2 eyes), chronic dacryocystitis in 4 cases (4 eyes), and primary puncta stenosis in 9 cases (10 eyes; 3 eyes mild, 4 eyes moderate and 3 eyes severe). All patients were examined by slit lamp microscopy and OCT to observe the morphological characteristics of abnormal punctum. RESULTS: Two types of complete membrane obstruction and incomplete membrane obstruction of puncta were observed in OCT images of 7 patients. No lacrimal punctum and lacrimal canalicular cavity were found in 1 case with punctum agenesis. OCT images showed that a narrow lumen remained in the lacrimal puncta in 1 patient with a mass protruded from the punctum. OCT of punctum in a patient with slit punctum after stent placement showed stent and abnormal lacrimal structure. No abnormal intraluminal structure was found in 2 cases of peri-puncta mass after OCT scan, and the lacunar space was narrower than that of the contralateral eye. OCT of puncta in 4 patients with chronic dacryocystitis showed that pus floated in tear with lump-like medium-low reflex. In 9 patients with primary lacrimal puncta stenosis, OCT image could clearly show the changes of puncta lumen in different degrees and shapes. CONCLUSION: OCT is feasible for the examination of pathological punctum, and can provide imaging basis for the diagnosis and treatment of punctum disease.

10.
Cancer Manag Res ; 12: 2711-2717, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32368148

RESUMO

Purpose: The purpose of this study is to investigate the diagnostic role of Hounsfield unit (HU) values on noncontrast computed tomography (CT) for differentiating benignity from malignancy in the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) 4-5 nodules with coarse calcifications. Patients and Methods: CT images of 216 ACR TI-RADS 4-5 nodules with coarse calcifications from 207 patients who underwent surgery in our hospital between 2017 and 2019 were retrospectively reviewed. The average HU values (AHUVs) and maximum HU values (MHUVs) of the nodules were measured on noncontrast CT. The distribution of AHUVs and MHUVs in benign and malignant nodules with coarse calcifications was analyzed using the Mann-Whitney test. Receiver operating characteristic (ROC) curves were used to identify the best cut-off values. Diagnostic performances were assessed according to the area under the ROC curve (AUC), sensitivity and specificity. Results: Of the 216 ACR TI-RADS 4-5 nodules with coarse calcifications, 170 were benign and 46 were malignant. The AHUVs of benign and malignant nodules were 791 HU [interquartile range (IQR), 543-1025 HU] and 486 HU (IQR, 406-670 HU), respectively (P < 0.001). The MHUVs of benign and malignant nodules were 1084 HU (IQR, 717-1477 HU) and 677 HU (IQR, 441-986 HU), respectively (P < 0.001). The AUCs for AHUVs and MHUVs for predicting benign nodules with coarse calcifications were 0.759 and 0.732, and the cut-off values were 627.5 HU and 806.0 HU, with sensitivities of 67.6% and 68.8% and specificities of 73.9% and 67.4%, respectively. The sensitivity and specificity of the combination were 68.8% and 76.1%. Conclusion: AHUVs and MHUVs were helpful in differentiating benignity from malignancy in ACR TI-RADS 4-5 nodules with coarse calcifications. This may provide an important basis for reducing misdiagnosis and unnecessary aspiration or surgical trauma.

11.
J Orthop Surg Res ; 15(1): 108, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32183855

RESUMO

BACKGROUND: To compare the efficacy of three-point locating versus routine locating techniques for implanting helical blades for proximal femoral nail anti-rotation-II in the treatment of trochanteric fractures. METHODS: From January 2010 to June 2013, 90 patients with intertrochanteric fractures were surgically treated, including 48 males and 42 females with an average age of 70.5 ± 7.2 years. According to the AO classification, there were 45 cases of A2.1, 35 cases of A2.2, and 10 cases of A2.3. Based on locating techniques, the 90 patients were divided into two groups: the three-point group and the routine group, with 45 patients in each group. All operations were performed by the same group of surgeons using proximal femoral nail anti-rotation (PFNA); the helical blade was inserted into the femoral neck with the three-point locating technique or by the usual method according to treatment group. Several figures including total operation time, elapsed time for implanting the helical blade, intraoperative blood loss, X-ray exposure time, and tip-apex distance (TAD) were measured and compared. RESULTS: The three-point group was significantly superior as compared to the routine group in terms of total operation time [(59.34 ± 9.42) min vs (67.61 ± 12.63) min, P < 0.01], elapsed time for implanting the helical blade [(4.58 ± 1.25) min vs (7.82 ± 2.19) min, P < 0.01], intraoperative blood loss [(92.78 ± 34.09) ml vs (154.01 ± 39.10) ml, P < 0.01], X-ray exposure time [(8.84 ± 1.45) vs (14.62 ± 2.91), P < 0.01], and tip-apex distance [(16.78 ± 1.55) mm vs (21.91 ± 3.01) mm, P < 0.01]. Among the 90 patients, 80 were followed up for an average time of 12 months (10-15 months), including 42 patients who were part of three-point group and 38 patients who were part of the routine group. No spiral blade cut was found on the femoral head in any patient in the three-point group, whereas it occurred in 2 patients in the routine group 1 month after surgery. However, there was no significant difference in the Harris score between the two groups 6 months after the operation. CONCLUSION: The three-point locating method is faster and more accurate than the routine locating method.


Assuntos
Pinos Ortopédicos , Fraturas do Fêmur/cirurgia , Fixação Interna de Fraturas/métodos , Fraturas do Quadril/cirurgia , Monitorização Intraoperatória/métodos , Rotação , Idoso , Idoso de 80 Anos ou mais , Feminino , Fraturas do Fêmur/diagnóstico por imagem , Seguimentos , Fixação Interna de Fraturas/instrumentação , Fraturas do Quadril/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
12.
Cancer Manag Res ; 12: 1947-1958, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32214852

RESUMO

Objective: The disease complexity of metastatic non-small-cell lung cancer (mNSCLC) makes it difficult for physicians to make clinical decisions efficiently and accurately. The Watson for Oncology (WFO) system of artificial intelligence might help physicians by providing fast and precise treatment regimens. This study measured the concordance of the medical treatment regimens of the WFO system and actual clinical regimens, with the aim of determining the suitability of WFO recommendations for Chinese patients with mNSCLC. Methods: Retrospective data of mNSCLC patients were input to the WFO, which generated a treatment regimen (WFO regimen). The actual regimen was made by physicians in a medical team for patients (medical-team regimen). The factors influencing the consistency of the two treatment options were analyzed by univariate and multivariate analyses. Results: The concordance rate was 85.16% between the WFO and medical-team regimens for mNSCLC patients. Logistic regression showed that the concordance differed significantly for various pathological types and gene mutations in two treatment regimens. Patients with adenocarcinoma had a lower rate of "recommended" regimen than those with squamous cell carcinoma. There was a statistically significant difference in EGFR-mutant patients for "not recommended" regimens with inconsistency rate of 18.75%. In conclusion, the WFO regimen has 85.16% consistency rate with medical-team regimen in our treatment center. The different pathological type and different gene mutation markedly influenced the agreement rate of the two treatment regimens. Conclusion: WFO recommendations have high applicability to mNSCLC patients in our hospital. This study demonstrates that the valuable WFO system may assist the doctors better to determine the accurate and effective treatment regimens for mNSCLC patients in the Chinese medical setting.

14.
Mol Ther Nucleic Acids ; 20: 164-175, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32169804

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is the sixth most frequently diagnosed cancer worldwide. However, the clinical outcomes remain unsatisfactory. The aim of this study is to unravel the functional role and regulatory mechanism of HOXA9 in HNSCC. A cohort of 25 HNSCC tumor tissues and normal tissue counterparts was collected. qRT-PCR and western blotting were performed to determine the levels of HOXA9 and epithelial-mesenchymal transition (EMT)-related markers. Cell Counting Kit-8 (CCK-8) and colony formation assays were conducted to monitor cell viability and cytotoxicity. Transwell and wound healing assays were used to determine cell migration and invasion. Annexin V-fluorescein isothiocyanate/propidium iodide (FITC/PI) staining was performed to detect cell apoptosis. Bioinformatic analysis, electrophoretic mobility shift assay and chromatin immunoprecipitation (ChIP) assays were performed to investigate the direct binding between HIF-1α or CCCTC binding factor (CTCF) and HOXA9. Glutathione S-transferase (GST) pull-down and RNA pull-down assays were used to validate the interaction between CTCF and HOTTIP. HOXA9 was upregulated in HNSCC tissues and cells. Knockdown of HOXA9 inhibited cell proliferation, migration, invasion, and chemoresistance but promoted apoptosis in CAL-27 and KB cells. Knockdown of HOXA9 also regulated EMT-related marker via targeting YAP1/ß-catenin. Silencing of HOTTIP or CTCF exerted similar tumor-suppressive effects in HNSCC. Mechanistically, HIF-1α or CTCF transcriptionally regulated HOXA9, and HOTTIP/CTCF cooperatively regulated HOXA9 in KB cells. HIF-1α or HOTTIP/CTCF transcriptionally modulates HOXA9 expression to regulate HNSCC progression and drug resistance.

15.
Asian J Androl ; 22(1): 79-87, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31210146

RESUMO

The transition from spermatogonia to spermatocytes and the initiation of meiosis are key steps in spermatogenesis and are precisely regulated by a plethora of proteins. However, the underlying molecular mechanism remains largely unknown. Here, we report that Src homology domain tyrosine phosphatase 2 (Shp2; encoded by the protein tyrosine phosphatase, nonreceptor type 11 [Ptpn11] gene) is abundant in spermatogonia but markedly decreases in meiotic spermatocytes. Conditional knockout of Shp2 in spermatogonia in mice using stimulated by retinoic acid gene 8 (Stra8)-cre enhanced spermatogonial differentiation and disturbed the meiotic process. Depletion of Shp2 in spermatogonia caused many meiotic spermatocytes to die; moreover, the surviving spermatocytes reached the leptotene stage early at postnatal day 9 (PN9) and the pachytene stage at PN11-13. In preleptotene spermatocytes, Shp2 deletion disrupted the expression of meiotic genes, such as disrupted meiotic cDNA 1 (Dmc1), DNA repair recombinase rad51 (Rad51), and structural maintenance of chromosome 3 (Smc3), and these deficiencies interrupted spermatocyte meiosis. In GC-1 cells cultured in vitro, Shp2 knockdown suppressed the retinoic acid (RA)-induced phosphorylation of extracellular-regulated protein kinase (Erk) and protein kinase B (Akt/PKB) and the expression of target genes such as synaptonemal complex protein 3 (Sycp3) and Dmc1. Together, these data suggest that Shp2 plays a crucial role in spermatogenesis by governing the transition from spermatogonia to spermatocytes and by mediating meiotic progression through regulating gene transcription, thus providing a potential treatment target for male infertility.


Assuntos
Meiose/genética , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Espermatócitos/metabolismo , Espermatogênese/genética , Espermatogônias/metabolismo , Animais , Proteínas de Ciclo Celular/genética , Linhagem Celular , Sobrevivência Celular , Proteoglicanas de Sulfatos de Condroitina/genética , Proteínas Cromossômicas não Histona/genética , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Infertilidade Masculina , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Proteínas de Ligação a Fosfato/genética , Rad51 Recombinase/genética , Reação em Cadeia da Polimerase em Tempo Real , Espermatócitos/citologia , Espermatogônias/citologia
16.
J Ind Microbiol Biotechnol ; 47(1): 63-72, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31754859

RESUMO

As the composition of animal cell culture medium becomes more complex, the identification of key variables is important for simplifying and guiding the subsequent medium optimization. However, the traditional experimental design methods are impractical and limited in their ability to explore such large feature spaces. Therefore, in this work, we developed a NRGK (nonparametric regression with Gaussian kernel) method, which aimed to identify the critical components that affect product titres during the development of cell culture media. With this nonparametric model, we successfully identified the important components that were neglected by the conventional PLS (partial least squares regression) method. The superiority of the NRGK method was further verified by ANOVA (analysis of variance). Additionally, it was proven that the selection accuracy was increased with the NRGK method because of its ability to model both the nonlinear and linear relationships between the medium components and titres. The application of this NRGK method provides new perspectives for the more precise identification of the critical components that further enable the optimization of media in a shorter timeframe.


Assuntos
Algoritmos , Animais , Células CHO , Cricetulus , Meios de Cultura , Análise dos Mínimos Quadrados , Projetos de Pesquisa
17.
Ying Yong Sheng Tai Xue Bao ; 30(10): 3385-3394, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31621224

RESUMO

To promote the application of domestic high-resolution satellite data in large-scale carbon storage estimation and measurement, a total of 206 high-resolution remote sensing images covering Hunan Province were used as the data source, and the estimated minimum unit was fixed as a 0.06 hm2 square composed of multiple pixels. Through the establishment and purification of the interpretation marks, in the extraction of forest information, the pixel-based method and object-oriented classification method were used to compare. In the estimation of carbon storage of arbor forest, the robust estimate, partial least squares method and k-NN estimate were used to compare. Finally, we estimated forest carbon storage in Hunan Province and generated the distribution map of carbon density levels. The results showed that the interpretation mark based on the automatic extraction of plots could increase the extraction accuracy of arbor forest after purification. For the estimation of forest carbon storage at large-scale, the k-NN algorithm embodied a large advantage in forest information extraction and arbor forest carbon storage modeling. The average classification accuracy of the 206 scene images was 76.8%, the average RMSE was 8.95 t·hm-2, the average RRMSE was 19.1%, and the total carbon stock in Hunan Province was 22.28 Mt. The results provided effective reference for the estimation and measurement of forest carbon storage at the provincial and national scales.


Assuntos
Sequestro de Carbono , Carbono , China , Florestas , Árvores
18.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 37(4): 378-383, 2019 Aug 01.
Artigo em Chinês | MEDLINE | ID: mdl-31512829

RESUMO

OBJECTIVE: To investigate the effect of the long chain non-coding RNA H19 (lncRNA H19) on the invasion and migration of oral cancer cells and its related molecular mechanism. METHODS: The expression levels of lncRNA H19, miR-107, and cyclin-dependent kinase 6 (CDK6) in the immortalized oral epithelial cell line HIOEC and the oral cancer cell line CAL27 were detected by real-time quantitative polymerase chain reaction. CAL27 cells were transfected with siRNA H19, miR-107 mimics, pcDNA H19, or anti-miR-107, and the effects of H19 and miR-107 on the invasion and migration of cells were examined via Transwell assay. The TargetScan database predicted the targeting of H19, miR-107, and CDK6. Double luciferase reporter gene assay was performed to detect interactions among H19, miR-107, and CDK6. Western blot analysis was conducted to examine the effects of H19 and miR-107 on the protein level of the target gene CDK6. RESULTS: Compared with that in HIOEC cells, the expression of H19 was significantly increased in CAL27 cells (P<0.05). After transfection with siRNA H19, the expression of H19 decreased, and the invasion and migration ability of CAL27 cells were inhibited (P<0.05). H19 could bind specifically to the 3'-UTR of miR-107 to modulate the expression of miR-107. Compared with that in HIOEC cells, the expression of miR-107 significantly decreased in CAL27 cells (P<0.05). The expression of miR-107 increased after transfection with siRNA H19, and anti-mir-107 co-transfection could promote the invasion and migration ability of siRNA H19 in CAL27 cells (P<0.05). Compared with that in HIOEC cells, CDK6 expression significantly increased in CAL27 cells (P<0.05), and the expression level of the gene was coregulated by H19 and miR-107 (P<0.05). CONCLUSIONS: lncRNA H19 plays an important role in the development of oral cancer. It can regulate the invasion and migration of oral cancer cells by targeting the miR-107/CDK6 signaling axis.


Assuntos
MicroRNAs , Neoplasias Bucais , RNA Longo não Codificante , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Humanos
19.
Materials (Basel) ; 12(18)2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31540464

RESUMO

Engineering surface structure of catalysts is an efficient way towards high catalytic performance. Here, we report on the synthesis of regular iridium nanospheres (Ir NSs), with abundant atomic steps prepared by a laser ablation technique. Atomic steps, consisting of one-atom level covering the surface of such Ir NSs, were observed by aberration-corrected high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM). The prepared Ir NSs exhibited remarkably enhanced activity both for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) in acidic medium. As a bifunctional catalyst for overall water splitting, they achieved a cell voltage of 1.535 V @ 10 mA/cm2, which is much lower than that of Pt/C-Ir/C couple (1.630 V @ 10 mA/cm2).

20.
J Int Med Res ; 47(6): 2446-2451, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31006358

RESUMO

OBJECTIVE: We aimed to investigate the role of the intestinal neurotransmitters vasoactive intestinal peptide (VIP) and substance P (SP) at different time points in infants with acute intussusception. METHODS: Thirty patients who were diagnosed with acute intussusception were enrolled in the study and classified as the experimental group. Another 30 patients with an indirect inguinal hernia who had no intestinal injury were included as the control group. Serum SP and VIP levels at different time points, including pre- and postoperation, were detected by enzyme-linked immunosorbent assay and compared between the two groups. RESULTS: Serum SP levels in patients with acute intussusception were significantly higher than those in controls. However, with recovery of acute intussusception, SP levels gradually decreased after treatment. Serum VIP levels in patients with acute intussusception were significantly lower than those in controls. However, with recovery of acute intussusception, VIP levels gradually increased after treatment. CONCLUSIONS: SP and VIP levels may have a potential relationship with the pathogenetic process of intussusception.


Assuntos
Biomarcadores/sangue , Intussuscepção/sangue , Intussuscepção/diagnóstico , Substância P/sangue , Peptídeo Intestinal Vasoativo/sangue , Doença Aguda , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Lactente , Masculino , Prognóstico , Estudos Retrospectivos
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