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1.
BMC Musculoskelet Disord ; 25(1): 364, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724954

RESUMO

PURPOSE: To evaluate the perioperative clinical outcomes of en bloc resection and anterior column reconstruction for thoracolumbar spinal tumors. METHODS: This study conducted a retrospective analysis of prospective data collection of 86 consecutive patients, including 40 males and 46 females, with an average age of 39 years (ranged from 10 to 71 years). There were 35 cases of a malignant primary tumor,42 cases of an aggressive benign tumor, and nine cases of metastases. The main lesions were located in 65 cases of thoracic spine, 17 cases of lumbar spine, and 4 cases of thoracolumbar spine. Tumors involved one level in 45 patients, two levels in 12 patients, three levels in 21 patients, four levels in five patients, five levels in two patients, and six levels in one patient. RESULTS: According to the Weinstein-Boriani-Biagini surgical staging system, all patients achieved en bloc resections, including 74 cases of total en bloc spondylectomy and 12 cases of sagittal resections. The mean surgical time was 559 min (210-1208 min), and the mean total blood loss was 1528 ml (260-5500 ml). A total of 122 complications were observed in 62(72.1%) patients, of which 18(20.9%) patients had 25 major complications and one patient (1.2%) died of complications. The combined approach (P = 0.002), total blood loss (P = 0.003), staged surgery (P = 0.004), previous surgical history (P = 0.045), the number of involved vertebrae (P = 0.021) and lumbar location (P = 0.012) were statistically significant risk factors for major complication. When all above risk factors were incorporated in multivariate analysis, only the combined approach (P = 0.052) still remained significant. CONCLUSIONS: En bloc resection and anterior column reconstruction is accompanied by a high incidence of complications, especially when a combined approach is necessary.


Assuntos
Vértebras Lombares , Procedimentos de Cirurgia Plástica , Complicações Pós-Operatórias , Neoplasias da Coluna Vertebral , Vértebras Torácicas , Humanos , Masculino , Feminino , Neoplasias da Coluna Vertebral/cirurgia , Pessoa de Meia-Idade , Vértebras Lombares/cirurgia , Adulto , Vértebras Torácicas/cirurgia , Estudos Retrospectivos , Idoso , Adolescente , Procedimentos de Cirurgia Plástica/métodos , Procedimentos de Cirurgia Plástica/efeitos adversos , Adulto Jovem , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Criança , Resultado do Tratamento
2.
J Hosp Infect ; 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38710306

RESUMO

Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Acinetobacter baumannii infections pose challenges for clinical treatment and cause high mortality, particularly in intensive care units (ICUs). Identifying the risk factors for MDR and XDR infection is crucial, and existing findings remain controversial. We aim to systematically summarize and analyze the risk factors for MDR/XDR A. baumannii-infected patients admitted to ICUs. We searched PubMed, Embase, Web of Science, and the Cochrane Library for eligible original studies published in English before October 2023. We conducted meta-analysis where appropriate, with mean differences (MD) and odds ratios (ORs) calculated for continuous and nominal scaled data. The quality of the included studies was assessed using the Newcastle Ottawa scale (NOS). Ten studies reporting 1199 ICU patients (604 from general ICUs, 435 from neonatal ICUs, and 160 from pediatric ICUs) from eight countries were included in our analysis. The risk factors associated with MDR A. baumannii infection among patients admitted to general ICUs included a high APACHE Ⅱ score (MD = 7.52; 95% CI 3.24-11.80; P = 0.0006), invasive procedures (OR = 3.47; 95% CI 1.70-7.10; P = 0.0006), longer ICU stay (MD = 3.40; 95% CI: 2.94-3.86; P < 0.00001), and the use of antibiotics (OR = 2.69; 95% CI 1.22-5.94; P = 0.01). Moreover, in our sub-group analysis, longer neonatal ICU stay (MD = 16.88; 95% CI 9.79-23.97; P < 0.00001) was found to be associated with XDR A. baumannii infection. These findings indicate that close attention should be paid to patients with longer ICU stays, undergoing invasive procedures, using antibiotics, and with high APACHE Ⅱ scores to reduce the risk of MDR and XDR A. baumannii infections.

3.
Sci Data ; 11(1): 461, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38710675

RESUMO

Oriental tobacco budworm (Helicoverpa assulta) and cotton bollworm (Helicoverpa armigera) are two closely related species within the genus Helicoverpa. They have similar appearances and consistent damage patterns, often leading to confusion. However, the cotton bollworm is a typical polyphagous insect, while the oriental tobacco budworm belongs to the oligophagous insects. In this study, we used Nanopore, PacBio, and Illumina platforms to sequence the genome of H. assulta and used Hifiasm to create a haplotype-resolved draft genome. The Hi-C technique helped anchor 33 primary contigs to 32 chromosomes, including two sex chromosomes, Z and W. The final primary haploid genome assembly was approximately 415.19 Mb in length. BUSCO analysis revealed a high degree of completeness, with 99.0% gene coverage in this genome assembly. The repeat sequences constituted 38.39% of the genome assembly, and we annotated 17093 protein-coding genes. The high-quality genome assembly of the oriental tobacco budworm serves as a valuable genetic resource that enhances our comprehension of how they select hosts in a complex odour environment. It will also aid in developing an effective control policy.


Assuntos
Genoma de Inseto , Haplótipos , Mariposas , Animais , Mariposas/genética , Cromossomos de Insetos , Helicoverpa armigera
4.
Medicine (Baltimore) ; 103(18): e37959, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38701270

RESUMO

It has been established that gut dysbiosis contributed to the pathogenesis of digestive disorders. We aimed to explore the causal relationships between intestinal microbiota, circulating inflammatory cytokines and chronic pancreatitis (CP). Summary statistics of genome-wide association studies (GWAS) of intestinal microbiome was retrieved from the MiBioGen study and the GWAS data of 91 circulating inflammatory cytokines and CP were obtained from the GWAS catalog. The 2-sample bidirectional Mendelian randomization (MR) analysis was performed between gut microbiota, circulating inflammatory cytokines and CP, in which the inverse variance weighted (IVW) method was regarded as the primary analysis approach. To prove the reliability of the causal estimations, multiple sensitivity analyses were utilized. IVW results revealed that genetically predicted 2 genera, including Sellimonas and Eubacteriumventriosumgroup, and plasm C-C motif chemokine 23 (CCL23) level were positively associated with CP risk, while genus Escherichia Shigella, Eubacteriumruminantiumgroup and Prevotella9, and plasma Caspase 8, Adenosine Deaminase (ADA), and SIR2-like protein 2 (SIRT2) level, demonstrated an ameliorative effect on CP. Leave-one-out analysis confirmed the robustness of the aforementioned causal effects and no significant horizontal pleiotropy or heterogeneity of the instrumental variables was detected. However, no association was found from the identified genera to the CP-related circulating inflammatory cytokines. Besides, the reverse MR analysis demonstrated no causal relationship from CP to the identified genera and circulating inflammatory cytokines. Taken together, our comprehensive analyses offer evidence in favor of the estimated causal connections from the 5 genus-level microbial taxa and 4 circulating inflammatory cytokines to CP risk, which may help to reveal the underlying pathogenesis of CP.


Assuntos
Citocinas , Microbioma Gastrointestinal , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Pancreatite Crônica , Humanos , Microbioma Gastrointestinal/genética , Citocinas/sangue , Pancreatite Crônica/microbiologia , Pancreatite Crônica/sangue , Pancreatite Crônica/genética
5.
Inorg Chem ; 63(19): 8863-8878, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38695487

RESUMO

The determination of the site occupancy of activators in phosphors is essential for precise synthesis, understanding the relationship between their luminescence properties and crystal structure, and tailoring their properties by modifying the host composition. Herein, one simple method was proposed to help determine the sites at which the doping of rare earth ions or transition metal ions occupies in the host lattice through site occupancy theory (SOT) for ions doped into the matrix lattice. SOT was established based on the fact that doping ions preferentially occupy the sites with the lowest bonding energy deviations. In order to provide detailed experimental evidence to prove the feasibility of SOT, several scheelite-type compounds were successfully synthesized using a high-temperature solid-phase method. When Eu3+ ions occupy a similar surrounding environment site, the photoluminescence spectra of the activators Eu3+ are similar. Therefore, by comparing the intensity ratio of photoluminescence spectra and the mechanism of all transitions of KEu(WO4)2, KY(WO4)2:Eu3+, Na5Eu(WO4)4, and Na5Y(WO4)4:Eu3+, it was proved that SOT can successfully confirm the site occupation when doped ions enter the matrix lattice. SOT was further applied to the sites occupied by Eu3+ ion-doped LiAl(MoO4)2 and LiLu(MoO4)2.

6.
bioRxiv ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38585739

RESUMO

Targeting cancer cell mitochondria holds great therapeutic promise, yet current strategies to specifically and effectively destroy cancer mitochondria in vivo are limited. Here, we introduce mLumiOpto, an innovative mitochondrial-targeted luminoptogenetics gene therapy designed to directly disrupt the inner mitochondrial membrane (IMM) potential and induce cancer cell death. We synthesize a blue light-gated channelrhodopsin (CoChR) in the IMM and co-express a blue bioluminescence-emitting Nanoluciferase (NLuc) in the cytosol of the same cells. The mLumiOpto genes are selectively delivered to cancer cells in vivo by using adeno-associated virus (AAV) carrying a cancer-specific promoter or cancer-targeted monoclonal antibody-tagged exosome-associated AAV. Induction with NLuc luciferin elicits robust endogenous bioluminescence, which activates mitochondrial CoChR, triggering cancer cell IMM permeability disruption, mitochondrial damage, and subsequent cell death. Importantly, mLumiOpto demonstrates remarkable efficacy in reducing tumor burden and killing tumor cells in glioblastoma or triple-negative breast cancer xenografted mouse models. These findings establish mLumiOpto as a novel and promising therapeutic strategy by targeting cancer cell mitochondria in vivo.

7.
Sci Rep ; 14(1): 9186, 2024 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649690

RESUMO

Osteosarcoma (OS) is the most common malignant bone tumor with high pathological heterogeneity. Our study aimed to investigate disulfidptosis-related modification patterns in OS and their relationship with survival outcomes in patients with OS. We analyzed the single-cell-level expression profiles of disulfidptosis-related genes (DSRGs) in both OS microenvironment and OS subclusters, and HMGB1 was found to be crucial for intercellular regulation of OS disulfidptosis. Next, we explored the molecular clusters of OS based on DSRGs and related immune cell infiltration using transcriptome data. Subsequently, the hub genes of disulfidptosis in OS were screened by applying multiple machine models. In vitro and patient experiments validated our results. Three main disulfidptosis-related molecular clusters were defined in OS, and immune infiltration analysis suggested high immune heterogeneity between distinct clusters. The in vitro experiment confirmed decreased cell viability of OS after ACTB silencing and higher expression of ACTB in patients with lower immune scores. Our study systematically revealed the underlying relationship between disulfidptosis and OS at the single-cell level, identified disulfidptosis-related subtypes, and revealed the potential role of ACTB expression in OS disulfidptosis.


Assuntos
Neoplasias Ósseas , Regulação Neoplásica da Expressão Gênica , Osteossarcoma , Análise de Célula Única , Transcriptoma , Microambiente Tumoral , Humanos , Osteossarcoma/genética , Osteossarcoma/patologia , Osteossarcoma/mortalidade , Osteossarcoma/metabolismo , Microambiente Tumoral/genética , Prognóstico , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/metabolismo , Linhagem Celular Tumoral , Perfilação da Expressão Gênica , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Actinas/metabolismo , Actinas/genética
8.
Artigo em Inglês | MEDLINE | ID: mdl-38639624

RESUMO

Objective: To explore the effect of traditional Chinese medicine (TCM) nursing under the integrated management mode during anesthesia recovery. Methods: The researchers' hospital admitted 114 patients who underwent general anesthesia between August 2022 and April 2023. Based on the admission order, these patients were divided into a control group (N=57) and an observation group (N=57). The control group received routine nursing intervention, while the observation group received comprehensive TCM nursing management, which included therapies such as cupping, acupressure, massage, herbal decoction, and mirabilite application. The study evaluated the psychological status, recovery indexes after anesthesia, comfort level, incidence of complications, and patient satisfaction with nursing care. Results: Compared to the control group, the observation group showed significant improvement in their psychological well-being (P < .05) and better recovery outcomes after anesthesia (P < .05). Additionally, the observation group reported higher levels of comfort (P < .05), a lower incidence of complications (8.77% vs 29.82%, P < .05), and greater satisfaction with nursing care (98.25% vs 84.21%, P < .05) compared to the control group. Conclusion: Integrated management of traditional Chinese medicine effectively reduces postoperative adverse events, improves treatment outcomes, and facilitates patient recovery. Its benefits are evident, and its feasibility is well-established.

9.
Elife ; 122024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38578205

RESUMO

Poly(ADP-ribose)ylation or PARylation by PAR polymerase 1 (PARP1) and dePARylation by poly(ADP-ribose) glycohydrolase (PARG) are equally important for the dynamic regulation of DNA damage response. PARG, the most active dePARylation enzyme, is recruited to sites of DNA damage via pADPr-dependent and PCNA-dependent mechanisms. Targeting dePARylation is considered an alternative strategy to overcome PARP inhibitor resistance. However, precisely how dePARylation functions in normal unperturbed cells remains elusive. To address this challenge, we conducted multiple CRISPR screens and revealed that dePARylation of S phase pADPr by PARG is essential for cell viability. Loss of dePARylation activity initially induced S-phase-specific pADPr signaling, which resulted from unligated Okazaki fragments and eventually led to uncontrolled pADPr accumulation and PARP1/2-dependent cytotoxicity. Moreover, we demonstrated that proteins involved in Okazaki fragment ligation and/or base excision repair regulate pADPr signaling and cell death induced by PARG inhibition. In addition, we determined that PARG expression is critical for cellular sensitivity to PARG inhibition. Additionally, we revealed that PARG is essential for cell survival by suppressing pADPr. Collectively, our data not only identify an essential role for PARG in normal proliferating cells but also provide a potential biomarker for the further development of PARG inhibitors in cancer therapy.


Assuntos
Antineoplásicos , Poli Adenosina Difosfato Ribose , Sobrevivência Celular , Fase S , Poli Adenosina Difosfato Ribose/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Antineoplásicos/farmacologia
10.
Eur Spine J ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38532182

RESUMO

PURPOSE: The purpose of this study was to establish an animal model capable of simulating the development and decompression process of symptomatic spinal epidural hematoma (SSEH). METHODS: A total of 16 male Bama miniature pigs were included in this study and randomly allocated into four groups: Group A (4 h 20 mmHg hematoma compression), Group B (4 h 24 mmHg hematoma compression), Group C (4 h 28 mmHg hematoma compression), and Group Sham (control). Real-time intra-wound hematoma compression values were obtained using the principle of connectors. Electrophysiological analyses, including the latency and amplitude of somatosensory evoked potentials (SSEP) and motor evoked potentials (MEP), along with behavioral observations (Tarlov score), were performed to assess this model. RESULTS: ANOVA tests demonstrated significant differences in the latency and relative amplitude of SSEP and MEP between Groups C and Sham after 4 h of hematoma compression and one month after surgery (P < 0.01). Behavioral assessments 8 h after surgery indicated that animals subjected to 28 mmHg hematoma compression suffered the most severe spinal cord injury. Pearson correlation coefficient test suggested a negative correlation between the epidural pressure and Tarlov score (r = -0.700, p < 0.001). With the progression of compression and the escalation of epidural pressure, the latency of SSEP and MEP gradually increased, while the relative amplitude gradually decreased. CONCLUSIONS: When the epidural pressure reaches approximately 24 mmHg, the spinal cord function occurs progressive dysfunction. Monitoring epidural pressure would be an effective approach to assist to identify the occurrence of postoperative SSEH.

11.
Protein Cell ; 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38430542

RESUMO

Ferroptosis has been recognized as a unique cell death modality driven by excessive lipid peroxidation and unbalanced cellular metabolism. In this study, we established a protein interaction landscape for ferroptosis pathways through proteomic analyses, and identified choline/ethanolamine phosphotransferase 1 (CEPT1) as a lysophosphatidylcholine acyltransferase 3 (LPCAT3)-interacting protein that regulates LPCAT3 protein stability. In contrast to its known role in promoting phospholipid synthesis, we showed that CEPT1 suppresses ferroptosis potentially by interacting with phospholipases and breaking down certain pro-ferroptotic polyunsaturated fatty acid (PUFA)-containing phospholipids. Together, our study reveals a previously unrecognized role of CEPT1 in suppressing ferroptosis.

12.
Cancer Discov ; 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38552003

RESUMO

Resistance to poly (ADP-ribose) polymerase inhibitors (PARPi) limits the therapeutic efficacy of PARP inhibition in treating breast cancer susceptibility gene 1 (BRCA1)-deficient cancers. Here we reveal that BRCA1 has a dual role in regulating ferroptosis. BRCA1 promotes the transcription of voltage-dependent anion channel 3 (VDAC3) and glutathione peroxidase 4 (GPX4); consequently, BRCA1 deficiency promotes cellular resistance to erastin-induced ferroptosis but sensitizes cancer cells to ferroptosis induced by GPX4 inhibitors (GPX4i). In addition, nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy and defective GPX4 induction unleash potent ferroptosis in BRCA1-deficient cancer cells upon PARPi and GPX4i co-treatment. Finally, we show that xenograft tumors derived from BRCA1-mutant breast cancer patients with PARPi resistance exhibit decreased GPX4 expression and high sensitivity to PARP and GPX4 co-inhibition. Our results show that BRCA1 deficiency induces a ferroptosis vulnerability to PARP and GPX4 co-inhibition and inform a therapeutic strategy for overcoming PARPi resistance in BRCA1-deficient cancers.

13.
ACS Omega ; 9(9): 10945-10957, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38463263

RESUMO

Zinc (Zn) is a bioabsorbable metal that shows great potential as an implant material for orthopedic applications. Suitable concentrations of zinc ions promote osteogenesis, while excess zinc ions cause apoptosis. As a result, the conflicting impacts of Zn2+ concentration on osteogenesis could prove to be significant problems for the creation of novel materials. This study thoroughly examined the cell viability, proliferation, and osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) cultured in various concentrations of Zn2+ in vitro and validated the osteogenesis effects of zinc implantation in vivo. The effective promotion of cell survival, proliferation, migration, and osteogenic differentiation of bone marrow mesenchymal stem cell (BMSCs) may be achieved at a low concentration of Zn2+ (125 µM). The excessively high concentration of zinc ions (>250 µM) not only reduces BMSCs' viability and proliferation but also causes them to suffer apoptosis due to the disturbed zinc homeostasis and excessive Zn2+. Moreover, transcriptome sequencing was used to examine the underlying mechanisms of zinc-induced osteogenic differentiation with particular attention paid to the PI3K-AKT and TGF-ß pathways. The present investigation elucidated the dual impacts of Zn2+ microenvironments on the osteogenic characteristics of rBMSCs and the associated processes and might offer significant insights for refining the blueprint for zinc-based biomaterials.

14.
Front Biosci (Landmark Ed) ; 29(2): 83, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38420794

RESUMO

BACKGROUND: Lactic acid, previously regarded only as an endpoint of glycolysis, has emerged as a major regulator of tumor invasion, growth, and the tumor microenvironment. In this study, we aimed to explore the reprogramming of lactic acid metabolism relevant to osteosarcoma (OS) microenvironment by decoding the underlying lactic acid metabolic landscape of OS cells and intercellular signaling alterations. METHODS: The landscape of OS metabolism was evaluated using single-cell gene expression data, lactic acid metabolism clustering, and screening of the hub genes in lactic acid metabolism of OS samples using transcriptome data. The role of the hub gene NADH:Ubiquinone Oxidoreductase Complex Assembly Factor 6 (NDUFAF6) was validated with in vitro studies and patient experiments. RESULTS: Single-cell RNA sequencing data validated a lactic acid metabolismhigh subcluster in OS. Further investigation of intercellular communications revealed a unique metabolic communication pattern between the lactic acid metabolismhigh subcluster and other subclusters. Next, two lactic acid metabolic reprogramming phenotypes were defined, and six lactic acid metabolism-related genes (LRGs), including the biomarker NDUFAF6, were screened in OS. In vitro studies and patient experiments confirmed that NDUFAF6 is a crucial lactic acid metabolism-associated gene in OS. CONCLUSIONS: The patterns of lactic acid metabolism in OS suggested metabolic reprogramming phenotypes relevant to the tumor microenvironment (TME) and identified NDUFAF6 as an LRG prognostic biomarker.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Ácido Láctico/metabolismo , Glicólise/genética , Osteossarcoma/metabolismo , Neoplasias Ósseas/metabolismo , Biomarcadores/metabolismo , Microambiente Tumoral/genética
15.
Dalton Trans ; 53(11): 5274-5283, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38407265

RESUMO

The discovery of phosphors with highly efficient broadband near-infrared emission is urgent for constructing NIR sources for various applications. Herein, we synthesized a series of near-infrared emitting garnet-type (A3B2C3O12) Lu2-xCaAl3.99Cr0.01SiO12:xGd/La and Lu2CaAl3.99-yCr0.01SiO12:ySc/Ga phosphors and systematically investigated the effect of A/B-site substitution on the crystal structure and luminescence properties. Structural and optical analyses revealed that the A/B-site substitution weakened the crystal field strength, further enhancing the broadband emission of the allowed 4T2 → 4A2transition and diminishing the narrow-peak emission of the forbidden 2E → 4A2 transition. As expected, NIR phosphors, exemplified by Lu1.7CaAl3.99Cr0.01SiO12:0.3Gd and Lu2CaAl3.49Cr0.01SiO12:0.5Sc, showed outstanding thermal stabilities at 423 K (150 °C) registering values of 103.02% and 94.91%, with high quantum efficiencies of 80.48% and 85.01%, respectively. In addition, pc-LEDs with broadband NIR output and good optoelectronic properties have been realized, demonstrating the great potential of broadband NIR pc-LEDs for applications. This work not only provides a series of high-efficiency phosphors for NIR pc-LED applications, but also provides a systematic idea and an efficient method to improve the luminescence performance of garnet-type phosphors.

16.
J Biol Eng ; 18(1): 15, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38360753

RESUMO

Recombinant adeno-associated virus (rAAV) has been developed as a safe and effective gene delivery vehicle to treat rare genetic diseases. This study aimed to establish a novel biomanufacturing process to achieve high production and purification of various AAV serotypes (AAV2, 5, DJ, DJ8). First, a robust suspensive production process was developed and optimized using Gibco Viral Production Cell 2.0 in 30-60 mL shaker flask cultures by evaluating host cells, cell density at the time of transfection and plasmid amount, adapted to 60-100 mL spinner flask production, and scaled up to 1.2-2.0-L stirred-tank bioreactor production at 37 °C, pH 7.0, 210 rpm and DO 40%. The optimal process generated AAV titer of 7.52-8.14 × 1010 vg/mL. Second, a new AAV purification using liquid chromatography was developed and optimized to reach recovery rate of 85-95% of all four serotypes. Post-purification desalting and concentration procedures were also investigated. Then the generated AAVs were evaluated in vitro using Western blotting, transmission electron microscope, confocal microscope and bioluminescence detection. Finally, the in vivo infection and functional gene expression of AAV were confirmed in tumor xenografted mouse model. In conclusion, this study reported a robust, scalable, and universal biomanufacturing platform of AAV production, clarification and purification.

17.
Orthop Surg ; 16(3): 613-619, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38287219

RESUMO

OBJECTIVE: Re-resection of spinal giant cell tumors is an exceedingly difficult procedure. Moreover, the prognosis of patients with en bloc resection or intralesional excision for re-resection has rarely been reported. This study aimed to compare the prognostic value of en bloc resection with that of intralesional excision in patients undergoing re-resection for giant cell tumors of the spine. METHODS: This retrospective analysis evaluated patients who underwent revision surgeries for relapse of giant cell tumors of the spine at our center between January 2005 and January 2021. Local progression-free survival represents the duration between en bloc resection or intralesional excision and tumor recurrence. Neurological recovery, survival rates, local control, and complications were evaluated. The Kaplan-Meier estimator was used for survival analysis. RESULTS: A total of 22 patients (nine men and 13 women) with a mean age of 34.1 (range 19-63) years were included. Significant statistical differences were found in the local tumor recurrence rate between patients treated with en bloc resection and those treated with intralesional excision (p < 0.05). The 5- and 10-year local progression-free survival rates were both 90% in the en bloc resection group, while in the intralesional excision group, the 5-year local progression-free survival rate was 80% with a 10-year rate of 45.7%. The en bloc resection group had a lower local tumor recurrence rate than that of the intralesional excision group (p < 0.05), but the former had a higher rate of complications (p = 0.015). CONCLUSIONS: This study revealed a low local recurrence rate in patients who underwent en bloc resection for giant cell tumors, while the perioperative complication rate was high.


Assuntos
Tumores de Células Gigantes , Neoplasias da Coluna Vertebral , Masculino , Humanos , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Recidiva Local de Neoplasia/cirurgia , Resultado do Tratamento
18.
Waste Manag ; 176: 117-127, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38277809

RESUMO

Hydrothermal carbonization of waste activated sludge suffers from a low degree of carbonization caused by limited hydrolysis of carbohydrates and proteins, resulting in a high nitrogen content in hydrochar. Thus, it is hypothesized that thermal hydrolysis could destroy the stable floc structure of waste activated sludge, leading to higher degree of carbonization and high quality hydrochar with low nitrogen content by improving the solubilization and hydrolysis of organic matter. In the current study, thermal hydrolysis at 90 °C, 125 °C, and 155 °C was performed prior to hydrothermal carbonization to obtain low-nitrogen-content hydrochar. Thermal hydrolysis greatly improved the hydrolysis of sewage sludge. The nitrogen and sulfur content in hydrochars obtained after thermal hydrolysis decreased to 1.5-1.6 % from 1.7 %, and to 0.4 % from 0.5 %, respectively, depending on the hydrolysis conditions. Thermal decomposition stability of hydrochars obtained after thermal hydrolysis were also improved. Thermal hydrolysis at 90 °C and 125 °C promoted hydrolysis, dehydration, and the Diels-Alder reaction during hydrothermal carbonization, resulting in lower hydrochar yield but higher H/C and O/C atomic ratio. The Maillard reaction occurred during thermal hydrolysis at 155 °C, leading to the formation of large molecular refractory compounds that were retained in the hydrochar and increased the hydrochar yield. Furthermore, thermal hydrolysis can accelerate pyrolysis reaction of hydrochars, resulting in reduced energy consumption. The newly established thermal hydrolysis-hydrothermal carbonization process using sewage sludge as the feedstock has the potential to contribute to the development of the hydrothermal carbonization industry.


Assuntos
Carbono , Esgotos , Carbono/química , Nitrogênio , Hidrólise , Temperatura , Enxofre
19.
Spine (Phila Pa 1976) ; 49(9): 661-669, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38251727

RESUMO

STUDY DESIGN: Retrospective study. OBJECTIVE: In this study, the authors explore the potential relationship between hypoxia inducible factor-1α (HIF-1α) and the prognosis of patients with spinal chordoma. SUMMARY OF BACKGROUND DATA: Currently, prognostic factors related to the clinical course in the setting of spinal chordoma are poorly understood. Although the close relationship between HIF-1α and tumor angiogenesis, metastasis, and recurrence have been widely reported, it has not been investigated in the context of spinal chordoma. MATERIALS AND METHODS: In this study, 32 samples of chordoma patients were compared with 14 nucleus pulposus tissues as controls. The specific expression of HIF-1α was detected by immunohistochemistry. Continuous disease-free survival (CDFS) was defined as the interval from tumor resection to confirmation of the first local recurrence or distant metastasis. Overall survival (OS) was defined as the interval from the date of surgery to death related to any cause. The relationship between HIF-1α expression and the clinicopathologic characteristics of patients with chordoma was analyzed using the Pearson χ 2 test. Multivariate Cox analysis was used to evaluate whether HIF-1α expression was associated with the prognosis of patients after controlling for confounders. RESULTS: HIF-1α was mainly expressed in the cytoplasm or nucleus in all of the chordoma samples, which showed significantly higher than that in the normal nucleus pulposus tissue ( P =0.004). Multivariate Cox regression analyses showed that high HIF-1α expression and location of HIF-1α expression were significantly associated with poor CDFS (hazard ratio (HR)=3.374; P =0.021) and OS (HR=4.511; P =0.012). In addition, we further found that high HIF-1α expression both in the cytoplasm and nucleus indicated a stronger prognostic factor for poor CDFS (HR=3.885; P =0.011) and OS (HR=4.014; P =0.011) in spinal chordoma patients. CONCLUSION: High HIF-1α expression may become a potential new biological indicator to predict a poor prognosis in patients with spinal chordoma. HIF-1α may also represent a novel therapeutic target for the treatment of spinal chordoma.


Assuntos
Cordoma , Subunidade alfa do Fator 1 Induzível por Hipóxia , Humanos , Estudos Retrospectivos , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Cordoma/diagnóstico , Cordoma/cirurgia , Prognóstico
20.
J Environ Manage ; 353: 120158, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38271883

RESUMO

Granular sludge has been recognized as an effective method for the application and industrialization of the anammox-based process due to its good biomass retention capacity and environmental tolerance. In this study, a one-stage autotrophic nitrogen removal (ANR) dual-partition system with airlift internal circulation was implemented for 320 days. A high nitrogen removal efficiency of 84.6% was obtained, while the nitrogen removal rate reached 1.28 g-N/L/d. ANR granular sludge dominated by Nitrosomonas and Candidatus Brocadia was successfully cultivated. Results showed that activity and abundance of functional flora first increased with granulation process, but eventually declined slightly when particle size exceeded the optimal range. Total anammox activity was observed to be significantly correlated with protein content (R2 = 0.9623) and nitrogen removal performance (R2 = 0.8796). Correlation network revealed that AnAOB had complex interactions with other bacteria, both synergy for nitrogen removal and competition for substrate. Changes in abundances of genes encoding the Carbohydrate Metabolism, Energy Metabolism, and Membrane Transport suggested energy production and material transfer were possibly blocked with further sludge granulation. Formation of ANR granular sludge promoted the interactions and metabolism of functional microorganisms, and the complex nitrogen metabolic pathways improved the performance stability. These results validated the feasibility of granule formation in the airlift dual-partition system and revealed the response of the ANR system to sludge granulation.


Assuntos
Nitrogênio , Esgotos , Oxirredução , Nitrogênio/análise , Desnitrificação , Reatores Biológicos/microbiologia
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