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1.
World J Surg Oncol ; 22(1): 168, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38918829

ABSTRACT

BACKGROUND: To investigate the prognosis of patients with Multiple Myeloma (MM) after surgery, analyze the risk factors leading to adverse postoperative outcomes, and establish a nomogram. METHODS: Clinical data from 154 patients with MM who underwent surgery at our institution between 2007 and 2019 were retrospectively analyzed. Assessing and comparing patients' pain levels, quality of life, and functional status before and after surgery (P < 0.05) were considered statistically significant. The Kaplan-Meier survival curve was used to estimate the median survival time. Adverse postoperative outcomes were defined as worsened symptoms, lesion recurrence, complication grade ≥ 2, or a postoperative survival period < 1 year. Logistic regression analysis was used to determine the prognostic factors. Based on the logistic regression results, a nomogram predictive model was developed and calibrated. RESULTS: Postoperative pain was significantly alleviated in patients with MM, and there were significant improvements in the quality of life and functional status (P < 0.05). The median postoperative survival was 41 months. Forty-nine patients (31.8%) experienced adverse postoperative outcomes. Multivariate logistic regression analysis identified patient age, duration of MM, International Staging System, preoperative Karnofsky Performance Status, and Hb < 90 g/L as independent factors influencing patient prognosis. Based on these results, a nomogram was constructed, with a C-index of 0.812. The calibration curve demonstrated similarity between the predicted and actual survival curves. Decision curve analysis favored the predictive value of the model at high-risk thresholds from 10% to-69%. CONCLUSION: This study developed a nomogram risk prediction model to assist in providing quantifiable assessment indicators for preoperative evaluation of surgical risk.


Subject(s)
Multiple Myeloma , Nomograms , Quality of Life , Humans , Multiple Myeloma/surgery , Multiple Myeloma/mortality , Multiple Myeloma/pathology , Male , Female , Middle Aged , Retrospective Studies , Prognosis , Aged , Survival Rate , Follow-Up Studies , Postoperative Complications/etiology , Adult , Risk Factors , Aged, 80 and over , Pain, Postoperative/etiology , Pain, Postoperative/diagnosis
2.
Discov Oncol ; 15(1): 192, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38806963

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is a prevalent malignancy with high mortality and morbidity rates. Although the significant efficacy of immunotherapy is well established, it is only beneficial for a limited number of individuals with CRC. METHODS: Differentially expressed immune-related genes (DE-IRGs) were retrieved from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and ImmPort databases. A prognostic signature comprising DE-IRGs was developed using univariate, LASSO, and multivariate Cox regression analyses. A nomogram integrating the independent prognostic factors was also developed. CIBERSORT was used to assess immune cell infiltration (ICI). Furthermore, wound-healing, colony formation, migration, and invasion assays were performed to study the involvement of ACTG1 in CRC. RESULTS: A signature including six DE-IRGs was developed. The overall survival (OS) rate was accurately estimated for TCGA and GSE38832 cohorts. The risk score (RS) of the signature was an independent factor for OS. Moreover, a nomogram encompassing age, RS, and pathological T stage accurately predicted the long-term OS probability of individuals with CRC. The high-risk group had an elevated proportion of patients treated with ICIs, including native B cells, relative to the low-risk group. Additionally, ACTG1 expression was upregulated, which supported the proliferation, migration, and invasion abilities of CRC cells. CONCLUSIONS: An immune-related prognostic signature was developed for predicting OS and for determining the immune status of individuals with CRC. The present study provides new insights into accurate immunotherapy for individuals with CRC. Moreover, ACTG1 may serve as a new immune biomarker.

3.
Acta Pharmacol Sin ; 2024 May 17.
Article in English | MEDLINE | ID: mdl-38760541

ABSTRACT

Senescence, an intricate and inevitable biological process, characterized by the gradual loss of homeostasis and declining organ functions. The pathological features of cellular senescence, including cell cycle arrest, metabolic disruptions, and the emergence of senescence-associated secretory phenotypes (SASP), collectively contribute to the intricate and multifaceted nature of senescence. Beyond its classical interaction with p53, murine double minute gene 2 (MDM2), traditionally known as an E3 ubiquitin ligase involved in protein degradation, plays a pivotal role in cellular processes governing senescence. Histone deacetylase (HDAC), a class of histone deacetylases mainly expressed in the nucleus, has emerged as a critical contributor to renal tissues senescence. In this study we investigated the interplay between MDM2 and HDAC1 in renal senescence. We established a natural aging model in mice over a 2-year period that was verified by SA-ß-GAL staining and increased expression of senescence-associated markers such as p21, p16, and TNF-α in the kidneys. Furthermore, we showed that the expression of MDM2 was markedly increased, while HDAC1 expression underwent downregulation during renal senescence. This phenomenon was confirmed in H2O2-stimulated HK2 cells in vitro. Knockout of renal tubular MDM2 alleviated renal senescence in aged mice and in H2O2-stimulated HK2 cells. Moreover, we demonstrated that MDM2 promoted renal senescence by orchestrating the ubiquitination and subsequent degradation of HDAC1. These mechanisms synergistically accelerate the aging process in renal tissues, highlighting the intricate interplay between MDM2 and HDAC1, underpinning the age-related organ function decline.

4.
Eur Spine J ; 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38647604

ABSTRACT

PURPOSE: To investigate the effectiveness and safety of separation surgery for Epidural Spinal Cord Compression (ESCC) graded ≥ 2 in patients with Multiple Myeloma (MM), analyze factors influencing surgical outcomes, and develop a preliminary treatment decision framework for these patients. METHODS: A retrospective analysis was conducted on clinical data from 35 MM patients who underwent separation surgery for ESCC graded ≥ 2 between 2013 and 2018. Patient data, including baseline information, surgical details, complications, and pre-operative as well as one-month post-operative efficacy evaluation indicators were recorded. Statistical analysis was performed on pre-operative and post-operative efficacy indicators to determine if there were significant improvements (p < 0.05). Ordered logistic regression was utilized to assess factors associated with an unfavorable post-operative quality of life outcome. RESULTS: Compared to pre-operative values, at one-month post-surgery, patients showed significant improvements in Frankel Score Classification (4 vs 5, p < 0.05), Karnofsky Performance Score (30 vs 70, p < 0.05), and Visual Analogue Scale (8 vs 3, p < 0.05). Complications occurred in 7 cases (20%). The number of segments with ESCC (OR = 0.171, p < 0.05) and pre-operative chemotherapy (OR = 5.202, p = 0.05) were identified as independent factors influencing patient outcomes. Patients with more than two vertebral segments with ESCC exhibited significantly worse post-operative conditions. CONCLUSIONS: Separation surgery effectively alleviates pain, improves neurological function, and enhances the quality of life in patients with ESCC graded ≥ 2 due to MM.

5.
Bioresour Technol ; 397: 130500, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38423487

ABSTRACT

This study investigates the behaviors and effects of F-53B, an alternative to perfluorooctane sulfonate on anaerobic ammonium oxidation (anammox) processes. Results showed that the nitrogen removal efficiency (NRE) reached 83.8 % at a F-53B concentration of 0.5 mg·L-1, while NRE decreased to 66.9 % with 5 mg·L-1 of F-53B. The defluorination rates of 17.8 % (0.5 mg·L-1) and 9.3 % (5 mg·L-1) were observed, respectively, suggesting the occurrence of F-53B degradation. The relative abundance of Ca. Kuenenia decreased from 26.1 % to 16.2 % with the F-53B concentration increasing from 0.5 mg·L-1 to 5 mg·L-1. Meanwhile, Denitratisoma was selectively enriched with a relative abundance of 40.7 % at an F-53B concentration of 0.5 mg·L-1. Ca. Kuenenia could reduce reactive oxygen species induced by F-53B to maintain the balance of oxidative stress. This study gains insight into the behaviors and metabolic mechanisms of F-53B in anammox consortia, suggesting the feasibility of anammox processes for industrial wastewater.


Subject(s)
Anaerobic Ammonia Oxidation , Ether , Animals , Ether/metabolism , Denitrification , Zebrafish/metabolism , Alkanesulfonates/metabolism , Nitrogen/metabolism , Oxidation-Reduction , Bioreactors
6.
Front Endocrinol (Lausanne) ; 15: 1334414, 2024.
Article in English | MEDLINE | ID: mdl-38318295

ABSTRACT

Background: Diabetic foot ulcers constitute a substantial healthcare burden on a global scale and present challenges in achieving healing. Our objective was to assess the efficacy of modified tibial cortex transverse transport surgery in managing refractory diabetic foot ulcers. Methods: We retrospectively analyzed clinical data from 98 patients suffering from diabetic foot ulcers classified as Wagner grade ≥II who were admitted to our medical facility between January 2020 and June 2022. All the patients were treated by modified tibial cortex transverse transport surgery, wherein the osteotomy scope was reduced to two rectangular bone windows measuring 1.5cm × 1.5cm each. Record the patient's general information and ulcer healing time; ulcer area, ankle-brachial index, WIFi classification, and visual analogue scale before and 3 months following the surgical intervention. Results: The average duration of diabetes of 98 patients with diabetic foot ulcer was 20.22 ± 8.02 years, 52 patients had more than one toe gangrene on admission. The postoperative wound healing rate was 95.83% and the average healing time was 53.18 ± 20.18 days. The patients showed significant improvement in ankle-brachial index, WIFi classification, and visual analogue scale at 3 months postoperatively compared to preoperatively, with statistically significant differences (P< 0.05). Eight patients experienced complications, and the incidence of complications was 8.16%. Throughout the follow-up period, there were no instances of ulcer recurrence noted. Conclusion: Modified tibial cortex transverse transport surgery demonstrates effectiveness in the management of diabetic foot ulcers by enhancing lower limb microcirculation and facilitating the process of wound healing.


Subject(s)
Diabetes Mellitus , Diabetic Foot , Humans , Diabetic Foot/surgery , Retrospective Studies , Tibia/surgery , Lower Extremity , Wound Healing
7.
Nat Struct Mol Biol ; 31(2): 300-310, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38177667

ABSTRACT

The cancer-specific fusion oncoprotein SS18-SSX1 disturbs chromatin accessibility by hijacking the BAF complex from the promoters and enhancers to the Polycomb-repressed chromatin regions. This process relies on the selective recognition of H2AK119Ub nucleosomes by synovial sarcoma X breakpoint 1 (SSX1). However, the mechanism underlying the selective recognition of H2AK119Ub nucleosomes by SSX1 in the absence of ubiquitin (Ub)-binding capacity remains unknown. Here we report the cryo-EM structure of SSX1 bound to H2AK119Ub nucleosomes at 3.1-Å resolution. Combined in vitro biochemical and cellular assays revealed that the Ub recognition by SSX1 is unique and depends on a cryptic basic groove formed by H3 and the Ub motif on the H2AK119 site. Moreover, this unorthodox binding mode of SSX1 induces DNA unwrapping at the entry/exit sites. Together, our results describe a unique mode of site-specific ubiquitinated nucleosome recognition that underlies the specific hijacking of the BAF complex to Polycomb regions by SS18-SSX1 in synovial sarcoma.


Subject(s)
Nucleosomes , Sarcoma, Synovial , Humans , Sarcoma, Synovial/metabolism , Chromatin , Cell Membrane/metabolism , Oncogene Proteins, Fusion/genetics
8.
J Nephrol ; 37(1): 149-158, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37882962

ABSTRACT

BACKGROUND: The discovery of antigen phospholipase A2 receptor (PLA2R) in 2009 ushered in the antigen-based study of membranous nephropathy. The further putative antigen exostosin 1/2 (EXT1/2) was described in 2019. However, the distribution spectrum of glomerular EXT1 deposits in membranous nephropathy has not been fully elucidated. METHODS: We conducted a retrospective cohort study of biopsy-proven membranous nephropathy patients. Patients with complete baseline data and adequate tissue specimens were included in this study. Tests for glomerular expression of PLA2R and EXT1 and circulating anti-PLA2R antibodies were performed. Clinicopathological and outcome data were reviewed. RESULTS: We included 626 patients, namely, 487 (77.8%) PLA2R-positive patients and 54 (8.6%) EXT1-positive patients; 32 (5.1%) patients were dual-positive for PLA2R and EXT1 (PLA2R + /EXT1 +). A higher percentage of dual-positive patients had low C3 levels (P < 0.001) and were more likely to have autoimmune diseases (P = 0.013) than PLA2R-positive and EXT1-negative (PLA2R + /EXT1-) patients. Kidney biopsy findings revealed that there was a higher percentage of glomerular IgG1, IgG2, IgA, C4, and C1q deposits (P < 0.05), "full-house" staining (P < 0.001), and stronger intensity of C1q staining (P = 0.002) in PLA2R + /EXT1 + patients. Based on Kaplan-Meier analysis, a higher percentage of PLA2R + /EXT1 + patients exhibited partial or complete remission of proteinuria. Furthermore, EXT1-positive expression was a favourable predictor for proteinuria remission, whereas interstitial fibrosis/tubular atrophy was an unfavourable predictor. A complement C3 level < 0.79 g/L was independently associated with EXT1 positivity in PLA2R-positive membranous nephropathy. CONCLUSIONS: We describe a subgroup of PLA2R and EXT1 dual-positive patients. Patients in this subset exhibited more signs of autoimmunity and more frequent clinical remission. In PLA2R-positive membranous nephropathy, a complement C3 level < 0.79 g/L was independently associated with EXT1 positivity, which was a favourable predictor for proteinuria remission.


Subject(s)
Glomerulonephritis, Membranous , Humans , Glomerulonephritis, Membranous/pathology , Receptors, Phospholipase A2 , Complement C3 , Retrospective Studies , Clinical Relevance , Complement C1q , Proteinuria , Autoantibodies
9.
Apoptosis ; 29(5-6): 849-864, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38117373

ABSTRACT

Sarcopenia manifests as muscle atrophy and loss that is complicated with malignancy. This study explored the mechanism of extracellular vesicles (EVs) in multiple myeloma (MM) with sarcopenia. SP2/0 conditioned medium (CM) was collected to isolate SP2/0-EVs. C2C12 cells were incubated with SP2/0 CM or SP2/0-EVs. ROS, TNF-α, IL-6, MuRF1 and MyHC levels were detected by DCF-DA fluorescent probe, ELISA, and Western blot. GW4869 was used to inhibit EV secretion in SP2/0 to confirm its effect on muscle atrophy. Serum was collected from MM patients with or without sarcopenia to detect RAGE mRNA expression. SP2/0 cells were transfected with RAGE siRNA and C2C12 cells were treated with the isolated si-RAGE-EVs or/and TLR4 agonist. SP2/0 tumor-bearing mouse model was established. Healthy mice and SP2/0-tumor bearing mice were treated with SP2/0-EVs or si-RAGE-EVs. SP2/0 CM or SP2/0-EVs stimulated ROS, inflammatory responses, and myotube atrophy in C2C12 cells. GW4869 blocked EV secretion and the effects of SP2/0 CM. RAGE mRNA expression in serum EVs was increased in MM&Sarcopenia patients and RAGE knockdown in SP2/0-EVs partially nullified SP2/0-EVs' effects. SP2/0-EVs activated the TLR4/NF-κB p65 pathway by translocating RAGE. SP2/0-EVs-derived RAGE elevated ROS production, inflammation, and myotube atrophy in C2C12 cells and caused muscle loss in SP2/0 tumor-bearing mice by activating the TLR4/NF-κB p65 pathway. SP2/0-EVs partially recapitulated muscle loss in healthy mice. SP2/0-EVs-derived RAGE increased ROS production, inflammation, and myotube atrophy in MM through TLR4/NF-κB p65 pathway activation.


Subject(s)
Extracellular Vesicles , Inflammation , Multiple Myeloma , Muscular Atrophy , Receptor for Advanced Glycation End Products , Signal Transduction , Toll-Like Receptor 4 , Transcription Factor RelA , Animals , Extracellular Vesicles/metabolism , Extracellular Vesicles/genetics , Humans , Multiple Myeloma/pathology , Multiple Myeloma/metabolism , Multiple Myeloma/genetics , Mice , Toll-Like Receptor 4/metabolism , Toll-Like Receptor 4/genetics , Receptor for Advanced Glycation End Products/metabolism , Receptor for Advanced Glycation End Products/genetics , Transcription Factor RelA/metabolism , Transcription Factor RelA/genetics , Inflammation/metabolism , Inflammation/pathology , Inflammation/genetics , Muscular Atrophy/metabolism , Muscular Atrophy/pathology , Muscular Atrophy/genetics , Cell Line, Tumor , Muscle Fibers, Skeletal/metabolism , Muscle Fibers, Skeletal/pathology , Male , Female
10.
Front Neurol ; 14: 1221912, 2023.
Article in English | MEDLINE | ID: mdl-37840916

ABSTRACT

Granular cell tumors are extremely uncommon soft tissue neoplasms that mostly occur in the head and neck regions. Granular cell tumors are generally benign, asymptomatic, and rarely involve the median nerve. Due to the lack of awareness about granular cell tumors, they are easily misdiagnosed and mistreated in primary hospitals. Here, we report a giant atypical granular cell tumor located on the median nerve, approximately 12 cm in size, with unusual symptoms of median nerve damage. Magnetic resonance imaging revealed a fusiform mass that was hyperintense on T2-weighted images and iso-hypointense on T1-weighted images. The mass was subsequently biopsied and found to be a granular cell tumor. The tumor was resected, and a pathological examination was performed. Pathological examination revealed necrotic foci, abundant eosinophilic granules, pustular ovoid bodies, and multiple mitoses. Immunohistochemical staining revealed that the tumor cells were positive for S-100, CD68, SMA, SOX-10, Calretinin, and TFE3. The integrated diagnosis was an atypical granular cell tumor. To the best of our knowledge, this is the first report of an atypical granular cell tumor involving the median nerve. Furthermore, we comprehensively reviewed the existing literature to provide a concise summary of the diagnostic criteria, imaging findings, and pathological features of granular cell tumors. Given the high recurrence and metastasis rates of this disease, granular cell tumors of the median nerve should be considered when a patient presents with symptoms of median nerve impairment. The diagnosis of atypical granular cell tumors relies on pathological examination. In addition, extensive resection and long-term follow-up are necessary to improve prognosis.

11.
J Orthop Surg Res ; 18(1): 650, 2023 Sep 02.
Article in English | MEDLINE | ID: mdl-37658426

ABSTRACT

OBJECTIVE: This study aimed to describe the learning curve of surgeons performing tibial cortex transverse transport (TTT) and explore its safety and effectiveness during the initial stages of surgeon's learning. METHODS: The clinical data of patients with diabetic foot ulcers classified as Wagner grade ≥ 2, who underwent TTT at our hospital from January 2020 to July 2021, were included in this retrospective analysis. The same physician performed all procedures. Patients were numbered according to the chronological order of their surgery dates. The cumulative sum and piecewise linear regression were used to evaluate the surgeon's learning curve, identify the cut-off point, and divide the patients into learning and mastery groups. A minimum follow-up period of 3 months was ensured for all patients. Baseline data, perioperative parameters, complications, and efficacy evaluation indicators were recorded and compared between the two groups. RESULTS: Sixty patients were included in this study based on the inclusion and exclusion criteria. After completing 20 TTT surgeries, the surgeon reached the cut-off point of the learning curve. Compared to the learning group, the mastery group demonstrated a significant reduction in the average duration of the surgical procedure (34.88 min vs. 54.20 min, P < 0.05) along with a notable decrease in intraoperative fluoroscopy (9.75 times vs. 16.9 times, P < 0.05) frequency, while no significant difference was found regarding intraoperative blood loss (P = 0.318). Of the patients, seven (11.7%) experienced complications, with three (15%) and four cases (10%) occurring during the learning phase and the mastery phase, respectively. The postoperative ulcer area was significantly reduced, and the overall healing rate was 94.8%. Significant improvements were observed in postoperative VAS, ABI, and WIFI classification (P < 0.05). There were no significant differences in the occurrence of complications or efficacy indicators between the learning and mastery groups (P > 0.05). CONCLUSION: Surgeons can master TTT after completing approximately 20 procedures. TTT is easy, secure, and highly efficient for treating foot ulcers. Furthermore, TTT's application by surgeons can achieve almost consistent clinical outcomes in the initial implementation stages, comparable to the mastery phase.


Subject(s)
Learning Curve , Surgeons , Humans , Retrospective Studies , Blood Loss, Surgical , Cerebral Cortex
12.
Mol Cell ; 83(17): 3080-3094.e14, 2023 09 07.
Article in English | MEDLINE | ID: mdl-37633270

ABSTRACT

Histone H2B monoubiquitylation plays essential roles in chromatin-based transcriptional processes. A RING-type E3 ligase (yeast Bre1 or human RNF20/RNF40) and an E2 ubiquitin-conjugating enzyme (yeast Rad6 or human hRAD6A), together, precisely deposit ubiquitin on H2B K123 in yeast or K120 in humans. Here, we developed a chemical trapping strategy and successfully captured the transient structures of Bre1- or RNF20/RNF40-mediated ubiquitin transfer from Rad6 or hRAD6A to nucleosomal H2B. Our structures show that Bre1 and RNF40 directly bind nucleosomal DNA, exhibiting a conserved E3/E2/nucleosome interaction pattern from yeast to humans for H2B monoubiquitylation. We also find an uncanonical non-hydrophobic contact in the Bre1 RING-Rad6 interface, which positions Rad6 directly above the target H2B lysine residue. Our study provides mechanistic insights into the site-specific monoubiquitylation of H2B, reveals a critical role of nucleosomal DNA in mediating E3 ligase recognition, and provides a framework for understanding the cancer-driving mutations of RNF20/RNF40.


Subject(s)
Nucleosomes , Saccharomyces cerevisiae Proteins , Humans , Nucleosomes/genetics , Histones/genetics , Saccharomyces cerevisiae/genetics , Ubiquitin , Ubiquitin-Protein Ligases/genetics , Saccharomyces cerevisiae Proteins/genetics
13.
Neurosci Lett ; 796: 137057, 2023 02 06.
Article in English | MEDLINE | ID: mdl-36621586

ABSTRACT

Heroin and methamphetamine cause great damage to individuals and society. However, numerous withdrawal mechanisms remain unidentified. In this study, 19 heroin short-term abstinent (HSTA) patients, 20 methamphetamine short-term abstinent (MSTA) patients, and 27 healthy controls (HCs) were scanned using multimodal magnetic resonance imaging. Degraded nodes of fiber tracts were identified using automated fiber quantification. Voxel- and surface-based morphometric measurements were performed to determine the gray matter volume and cortical thickness. The MSTA and HSTA groups had abnormal diffusion metrics in a variety of bilateral corticospinal tract (CST) and left superior longitudinal tract (SLT) nodes compared with the HC group. The MSTA patients reported more severely disrupted diffusion metrics in certain nodes of the bilateral anterior thalamic radiation and left inferior fronto-occipital tract than the HSTA patients. The MSTA and HSTA groups exhibited identical cortical damage in the fusiform and superior temporal gyri, as well as in the superior frontal gyrus, posterior cerebellum, and precentral gyrus. Extensive differences in gray matter lesions were observed between the MSTA and HSTA groups. Neuroimaging mechanisms of short-term abstinence may aid in the development of rehabilitation strategies.


Subject(s)
Methamphetamine , Humans , Methamphetamine/adverse effects , Heroin , Neuroimaging , Gray Matter/diagnostic imaging , Magnetic Resonance Imaging , Brain/diagnostic imaging , Brain/pathology
14.
Bioresour Technol ; 363: 127939, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36100183

ABSTRACT

The expensive carbon matrix is a bottleneck restricting the industrialization of polyhydroxyalkanoates (PHAs). Volatile fatty acids (VFAs) derived from waste activated sludge via anaerobic fermentation might be alternative carbon matters for PHAs synthesis. In this study, the effect of enzymes on VFAs yields and the feasibility of the produced VFAs for PHAs fermentation by Paracoccus sp. TOH were investigated. The optimum cumulative VFAs concentration reached 4076.6 mg-COD·L-1 in the lysozyme treatment system. Correspondingly, the highest poly(3-hydroxybuturate-co-3-hydroxyvalerate) (PHBV) concentration (119.1 mg·L-1) containing 20.3 mol% 3-hydroxyvalerate was obtained. It proved that Paracoccus sp. TOH possesses the capability for PHBV accumulation. The functional hydrolytic-acidogenic microorganisms, such as Clostridium sensu stricto and Bacteroides sp. were accumulated. The functional genes encoding hydrolysis, carbohydrates metabolism, VFAs generation were enriched. This study offered a possible strategy for VFAs production and verified the feasibility of sludge hydrolysate as a high-quality carbon substrate for PHAs fermentation.


Subject(s)
Paracoccus , Polyhydroxyalkanoates , Carbohydrates/chemistry , Carbon , Fatty Acids, Volatile/metabolism , Fermentation , Hydrogen-Ion Concentration , Muramidase/metabolism , Paracoccus/metabolism , Pentanoic Acids , Polyhydroxyalkanoates/metabolism , Sewage/chemistry
15.
J Am Chem Soc ; 144(40): 18329-18337, 2022 10 12.
Article in English | MEDLINE | ID: mdl-36166692

ABSTRACT

The chemical synthesis of homogeneously modified histones is a powerful approach to quantitatively decipher how post-translational modifications (PTMs) modulate epigenetic events. Herein, we describe the expedient syntheses of a selection of phosphorylated and ubiquitinated H2AX proteins in a strategy integrating expressed protein hydrazinolysis and auxiliary-mediated protein ligation. These modified H2AX proteins were then used to discover that although H2AXS139 phosphorylation can enhance the binding of the DNA damage repair factor 53BP1 to either an unmodified nucleosome or that bearing a single H2AXK15ub or H4K20me2 modification, it augments 53BP1's binding only weakly to nucleosomes bearing both H2AXK15ub and H4K20me2. To better understand why such a trivalent additive effect is lacking, we solved the cryo-EM structure (3.38 Å) of the complex of 53BP1 with the H2AXK15ub/S139ph_H4K20me2 nucleosome, which showed that H2AXS139 phosphorylation distorts the interaction interface between ubiquitin and 53BP1's UDR motif. Our study revealed that there is redundancy in the interplay of multiple histone PTMs, which may be useful for controlling the dynamic distribution of effector proteins onto nucleosomes bearing different histone variants and PTMs in a time-dependent fashion, through specific cellular biochemical events.


Subject(s)
Histones , Nucleosomes , Histones/chemistry , Methylation , Phosphorylation , Protein Processing, Post-Translational , Ubiquitin/metabolism , Ubiquitination
16.
Front Immunol ; 13: 902063, 2022.
Article in English | MEDLINE | ID: mdl-35924242

ABSTRACT

Metabolic syndrome (MS) is a group of clinical abnormalities characterized by central or abdominal obesity, hypertension, hyperuricemia, and metabolic disorders of glucose or lipid. Currently, the prevalence of MS is estimated about 25% in general population and is progressively increasing, which has become a challenging public health burden. Long-term metabolic disorders can activate the immune system and trigger a low-grade chronic inflammation named "metaflammation." As an important organ involved in metabolism, the kidney is inevitably attacked by immunity disequilibrium and "metaflammation." Recently, accumulating studies have suggested that the complement system, the most important and fundamental component of innate immune responses, is actively involved in the development of metabolic kidney diseases. In this review, we updated and summarized the different pathways through which the complement system is activated in a series of metabolic disturbances and the mechanisms on how complement mediate immune cell activation and infiltration, renal parenchymal cell damage, and the deterioration of renal function provide potential new biomarkers and therapeutic options for metabolic kidney diseases.


Subject(s)
Kidney Diseases , Metabolic Diseases , Metabolic Syndrome , Complement System Proteins/metabolism , Humans , Kidney Diseases/complications , Metabolic Diseases/metabolism , Obesity/complications
17.
Environ Pollut ; 309: 119700, 2022 Sep 15.
Article in English | MEDLINE | ID: mdl-35780998

ABSTRACT

Carcinogenic and neurotoxic polybrominated diphenyl ethers (PBDEs) are environmentally ubiquitous and have been widely investigated. However, little is understood regarding their pollution status, sources, and potential risk to persons in public transportation microenvironments (PTMs). We collected 60 dust samples from PTMs and then selected four materials typical of bus interiors to determine the sources of PBDEs in dust using principal component analysis coupled with Mantel tests. We then evaluated the risk of PBDEs to public health using Monte Carlo simulations. We found that PBDE concentrations in dust were 2-fold higher in buses than at bus stops and that brominated diphenyl ether (BDE)-209 was the main pollutant. The number of buses that passed through a bust stop contributed to the extent of PBDE pollution, and the primary potential sources of PBDEs in dust were plastic handles and curtains inside buses; BDE-209 and BDE-154 were the main contributors of pollution. We found that health risk was 8-fold higher in toddlers than in adults and that the reference doses of PBDEs in dust were far below the United States Environmental Protection Agency limits. Our findings provide a scientific basis that may aid in preventing PBDE pollution and guiding related pollution management strategies in PTMs.


Subject(s)
Air Pollution, Indoor , Environmental Pollutants , Air Pollution, Indoor/analysis , Dust/analysis , Environmental Exposure/analysis , Environmental Monitoring , Environmental Pollutants/analysis , Halogenated Diphenyl Ethers/analysis , United States
18.
Int J Gen Med ; 15: 6073-6084, 2022.
Article in English | MEDLINE | ID: mdl-35821766

ABSTRACT

Purpose: Methamphetamine use may cause severe neurotoxicity and cognitive impairment, leading to addiction, overdose, and high rates of relapse. However, few studies have systematically focused on functional impairments detected by neuroimaging in methamphetamine abstainers (MAs) during short-term abstinence. This study aimed to investigate effective connectivity, resting-state networks, and internetwork functional connectivity in MA brains to improve clinical treatment. Methods: Twenty MAs and 27 age- and education-matched healthy controls underwent resting-state functional magnetic resonance imaging. The amplitude of low-frequency fluctuations and Granger causality were analyzed to investigate disrupted brain regions and effective connectivity, respectively. Independent component analysis and functional network connectivity were used to identify resting-state networks and internetwork functional connectivity, respectively. Results: Compared with healthy controls, MAs demonstrated abnormal amplitudes of low-frequency fluctuations in the bilateral precuneus, left posterior cingulate cortex (PCC), left middle frontal gyrus (MFG), left superior parietal lobule, left supplementary motor area (SMA), and left inferior parietal lobule (IPL). Moreover, MAs showed decreased effective connectivity from the left PCC to the left precuneus, increased effective connectivity from the left precuneus to the left MFG and from the right precuneus to the left SMA, and altered functional connectivity within the default mode network (DMN), frontoparietal network, sensorimotor network, ventral attention network, cerebellar network, and visual network. Importantly, hyperconnectivity between the DMN and ventral attention network and hypoconnectivity between the DMN and cerebellar network as well as the DMN and frontoparietal network were demonstrated in MAs. Conclusion: Our study implies that in short-term methamphetamine abstinence, disruptions to the DMN and executive network may a play key role, providing new insights for early rehabilitation.

19.
World J Clin Cases ; 10(14): 4380-4394, 2022 May 16.
Article in English | MEDLINE | ID: mdl-35663088

ABSTRACT

BACKGROUND: The neutrophil-lymphocyte ratio (NLR) is often used to predict a poor prognosis in patients with tumors. This study investigated the preoperative peripheral blood NLR in predicting postoperative survival (POS) in patients with multiple myeloma bone disease (MMBD). AIM: To evaluate whether NLR can be used to predict the prognosis of MMBD patients after surgery. METHODS: The clinical data of 82 MMBD patients who underwent surgical treatments in Beijing Chao-yang Hospital were collected. The NLR was obtained from the absolute number of neutrophils and lymphocytes, calculated by the number of neutrophils and divided by the number of lymphocytes. The peripheral blood lymphocyte percentage was used as the major marker to analyze the change in characteristics of the immune statuses of multiple myeloma patients. RESULTS: The NLR cut-off values of NLR ≥ 3 patients and NLR ≥ 4 patients were significantly correlated with POS. The 3- and 5-year cumulative survival rates of the high NLR group (NLR ≥ 3 patients) were 19.1% and 0.0%, respectively, which were lower than those of the low NLR group (NLR < 3 patients) (67.2% and 48.3%) (P = 0.000). In the high NLR group, POS (14.86 ± 14.28) was significantly shorter than that in the low NLR group (32.68 ± 21.76). Univariate analysis showed that the lymphocyte percentage 1 wk after the operation (19.33 ± 9.08) was significantly lower than that before the operation (25.72 ± 11.02). Survival analysis showed that postoperative chemotherapy, preoperative performance status and preoperative peripheral blood NLR ≥ 3 were independent risk factors for POS. CONCLUSION: The preoperative peripheral blood NLR can predict POS in MMBD patients. MMBD patients with a high preoperative NLR (NLR ≥ 3) showed poor prognosis.

20.
World J Clin Cases ; 9(30): 9023-9037, 2021 Oct 26.
Article in English | MEDLINE | ID: mdl-34786385

ABSTRACT

BACKGROUND: Multiple myeloma is an incurable malignant plasma cell disorder that represents the most common primary malignant bone tumor. It commonly involves bone metastasis in multiple vertebral bodies, and the Spinal Instability Neoplastic Score scoring system may not be fully applicable to multiple myeloma (MM) patients. AIM: To evaluate the spinal stability of patients with MM spinal involvement to guide their clinical treatment. METHODS: By using the Delphi method, we collected and extracted information through a series of questionnaires and improved it via feedback. We also preliminarily established a spinal stability scoring system for multiple myeloma. RESULTS: Fifteen clinicians completed a second round of questionnaires and compared their answers with those of the first round of questionnaires to identify significant comments or changes that required group discussions. As a result, no further feedback was used to improve the scoring system. After integrating the information from the expert consultation questionnaire, we established the initial scoring system for MM spine stability and used the scoring system to assess a series of representative clinical cases. The MM spinal stability scoring system was created by calculating the scores of the six separate components: location, pain, number of segments, physiological curvature, comorbidities, and neurological function. The minimum value was "0", and the maximum value was "24". A score of "0-10" indicated "spine stability", a score of "11-17" indicated "potential instability", and a score of "18-24" indicated "spine instability". Patients with a score of "11-24" need an intervention such as surgery. CONCLUSION: The initial establishment of the MM spine stability scoring system provides a vital theoretical basis for the evaluation of spine stability in individuals with MM.

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