ABSTRACT
A Gram-stain-negative, aerobic, motile and rod-shaped bacterium, the color of the bacterial colony ranges from light yellow to yellow, designated YC-2023-2T, was isolated from sediment sample of Yuncheng salt lake. Growth occurred at 15-45â (optimum 37â), pH 6.0-9.0 (optimum pH 7.0-8.0) and with 0-8.0% NaCl (w/v, optimum 2.0%). The phylogenetic analysis based on 16S rRNA gene sequences showed that strain YC-2023-2T belonged to the family Kordiimonadaceae. The closely related members were Gimibacter soli 6D33T (92.38%), Kordiimonas lipolytica M41T (91.88%), Eilatimonas milleporae DSM 25217T (91.88%) and Kordiimonas gwangyangensis JCM 12864T (91.84%). The genome of strain YC-2023-2T was 2957513 bp, and the genomic DNA G+C content was 63.91%. The main respiratory quinone was Q-10 and the major fatty acids (>10%) were iso-C15:0, C16:0, C19:0 cyclo ω8c, Summed Feature 8 (C18:1 ω6c or C18:1 ω7c) and Summed Feature 9 (iso-C17:1 ω9c or C16:0 10-methyl). The major polar lipids consisted of phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, unidentified glycolipid, unidentified lipid, and two unidentified aminolipids. Based on the phylogenetic, phenotypic and chemotaxonomic characteristics, strain YC-2023-2T is proposed to represent a novel species of a novel genus named Yunchengibacter salinarum gen. nov., sp. nov., within the family Kordiimonadaceae. The type strain is YC-2023-2T (= GDMCC 1.4502T = KCTC 8546T).
Subject(s)
Base Composition , DNA, Bacterial , Fatty Acids , Geologic Sediments , Lakes , Phylogeny , RNA, Ribosomal, 16S , Geologic Sediments/microbiology , Lakes/microbiology , RNA, Ribosomal, 16S/genetics , DNA, Bacterial/genetics , Fatty Acids/analysis , Bacterial Typing Techniques , China , Sequence Analysis, DNA , Sodium Chloride/metabolismABSTRACT
The kinetics and durability of conversion-based anodes greatly depend on the intrinsic stress regulating ability of the electrode materials, which has been significantly neglected. Herein, a stress dissipation strategy driven by multi-interface built-in electric fields (BEFs) and architected structure, is innovatively proposed to design ultrafast and long-term sodium ion storage anodes. Binary Mo/Fe sulfide heterostructured nanorods with multi-interface BEFs and staggered cantilever configuration are fabricated to prove our concept. Multi-physics simulations and experimental results confirm that the inner stress in multiple directions can be dissipated by the multi-interface BEFs at the micro-scale, and by the staggered cantilever structure at the macro-scale, respectively. As a result, our designed heterostructured nanorods anode exhibits superb rate capability (332.8â mAh g-1 at 10.0â A g-1 ) and durable cyclic stability over 900 cycles at 5.0â A g-1 , outperforming other metal chalcogenides. This proposed stress dissipation strategy offers a new insight for developing stable structures for conversion-based anodes.
ABSTRACT
Alzheimer's disease (AD) is one of the most prevalent forms of dementia in older individuals. Convergent evidence suggests structural connectome abnormalities in specific brain regions are linked to AD progression. The biological basis underpinnings of these connectome changes, however, have remained elusive. We utilized an individual regional mean connectivity strength (RMCS) derived from a regional radiomics similarity network to capture altered morphological connectivity in 1654 participants (605 normal controls, 766 mild cognitive impairment [MCI], and 283 AD). Then, we also explored the biological basis behind these morphological changes through gene enrichment analysis and cell-specific analysis. We found that RMCS probes of the hippocampus and medial temporal lobe were significantly altered in AD and MCI, with these differences being spatially related to the expression of AD-risk genes. In addition, gene enrichment analysis revealed that the modulation of chemical synaptic transmission is the most relevant biological process associated with the altered RMCS in AD. Notably, neuronal cells were found to be the most pertinent cells in the altered RMCS. Our findings shed light on understanding the biological basis of structural connectome changes in AD, which may ultimately lead to more effective diagnostic and therapeutic strategies for this devastating disease.
Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Connectome , Humans , Aged , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Magnetic Resonance Imaging , Brain/diagnostic imaging , Brain/metabolism , Temporal Lobe/diagnostic imaging , Temporal Lobe/metabolism , Cognitive Dysfunction/diagnostic imaging , Transcription, GeneticABSTRACT
BACKGROUND: Zika virus (ZIKV) infection is clinically known to induce testicular swelling, termed orchitis, and potentially impact male sterility, but the underlying mechanisms remain unclear. Previous reports suggested that C-type lectins play important roles in mediating virus-induced inflammatory reactions and pathogenesis. We thus investigated whether C-type lectins modulate ZIKV-induced testicular damage. METHODS: C-type lectin domain family 5 member A (CLEC5A) knockout mice were generated in a STAT1-deficient immunocompromised background (denoted clec5a-/-stat1-/-) to enable testing of the role played by CLEC5A after ZIKV infection in a mosquito-to-mouse disease model. Following ZIKV infection, mice were subjected to an array of analyses to evaluate testicular damage, including ZIKV infectivity and neutrophil infiltration estimation via quantitative RT-PCR or histology and immunohistochemistry, inflammatory cytokine and testosterone detection, and spermatozoon counting. Furthermore, DNAX-activating proteins for 12 kDa (DAP12) knockout mice (dap12-/-stat1-/-) were generated and used to evaluate ZIKV infectivity, inflammation, and spermatozoa function in order to investigate the potential mechanisms engaged by CLEC5A. RESULTS: Compared to experiments conducted in ZIKV-infected stat1-/- mice, infected clec5a-/-stat1-/- mice showed reductions in testicular ZIKV titer, local inflammation and apoptosis in testis and epididymis, neutrophil invasion, and sperm count and motility. CLEC5A, a myeloid pattern recognition receptor, therefore appears involved in the pathogenesis of ZIKV-induced orchitis and oligospermia. Furthermore, DAP12 expression was found to be decreased in the testis and epididymis tissues of clec5a-/-stat1-/- mice. As for CLEC5A deficient mice, ZIKV-infected DAP12-deficient mice also showed reductions in testicular ZIKV titer and local inflammation, as well as improved spermatozoa function, as compared to controls. CLEC5A-associated DAP12 signaling appears to in part regulate ZIKV-induced testicular damage. CONCLUSIONS: Our analyses reveal a critical role for CLEC5A in ZIKV-induced proinflammatory responses, as CLEC5A enables leukocytes to infiltrate past the blood-testis barrier and induce testicular and epididymal tissue damage. CLEC5A is thus a potential therapeutic target for the prevention of injuries to male reproductive organs in ZIKV patients.
Subject(s)
Orchitis , Zika Virus Infection , Zika Virus , Humans , Male , Mice , Animals , Semen/metabolism , Mice, Knockout , Inflammation/genetics , Lectins, C-Type/genetics , Receptors, Cell Surface/genetics , Receptors, Cell Surface/metabolismABSTRACT
The Brain Age Gap (BAG), which refers to the difference between chronological age and predicted neuroimaging age, is proposed as a potential biomarker for age-related brain degeneration. However, existing brain age prediction models usually rely on a single marker and can not discover meaningful hidden information in radiographic images. This study focuses on the application of radiomics, an advanced imaging analysis technique, combined with automated machine learning to predict BAG. Our methods achieve a promising result with a mean absolute error of 1.509 using the Alzheimer's Disease Neuroimaging Initiative dataset. Furthermore, we find that the hippocampus and parahippocampal gyrus play a significant role in predicting age with interpretable method called SHapley Additive exPlanations. Additionally, our investigation of age prediction discrepancies between patients with Alzheimer's disease (AD) and those with mild cognitive impairment (MCI) reveals a notable correlation with clinical cognitive assessment scale scores. This suggests that BAG has the potential to serve as a biomarker to support the diagnosis of AD and MCI. Overall, this study presents valuable insights into the application of neuroimaging models in the diagnosis of neurodegenerative diseases.
ABSTRACT
It is unclear whether hepatitis B surface antibody (HBsAb) confers clinical benefits after HBsAg seroclearance, especially in hepatitis B surface antigen (HBsAg) seroreversion and maintenance of HBsAb. We evaluated this in patients (n = 222) with HBsAg loss following treatment with pegylated interferon (PEG-IFN)-based therapy who completed a 48-week follow-up period. Serum hepatitis B virus (HBV) markers and biochemical indicators were evaluated every 3 months. The primary endpoint was HBsAg seroreversion. Factors associated with HBsAg seroreversion were also investigated. HBsAb ≥100 mIU/ml resulted in a lower HBsAg seroreversion rate than an HBsAb-negative status (5.5% vs. 29.5%, p < .001); however, the seroreversion rate was not significantly different between patients with HBsAb 10-100 mIU/ml and those in the HBsAb-negative group. Patients with HBsAb ≥100 mIU/ml had a lower HBsAb loss rate than those with HBsAb 10-100 mIU/ml (7.3% vs. 21.7%, p = .005). The final HBsAg seroreversion and HBV DNA relapse rates were 13.5% and 1.8%, respectively. HBsAb ≥100 mIU/ml at the off-treatment time (odds ratio [OR] 0.110, 95% confidence interval [CI]: 0.034-0.353, p < .001) and treatment time to attain HBsAg loss >28 weeks (OR 2.508, 95% CI: 1.068-5.890, p = .035) were predictors of HBsAg seroreversion. Consolidation therapy for 12-24 weeks resulted in higher HBsAb titres than consolidation therapy for ≤12 weeks in HBsAb-negative patients at the off-treatment time (p < .001). HBsAg seroconversion with HBsAb ≥100 mIU/ml decreases HBsAg seroreversion and provides an efficient maintenance rate of HBsAb. HBsAg seroconversion with high HBsAb titres may be clinically beneficial for chronic hepatitis B treated with PEG-IFN-based therapy.
Subject(s)
Hepatitis B Surface Antigens , Hepatitis B, Chronic , Antiviral Agents/therapeutic use , DNA, Viral , Hepatitis B Antibodies , Hepatitis B e Antigens , Hepatitis B virus , Hepatitis B, Chronic/drug therapy , Humans , Interferons/therapeutic use , Polyethylene Glycols/therapeutic useABSTRACT
Halophilic phage are a type of virus that exist in salty environments within halophilic archaeal or bacterial hosts. However, relatively few reports on halophilic bacteriophages exist, and our overall understanding of halophilic bacteriophages is quite limited. We used SYBR Green I fluorescent staining to detect the abundance of viruses in Yuncheng Saline Lake, China. Using the double-layer plate method, a lytic phage that could infect halophilic bacterium Salinivibrio sp. YM-43 was isolated and named YXM43. We studied host range, optimal host, morphological characteristics, nucleic acid type, protein composition, and other biological characteristics of the virus. Results reveal a high abundance of this halophilic virus in Yuncheng Saline Lake. The newly isolated bacteriophage YXM43 has a narrow host range, with the most suitable host being Virgibacillus sp. SK39. After purification and enrichment, YXM43 is observed as a spherical particle with a diameter of approximately 30 nm, with no tail. No lipid envelope can be seen in YXM43. The capsid protein of the virus can be separated into seven proteins with molecular weights ranging from 62.0 to 13.0 kDa. YXM43 is a DNA virus with a genome approximately 23 kb. The virus is tolerant of low salinity, and its activity is highest at a temperature of 60 °C and a pH of 10. YXM43 is temperature and pH tolerant, and can adapt to environmental change, even withstanding chloroform treatment. The results indicate that bacteriophage YXM43 is a novel halophilic bacteriophage with broad tolerance to environmental change.
ABSTRACT
Noise-induced hearing loss (NIHL) seriously affects the life quality of humans and causes huge economic losses to society. To identify novel genetic loci involved in NIHL, we conducted a genome-wide association study (GWAS) for this symptom in Chinese populations. GWAS scan was performed in 89 NIHL subjects (cases) and 209 subjects with normal hearing who have been exposed to a similar noise environment (controls), followed by a replication study consisting of 53 cases and 360 controls. We identified that four candidate pathways were nominally significantly associated with NIHL, including the Erbb, Wnt, hedgehog and intraflagellar transport pathways. In addition, two novel index single-nucleotide polymorphisms, rs35075890 in the intron of AUTS2 gene at 7q11.22 (combined P = 1.3 × 10-6 ) and rs10081191 in the intron of PTPRN2 gene at 7q36.3 (combined P = 2.1 × 10-6 ), were significantly associated with NIHL. Furthermore, the expression quantitative trait loci analyses revealed that in brain tissues, the genotypes of rs35075890 are significantly associated with the expression levels of AUTS2, and the genotypes of rs10081191 are significantly associated with the expressions of PTPRN2 and WDR60. In conclusion, our findings highlight two novel loci at 7q11.22 and 7q36.3 conferring susceptibility to NIHL.
Subject(s)
Genome-Wide Association Study/methods , Hearing Loss, Noise-Induced/genetics , Polymorphism, Single Nucleotide/genetics , Adaptor Proteins, Signal Transducing/genetics , China , Cytoskeletal Proteins/genetics , Genetic Predisposition to Disease/genetics , Humans , Male , Receptor-Like Protein Tyrosine Phosphatases, Class 8/genetics , Transcription Factors/geneticsABSTRACT
BACKGROUND: When following catheter-directed thrombolysis (CDT) for deep vein thrombosis (DVT), the stenosed iliac veins is controversy. To evaluate the mid-term outcomes of CDT with or without stent implantation for DVT in the presence of iliac vein compression. METHODS: Seventy-three patients with iliac vein compression following CDT for acute lower extremity DVT from January 2009 to December 2014 were retrospectively analyzed. There were 32 males and 41 females, with average age of 53.57 ± 15.60 years (median: 45 years, range: 20-79 years). After CDT, patients with iliac vein compression were divided into 2 groups: the stenting group (n = 40) and the nonstenting group (n = 33). Patency rate of the deep vein, chronic change of vessels, clinical, etiological, anatomical, and pathological elements (CEAP) classification, venous clinical severity score, and Villalta scale were chosen to evaluate the midterm and long-term outcomes. RESULTS: Eighty-eight limbs among the patients (58 unilateral and 15 bilateral) were followed with mean time of 38.38 ± 14.91 months. The difference in vein patency between 2 groups (85.17 ± 25.62 vs. 54.61 ± 40.42) was statistically significant (P < 0.05). According to the C in CEAP classification, the difference in clinical manifestations between the 2 groups was statistically significant (P < 0.05). In addition, the Villalta scale scores were also significantly different between the 2 groups (1.73 ± 2.86 vs. 4.39 ± 5.16, P < 0.05). CONCLUSIONS: Stent implantation in severely stenosed iliac segments following CDT for lower extremity DVT increased the patency of deep veins and improved midterm quality of life compared with that of nonstenting.
Subject(s)
Catheterization, Peripheral , Endovascular Procedures/instrumentation , Fibrinolytic Agents/administration & dosage , Iliac Vein , Stents , Thrombolytic Therapy/methods , Venous Thrombosis/therapy , Adult , Aged , Catheterization, Peripheral/adverse effects , Constriction, Pathologic , Endovascular Procedures/adverse effects , Female , Fibrinolytic Agents/adverse effects , Humans , Iliac Vein/diagnostic imaging , Iliac Vein/physiopathology , Kaplan-Meier Estimate , Male , Middle Aged , Quality of Life , Retrospective Studies , Severity of Illness Index , Thrombolytic Therapy/adverse effects , Time Factors , Treatment Outcome , Vascular Patency , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/physiopathology , Young AdultABSTRACT
OBJECTIVES: To explore the risk factors for recurrence of inferior vena cava (IVC)-type Budd-Chiari syndrome (BCS) after stenting and evaluate the feasibility and primary outcomes of endovascular therapies for recurrent BCS. METHODS: A retrospective analysis of 219 patients was performed to identify risk factors for recurrence. The images of the recurrent patients during follow-up duration and interventional surgery were also reviewed to find the possible reasons of recurrence. The outcome of endovascular therapies for recurrent BCS was evaluated by Kaplan-Meier analysis. RESULTS: Among the 219 patients, 172 patients with primary IVC-type BCS underwent stenting and 28 patients experienced recurrence. Multivariate analysis identified age, Child-Pugh score, MELD and total bilirubin as independent recurrent indicators. Possible causes of recurrence include thrombosis in the stent, re-obstruction in or above the stent, and stent-related hepatic vein obstruction. Twenty-five patients with recurrent BCS underwent endovascular therapies with a few complications and achieved a high level of short- and mid-term patency. CONCLUSION: Age, total bilirubin and severity of liver function are the main risk factors for BCS recurrence. These risks might contribute to thrombosis or subsequent fibrous obstruction. Endovascular therapies are effective and safe management options that yield positive outcomes for recurrent BCS. KEY POINTS: ⢠Risk factors for recurrent Budd-Chiari syndrome were identified by multivariate analysis. ⢠Causes of recurrent Budd-Chiari syndrome were investigated by assessing radiological images. ⢠There is a correlation between risk factors and causes of recurrence. ⢠Endovascular therapies for recurrent Budd-Chiari syndrome are effective and safe.
Subject(s)
Budd-Chiari Syndrome/therapy , Endovascular Procedures/methods , Postoperative Complications/therapy , Stents , Adult , Age Factors , China , Cohort Studies , Feasibility Studies , Female , Humans , Kaplan-Meier Estimate , Liver/physiopathology , Male , Middle Aged , Recurrence , Retrospective Studies , Risk Factors , Severity of Illness Index , Treatment Outcome , Vena Cava, Inferior/physiopathologyABSTRACT
BACKGROUND IVC filters have been widely accepted as an effective method to prevent pulmonary embolism (PE) in patients with deep venous thrombosis (DVT). However, the placement of IVC filters is associated with significant complications and filter retrieval can be challenging when the filter struts are embedded into the caval wall. MATERIAL AND METHODS Over 26 months, we reviewed the safety and efficacy of the bidirectional pull-back technique for removing strut-embedded IVC filters in 15 consecutive patients. Retrieval procedural data such as in-dwell time, retrieval time, and fluoroscopy time were recorded. Clinical outcomes and procedure-related complications were evaluated by venography or enhanced computed tomography. Histologic tissue was analyzed to reveal the pathologic effects of chronic filter implantation. All patients underwent routine clinical follow-up at a mean time of 12 months (range, 8-14 months). RESULTS Technical success of filter retrieval was achieved in 100%, with mean implantation of 46.6 days (range, 27-66 days). Filter types were as follows: OptEase (n=11) and Aegisy (n=4). The mean retrieval time and fluoroscopy time were 21.43±5.42 min and 7.63±2.67 min, respectively. Immediate postprocedure venography showed no procedure-related complications. Thirteen patients discontinued previously prescribed lifelong anticoagulation. There were no long-term complications during follow-up. CONCLUSIONS The bidirectional pull-back technique is safe and efficient for filter retrieval. This complex technique can be particularly useful in selected patients to remove strut-embedded cylindrical-shaped IVC filters previously considered irretrievable.
Subject(s)
Vena Cava Filters , Vena Cava, Inferior/physiology , Adult , Device Removal , Female , Humans , Male , Middle AgedABSTRACT
A halophilic strain W33 showing lipolytic activity was isolated from the saline soil of Yuncheng Salt Lake, China. Biochemical and physiological characterization along with 16S rRNA gene sequence analysis placed the isolate in the genus Idiomarina. The extracellular lipase was purified to homogeneity by 75% ammonium sulphate precipitation, DEAE-Sepharose anion exchange and Sephacryl S-200 gel filtration chromatography. The molecular mass of the purified lipase was estimated to be 67 kDa by SDS-PAGE. Substrate specificity test indicated that it preferred long-chain p-nitrophenyl esters. Optimal lipase activity was found to be at 60 °C, pH 7.0-9.0 and 10% NaCl, and it was highly active and stable over broad temperature (30-90 °C), pH (7.0-11.0) and NaCl concentration (0-25%) ranges, showing excellent thermostable, alkali-stable and halotolerant properties. Significant inhibition by diethyl pyrocarbonate and phenylarsine oxide was observed, implying histidine and cysteine residues were essential for enzyme catalysis. In addition, the lipase displayed high stability and activity in the presence of hydrophobic organic solvents with log P(ow) ≥ 2.13. The free and immobilized lipases produced by Idiomarina sp. W33 were applied for biodiesel production using Jatropha oil, and about 84 and 91% of yields were achieved, respectively. This study formed the basic trials conducted to test the feasibility of using lipases from halophile for biodiesel production.
Subject(s)
Alteromonadaceae/enzymology , Bacterial Proteins/metabolism , Biofuels , Industrial Microbiology/methods , Lipase/metabolism , Plant Oils/metabolism , Alteromonadaceae/isolation & purification , Alteromonadaceae/metabolism , Enzyme Stability , Jatropha/chemistry , Salinity , Soil Microbiology , Solvents , Substrate SpecificityABSTRACT
Polyploid giant cancer cells (PGCCs) are characterized by the presence of either a single enlarged nucleus or multiple nuclei and are closely associated with tumor progression and treatment resistance. These cells contribute significantly to cellular heterogeneity and can arise from various stressors, including radiation, chemotherapy, hypoxia, and environmental factors. The formation of PGCCs can occur through mechanisms such as endoreplication, cell fusion, cytokinesis failure, mitotic slippage, or cell cannibalism. Notably, PGCCs exhibit traits similar to cancer stem cells (CSCs) and generate highly invasive progeny through asymmetric division. The presence of PGCCs and their progeny is pivotal in conferring resistance to chemotherapy and radiation, as well as facilitating tumor recurrence and metastasis. This review provides a comprehensive analysis of the origins, potential formation mechanisms, stressors, unique characteristics, and regulatory pathways of PGCCs, alongside therapeutic strategies targeting these cells. The objective is to enhance the understanding of PGCC initiation and progression, offering novel insights into tumor biology.
ABSTRACT
Background: This article employs bibliometric methods and visual maps to delineate the research background, collaborative relationships, hotspots, and trends in the study of gut fungi in human diseases and health. Methods: Publications related to human gut fungi were retrieved from the Web of Science Core Collection. VOSviewer, CiteSpace, R software and Microsoft Excel were employed to generate visual representations illustrating the contributions made by countries/regions, authors, organizations, and journals. Employing VOSviewer and CiteSpace, we conducted a comprehensive analysis of the retrieved publications, revealing underlying tendencies, research hotspots, and intricate knowledge networks. Results: This study analyzed a total of 3,954 publications. The United States ranks first in the number of published papers and has the highest number of citations and h-index. Mostafa S Elshahed is the most prolific author. The University of California System is the institution that published the most papers. Frontiers In Microbiology is the journal with the largest number of publications. Three frequently co-cited references have experienced a citation burst lasting until 2024. Conclusion: Advancements in sequencing technologies have intensified research into human gut fungi and their health implications, shifting the research focus from gut fungal infections towards microbiome science. Inflammatory bowel diseases and Candida albicans have emerged as pivotal areas of interest in this endeavor. Through this study, we have gained a deeper insight into global trends and frontier hotspots within this field, thereby enhancing our understanding of the intricate relationship between gut fungi and human health.
Subject(s)
Bibliometrics , Fungi , Gastrointestinal Microbiome , Humans , Mycoses/epidemiology , Mycoses/microbiology , Biomedical Research/trendsABSTRACT
Docetaxel (Doc) plays a crucial role in clinical antineoplastic practice. However, it is continuously documented that tumors frequently develop chemoresistance and relapse, which may be related to polyploid giant cancer cells (PGCCs). The aim of this study was investigate the formation mechanism and biological behavior of PGCCs induced by Doc. Ovarian cancer cells were treated with Doc, and then the effect of Doc on cellular viability was evaluated by MTT assay and microscopic imaging analysis. The biological properties of PGCCs were further evaluated by Hoechst 33342 staining, cell cycle and DNA content assay, DNA damage response (DDR) signaling detection, ß-galactosidase staining, mitochondrial membrane potential detection, and reverse transcription-quantitative polymerase chain reaction. The results indicated that Doc reduced cellular viability; however, many cells were still alive, and were giant and polyploid. Doc increased the proportion of cells stayed in the G2/M phase and reduced the number of cells. In addition, the expression of γ-H2A.X was constantly increased after Doc treatment. PGCCs showed senescence-associated ß-galactosidase activity and an increase in the monomeric form of JC-1. The mRNA level of octamer-binding transcription factor 4 (OCT4) and krüppel-like factor 4 (KLF4) was significantly increased in PGCCs. Taken together, our results suggest that Doc induces G2/M cell cycle arrest, inhibits the proliferation and activates persistent DDR signaling to promote the formation of PGCCs. Importantly, PGCCs exhibit a senescence phenotype and express stem cell markers.
Subject(s)
Cellular Senescence , Docetaxel , Kruppel-Like Factor 4 , Neoplastic Stem Cells , Ovarian Neoplasms , Polyploidy , Humans , Docetaxel/pharmacology , Female , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/genetics , Cellular Senescence/drug effects , Cell Line, Tumor , Neoplastic Stem Cells/drug effects , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathology , Octamer Transcription Factor-3/metabolism , Octamer Transcription Factor-3/genetics , Giant Cells/drug effects , Giant Cells/metabolism , Antineoplastic Agents/pharmacology , Phenotype , Cell Survival/drug effects , Membrane Potential, Mitochondrial/drug effects , Kruppel-Like Transcription Factors/metabolism , Kruppel-Like Transcription Factors/genetics , Taxoids/pharmacology , DNA Damage/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/geneticsABSTRACT
Objective: Colorectal carcinoma (CRC) is the third most common malignancy. In addition to comprehensive cancer treatments, such as surgery, chemotherapy, and radiotherapy, the adoptive immune cell therapy (ACT) has played an increasingly important role in recent years, and the adaptive transfusion of autologous NK cells and CIK cells is a brand-new approach to cellular therapy for solid tumors. Case Presentation: A 57-year-old man underwent a radical resection of microsatellite stable (MSS) rectal cancer with synchronous liver metastases. After surgery of the primary lesion surgery, he was treated with autologous CIK/NK cells combined with XELOX translational therapy. Each cycle can obtain over 10 × 109 CIK cells or over 6 × 109 NK cells combined chemotherapy of XELOX every 3 weeks. After 2 cycles of therapy, he achieved partial response (PR). He immediately underwent a hepatic metastasis resection. After surgery, the patient continued to receive autologous CIK/NK cells in combined with 4 cycles of XELOX. To date, he has achieved and maintained no evidence of disease (NED) for over 40 months. Conclusion: This is a case of successful treatment of rectal cancer with liver metastasis using ACT in conjunction with first-line chemotherapy. The advantage of this treatment plan is that it has few side effects and achieves long-term control of tumor recurrence by improving the patient's immune function. However, its responsiveness and benefit rate still need further investigation.
ABSTRACT
The community structure and co-occurrence pattern of eukaryotic algae in Yuncheng Salt Lake were analyzed based on marker gene analysis of the 18S rRNA V4 region to understand the species composition and their synergistic adaptations to the environmental factors in different salinity waters. The results showed indicated that the overall algal composition of Yuncheng Salt Lake showed a Chlorophyta-Pyrrophyta-Bacillariophyta type structure. Chlorophyta showed an absolute advantage in all salinity waters. In addition, Cryptophyta dominated in the least saline waters; Pyrrophyta and Bacillariophyta were the dominant phyla in the waters with salinity ranging from 13.2 to 18%. Picochlorum, Nannochloris, Ulva, and Tetraselmis of Chlorophyta, Biecheleria and Oxyrrhis of Pyrrophyta, Halamphora, Psammothidium, and Navicula of Bacillariophyta, Guillardia and Rhodomonas of Cryptophyta were not observed in previous surveys of the Yuncheng Salt Lake, suggesting that the algae are undergoing a constant turnover as the water environment of the Salt Lake continues to change. The network diagram demonstrated that the algae were strongly influenced by salinity, NO3-, and pH, changes in these environmental factors would lead to changes in the algal community structure, thus affecting the stability of the network structure.
Subject(s)
Chlorophyta , Diatoms , Dinoflagellida , Lakes/chemistry , Phytoplankton , Salinity , Chlorophyta/genetics , ChinaABSTRACT
BACKGROUND: The highly heterogeneity of neuropsychiatric symptoms (NPSs) hinder further exploration of their role in neurobiological mechanisms and Alzheimer's disease (AD). We aimed to delineate NPS patterns based on brain macroscale connectomics to understand the biological mechanisms of NPSs on the AD continuum. METHODS: We constructed Regional Radiomics Similarity Networks (R2SN) for 550 participants (AD with NPSs [AD-NPS, n=376], AD without NPSs [AD-nNPS, n=111], and normal controls [n=63]) from CIBL study. We identified R2SN connections associated with NPSs, and then cluster distinct subtypes of AD-NPS. An independent dataset (n=189) and internal validation were performed to assess the robustness of the NPS subtypes. Subsequent multiomics analysis were performed to assess the distinct clinical phenotype and biological mechanisms in each NPS subtype. RESULTS: AD-NPS patients were clustered into severe (n=187), moderate (n=87), and mild NPS (n=102) subtypes, each exhibiting distinct brain network dysfunction patterns. A high level of consistency in clustering NPS was internally and externally validated. Severe and moderate NPSs showed significant cognitive impairment, increased plasma p-Tau181 levels, extensive decreased brain volume and cortical thickness, and accelerated cognitive decline. Gene set enrichment analysis (GSEA) revealed enrichment of differentially expressed genes in ion transport and synaptic transmission with variations for each NPS subtype. Genome-wide association studies (GWAS) analysis defined the specific gene loci for each subtype of AD-NPS (i.e, logical memory), aligning with clinical manifestations and progression patterns. CONCLUSIONS: This study identified and validated three distinct NPS subtypes, underscoring the role of NPSs in neurobiological mechanisms and progression of the AD continuum.
ABSTRACT
A haloarchaeal strain LLSG7 with cellulolytic activity was isolated from the saline soil of Yuncheng Salt Lake, China. Biochemical and physiological characterization along with 16S rRNA gene sequence analysis placed the isolate in the genus Haloarcula. Cellulase production was strongly influenced by the salinity of the culture medium with the maximum obtained in the presence of 25 % NaCl. Substrate specificity tests showed that the crude cellulase was a multicomponent enzyme system, and zymogram analysis revealed that five different endoglucanases were secreted by strain LLSG7. Optimal cellulase activity was at 50 °C, pH 8.0, and 20 % NaCl. In addition, it was highly active and stable over broad ranges of temperature (40-80 °C), pH (7.0-11.0), and NaCl concentration (17.5-30 %). The cellulase displayed remarkable stability in the presence of non-polar organic solvents with log P ow ≥ 1.97. The crude cellulase secreted by strain LLSG7 was further applied to hydrolyze alkali-pretreated rice straw and the enzymatic hydrolysate was used as the substrate for bioethanol fermentation by Saccharomyces cerevisiae. The yield of ethanol was 0.177 g per gram of pretreated rice straw, suggesting that it might be potentially useful for bioethanol production.
Subject(s)
Cellulase/metabolism , Ethanol/metabolism , Fermentation , Haloarcula/enzymology , Oryza/chemistry , Solvents/chemistry , Agriculture , Biocatalysis , Electrophoresis, Polyacrylamide Gel , Enzyme Stability , Haloarcula/classification , Haloarcula/growth & development , Hydrogen-Ion Concentration , Phylogeny , Refuse Disposal , Saccharomyces cerevisiae/metabolism , Sodium Chloride , Substrate Specificity , TemperatureABSTRACT
OBJECTIVE: To explore the effect of autologous cytokine-induced killer cells on the quality of life in patient with breast cancer who have already finished the adjuvant chemotherapy. METHODS: One hundred and twenty-eight postoperative patients with breast cancer who underwent anthracycline-based adjuvant chemotherapy were enrolled in this prospective study, and they were randomized into 2 groups, i.e., treatment group, which received the therapy of CIK cells transfusion, and control group, which was given regular follow-up. Meanwhile, patients with positive hormone receptor in the two groups were given endocrine therapy, and the patients with positive axillary lymph nodes were given radiotherapy to the chest wall and regional lymph nodes. The difference of quality of life between the two groups was analyzed according to the EORTC QLQ-BR53 quality of life questionnaire, and the adverse reactions were monitored. RESULTS: As regarding the functional evaluation, the physical function scores of patients of the treatment group were (83.43 ± 14.87) and (88.55 ± 11.62) at 3 and 6 months after the CIK cell therapy, respectively, significantly higher than the baseline value [(74.83 ± 13.82), P < 0.05)]. Global health status/QOL scores were (83.30 ± 19.09) and (89.68 ± 10.81), significantly higher than the baseline value [(77.72 ± 21.05), P < 0.05]. As regarding symptoms, the scores of fatigue, nausea, vomiting and loss of appetite of patients in the treatment group were higher than the baseline value, with significant differences (P < 0.05). The nausea and vomiting scores in the control group at 3 and 6 months of followed-up were (26.67 ± 22.56) and (21.47 ± 21.06), significantly lower than the baseline values [(33.31 ± 27.07), P < 0.05]. The scores of worrying about the future in the patients of treatment group were (47.56 ± 30.84) and (42.33 ± 26.95) after 3 and 6 months, significantly better than the baseline value [(57.41 ± 30.63), P < 0.05]. The systematic therapy side effects scores were (31.95 ± 27.52) and (23.72 ± 22.87), significantly better than the baseline value [(40.56 ± 26.28), P < 0.05]. The scores of arm edema were (45.26 ± 25.42) and (36.61 ± 20.51), significantly milder than the baseline value [(55.11 ± 22.82), P < 0.05]. In the control group, the scores of arm edema were (44.85 ± 28.94) and (38.64 ± 23.68), significantly lower than the baseline values [(53.26 ± 23.84) points, P < 0.05]. Alopecia scores were (29.93 ± 24.72) and (24.18 ± 22.66), significantly lower than the baseline values [(35.92 ± 22.08), P < 0.05]. In the treatment group, the patients' physical function, social function and global health status/QOL, fatigue, insomnia, and worrying about the future rates were significantly higher than that of the control group (P < 0.05 for all). Three patients after CIK reinfusion had transient fever, and 6 cases felt pain in the lower limb, but the symptoms were relieved after symptomatic treatment. CONCLUSIONS: Therapy of autologous CIK cells transfusion can significantly improve the quality of life of breast cancer patients, and the adverse reactions during the treatment can be alleviated by symptomatic treatment.