Subject(s)
Adenoma , Colon, Ascending , Colonic Neoplasms , Endoscopic Mucosal Resection , Humans , Endoscopic Mucosal Resection/methods , Endoscopic Mucosal Resection/instrumentation , Adenoma/surgery , Colonic Neoplasms/surgery , Colon, Ascending/surgery , Nylons , Male , Traction/methods , Traction/instrumentation , Colonoscopy/methods , FemaleABSTRACT
The alteration of stand age instigates modifications in soil properties and microbial communities. Understanding the impacts of stand age on soil enzyme stoichiometry and microbial nutrient limitations in Camellia oleifera plantation is crucial for nutrient management. Taking C. oleifera plantation across four age groups (<10 a, 15-25 a, 30-50 a, >60 a) in a subtropical red soil region as test objects, we examined the response of soil enzyme stoichiometry and microbial nutrient limitations to change in stand age and analyzed the pathways for such responses. The results showed that, compared to that of stand age <10 a, enzyme C:N in the 15-25 a was increased and enzyme N:P was significantly reduced. Microbial biomass carbon (MBC), microbial biomass nitrogen (MBN), and microbial biomass phosphorus (MBP) exhibited a trend of initially decreasing and then increasing with stand age. MBN and MBN:MBP were significantly higher in the <10 a compared to that in the 30-50 a. MBC:MBN was significantly higher in the 30-50 a and >60 a compared to the <10 a and 15-25 a. Results of redundancy analysis revealed that soil nutrients, microbial biomass and their stoichiometry explained 92.4% of the variations in enzyme stoichiometry. Partial least squares path modeling (PLS-PM) results demonstrated that soil organic carbon (SOC) had a positive effect on microbial C limitation; MBN, MBN:MBP, MBC:MBP, SOC, and total nitrogen had a nega-tive overall effect on microbial P limitation, whereas soil C:N had a positive overall effect on microbial P limitation. There was a significant positive correlation between microbial C and P limitations. With increasing stand age, microbial nutrient limitation shifted from N and P limitation (<10 a) to C and P limitation (15-25 a, 30-50 a, >60 a).
Subject(s)
Camellia , Carbon , Nitrogen , Phosphorus , Soil Microbiology , Soil , Camellia/metabolism , Camellia/growth & development , Camellia/chemistry , Soil/chemistry , Nitrogen/metabolism , Nitrogen/analysis , Carbon/metabolism , Phosphorus/metabolism , Nutrients/metabolism , Nutrients/analysis , Time Factors , China , BiomassABSTRACT
The corticospinal tract (CST) is the principal neural pathway responsible for conducting voluntary movement in the vertebrate nervous system. Netrin-1 is a well-known guidance molecule for midline crossing of commissural axons during embryonic development. Families with inherited Netrin-1 mutations display congenital mirror movements (CMM), which are associated with malformations of pyramidal decussation in most cases. Here, we investigated the role of Netrin-1 in CST formation by generating conditional knockout (CKO) mice using a Gfap-driven Cre line. A large proportion of CST axons spread laterally in the ventral medulla oblongata, failed to decussate and descended in the ipsilateral spinal white matter of Ntn1Gfap CKO mice. Netrin-1 mRNA was expressed in the ventral ventricular zone (VZ) and midline, while Netrin-1 protein was transported by radial glial cells to the ventral medulla, through which CST axons pass. The level of transported Netrin-1 protein was significantly reduced in Ntn1Gfap CKO mice. In addition, Ntn1Gfap CKO mice displayed increased symmetric movements. Our findings indicate that VZ-derived Netrin-1 deletion leads to an abnormal trajectory of the CST in the spinal cord due to the failure of CST midline crossing and provides novel evidence supporting the idea that the Netrin-1 signalling pathway is involved in the pathogenesis of CMM.
Subject(s)
Mice, Knockout , Netrin-1 , Pyramidal Tracts , Animals , Netrin-1/metabolism , Netrin-1/genetics , Mice , Pyramidal Tracts/metabolism , Pyramidal Tracts/pathology , Axons/metabolism , Axons/pathologyABSTRACT
A total of five samples of Chrysomya megacephala samples - three fresh samples, one sample stored in alcohol for 2 years, and one sample stored in dry sealed storage for 2 years protected from light only - were selected to investigate whether a blood DNA extraction kit could extract DNA from necrophilous flies and to determine whether alcohol could prolong the preservation of necrophilous flies' DNA. First, the blood DNA extraction kit was used to extract DNA from their thorax tissues. Then, the DNA purity and concentration were examined using a microplate reader and a fluorometer. Finally, PCR amplification and electrophoresis of the extracted DNA were done with necrophilic fly-specific primers located in the mitochondrial CO I gene sequence. The results showed that the DNA purity of all samples was greater than 2.0. The DNA concentration was observed to be of the following order: fresh samples > alcohol-preserved old samples > untreated, old samples. All samples had specific electrophoretic bands after PCR amplification. In conclusion, a blood DNA extraction kit can be used to extract DNA from necrophilic flies successfully, and the DNA concentration of fresh fly samples is greater than that of old fly samples. The flies can be stored in alcohol for a long time.
Subject(s)
DNA , Polymerase Chain Reaction , Animals , DNA/isolation & purification , DNA/genetics , Polymerase Chain Reaction/methods , Calliphoridae/genetics , Calliphoridae/chemistryABSTRACT
More and more evidence shows that small noncoding RNAs (ncRNAs) play diverse roles in development, stress response and other cellular processes, but functional study of intermediate-size ncRNAs is still rare. Here, the expression profile of 16 intermediate-size ncRNAs in ovary and testis of silkworm Bombyx mori were analyzed. Twelve ncRNAs, including 5 small nucleolar RNAs (snoRNAs) and 7 unclassified ncRNAs, accumulated more in the testis than in the ovary of silkworm, especially Bm-163, Bm-51 and Bm-68. Four ncRNAs (including three orphan snoRNAs and one unclassified ncRNA) had higher expression level in the ovary than in the testis, especially Bm-86. Overexpression of the testis-enriched snoRNA Bm-68 in the female led to the accumulation of male-specific isoform of doublesex (BmdsxM) and increased the expression ratio of BmdsxM: BmdsxF. While overexpression of ovary-enriched snoRNA Bm-86 in the male decreased the expression ratio of BmdsxM: BmdsxF, indicating the roles of the two snoRNAs played in the alternative splicing of Bmdsx of silkworm, which will provide new clues for the functional study of snoRNAs in insects.
Subject(s)
Alternative Splicing , Bombyx , DNA-Binding Proteins , Insect Proteins , RNA, Small Nucleolar , Animals , Female , Male , Bombyx/genetics , Bombyx/metabolism , Insect Proteins/genetics , Insect Proteins/metabolism , Ovary/metabolism , RNA, Small Nucleolar/genetics , RNA, Small Nucleolar/metabolism , Testis/metabolismABSTRACT
This study investigated the correlation of newly identified inflammatory and insulin resistance indices with cerebral amyloid angiopathy (CAA), and explored their potential to differentiate CAA from hypertensive arteriopathy (HA). We retrospectively analyzed 514 consecutive patients with cerebral small vessel disease (CSVD)-related haemorrhage, comparing the differences in novel inflammatory and insulin resistance indices between patients with CAA and HA. Univariate regression, LASSO and multivariate regression were used to screen variables and construct a classification diagnosis nomogram. Additionally, these biomarkers were explored in patients with mixed haemorrhagic CSVD. Inflammatory indices were higher in CAA patients, whereas insulin resistance indices were higher in HA patients. Further analysis identified neutrophil-to-lymphocyte ratio (NLR, OR 1.17, 95% CI 1.07-1.30, P < 0.001), and triglyceride-glucose index (TyG, OR = 0.56, 95% CI 0.36-0.83, P = 0.005) as independent factors for CAA. Therefore, we constructed a CAA prediction nomogram without haemorrhagic imaging markers. The nomogram yielded an area under the curve (AUC) of 0.811 (95% CI 0.764-0.865) in the training set and 0.830 (95% CI 0.718-0.887) in the test set, indicating an ability to identify high-risk CAA patients. These results show that CSVD patients can be phenotyped using novel inflammatory and insulin resistance indices, potentially allowing identification of high-risk CAA patients without haemorrhagic imaging markers.
Subject(s)
Biomarkers , Cerebral Amyloid Angiopathy , Inflammation , Insulin Resistance , Humans , Male , Female , Cerebral Amyloid Angiopathy/pathology , Aged , Retrospective Studies , Biomarkers/blood , Inflammation/pathology , Middle Aged , Neutrophils/metabolism , Cerebral Small Vessel Diseases/pathology , Cerebral Small Vessel Diseases/blood , Nomograms , Lymphocytes/metabolism , Triglycerides/bloodABSTRACT
The analytical equation based on Monin-Obukhov (M-O) similarity theory (i.e., wind profile equation) has been adopted since 1970s for using in the prediction of wind vertical profile over flat terrains, which is mature and accurate. However, its applicability over complex terrains remains unknown. This applicability signifies the accuracy of the estimations of aerodynamic parameters for the boundary layer of non-flat terrain, such as zero-displacement height (d) and aerodynamic roughness length (z0), which will determine the accuracy of frequency correction and source area analysis in calculating carbon, water, and trace gas fluxes based on vorticity covariance method. Therefore, the validation of wind profile model in non-flat terrain is the first step to test whether the flux model needs improvement. We measured three-dimensional wind speed data by using the Ker Towers (three towers in a watershed) at Qingyuan Forest CERN in the Mountainous Region of east Liaoning Province, and compared them with data from Panjin Agricultural Station in the Liaohe Plain, to evaluate the applicability of a generalized wind profile model based on the Monin-Obukhov similarity theory on non-flat terrain. The results showed that the generalized wind profile model could not predict wind speeds accurately of three flux towers separately located in different sites, indicating that wind profile model was not suitable for predicting wind speeds in complex terrains. In the leaf-off and leaf-on periods, the coefficient of determination (R2) between observed and predicted wind speeds ranged from 0.12 to 0.30. Compared to measured values, the standard error of the predicted wind speeds was high up to 2 m·s-1. The predicted wind speeds were high as twice as field-measured wind speed, indicating substantial overestimation. Nevertheless, this model correctly predicted wind speeds in flat agricultural landscape in Panjin Agricultural Station. The R2 between observed wind speeds and predicted wind speed ranged from 0.90 to 0.93. The standard error between observed and predicted values was only 0.5 m·s-1. Results of the F-test showed that the root-mean-square error of the observed and predicted wind speeds in each secondary forest complex terrain was much greater than that in flat agricultural landscape. Terrain was the primary factor affecting the applicability of wind profile model, followed by seasonality (leaf or leafless canopy). The wind profile model was not applicable to the boundary-layer flows over forest canopies in complex terrains, because the d was underestimated or both the d and z0 were underestimated, resulting in inaccurate estimation of aerodynamic height.
Subject(s)
Forests , Models, Theoretical , Wind , China , Trees/growth & development , Environmental Monitoring/methods , Ecosystem , AltitudeABSTRACT
In order to study the safe utilization of acid cadmium ï¼Cdï¼ contaminated soilï¼ light and moderate Cd-contaminated farmland in Shangluoï¼ Shaanxi Province was taken as the research objectï¼ and limeï¼ biocharï¼ and calcium magnesium phosphate fertilizer were applied. Through the wheat-maize rotation experimentï¼ the safe utilization effect of different amounts of passivator on Cd-contaminated soil was exploredï¼ and the best ratio of passivator was selected. The results showed thatï¼ â the soil quality could be improved to varying degrees by applying the passivator. â¡ After the application of amendmentsï¼ the grain yield of wheat and maize increased to different degrees. ⢠The lime 2 340 kg·hm-2 ï¼C3ï¼ treatment had the best effectï¼ which increased the soil pH of wheat and corn by 1.453 and 1.717 unitsï¼ respectivelyï¼ and reduced the available Cd content by 34.38% and 30.20%ï¼ respectively. ⣠The application of biochar 1 800 kg·hm-2 ï¼B2ï¼ treatment had the best effect on reducing the Cd contents in wheat rootsï¼ strawsï¼ and grainsï¼ which were significantly reduced by 53.60%ï¼ 38.86%ï¼ and 52.96%ï¼ respectivelyï¼ compared with that in CK. The Cd content in wheat grains was reduced to 0.09 mg·kg-1ï¼ which was lower than the limit value of wheat Cd ï¼0.1 mg·kg-1ï¼ specified in the "National food safety standard food pollutant limit" ï¼GB 2762-2017ï¼. The application of the biochar 1 260 kg·hm-2 ï¼B1ï¼ treatment had the best comprehensive effect on reducing the Cd contents of maize rootsï¼ strawsï¼ and grainsï¼ which were significantly reduced by 43.74%ï¼ 53.20%ï¼ and 94.57%ï¼ respectivelyï¼ compared with that in CK. The Cd content of maize grains was reduced to 0.001 9 mg·kg-1ï¼ which was far lower than the limit value of maize Cd ï¼0.1 mg·kg-1ï¼ specified in the "National food safety standard food pollutant limit" ï¼GB 2762-2017ï¼. Thereforeï¼ under the conditions of the field experimentï¼ considering the influence of various indexesï¼ biochar had the best effect on farmland soil in the wheat-maize rotation area with mild to moderate Cd pollution.
Subject(s)
Calcium Compounds , Environmental Pollutants , Oryza , Oxides , Soil Pollutants , Farms , Cadmium/analysis , Soil Pollutants/analysis , Charcoal/chemistry , Soil/chemistry , TriticumABSTRACT
BACKGROUND: Active vitamin D analog eldecalcitol is clinically applied in treatment of postmenopausal osteoporosis. This study aims to determine the role of eldecalcitol in the protection of osteocytes from senescence and the associated ferroptosis. METHODS: The MLO-Y4 osteocytes were exposed to D-gal inducing senescence. The ovariectomized (OVX) mice treated with D-gal using as an aging inducer were intraperitoneally injected with eldecalcitol. The multiplexed confocal imaging, fluorescence in situ hybridization and transmission electron microscopy were applied in assessing osteocytic properties. Immunochemical staining and immunoblotting were carried out to detect abundance and expression of molecules. RESULTS: The ablation of vitamin D receptor led to a reduction in amounts of osteocytes, a loss of dendrites, an increase in mRNA expression of SASP factors and in protein expression of senescent factors, as well as changes in mRNA expression of ferroptosis-related genes (PTGS2 & RGS4). Eldecalcitol reversed senescent phenotypes of MLO-Y4 cells shown by improving cell morphology and density, decreasing ß-gal-positive cell accumulation, and down-regulating protein expression (P16, P21 & P53). Eldecalcitol reduced intracellular ROS and MDA productions, elevated JC-1 aggregates, and up-regulated expression of Nrf2 and GPX4. Eldecalcitol exhibited osteopreserve effects in D-gal-induced aging OVX mice. The confocal imaging displayed its improvement on osteocytic network organization. Eldecalcitol decreased the numbers of senescent osteocytes at tibial diaphysis by SADS assay and attenuated mRNA expression of SASP factors as well as down-regulated protein expression of senescence-related factors and restored levels of ferroptotic biomarkers in osteocytes-enriched bone fraction. It reduced 4-HNE staining area, stimulated Nrf2-positive staining, and promoted nuclear translocation of Nrf2 in osteocytes of mice as well as inhibited and promoted protein expression of 4-HNE and Nrf2, respectively, in osteocytes-enriched bone fraction. CONCLUSIONS: The present study revealed the ameliorative effects of eldecalcitol on senescence and the associated ferroptosis of osteocytes, contributing to its preservation against osteoporosis of D-gal-induced senescent ovariectomized mice.
Subject(s)
Ferroptosis , Osteocytes , Vitamin D/analogs & derivatives , Mice , Animals , Osteocytes/metabolism , In Situ Hybridization, Fluorescence , NF-E2-Related Factor 2/metabolism , Vitamin D/metabolism , RNA, Messenger/metabolismABSTRACT
Gastric cancer (GC) is one of the most prevalent malignant tumors of the gastrointestinal system in the globe. The effect of PIEZO2 on the immune function and pathological features of gastric cancer remains to be explored. The Online database of cancer genes and GSE54129 have been used to analyze the clinical characteristics of PIEZO2 expression. We looked at the relationship between PIEZO2 and the immune systems of GC patients. The TIDE algorithm was used to explore the value of PIEZO2 in immunotherapy. Investigated the enrichment of PIEZO2 gene ontology and associated signal pathways using Online gene databases. The results show that overexpression of PIEZO2 was identified as an independent risk factor for patients with GC who had poor overall survival. Individuals may have a better prognosis if they had poorly differentiated GC and increased PIEZO2 expression (P < 0.05). We demonstrated a strong correlation between PIEZO2 and immune cells. The majority of immune checkpoint and immunological-related genes were associated with PIEZO2 expression. And PIEZO2 might be used as an immunotherapy target. Finally, the differential PIEZO2 genes in GC were mostly implicated in the processes of inflammation, immunological response, and tumor metastasis, according to functional analysis. PIEZO2 has a negative correlation with cell stemness and mutation levels in patients with GC and a positive correlation with immune cell infiltration and gene expression in the tumor microenvironment. These findings point to PIEZO2 as a potential new immunotherapy target of GC.
Subject(s)
Stomach Neoplasms , Humans , Biomarkers , Immunotherapy , Ion Channels/genetics , Oncogenes , Prognosis , Stomach Neoplasms/genetics , Stomach Neoplasms/therapy , Tumor Microenvironment/geneticsABSTRACT
PURPOSE: Studies of unresectable colorectal cancer pulmonary metastasis (CRPM) have rarely analyzed patient prognosis from the perspective of colonic subsites. This study aimed to evaluate the effects of primary tumor resection (PTR) on the prognosis of patients with unresectable pulmonary metastases of transverse colon cancer pulmonary metastasis (UTCPM), hepatic flexure cancer pulmonary metastasis (UHFPM), and splenic flexure cancer pulmonary metastasis (USFPM). METHODS: Patients were identified from the Surveillance, Epidemiology, and End Results database between 2000 and 2018. The Cox proportional hazards regression models were used to identify prognostic factors of overall survival (OS) and cause-specific survival (CSS). The Kaplan-Meier analyses and log-rank tests were conducted to assess the effectiveness of PTR on survival. RESULTS: This study included 1294 patients: 419 with UHFPM, 636 with UTCPM, and 239 with USFPM. Survival analysis for OS and CSS in the PTR groups, showed that there were no statistical differences in the the UHFPM, UTCPM, and USFPM patients. There were statistical differences in the UHFPM, UTCPM, and USFPM patients for OS and CSS. Three non-PTR subgroups showed significant statistical differences for OS and CSS. CONCLUSION: We confirmed the different survival rates of patients with UTCPM, UHFPM, and USFPM and proved for the first time that PTR could provide survival benefits for patients with unresectable CRPM from the perspective of the colonic subsites of the transverse colon, hepatic flexure, and splenic flexure.
Subject(s)
Carcinoma , Colon, Transverse , Colonic Neoplasms , Colorectal Neoplasms , Lung Neoplasms , Humans , Colon, Transverse/surgery , Colon, Transverse/pathology , Cohort Studies , Retrospective Studies , Prognosis , Colorectal Neoplasms/pathology , Colonic Neoplasms/pathology , Lung Neoplasms/surgeryABSTRACT
S-adenosyl-l-methionine (SAM), a vital physiologically active substance in living organisms, is produced by fermentation over Saccharomyces cerevisiae. The main limitation in SAM production was the low biosynthesis ability of SAM in S. cerevisiae. The aim of this work is to breed an SAM-overproducing mutant through UV mutagenesis coupled with high-throughput selection. Firstly, a high-throughput screening method by rapid identification of positive colonies was conducted. White colonies on YND medium were selected as positive strains. Then, nystatin/sinefungin was chosen as a resistant agent in directed mutagenesis. After several cycles of mutagenesis, a stable mutant 616-19-5 was successfully obtained and exhibited higher SAM production (0.41 g/L vs 1.39 g/L). Furthermore, the transcript levels of the genes SAM2, ADO1, and CHO2 involved in SAM biosynthesis increased, while ergosterol biosynthesis genes in mutant 616-19-5 significantly decreased. Finally, building on the above work, S. cerevisiae 616-19-5 could produce 10.92 ± 0.2 g/L SAM in a 5-L fermenter after 96 h of fermentation, showing a 2.02-fold increase in the product yield compared with the parent strain. Paving the way of breeding SAM-overproducing strain has improved the good basis for SAM industrial production.
Subject(s)
Methionine , S-Adenosylmethionine , Saccharomyces cerevisiae/genetics , High-Throughput Screening Assays , Plant Breeding , RacemethionineABSTRACT
Postherpetic neuralgia (PHN) seriously affects the quality of life of the elderly population. This study aimed to evaluate the efficacy of ozonated autohemotherapy (O3-AHT) combined with pulsed radiofrequency (PRF) in the treatment of thoracic PHN in older adults. The medical records of patients with thoracic PHN aged 65 years and older from June 2018 until March 2021 in Shengli Oilfield Central Hospital were reviewed. They were assigned into two groups: PRF alone (PRF group, n = 107) and PRF combined with O3-AHT (PRF + O3-AHT group, n = 109). Visual Analogue Scale for pain was evaluated at pre-treatment, 1 day, 1, 3 and 6 months after treatment. Quality of life and sleep quality were assessed using Short-Form 36 Health Survey and Athens Insomnia Scale at pre-treatment and 6 months post-treatment, respectively. The median age of patients in the PRF and PRF + O3-AHT groups were 69 (67-73) years and 68 (67-72) years, respectively. The former included 62 females and the latter included 51 females. Compared with pre-treatment, the Visual Analogue Scale scores of two groups declined at post-treatment. Patients in the PRF + O3-AHT group showed obviously lower Visual Analogue Scale scores compared with those in the PRF group at 1, 3, and 6 months after treatment and they had earlier withdrawal time for drugs. However, dizziness, tachycardia, sleepiness, and nausea were presented after combination therapy. These symptoms resolved spontaneously after a period of rest. Additionally, O3-AHT combined with PRF was associated with a significant decrease in the Athens Insomnia Scale score and with a significant improvement in every dimension of the Short-Form 36 Health Survey. To conclude, O3-AHT combined with PRF is an effective way to relieve thoracic PHN in older patients.
Subject(s)
Neuralgia, Postherpetic , Pulsed Radiofrequency Treatment , Sleep Initiation and Maintenance Disorders , Female , Humans , Aged , Neuralgia, Postherpetic/therapy , Retrospective Studies , Pulsed Radiofrequency Treatment/methods , Quality of LifeABSTRACT
The discovery of magnetism in van der Waals (vdW) materials has established unique building blocks for the research of emergent spintronic phenomena. In particular, owing to their intrinsically clean surface without dangling bonds, the vdW magnets hold the potential to construct a superior interface that allows for efficient electrical manipulation of magnetism. Despite several attempts in this direction, it usually requires a cryogenic condition and the assistance of external magnetic fields, which is detrimental to the real application. Here, we fabricate heterostructures based on Fe3GaTe2 flakes that have room-temperature ferromagnetism with excellent perpendicular magnetic anisotropy. The current-driven nonreciprocal modulation of coercive fields reveals a high spin-torque efficiency in the Fe3GaTe2/Pt heterostructures, which further leads to a full magnetization switching by current. Moreover, we demonstrate the field-free magnetization switching resulting from out-of-plane polarized spin currents by asymmetric geometry design. Our work could expedite the development of efficient vdW spintronic logic, memory, and neuromorphic computing devices.
ABSTRACT
Metabolic associated fatty liver disease (MAFLD) is a liver disease with hepatocyte steatosis caused by metabolic disorders, which is closely related to obesity, diabetes, metabolic dysfunction, and other factors. Its pathological process changes from simple steatosis, liver inflammation to non-alcoholic steatohepatitis (NASH), and then leads to liver fibrosis, cirrhosis, and liver cancer. At present, no specific therapeutics are available for treatment of MAFLD targeting its etiology. Celastrol is the main active component of the traditional Chinese medicine Celastrus orbiculatus Thunb. In recent years, it has been found that celastrol shows important medicinal value in regulating lipid metabolism, reducing fat and weight, and protecting liver, and then ameliorates MAFLD. This article reviews the related research progress of celastrol in the prevention and treatment of MAFLD, so as to provide a reference for the comprehensive development and utilization of celastrol.
Subject(s)
Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Liver/pathology , Pentacyclic Triterpenes/metabolism , ObesityABSTRACT
OBJECTIVE: Lung adenocarcinoma (LA) is one of the most common malignancies and is responsible for the greatest number of tumor-related deaths. Our research aimed to explore the molecular subtype signatures of LA to clarify the correlation among the immune microenvironment, clinical outcomes, and therapeutic response. METHODS: The LA immune cell marker genes (LICMGs) identified by single-cell RNA sequencing (scRNA-seq) analysis were used to discriminate the molecular subtypes and homologous immune and metabolic traits of GSE72094 LA cases. In addition, the model-building genes were identified from 1441 LICMGs by Cox-regression analysis, and a LA immune difference score (LIDscore) was developed to quantify individual differences in each patient, thereby predicting prognosis and susceptibility to immunotherapy and chemotherapy of LA patients. RESULTS: Patients of the GSE72094 cohort were divided into two distinct molecular subtypes based on LICMGs: immune activating subtype (Cluster-C1) and metabolically activating subtype (cluster-C2). The two molecular subtypes have distinct characteristics regarding prognosis, clinicopathology, genomics, immune microenvironment, and response to immunotherapy. Among the LICMGs, LGR4, GOLM1, CYP24A1, SFTPB, COL1A1, HLA-DQA1, MS4A7, PPARG, and IL7R were enrolled to construct a LIDscore model. Low-LIDscore patients had a higher survival rate due to abundant immune cell infiltration, activated immunity, and lower genetic variation, but probably the higher levels of Treg cells in the immune microenvironment lead to immune cell dysfunction and promote tumor immune escape, thus decreasing the responsiveness to immunotherapy compared with that of the high-LIDscore patients. Overall, high-LIDscore patients had a higher responsiveness to immunotherapy and a higher sensitivity to chemotherapy than the low-LIDscore group. CONCLUSIONS: Molecular subtypes based on LICMGs provided a promising strategy for predicting patient prognosis, biological characteristics, and immune microenvironment features. In addition, they helped identify the patients most likely to benefit from immunotherapy and chemotherapy.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Humans , Prognosis , Genes, Regulator , Adenocarcinoma of Lung/drug therapy , Adenocarcinoma of Lung/genetics , Phenotype , Immunotherapy , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Tumor Microenvironment/genetics , Membrane ProteinsABSTRACT
Cerebral small vessel disease (CSVD) causes 20%-25% of stroke and contributes to 45% of dementia cases worldwide. However, since its early symptoms are inconclusive in addition to the complexity of the pathological basis, there is a rather limited effective therapies and interventions. Recently, accumulating evidence suggested that various brain-waste-clearance dysfunctions are closely related to the pathogenesis and prognosis of CSVD, and after a comprehensive and systematic review we classified them into two broad categories: trans-barrier transport and lymphatic drainage. The former includes blood brain barrier and blood-cerebrospinal fluid barrier, and the latter, glymphatic-meningeal lymphatic system and intramural periarterial drainage pathway. We summarized the concepts and potential mechanisms of these clearance systems, proposing a relatively complete framework for elucidating their interactions with CSVD. In addition, we also discussed recent advances in therapeutic strategies targeting clearance dysfunction, which may be an important area for future CSVD research.
Subject(s)
Cerebral Small Vessel Diseases , Glymphatic System , Stroke , Humans , Blood-Brain Barrier/metabolism , Meninges , Brain/metabolismABSTRACT
Diatom testing is an essential auxiliary means in forensic practice to determine whether the corpse drowned in water and to infer the drowning location. Diatom testing is also an important research content in the field of the environment and plankton. The diatom molecular biology testing technology, which focuses on diatom DNA as the primary research object, is a new method of diatom testing. Diatom DNA extraction is the basis of diatom molecular testing. At present, the kits commonly used for diatom DNA extraction are expensive, which increases the cost of carrying out related research. Our laboratory improved the general whole blood genomic DNA rapid extraction kit and obtained a satisfactory diatom DNA extraction effect, thus providing an alternative economical and affordable DNA extraction solution based on glass beads for related research. The diatom DNA extracted using this protocol could satisfy many downstream applications, such as PCR and sequencing.
Subject(s)
Diatoms , Drowning , Humans , Diatoms/genetics , DNA/genetics , Plankton , Polymerase Chain Reaction , Water , LungABSTRACT
OBJECTIVE: Lipopolysaccharide-induced tumor necrosis factor-α factor (LITAF) protein is a newly discovered inflammatory protein. This study aims to study the role of LITAF in the formation of atherosclerosis. METHODS: A total of 10 C57BL/6J mice and 10 C57BL/6J mice with knockout of LITAF gene (C57BL/6J-LITAF-) were divided into two groups: the control group and the LITAF-/- group. The animals were accommodated for 16 weeks and then euthanized with their hearts and aortas isolated thereafter. Next, the roots of the mouse aorta were cryosectioned and stained with Oil Red O staining and immunohistochemical staining (CD68, α-SMA, and Masson), respectively. The area of Oil Red O staining and the proportion of positive expression after immunohistochemical staining were then compared between the control and LITAF-/- groups. At the same time, the blood of mice was collected for the extraction of proteins and RNA. The proteins and RNA were used to detect the expression of major molecules of the NF-κB inflammatory pathway in mice in the control group and the LITAF-/- group by Western blotting and RT-PCR. RESULTS: Oil Red O staining of the aortic root sections of the mice in each group revealed that the area of atherosclerotic plaques in the LITAF-/- group was substantially lower than that in the control group (P<0.05). Moreover, immunohistochemical staining determined that the expression level of α-SMA and CD68 in the LITAF-/- group was significantly lower than that in the control group, whereas the results were reversed following Masson staining (P<0.05). The expression levels of P65 and caspase 3 were significantly lower in the LITAF-/- group than in the control group (P<0.05), whereas the expression level of IκB was higher in the LITAF-/- group. CONCLUSION: LITAF might participate in the formation of atherosclerotic plaque through the NF-κB pathway and play a promoting role in the formation of atherosclerosis.
Subject(s)
Atherosclerosis , Plaque, Atherosclerotic , Animals , Mice , Atherosclerosis/metabolism , Lipopolysaccharides , Mice, Inbred C57BL , NF-kappa B/genetics , NF-kappa B/metabolism , Plaque, Atherosclerotic/genetics , Plaque, Atherosclerotic/pathology , RNA , Signal Transduction , Tumor Necrosis Factor-alphaABSTRACT
BACKGROUND: Obstructive sleep apnea (OSA) is one of the most common forms of sleep-disordered breathing. Studies have shown that certain changes in metabolism play an important role in the pathophysiology of OSA. However, the causal relationship between these metabolites and OSA remains unclear. AIMS: We use a mendelian randomization (MR) approach to investigate the causal associations between the genetic liability to metabolites and OSA. METHODS: We performed a 2-sample inverse-variance weighted mendelian randomization analysis to evaluate the causal effects of genetically determined 486 metabolites on OSA. Multiple sensitivity analyses were performed to assess pleiotropy. We used multivariate mendelian randomization analyses to assess confounding factors and mendelian randomization Bayesian model averaging to rank the significant biomarkers by their genetic evidence. We also conducted a metabolic pathway analysis to identify potential metabolic pathways. RESULTS: We identified 14 known serum metabolites (8 risk factors and 6 protective factors) and 12 unknown serum metabolites associated with OSA. These 14 known metabolites included 8 lipids( 1-arachidonoylglycerophosphoethanolamine, Tetradecanedioate, Epiandrosteronesulfate, Acetylca Glycerol3-phosphate, 3-dehydrocarnitine, Margarate17:0, Docosapentaenoaten3;22:5n3), 3 Aminoacids (Isovalerylcarnitine,3-methyl-2-oxobutyrate,Methionine), 2 Cofactors and vitamins [Bilirubin(E,ZorZ,E),X-11593--O-methylascorbate], 1Carbohydrate(1,6-anhydroglucose). We also identified several metabolic pathways that involved in the pathogenesis of OSA. CONCLUSION: MR (mendelian randomization) approach was performed to identify 6 protective factors and 12 risk factors for OSA in the present study. 3-Dehydrocarnitine was the most significant risk factors for OSA. Our study also confirmed several significant metabolic pathways that were involved in the pathogenesis of OSA. Valine, leucine and isoleucine biosynthesis metabolic pathways were the most significant metabolic pathways that were involved in the pathogenesis of OSA.