ABSTRACT
Synthetic lethality through combinatorial targeting DNA damage response (DDR) pathways provides exciting anticancer therapeutic benefit. Currently, the long noncoding RNAs (lncRNAs) have been implicated in tumor drug resistance; however, their potential significance in DDR is still largely unknown. Here, we report that a human lncRNA, CTD-2256P15.2, encodes a micropeptide, named PAR-amplifying and CtIP-maintaining micropeptide (PACMP), with a dual function to maintain CtIP abundance and promote poly(ADP-ribosyl)ation. PACMP not only prevents CtIP from ubiquitination through inhibiting the CtIP-KLHL15 association but also directly binds DNA damage-induced poly(ADP-ribose) chains to enhance PARP1-dependent poly(ADP-ribosyl)ation. Targeting PACMP alone inhibits tumor growth by causing a synthetic lethal interaction between CtIP and PARP inhibitions and confers sensitivity to PARP/ATR/CDK4/6 inhibitors, ionizing radiation, epirubicin, and camptothecin. Our findings reveal that a lncRNA-derived micropeptide regulates cancer progression and drug resistance by modulating DDR, whose inhibition could be employed to augment the existing anticancer therapeutic strategies.
Subject(s)
Endodeoxyribonucleases , Neoplasms , Peptides , Poly ADP Ribosylation , RNA, Long Noncoding , DNA Repair , Endodeoxyribonucleases/metabolism , Humans , Microfilament Proteins/genetics , Microfilament Proteins/metabolism , Neoplasms/genetics , Neoplasms/metabolism , Peptides/pharmacology , Poly Adenosine Diphosphate Ribose/metabolism , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Poly(ADP-ribose) Polymerases/genetics , Poly(ADP-ribose) Polymerases/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolismABSTRACT
Survival analysis is critical to cancer prognosis estimation. High-throughput technologies facilitate the increase in the dimension of genic features, but the number of clinical samples in cohorts is relatively small due to various reasons, including difficulties in participant recruitment and high data-generation costs. Transcriptome is one of the most abundantly available OMIC (referring to the high-throughput data, including genomic, transcriptomic, proteomic and epigenomic) data types. This study introduced a multitask graph attention network (GAT) framework DQSurv for the survival analysis task. We first used a large dataset of healthy tissue samples to pretrain the GAT-based HealthModel for the quantitative measurement of the gene regulatory relations. The multitask survival analysis framework DQSurv used the idea of transfer learning to initiate the GAT model with the pretrained HealthModel and further fine-tuned this model using two tasks i.e. the main task of survival analysis and the auxiliary task of gene expression prediction. This refined GAT was denoted as DiseaseModel. We fused the original transcriptomic features with the difference vector between the latent features encoded by the HealthModel and DiseaseModel for the final task of survival analysis. The proposed DQSurv model stably outperformed the existing models for the survival analysis of 10 benchmark cancer types and an independent dataset. The ablation study also supported the necessity of the main modules. We released the codes and the pretrained HealthModel to facilitate the feature encodings and survival analysis of transcriptome-based future studies, especially on small datasets. The model and the code are available at http://www.healthinformaticslab.org/supp/.
Subject(s)
Algorithms , Neoplasms , Humans , Proteomics , Survival AnalysisABSTRACT
BACKGROUND: Culex tritaeniorhynchus is widely distributed in China, from Hainan Island in the south to Heilongjiang in the north, covering tropical, subtropical, and temperate climate zones. Culex tritaeniorhynchus carries 19 types of arboviruses. It is the main vector of the Japanese encephalitis virus (JEV), posing a serious threat to human health. Understanding the effects of environmental factors on Culex tritaeniorhynchus can provide important insights into its population structure or isolation patterns, which is currently unclear. RESULTS: In total, 138 COI haplotypes were detected in the 552 amplified sequences, and the haplotype diversity (Hd) value increased from temperate (0.534) to tropical (0.979) regions. The haplotype phylogeny analysis revealed that the haplotypes were divided into two high-support evolutionary branches. Temperate populations were predominantly distributed in evolutionary branch II, showing some genetic isolation from tropical/subtropical populations and less gene flow between groups. The neutral test results of HNQH (Qionghai) and HNHK(Haikou) populations were negative (P < 0.05), indicating many low-frequency mutations in the populations and that the populations might be in the process of expansion. Moreover, Wolbachia infection was detected only in SDJN (Jining) (2.24%), and all Wolbachia genotypes belonged to supergroup B. To understand the influence of environmental factors on mosquito-borne viruses, we examined the prevalence of Culex tritaeniorhynchus infection in three ecological environments in Shandong Province. We discovered that the incidence of JEV infection was notably greater in Culex tritaeniorhynchus from lotus ponds compared to those from irrigation canal regions. In this study, the overall JEV infection rate was 15.27 per 1000, suggesting the current risk of Japanese encephalitis outbreaks in Shandong Province. CONCLUSIONS: Tropical and subtropical populations of Culex tritaeniorhynchus showed higher genetic diversity and those climatic conditions provide great advantages for the establishment and expansion of Culex tritaeniorhynchus. There are differences in JEV infection rates in wild populations of Culex tritaeniorhynchus under different ecological conditions. Our results suggest a complex interplay of genetic differentiation, population structure, and environmental factors in shaping the dynamics of Culex tritaeniorhynchus. The low prevalence of Wolbachia in wild populations may reflect the recent presence of Wolbachia invasion in Culex tritaeniorhynchus.
Subject(s)
Culex , Haplotypes , Phylogeny , Culex/genetics , Culex/virology , Culex/microbiology , Animals , China , Climate , Genetic Variation , Genetics, Population , Wolbachia/genetics , Mosquito Vectors/genetics , Mosquito Vectors/virology , Mosquito Vectors/microbiology , Electron Transport Complex IV/geneticsABSTRACT
Sterigmatocystin (ST) is a known toxin whose aptamer has rarely been reported because ST is a water-insoluble small-molecule target with few active sites, leading to difficulty in obtaining its aptamer using traditional target fixation screening methods. To obtain aptamer for ST, we incorporated FAM tag size separation into the capture-systematic evolution of ligands by exponential enrichment and combined it with molecular activation for aptamer screening. The screening process was monitored using a quantitative polymerase chain reaction fluorescence amplification curve and recovery of negative-, counter-, and positive-selected ssDNA. The affinity and specificity of the aptamer were verified by constructing an aptamer-affinity column, and the binding sites were predicted using molecular docking simulations. The results showed that the Kd value of the H Seq02 aptamer was 25.3 nM. The aptamer-affinity column based on 2.3 nmol of H Seq02 exhibited a capacity of about 80 ng, demonstrating better specificity than commercially available antibody affinity columns. Molecular simulation docking predicted the binding sites for H Seq02 and ST, further explaining the improved specificity. In addition, circular dichroism and isothermal titration calorimetry were used to verify the interaction between the aptamer and target ST. This study lays the foundation for the development of a new ST detection method.
Subject(s)
Aptamers, Nucleotide , Aptamers, Nucleotide/chemistry , Sterigmatocystin , SELEX Aptamer Technique/methods , Molecular Docking Simulation , LigandsABSTRACT
Triple-negative breast cancer (TNBC) is a highly heterogeneous subtype of breast cancer, characterized by aggressiveness and high recurrence rate. As monotherapy provides limited benefit to TNBC patients, combination therapy emerges as a promising treatment approach. Gambogic acid (GA) is an exceedingly promising anticancer agent. Nonetheless, its application potential is hampered by low drug loading efficiency and associated toxic side effects. To overcome these limitations, using mesoporous polydopamine (MPDA) endowed with photothermal conversion capabilities is considered as a delivery vehicle for GA. Meanwhile, GA can inhibit the activity of heat shock protein 90 (HSP90) to enhance the photothermal effect. Herein, GA-loaded MPDA nanoparticles (GA@MPDA NPs) are developed with a high drug loading rate of 75.96% and remarkable photothermal conversion performance. GA@MPDA NPs combined with photothermal treatment (PTT) significantly inhibit the tumor growth, and effectively trigger the immunogenic cell death (ICD), which thereby increase the number of activated effector T cells (CD8+ T cells and CD4+ T cells) in the tumor, and hoist the level of immune-inflammatory cytokines (IFN-γ, IL-6, and TNF-α). The above results suggest that the combination of GA@MPDA NPs with PTT expected to activate the antitumor immune response, thus potentially enhancing the clinical therapeutic effect on TNBC.
Subject(s)
Indoles , Polymers , Triple Negative Breast Neoplasms , Xanthones , Xanthones/chemistry , Xanthones/pharmacology , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/pathology , Indoles/chemistry , Indoles/pharmacology , Polymers/chemistry , Humans , Animals , Cell Line, Tumor , Female , Porosity , Mice , Nanoparticles/chemistryABSTRACT
A fast evolution within mitochondria genome(s) often generates discords between nuclear and mitochondria, which is manifested as cytoplasmic male sterility (CMS) and fertility restoration (Rf) system. The maize CMS-C trait is regulated by the chimeric mitochondrial gene, atp6c, and can be recovered by the restorer gene ZmRf5. Through positional cloning in this study, we identified the nuclear restorer gene, ZmRf5, which encodes a P-type pentatricopeptide repeat (PPR) family protein. The over-expression of ZmRf5 brought back the fertility to CMS-C plants, whereas its genomic editing by CRISPR/Cas9 induced abortive pollens in the restorer line. ZmRF5 is sorted to mitochondria, and recruited RS31A, a splicing factor, through MORF8 to form a cleaving/restoring complex, which promoted the cleaving of the CMS-associated transcripts atp6c by shifting the major cleavage site from 480th nt to 344 th nt for fast degradation, and preserved just right amount of atp6c RNA for protein translation, providing adequate ATP6C to assembly complex V, thus restoring male fertility. Interestingly, ATP6C in the sterile line CMo17A, with similar cytology and physiology changes to YU87-1A, was accumulated much less than it in NMo17B, exhibiting a contrary trend in the YU87-1 nuclear genome previously reported, and was restored to normal level in the presence of ZmRF5. Collectively these findings unveil a new molecular mechanism underlying fertility restoration by which ZmRF5 cooperates with MORF8 and RS31A to restore CMS-C fertility in maize, complemented and perfected the sterility mechanism, and enrich the perspectives on communications between nucleus and mitochondria.
Subject(s)
Fertility , Zea mays , Zea mays/genetics , RNA Splicing Factors , Cytoplasm/genetics , Fertility/genetics , Mitochondria/genetics , Plant Infertility/geneticsABSTRACT
Lupus erythematosus (LE) is a heterogeneous, antibody-mediated autoimmune disease. Isolate discoid LE (IDLE) and systematic LE (SLE) are traditionally regarded as the two ends of the spectrum, ranging from skin-limited damage to life-threatening multi-organ involvement. Both belong to LE, but IDLE and SLE differ in appearance of skin lesions, autoantibody panels, pathological changes, treatments, and immunopathogenesis. Is discoid lupus truly a form of LE or is it a completely separate entity? This question has not been fully elucidated. We compared the clinical data of IDLE and SLE from our center, applied multi-omics technology, such as immune repertoire sequencing, high-resolution HLA alleles sequencing and multi-spectrum pathological system to explore cellular and molecular phenotypes in skin and peripheral blood from LE patients. Based on the data from 136 LE patients from 8 hospitals in China, we observed higher damage scores and fewer LE specific autoantibodies in IDLE than SLE patients, more uCDR3 sharing between PBMCs and skin lesion from SLE than IDLE patients, elevated diversity of V-J recombination in IDLE skin lesion and SLE PBMCs, increased SHM frequency and class switch ratio in IDLE skin lesion, decreased SHM frequency but increased class switch ratio in SLE PBMCs, HLA-DRB1*03:01:01:01, HLA-B*58:01:01:01, HLA-C*03:02:02:01, and HLA-DQB1*02:01:01:01 positively associated with SLE patients, and expanded Tfh-like cells with ectopic germinal center structures in IDLE skin lesions. These findings suggest a significant difference in the immunopathogenesis of skin lesions between SLE and IDLE patients. SLE is a B cell-predominate systemic immune disorder, while IDLE appears limited to the skin. Our findings provide novel insights into the pathogenesis of IDLE and other types of LE, which may direct more accurate diagnosis and novel therapeutic strategies.
Subject(s)
Autoantibodies , Lupus Erythematosus, Discoid , Lupus Erythematosus, Systemic , Skin , Humans , Lupus Erythematosus, Discoid/immunology , Lupus Erythematosus, Discoid/pathology , Female , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/diagnosis , Male , Autoantibodies/immunology , Autoantibodies/blood , Skin/pathology , Skin/immunology , Skin/metabolism , Adult , Middle Aged , Alleles , HLA Antigens/genetics , HLA Antigens/immunology , Young Adult , MultiomicsABSTRACT
Drought stress poses a serious threat to global agricultural productivity and food security. Plant resistance to drought is typically accompanied by a growth deficit and yield penalty. Herein, we report a previously uncharacterized, dicotyledon-specific gene, Stress and Growth Interconnector (SGI), that promotes growth during drought in the oil crop rapeseed (Brassica napus) and the model plant Arabidopsis (Arabidopsis thaliana). Overexpression of SGI conferred enhanced biomass and yield under water-deficient conditions, whereas corresponding CRISPR SGI mutants exhibited the opposite effects. These attributes were achieved by mediating reactive oxygen species (ROS) homeostasis while maintaining photosynthetic efficiency to increase plant fitness under water-limiting environments. Further spatial-temporal transcriptome profiling revealed dynamic reprogramming of pathways for photosynthesis and stress responses during drought and the subsequent recovery. Mechanistically, SGI represents an intrinsically disordered region-containing protein that interacts with itself, catalase isoforms, dehydrins, and other drought-responsive positive factors, restraining ROS generation. These multifaceted interactions stabilize catalases in response to drought and facilitate their ROS-scavenging activities. Taken altogether, these findings provide insights into currently underexplored mechanisms to circumvent trade-offs between plant growth and stress tolerance that will inform strategies to breed climate-resilient, higher yielding crops for sustainable agriculture.
Subject(s)
Arabidopsis , Droughts , Reactive Oxygen Species/metabolism , Plant Breeding , Arabidopsis/metabolism , Water/metabolism , Stress, Physiological/genetics , Gene Expression Regulation, PlantABSTRACT
The optimal timing of the transition from vegetative growth to reproductive growth is critical for plant reproductive success, and the underlying regulatory mechanisms have been well studied in angiosperm model species, but relatively little in gymnosperms. DAL1, a MADS domain transcription factor (TF) gene that shows a conserved age-related expression profile in conifers, may be an age timer. However, how the DAL1 mediates the onset of reproductive growth remains poorly understood. Here, we have shown that the PtDAL1 directly regulates the PtDAL10 transcription by binding to its promoter region in vitro. PtDAL1, forms ternary complexes in vitro and in N. benthamiana with PtDAL10 and PtMADS11, two potential candidate regulators of the vegetative to reproductive transition in Chinese pine (Pinus tabuliformis). The PtDAL10 was progressively induced in new shoots with age and highly accumulated in male and female cones. Overexpression of PtDAL10 rescued the flowering of ft-10 and soc1-1-2 mutants in Arabidopsis. We provide insight into the molecular components associated with the PtDAL1, which integrates the vegetative to reproductive phase transition into age-mediated progressive development of the whole plant in conifers.
ABSTRACT
RESEARCH HIGHLIGHTS: Urate tophi were found in the kidneys, liver, spleen and lungs.IFA confirmed the co-expression of GoAstV-I and II antigens in the same kidney.
Subject(s)
Astroviridae Infections , Astroviridae , Avastrovirus , Coinfection , Gout , Poultry Diseases , Animals , Geese , Astroviridae Infections/veterinary , Coinfection/veterinary , Astroviridae/genetics , Gout/veterinary , Avastrovirus/genetics , ChinaABSTRACT
The Brust-Schiffrin two-phase method is a facile way to prepare thiolate-protected metal nanoparticles, but its mechanism remains controversial. In this work, we demonstrate the use of the Brust-Schiffrin method based on coordination compound theory. We confirmed that the formation of stable complexes is the driving force for a series chemical reaction in the organic phase. We found that the stable Cu(I)-thiolate complex decreased the half-cell reduction potential of Cu(I)/Cu(0). Thus, when thiol ligands were in excess, thiolate-protected Cu(I) clusters formed rather than Cu(0)-cored nanoparticles. The thiolate-protected metal-hydride nanoclusters were the intermediate between the metal complexes and nanoparticles. The "metallophilic" interactions of the d10 closed-shell electronic configuration of the metal coordination centers were proposed as the driving force for nanocluster and nanoparticle formation. To confirm this mechanism, we synthesized Au, Ag, and Cu monometallic nanoparticles and bi- and trimetallic nanoparticles. We found that although thiolate-protected Cu(I) nanoclusters are not easily reduced, they can combine with Au and/or Ag nanoclusters to form nanoparticles. The proposed mechanism is expected to provide deeper insight into the Brust-Schiffrin method and further extend its application to metals other than Au, Ag and Cu.
ABSTRACT
BACKGROUND: Hypothermia is a promising therapy for traumatic brain injury (TBI) in the clinic. However, the neuroprotective outcomes of hypothermia-treated TBI patients in clinical studies are inconsistent due to several severe side effects. Here, an injectable refrigerated hydrogel was designed to deliver 3-iodothyronamine (T1AM) to achieve a longer period of local hypothermia for TBI treatment. Hydrogel has four advantages: (1) It can be injected into injured sites after TBI, where it forms a hydrogel and avoids the side effects of whole-body cooling. (2) Hydrogels can biodegrade and be used for controlled drug release. (3) Released T1AM can induce hypothermia. (4) This hydrogel has increased medical value given its simple operation and ability to achieve timely treatment. METHODS: Pol/T hydrogels were prepared by a low-temperature mixing method and characterized. The effect of the Pol/T hydrogel on traumatic brain injury in mice was studied. The degradation of the hydrogel at the body level was observed with a small animal imager. Brain temperature and body temperature were measured by brain thermometer and body thermometer, respectively. The apoptosis of peripheral nerve cells was detected by immunohistochemical staining. The protective effect of the hydrogels on the blood-brain barrier (BBB) after TBI was evaluated by the Evans blue penetration test. The protective effect of hydrogel on brain edema after injury in mice was detected by Magnetic resonance (MR) in small animals. The enzyme linked immunosorbent assay (ELISA) method was used to measure the levels of inflammatory factors. The effects of behavioral tests on the learning ability and exercise ability of mice after injury were evaluated. RESULTS: This hydrogel was able to cool the brain to hypothermia for 12 h while maintaining body temperature within the normal range after TBI in mice. More importantly, hypothermia induced by this hydrogel leads to the maintenance of BBB integrity, the prevention of cell death, the reduction of the inflammatory response and brain edema, and the promotion of functional recovery after TBI in mice. This cooling method could be developed as a new approach for hypothermia treatment in TBI patients. CONCLUSION: Our study showed that injectable and biodegradable frozen Pol/T hydrogels to induce local hypothermia in TBI mice can be used for the treatment of traumatic brain injury.
Subject(s)
Blood-Brain Barrier , Brain Injuries, Traumatic , Hydrogels , Hypothermia, Induced , Animals , Brain Injuries, Traumatic/therapy , Brain Injuries, Traumatic/drug therapy , Mice , Hydrogels/chemistry , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/drug effects , Male , Hypothermia, Induced/methods , Neuroprotection/drug effects , Brain/pathology , Disease Models, Animal , Neuroprotective Agents/pharmacology , Neuroprotective Agents/chemistry , Body Temperature , Mice, Inbred C57BLABSTRACT
In this study, a ligand fishing method for the screening of α-glucosidase inhibitors from Ginkgo biloba leaf was established for the first time using α-glucosidase immobilized on the magnetic metal-organic framework. The immobilized α-glucosidase exhibited enhanced resistance to temperature and pH, as well as good thermal stability and reusability. Two ligands, namely quercitrin and quercetin, were screened from Ginkgo biloba leaf and identified by ultra-high performance liquid chromatography-tandem mass spectrometry. The half-maximal inhibitory concentration values for quercitrin and quercetin were determined to be 105.69 ± 0.39 and 83.49 ± 0.79 µM, respectively. Molecular docking further confirmed the strong inhibitory effect of these two ligands. The proposed approach in this study demonstrates exceptional efficiency in the screening of α-glucosidase inhibitors from complex natural medicinal plants, thus exhibiting significant potential for the discovery of antidiabetic compounds.
Subject(s)
Enzymes, Immobilized , Ginkgo biloba , Glycoside Hydrolase Inhibitors , Metal-Organic Frameworks , Plant Leaves , alpha-Glucosidases , Ginkgo biloba/chemistry , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/pharmacology , Metal-Organic Frameworks/chemistry , Plant Leaves/chemistry , alpha-Glucosidases/metabolism , alpha-Glucosidases/chemistry , Enzymes, Immobilized/chemistry , Enzymes, Immobilized/antagonists & inhibitors , Enzymes, Immobilized/metabolism , Molecular Docking Simulation , Drug Evaluation, Preclinical , Plant Extracts/chemistry , Plant Extracts/pharmacology , Quercetin/chemistry , Quercetin/analysis , Quercetin/pharmacology , Quercetin/analogs & derivatives , Chromatography, High Pressure LiquidABSTRACT
A fast and effective analytical method with biomass solid-phase microextraction sorbent combined with a high-performance liquid chromatography-ultraviolet detector was proposed for the determination of benzoylurea (BU) insecticides in tea products. The novel sorbent was prepared by activating and then carbonizing water hyacinth with a fast growth rate and low application value as raw material and showed a high specific surface area and multiple interactions with analytes, such as electrostatic action, hydrogen bonding, and π-π conjugation. After optimizing the three most important extraction parameters (pH [X1], sample loading rate [X2], and solution volume [X3]) by Box-Behnken design, the as-established analytical method showed good extraction performance: excellent recovery (80.13%-106.66%) and wide linear range (1-400 µg/L) with a determination coefficient of 0.9992-0.9999, a low limit of detection of 0.02-0.1 µg/L and the satisfactory practical application results in tea products. All these indicate that the water hyacinth-derived material has the potential as a solid-phase extraction sorbent for the detection and removal of BU insecticides from tea products, and at the same time, it can also achieve the effect of rational use of biological resources, maintaining ecological balance, turning waste into treasure, and achieving industrial production.
Subject(s)
Biomass , Eichhornia , Insecticides , Tea , Insecticides/analysis , Insecticides/chemistry , Insecticides/isolation & purification , Eichhornia/chemistry , Tea/chemistry , Adsorption , Chromatography, High Pressure Liquid , Solid Phase Microextraction , Phenylurea Compounds/analysis , Phenylurea Compounds/chemistry , Phenylurea Compounds/isolation & purificationABSTRACT
In this work, core-shell material with a special structure was designed and applied in solid-phase extraction (SPE) for non-steroidal anti-inflammatory drugs (NSAIDs) combined with high-performance liquid chromatography. Based on the advantages of core-shell ZIF-8@ZIF-67 (Zeolite imidazole ester framework materials [ZIFs]), effective derivatization treatment was carried out to partially vulcanize the original ZIFs, resulting in a special and new double-core-shell structural material CoS/ZIF-67/ZnS/ZIF-8 (ZIFs@ZnS@CoS) with porous surface and center hollow. The multiple forces caused by the rich chemical structure, the large specific surface area caused by the special pore structure, and the effective protection of the ZIFs core by sulfide shell make the designed material have higher extraction efficiency and longer service life, compared with ZIF-8@ZIF-67 and ZIF-8. At the same time, the established analytical method for non-steroidal drugs had a high recovery rate (98.93%-102.10%), low detection limit (0.11-0.27 µg/L), and wide linear range (1-200 µg/L) within a good correlation coefficient R2 (0.9978-0.9993). Satisfactory results were also obtained from the extraction of NSAIDs from the Yellow River water samples. These results indicate that the designed double-core-shell structure material can effectively exert its structural advantages and become a promising extraction material.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Solid Phase Extraction , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Anti-Inflammatory Agents, Non-Steroidal/analysis , Solid Phase Extraction/methods , Chromatography, High Pressure Liquid , Surface Properties , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/isolation & purification , Water Pollutants, Chemical/analysis , Particle Size , Metal-Organic Frameworks/chemistry , Molecular Structure , Porosity , Zeolites/chemistry , Adsorption , Imidazoles/chemistryABSTRACT
OBJECTIVE: This study developed and validated a nomogram utilizing clinical and multi-slice spiral computed tomography (MSCT) features for the preoperative prediction of Ki-67 expression in stage IA lung adenocarcinoma. Additionally, we assessed the predictive accuracy of Ki-67 expression levels, as determined by our model, in estimating the prognosis of stage IA lung adenocarcinoma. MATERIALS AND METHODS: We retrospectively analyzed data from 395 patients with pathologically confirmed stage IA lung adenocarcinoma. A total of 322 patients were divided into training and internal validation groups at a 6:4 ratio, whereas the remaining 73 patients composed the external validation group. According to the pathological results, the patients were classified into high and low Ki-67 labeling index (LI) groups. Clinical and CT features were subjected to statistical analysis. The training group was used to construct a predictive model through logistic regression and to formulate a nomogram. The nomogram's predictive ability and goodness-of-fit were assessed. Internal and external validations were performed, and clinical utility was evaluated. Finally, the recurrence-free survival (RFS) rates were compared. RESULTS: In the training group, sex, age, tumor density type, tumor-lung interface, lobulation, spiculation, pleural indentation, and maximum nodule diameter differed significantly between patients with high and low Ki-67 LI. Multivariate logistic regression analysis revealed that sex, tumor density, and maximum nodule diameter were significantly associated with high Ki-67 expression in stage IA lung adenocarcinoma. The calibration curves closely resembled the standard curves, indicating the excellent discrimination and accuracy of the model. Decision curve analysis revealed favorable clinical utility. Patients with a nomogram-predicted high Ki-67 LI exhibited worse RFS. CONCLUSION: The nomogram utilizing clinical and CT features for the preoperative prediction of Ki-67 expression in stage IA lung adenocarcinoma demonstrated excellent performance, clinical utility, and prognostic significance, suggesting that this nomogram is a noninvasive personalized approach for the preoperative prediction of Ki-67 expression.
Subject(s)
Adenocarcinoma of Lung , Ki-67 Antigen , Lung Neoplasms , Neoplasm Staging , Nomograms , Humans , Ki-67 Antigen/metabolism , Male , Female , Middle Aged , Retrospective Studies , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Adenocarcinoma of Lung/diagnostic imaging , Adenocarcinoma of Lung/metabolism , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/surgery , Prognosis , Aged , Tomography, Spiral Computed/methods , AdultABSTRACT
BACKGROUND: The role of mechanical power on pulmonary outcomes after thoracic surgery with one-lung ventilation was unclear. We investigated the association between mechanical power and postoperative pulmonary complications in patients undergoing thoracoscopic lung resection surgery. METHODS: In this single-center, prospective observational study, 622 patients scheduled for thoracoscopic lung resection surgery were included. Volume control mode with lung protective ventilation strategies were implemented in all participants. The primary endpoint was a composite of postoperative pulmonary complications during hospital stay. Multivariable logistic regression models were used to evaluate the association between mechanical power and outcomes. RESULTS: The incidence of pulmonary complications after surgery during hospital stay was 24.6% (150 of 609 patients). The multivariable analysis showed that there was no link between mechanical power and postoperative pulmonary complications. CONCLUSIONS: In patients undergoing thoracoscopic lung resection with standardized lung-protective ventilation, no association was found between mechanical power and postoperative pulmonary complications. TRIAL REGISTRATION: Trial registration number: ChiCTR2200058528, date of registration: April 10, 2022.
Subject(s)
One-Lung Ventilation , Postoperative Complications , Humans , Prospective Studies , Male , Female , One-Lung Ventilation/methods , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Middle Aged , Aged , Pneumonectomy/adverse effects , Pneumonectomy/methods , Thoracoscopy/methods , Lung Diseases/etiology , Lung Diseases/epidemiology , Thoracic Surgery, Video-Assisted/methods , Thoracic Surgery, Video-Assisted/adverse effectsABSTRACT
BACKGROUND: Noninvasive energy-based device (NI-EBD) aesthetic procedures has recently gained widespread usage for treating various skin conditions, enhancing skin texture and performing rejuvenation-related procedures. However, practically all NI-EBD procedures result in variable degrees of damage to the skin barrier, inducing pathological and physiological processes such as oxidative stress and inflammation, and only a small percentage of individuals possess the innate ability to restore it. OBJECTIVE: To introduce the concept of integrated skincare and establish standardized operational procedures for perioperative integrated skincare, and furnish a theoretical basis for clinical diagnosis and treatment performed by professional medical aestheticians. METHODS: The author leveraged domestic and international guidelines, clinical practice expertise and evidence-based research, adapting them to suit the specific circumstances in China. RESULTS: The consensus were provided four parts, including concept and essence of integrated skincare, integrated skincare significance during the perioperative phase of NI-EBD procedures, active ingredients and functions of effective skincare products, standardized perioperative skincare procedure for NI-EBD procedures and precautions. For the standardized perioperative skincare procedure, four recommendations were listed according to different stages during NI-EBD procedures. CONCLUSION: These recommendations create the 'Expert Consensus on Perioperative Integrated Skincare for Noninvasive Energy-Based Device Aesthetic Procedures in Clinical Practice in China'.
Subject(s)
Cosmetic Techniques , Humans , China , Perioperative Care , Consensus , Rejuvenation , Skin Care/methods , Skin Aging , EstheticsABSTRACT
OBJECTIVE: Osteoarthritis (OA) is characterized by progressive cartilage degeneration and absence of curative therapies. Therefore, more efficient therapies are compellingly needed. Both mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) and Icariin (ICA) are promising for repair of cartilage defect. This study proposes that ICA may be combined to potentiate the cartilage repair capacity of MSC-EVs. MATERIALS AND METHODS: MSC-EVs were isolated from sodium alginate (SA) and hyaluronic acid (HA) composite hydrogel (SA-HA) cell spheroid culture. EVs and ICA were combined in SA-HA hydrogel to test therapeutic efficacy on cartilage defect in vivo. RESULTS: EVs and ICA were synergistic for promoting both proliferation and migration of MSCs and inflammatory chondrocytes. The combination therapy led to strikingly enhanced repair on cartilage defect in rats, with mechanisms involved in the concomitant modulation of both cartilage degradation and synthesis makers. CONCLUSION: The MSC-EVs-ICA/SA-HA hydrogel potentially constitutes a novel therapy for cartilage defect in OA.
Subject(s)
Extracellular Vesicles , Mesenchymal Stem Cells , Osteoarthritis , Animals , Rats , Hydrogels/pharmacology , Hyaluronic Acid/pharmacology , Hyaluronic Acid/metabolism , Cartilage , Chondrocytes/metabolism , Osteoarthritis/drug therapy , Regeneration , Extracellular Vesicles/metabolismABSTRACT
PURPOSE: Melasma remains a refractory skin condition that needs to be actively explored. Azelaic acid has been used for decades as a topical agent to improve melasma through multiple mechanisms, however, there is a lack of research on its combination with laser therapy. This study evaluated the effectiveness of isolated treatment with topical 20% azelaic acid and its combination with 755-nm picosecond laser in facial melasma patients. METHODS: A randomized, evaluator-blinded, controlled study was conducted on 30 subjects with facial melasma in a single center from October 2021 to April 2022. All subjects received topical 20% azelaic acid cream (AA) for 24 weeks, and after 4 weeks, a hemiface was randomly assigned to receive 755-nm picosecond (PS) laser therapy once every 4 weeks for 3 treatments. Treatment efficacy was determined by mMASI score evaluations, dermoscopic assessment, reflectance confocal microscopy (RCM) assessments and patient's satisfaction assessments (PSA). RESULTS: Treatment with 20% azelaic acid, with or without picosecond laser therapy, significantly reduced the hemi-mMASI score (P < 0.0001) and resulted in higher patient satisfaction. Improvements in dermoscopic and RCM assessments were observed in both sides of the face over time, with no difference between the two sides. RCM exhibited better dentritic cell improvement in the combined treatment side. No patients had serious adverse effects at the end of treatment or during the follow-up period. CONCLUSION: The additional use of picosecond laser therapy showed no clinical difference except for subtle differences detected by RCM assessments.The study was registered in the Chinese Clinical Trial Registry (ChiCTR2100051294; 18 September 2021).