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1.
J Hazard Mater ; 476: 135062, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38959831

ABSTRACT

Microplastics (MPs) are emerging pollutants, causing potential threats to aquatic ecosystems and serious concern in aggregating with microalgae (critical primary producers). When entering water bodies, MPs are expected to sink below the water surface and disperse into varying water compartments with different light intensities. However, how light influences the aggregation processes of algal cells onto MPs and the associated molecular coupling mechanisms and derivative risks remain poorly understood. Herein, we investigated the aggregation behavior between polystyrene microplastics (mPS, 10 µm) and Chlorella pyrenoidosa under low (LL, 15 µmol·m-2·s-1), normal (NL, 55 µmol·m-2·s-1), and high light (HL, 150 µmol·m-2·s-1) conditions from integrated in vivo and in silico assays. The results indicated that under LL, the mPS particles primarily existed independently, whereas under NL and HL, C. pyrenoidosa tightly bounded to mPS by secreting more protein-rich extracellular polymeric substances. Infrared spectroscopy analysis and density functional theory calculation revealed that the aggregation formation was driven by non-covalent interaction involving van der Waals force and hydrogen bond. These processes subsequently enhanced the deposition and adherence capacity of mPS and relieved its phytotoxicity. Overall, our findings advance the practical and theoretical understanding of the ecological impacts of MPs in complex aquatic environments.

2.
Eur Clin Respir J ; 11(1): 2372901, 2024.
Article in English | MEDLINE | ID: mdl-38946716

ABSTRACT

Background: Bronchiectasis is a disease with predominantly neutrophilic inflammation. As a readily available biomarker, there is little evidence to support the use of blood neutrophil-to-lymphocyte ratio (NLR) to predict bronchiectasis exacerbation severe enough to warrant hospitalization. Methods: A registry-based retrospective cohort study was conducted at a in Hong Kong. Chinese patients with non-cystic fibrosis (CF) bronchiectasis were retrospectively reviewed and subsequently followed up to investigate the association of NLR and the need for hospitalization for bronchiectasis exacerbation. Data on the NLR for patients in a clinically stable state in 2018 were collected and patients followed up from 1 January 2019 to 31 December 2022. The primary outcome was the need for hospitalization due to bronchiectasis exacerbation over the next 4 years. Results: We reviewed 473 Chinese patients with non-CF bronchiectasis, of whom 94 required hospitalization for bronchiectasis exacerbation during the 4-year follow-up period. Multi-variable logistic regression adjusted for E-FACED score (Exacerbation, Forced expiratory volume in 1 s (FEV1), Age, Chronic colonization, Extension, and Dyspnea score), gender, age, smoking status, and presence of co-existing chronic obstructive pulmonary disease (COPD) was conducted to compare patients with highest and lowest quartile NLR. Results revealed that those with NLR at the highest quartile were at increased risk of hospitalization for bronchiectasis exacerbation with an adjusted odds ratio (aOR) of 2.02 (95% confidence interval = 1.00-4.12, p = 0.05). Conclusion: Blood NLR may serve as a marker to predict the need for hospitalization due to bronchiectasis exacerbation.

3.
Chem Sci ; 15(26): 10135-10145, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38966363

ABSTRACT

The dual catalysis strategy is an efficient and powerful tool to fulfill the stereodivergent synthesis of stereoisomeric products from the same set of starting materials. Great attention has been given to the construction of chiral compounds with two contiguous stereocenters. However, the synthesis of two remote noncontiguous stereocenters is more challenging and is less developed, despite the high demand for synthetic tactics. We herein developed an unprecedented example of the stereodivergent preparation of synthetically useful and biologically important chiral ζ-hydroxy amino ester derivatives containing remote 1,6-noncontiguous stereocenters and a unique ß,γ-unsaturation moiety. This cascade dehydrogenation/1,6-Michael addition/hydrogenation protocol between readily-available ketoimine esters and racemic branched dienyl carbinols was rationally realized with bimetallic copper/ruthenium relay catalysis. The key features of the process were atom economy, step economy, and redox-neutrality. All four stereoisomers of chiral ζ-hydroxy amino ester derivatives were easily achieved by the orthogonal permutations of a chiral copper catalyst and chiral ruthenium catalyst. Importantly, a much more challenging stereodivergent synthesis of all eight stereoisomers of chiral peptide products containing three remote stereocenters was accomplished with excellent results through the cooperation of two chiral catalyst pairs and substrate enantiomers.

4.
Infect Drug Resist ; 17: 2883-2896, 2024.
Article in English | MEDLINE | ID: mdl-39005858

ABSTRACT

Purpose: To systematically assess the distribution and antimicrobial susceptibility of pathogens in wound infections, and analyze risk factors associated with multidrug resistance (MDR). Patients and Methods: Retrospectively analyzing Jiaxing-region medical records between January 2021 and December 2023, we identified a cohort of 461 wound infection patients. Cultures were grown on various agars, with bacteria identified via Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry. The antimicrobial susceptibility of the organisms were conducted by VITEK 2 system, Kirby-Bauer disk diffusion method and Epsilometer test. Statistical Package for the Social Sciences (SPSS) version 22 was used for statistical analysis. Multivariable logistic regression models were developed to pinpoint risk factors for multidrug-resistant organism (MDRO) infections and predict occurrences. Results: From 461 patients, 549 bacterial pathogens were isolated, predominantly consisting of Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, Enterobacter cloacae, and Enterococcus faecalis. Vancomycin, linezolid, and tigecycline maintained their efficacy against Staphylococcus aureus and Enterococcus species, while Pseudomonas aeruginosa demonstrated sensitivity to aminoglycosides. Conversely, Escherichia coli exhibited high amoxicillin resistance (85.4%). More than half of the isolates were resistant to levofloxacin, ceftriaxone, cotrimoxazole, and gentamicin, with Acinetobacter baumannii strains showing considerable resistance (65.8-68.4%) to advanced cephalosporins and carbapenems. Within this group, 58 MDROs were detected, primarily originating from Burn Plastic Surgery, Emergency, and Intensive Care Unit (ICU) departments. Multivariate logistic regression identified hyperglycemia, hypoalbuminemia, surgery, extended hospitalization, and exposure to multiple antibiotic classes as independent risk factors for MDRO wound infections. Based on these findings, a predictive model for MDRO occurrence in wounds was constructed, which had a sensitivity of 0.627, specificity of 0.933, and an Area Under the Curve (AUC) of 0.838. Conclusion: Staphylococcus aureus and Pseudomonas aeruginosa dominated in wound infections with differential antibiotic resistance. Independent risk factors included hyperglycemia, hypoalbuminemia, surgery, extended hospitalization, and polyantibiotic use. We urge prioritizing culture, susceptibility tests, and personalized antibiotic strategies to address MDRO risks and improve wound infection management specificity and efficacy.

5.
Hematology ; 29(1): 2374127, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39007736

ABSTRACT

OBJECTIVE: To investigate and compare the effects of basic preconditioning regimens Bu/Cy, Cy/TBI and Flu/Bu for the treatment of patients in allogeneic hematopoietic stem cell transplantation. METHODS: It comprised exploring the published literature in the databases of PubMed, EMBASE, Cochrane Library, and Web of Science, using suitable keywords pertaining to various basic pretreatments Bu/Cy, Cy/TBI, and Flu/Bu, prior to allogeneic hematopoietic stem cell transplantation, and then extracting the searched outcome indicators of Overall Survival (OS) and survival (herein represented as OS and survival). Further, the results were estimated with meta-analysis using R, where the incidence of GVHD was reported in odds ratio (OR) with its 95% confidence interval (95%CI). RESULTS AND DISCUSSION: A total of 14 papers were included in this study, including 1436 cases were treated with Bu/Cy, 1816 cases with Cy/TBI, and 549 cases with Flu/Bu in the preconditioning regimen. After OS was the outcome pooled, compared with Flu/Bu in the preconditioning group, the results (Cy/TBI HR = 1.12 (95% Cl:1.04,1.61), Bu/Cy HR = 1.24 (95% Cl. 1.13,2.06)) showed that Flu/Bu preconditioning regimen significantly improved the overall survival rate of allogeneic HSCT patients. With the incidence of GVHD as the outcome summary, compared with Flu/Bu in the pretreatment group, the results (Cy/TBI HR = 1.24 (95% Cl:1.12, 1.82), Bu/Cy HR = 1.14 (95% Cl. 1.03, 2.12)) indicated that Flu/Bu in the pretreatment regimen group also significantly reduced the incidence of GVHD after allogeneic HSCT. CONCLUSION: Patients who received the basal preconditioning regimen Flu/Bu before allogeneic hematopoietic stem cell transplantation had the lowest hazard ratio for overall survival (OS) development. This indicates that the use of the basal preconditioning regimen Flu/Bu for the treatment of patients was the most effective, although the quality of the studies included needs to be confirmed by high-quality randomized controlled trials.


Subject(s)
Hematopoietic Stem Cell Transplantation , Transplantation Conditioning , Humans , Graft vs Host Disease/prevention & control , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/methods , Network Meta-Analysis , Transplantation Conditioning/methods , Transplantation, Homologous
6.
Nano Lett ; 24(28): 8752-8762, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-38953881

ABSTRACT

Acute methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is a common and serious lung infection with high morbidity and mortality rates. Due to the increasing antibiotic resistance, toxicity, and pathogenicity of MRSA, there is an urgent need to explore effective antibacterial strategies. In this study, we developed a dry powder inhalable formulation which is composed of porous microspheres prepared from poly(lactic-co-glycolic acid) (PLGA), internally loaded with indocyanine green (ICG)-modified, heat-resistant phages that we screened for their high efficacy against MRSA. This formulation can deliver therapeutic doses of ICG-modified active phages to the deep lung tissue infection sites, avoiding rapid clearance by alveolar macrophages. Combined with the synergistic treatment of phage therapy and photothermal therapy, the formulation demonstrates potent bactericidal effects in acute MRSA pneumonia. With its long-term stability at room temperature and inhalable characteristics, this formulation has the potential to be a promising drug for the clinical treatment of MRSA pneumonia.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Polylactic Acid-Polyglycolic Acid Copolymer , Methicillin-Resistant Staphylococcus aureus/drug effects , Animals , Mice , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Microspheres , Photothermal Therapy , Pneumonia, Staphylococcal/therapy , Phage Therapy/methods , Indocyanine Green/chemistry , Indocyanine Green/pharmacology , Indocyanine Green/therapeutic use , Indocyanine Green/administration & dosage , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Administration, Inhalation , Humans , Bacteriophages/chemistry
7.
World J Oncol ; 15(4): 550-561, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38993243

ABSTRACT

Background: Domestic and foreign studies on lung cancer have been oriented to the medical efficacy of low-dose computed tomography (LDCT), but there is a lack of studies on the costs, value and cost-effectiveness of the treatment. There is a scarcity of conclusive evidence regarding the cost-effectiveness of LDCT within the specific context of Taiwan. This study is designed to address this gap by conducting a comprehensive analysis of the cost-effectiveness of LDCT and chest X-ray (CXR) as screening methods for lung cancer. Methods: Markov decision model simulation was used to estimate the cost-effectiveness of biennial screening with LDCT and CXR based on a health provider perspective. Inputs are based on probabilities, health status utility (quality-adjusted life years (QALYs)), costs of lung cancer screening, diagnosis, and treatment from the literatures, and expert opinion. A total of 1,000 simulations and five cycles of Markov bootstrapping simulations were performed to compare the incremental cost-utility ratio (ICUR) of these two screening strategies. Probability and one-way sensitivity analyses were also performed. Results: The ICUR of early lung cancer screening compared LDCT to CXR is $-24,757.65/QALYs, and 100% of the probability agree to adopt it under a willingness-to-pay (WTP) threshold of the Taiwan gross domestic product (GDP) per capita ($35,513). The one-way sensitivity analysis also showed that ICUR depends heavily on recall rate. Based on the prevalence rate of 39.7 lung cancer cases per 100,000 people in 2020, it could be estimated that LDCT screening for high-risk populations could save $17,154,115. Conclusion: LDCT can detect more early lung cancers, reduce mortality and is cost-saving than CXR in a long-term simulation of Taiwan's healthcare system. This study provides valuable insights for healthcare decision-makers and suggests analyzing cost-effectiveness for additional variables in future research.

8.
World J Clin Cases ; 12(19): 3760-3766, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38994283

ABSTRACT

BACKGROUND: Numerous studies have found that patients experiencing sudden sensorineural hearing loss (SSHL), with or without accompanying vertigo, often show impaired vestibular function. However, there is a dearth of studies analyzing vestibular-evoked myogenic potentials (VEMPs) in SSHL patients across various age groups. AIM: To investigate vestibular condition in SSHL patients across various age demographics. METHODS: Clinical data of 84 SSHL patients were investigated retrospectively. Audiometry, cervical vestibular evoked myogenic potentials (c-VEMPs), and ocular vestibular evoked myogenic potentials (o-VEMPs) were conducted on these patients. Parameters assessed included the latencies of P1 and N1 waves, as well as the amplitudes of P1-N1 waves. Moreover, the study evaluated the influence of factors such as sex, affected side, configuration of hearing loss, and presence of accompanying vertigo. RESULTS: Among the 84 SSHL patients, no significant differences were observed among the three groups in terms of gender, affected side, and the presence or absence of vertigo. Group II (aged 41-60 years) had the highest number of SSHL cases. The rates of absent o-VEMPs in the affected ears were 20.83%, 31.58%, and 22.72% for the three age groups, respectively, with no statistically significant difference among them. The rates of absent c-VEMPs in the affected ears were 8.3%, 34.21%, and 18.18% for the three age groups, respectively, with significant differences. In the unaffected ears, there were differences observed in the extraction rates of o-VEMPs in the unaffected ears among the age groups. In the three age groups, no significant differences were noted in the three age groups in the latencies of P1 and N1 waves or in the amplitude of N1-P1 waves for c-VEMPs and o-VEMPs, either on the affected side or on the unaffected side, across the three age groups. CONCLUSION: The extraction rate of VEMPs is more valuable than parameters. Regardless of the presence of vertigo, vestibular organs are involved in SSHL. Notably, SSHL patients aged 41-60 appear more susceptible to damage to the inferior vestibular nerve and saccule.

9.
Sci Rep ; 14(1): 15939, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38987651

ABSTRACT

In order to grasp the influence of the pH value of mixing water and environmental water on the properties of ultra-high water materials, this article separately carried out the influence of different pH values of mixing water on the properties of ultra-high water materials and the conservation of high-water materials in water environments with different pH values. Using test methods such as loss of flow time, compressive strength, Scanning Electron Microscope (SEM), X-Ray Diffraction (XRD), Thermogravimetric-Differential Thermal Analysis (TG-DTA), to conduct regular exploration and mechanism analysis. The study found that with the continuous increase of the pH value of the mixing water, the loss of flow time of the ultra-high water material gradually decreased, and the compressive strength of the samples at the same age continued to increase. A lower pH value will affect the compressive strength of the consolidated body of the ultra-high water material, but when the pH = 13 in the reaction solution, the compressive strength of the consolidated body will no longer increase and begin to produce a weakening effect. The pH of the construction water for ultra-high water materials is recommended to be 4-13. At the same time, it was found that under the conservation of an acidic environment, the consolidated body was severely eroded and the strength loss was large. The acid-base environment of the goaf suitable for filling with the ultra-high water material should be between pH = 7-10 to ensure that the filling body is not weakened by erosion.

10.
PeerJ ; 12: e17661, 2024.
Article in English | MEDLINE | ID: mdl-38978758

ABSTRACT

Leaf mustard (Brassica juncea L. Czern & Coss), an important vegetable crop, experiences pronounced adversity due to seasonal drought stress, particularly at the seed germination stage. Although there is partial comprehension of drought-responsive genes, the role of long non-coding RNAs (lncRNAs) in adjusting mustard's drought stress response is largely unexplored. In this study, we showed that the drought-tolerant cultivar 'Weiliang' manifested a markedly lower base water potential (-1.073 MPa vs -0.437 MPa) and higher germination percentage (41.2% vs 0%) than the drought-susceptible cultivar 'Shuidong' under drought conditions. High throughput RNA sequencing techniques revealed a significant repertoire of lncRNAs from both cultivars during germination under drought stress, resulting in the identification of 2,087 differentially expressed lncRNAs (DELs) and their correspondingly linked 12,433 target genes. It was noted that 84 genes targeted by DEL exhibited enrichment in the photosynthesis pathway. Gene network construction showed that MSTRG.150397, a regulatory lncRNA, was inferred to potentially modulate key photosynthetic genes (Psb27, PetC, PetH, and PsbW), whilst MSTRG.107159 was indicated as an inhibitory regulator of six drought-responsive PIP genes. Further, weighted gene co-expression network analysis (WGCNA) corroborated the involvement of light intensity and stress response genes targeted by the identified DELs. The precision and regulatory impact of lncRNA were verified through qPCR. This study extends our knowledge of the regulatory mechanisms governing drought stress responses in mustard, which will help strategies to augment drought tolerance in this crop.


Subject(s)
Droughts , Gene Expression Regulation, Plant , Germination , Mustard Plant , RNA, Long Noncoding , Mustard Plant/genetics , Germination/genetics , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Stress, Physiological/genetics , Seeds/genetics , Seeds/growth & development , RNA, Plant/genetics , RNA, Plant/metabolism , Gene Regulatory Networks
11.
J Plant Physiol ; 301: 154313, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38991233

ABSTRACT

Drought is a principal environmental factor that affects the growth and development of plants. Accordingly, plants have evolved adaptive mechanisms to cope with adverse environmental conditions. One of the mechanisms is gene regulation mediated by microRNAs (miRNAs). miRNAs are regarded as primary modulators of gene expression at the post-transcriptional level and have been shown to participate in drought stress response, including ABA response, auxin signaling, antioxidant defense, and osmotic regulation through downregulating the corresponding targets. miRNA-based genetic reconstructions have the potential to improve the tolerance of plants to drought. However, there are few precise classification and discussion of miRNAs in specific response behaviors to drought stress and their applications. This review summarized and discussed the specific response behaviors of miRNAs under drought stress and the role of miRNAs as regulators in the response of plants to drought and highlighted that the modification of miRNAs might effectively improve the tolerance of plants to drought.

12.
J Biol Methods ; 11: e99010010, 2024.
Article in English | MEDLINE | ID: mdl-38988499

ABSTRACT

Alzheimer's disease (AD) is a serious dementia afflicting aging population and is characterized by cognitive decline, amyloid-ß plaques, and neurofibrillary tangles. AD substantially impairs the life quality of the victims and poses a heavy burden on the society at large. The number of people with dementia due to AD, prodromal AD, and preclinical AD is estimated to stand at roughly 3.2, 69, and 315 million worldwide, respectively. Current clinical diagnosis is based on clinical symptoms, and clinical research demonstrated that positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers had excellent diagnostic performance. However, the application of CSF biomarker tests and PET are restricted by the invasiveness and high cost. The presence of clinical symptoms means that AD pathology has been progressing for many years, and only a few drugs have been approved for the traetemnt of AD. Therefore, early diagnosis is extremely important for controlling the outcomes caused by AD. In this review, we provided an overview of developing clinical diagnostic criteria, diagnostic strategies under clinical research, developing blood based-biomarker assays, and promising nanotechnologically-based assays.

13.
Cancer Lett ; 598: 217104, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38969163

ABSTRACT

Results of measurable residual disease (MRD)-testing by next-generation sequencing (NGS) correlate with relapse risk in adults with B-cell acute lymphoblastic leukemia (ALL) receiving chemotherapy or an allotransplant from a human leukocyte antigen (HLA)-identical relative or HLA-matched unrelated donor. We studied cumulative incidence of relapse (CIR) and survival prediction accuracy using a NGS-based MRD-assay targeting immunoglobulin genes after 2 courses of consolidation chemotherapy cycles in 93 adults with B-cell ALL most receiving HLA-haplotype-matched related transplants. Prediction accuracy was compared with MRD-testing using multi-parameter flow cytometry (MPFC). NGS-based MRD-testing detected residual leukemia in 28 of 65 subjects with a negative MPFC-based MRD-test. In Cox regression multi-variable analyses subjects with a positive NGS-based MRD-test had a higher 3-year CIR (Hazard Ratio [HR] = 3.37; 95 % Confidence Interval [CI], 1.34-8.5; P = 0.01) and worse survival (HR = 4.87 [1.53-15.53]; P = 0.007). Some data suggest a lower CIR and better survival in NGS-MRD-test-positive transplant recipients but allocation to transplant was not random. Our data indicate MRD-testing by NGS is more accurate compared with testing by MPFC in adults with B-cell ALL in predicting CIR and survival. (Registered in the Beijing Municipal Health Bureau Registration N 2007-1007 and in the Chinese Clinical Trial Registry [ChiCTR-OCH-10000940 and ChiCTROPC-14005546]).

14.
Front Oncol ; 14: 1400313, 2024.
Article in English | MEDLINE | ID: mdl-39022589

ABSTRACT

Purpose: The aim of this study was to analyze the effect of chronic kidney disease (CKD) on the short-term outcomes and prognosis of colorectal cancer (CRC) patients who underwent primary surgery. Methods: CRC patients who underwent radical surgery were included from Jan 2011 to Jan 2020 in a single hospital. The short-term outcomes and prognosis were compared between the CKD group and the Non-CKD group using propensity score matching (PSM) analysis. Results: A total of 4056 patients undergoing CRC surgery were included, including 723 patients in the CKD group and 3333 patients in the Non-CKD group. After 1:1 PSM, there were 666 patients in each group, respectively. No significant difference was found in baseline characteristics between the two groups. (p>0.05). After PSM, the CKD group had a longer postoperative hospital stay (P=0.009) and a higher incidence of overall complications (p=0.050). Cox analysis was performed on matched patients to find predictors of overall survival (OS) and disease-free survival (DFS). We found that age (p<0.01, HR=1.045, 95% CI=1.028-1.062), tumor stage (p<0.01, HR=1.931, 95% CI=1.564-2.385) and overall complications (p<0.01, HR=1.858, 95% CI=1.423-2.425) were independent predictors of OS. Age (p<0.01, HR=1.034, 95% CI=1.020-1.049), tumor stage (p<0.01, HR=1.852, 95% CI=1.537-2.231), and overall complications (p<0.01, HR=1.651, 95% CI=1.295-2.10) were independent predictors of DFS. However, CKD was not an independent predictor of OS or DFS (OS: p=0.619, HR=1.070, 95% CI=0.820-1.396; DFS: p=0.472, HR=1.092, 95% CI=0.859-1.389). Conclusion: CKD prolonged postoperative hospital stay; however, CKD might not affect major postoperative complications, OS or DFS of CRC.

15.
J Cardiothorac Surg ; 19(1): 453, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39014449

ABSTRACT

BACKGROUND: With a considerable variety of cancer subtypes, Non-small cell lung cancer (NSCLC) poses a substantial threat to public health, affecting a large number of individuals and resulting in a high mortality rate. Circular RNA (circRNA) has been applied in various diseases, including cancers. This study aims to investigate the clinial significance and functional role of circPTP4A2 in NSCLC. METHODS: The serum and tissue samples were collected for detecting circPTP4A2 expression in NSCLC using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Actinomycin D was used to treat NSCLC cells to detect circPTP4A2 stability. The CCK-8 and Transwell assays were utilized to assess the effects of circPTP4A2 in NSCLC cells. The ELISA assay and cytotoxicity analysis were used to detect the roles of circPTP4A2 in immune escape. RESULTS: The serum and tissue circPTP4A2 expression was upregulated in NSCLC. The high circPTP4A2 had a relatively high value in differentiating NSCLC patients from healthy individuals. The proliferation, invasion, and immune escape were repressed by circPTP4A2 knockdown. CONCLUSIONS: High circPTP4A2 has the potential to be a diagnostic biomarker in NSCLC. Silencing of circPTP4A2 receded the progression of NSCLC and enhanced antitumor immunity, which might provide potential targets and new ideas for improving the diagnosis and effect of immunotherapy in NSCLC patients.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Cell Proliferation , Lung Neoplasms , RNA, Circular , Humans , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/immunology , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lung Neoplasms/immunology , RNA, Circular/genetics , Cell Proliferation/genetics , Disease Progression , Gene Expression Regulation, Neoplastic , Male , Female , Cell Line, Tumor , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Middle Aged , Gene Knockdown Techniques
16.
Chem Pharm Bull (Tokyo) ; 72(6): 584-595, 2024.
Article in English | MEDLINE | ID: mdl-38945947

ABSTRACT

In order to introduce a cost-effective strategy method for commercial scale dry granulation at the early clinical stage of drug product development, we developed dry granulation process using formulation without API, fitted and optimized the process parameters adopted Design of Experiment (DOE). Then, the process parameters were confirmed using one formulation containing active pharmaceutical ingredient (API). The results showed that the roller pressure had significant effect on particle ratio (retained up to #60 mesh screen), bulk density and tapped density. The roller gap had significant influence on particle ratio and specific energy. The particle ratio was significantly affected by the mill speed (second level). The tabletability of the powder decreased after dry granulation. The effect of magnesium stearate on the tabletability was significant. In the process validation study, the properties of the prepared granules met the requirements for each response studied in the DOE. The prepared tablets showed higher tensile strength, good content uniformity of filled capsules, and the dissolution profiles of which were consistent with that of clinical products. This drug product process development and research strategies could be used as a preliminary experiment for the dry granulation process in the early clinical stage.


Subject(s)
Tablets , Tablets/chemistry , Particle Size , Drug Compounding , Powders/chemistry , Stearic Acids/chemistry , Tensile Strength , Excipients/chemistry , Solubility
17.
PLoS Negl Trop Dis ; 18(6): e0012281, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38905319

ABSTRACT

BACKGROUND: Pathogens can impact host RNA modification machinery to establish a favorable cellular environment for their replication. In the present study, we investigated the effect of Toxoplasma gondii infection on host RNA modification profiles and explored how these modifications may influence the host-parasite interaction. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the modification levels of ∼ 80 nt tRNA and 17-50 nt sncRNAs in mouse liver, spleen, and serum using liquid chromatography and tandem mass spectrometry analysis. The results revealed alterations in RNA modification profiles, particularly during acute infection. The liver exhibited more differentially abundant RNA modifications than the spleen. RNA modification levels in serum were mostly downregulated during acute infection compared to control mice. Correlations were detected between different RNA modifications in the liver and spleen during infection and between several RNA modifications and many cytokines. Alterations in RNA modifications affected tRNA stability and protein translation. CONCLUSIONS/SIGNIFICANCE: These findings provide new insight into the role of RNA modifications in mediating the murine host response to T. gondii infection.


Subject(s)
Liver , RNA, Transfer , Spleen , Toxoplasma , Animals , Toxoplasma/genetics , Liver/parasitology , Mice , Spleen/parasitology , Spleen/metabolism , RNA, Transfer/genetics , RNA, Transfer/metabolism , RNA Processing, Post-Transcriptional , Female , Host-Parasite Interactions , RNA/genetics , RNA/metabolism , Toxoplasmosis, Animal/parasitology , Toxoplasmosis/parasitology , Mice, Inbred C57BL
18.
Adv Mater ; : e2404492, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38935237

ABSTRACT

Wearable and implantable active medical devices (WIMDs) are transformative solutions for improving healthcare, offering continuous health monitoring, early disease detection, targeted treatments, personalized medicine, and connected health capabilities. Commercialized WIMDs use primary or rechargeable batteries to power their sensing, actuation, stimulation, and communication functions, and periodic battery replacements of implanted active medical devices pose major risks of surgical infections or inconvenience to users. Addressing the energy source challenge is critical for meeting the growing demand of the WIMD market that is reaching valuations in the tens of billions of dollars. This review critically assesses the recent advances in energy harvesting and storage technologies that can potentially eliminate the need for battery replacements. With a key focus on advanced materials that can enable energy harvesters to meet the energy needs of WIMDs, this review examines the crucial roles of advanced materials in improving the efficiencies of energy harvesters, wireless charging, and energy storage devices. This review concludes by highlighting the key challenges and opportunities in advanced materials necessary to achieve the vision of self-powered wearable and implantable active medical devices, eliminating the risks associated with surgical battery replacement and the inconvenience of frequent manual recharging.

19.
Front Biosci (Landmark Ed) ; 29(6): 233, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38940043

ABSTRACT

BACKGROUND: This study investigated the mechanism by which tazarotene-induced gene 1 (TIG1) inhibits melanoma cell growth. The main focus was to analyze downstream genes regulated by TIG1 in melanoma cells and its impact on cell growth. METHODS: The effects of TIG1 expression on cell viability and death were assessed using water-soluble tetrazolium 1 (WST-1) mitochondrial staining and lactate dehydrogenase release assays. RNA sequencing and Western blot analysis were employed to investigate the genes regulated by TIG1 in melanoma cells. Additionally, the correlation between TIG1 expression and its downstream genes was analyzed in a melanoma tissue array. RESULTS: TIG1 expression in melanoma cells was associated with decreased cell viability and increased cell death. RNA-sequencing (RNA-seq), quantitative reverse transcription PCR (reverse RT-QPCR), and immunoblots revealed that TIG1 expression induced the expression of Endoplasmic Reticulum (ER) stress response-related genes such as Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 (HERPUD1), Binding immunoglobulin protein (BIP), and DNA damage-inducible transcript 3 (DDIT3). Furthermore, analysis of the melanoma tissue array revealed a positive correlation between TIG1 expression and the expression of HERPUD1, BIP, and DDIT3. Additionally, attenuation of the ER stress response in melanoma cells weakened the impact of TIG1 on cell growth. CONCLUSIONS: TIG1 expression effectively hinders the growth of melanoma cells. TIG1 induces the upregulation of ER stress response-related genes, leading to an increase in caspase-3 activity and subsequent cell death. These findings suggest that the ability of retinoic acid to prevent melanoma formation may be associated with the anticancer effect of TIG1.


Subject(s)
Cell Survival , Endoplasmic Reticulum Stress , Gene Expression Regulation, Neoplastic , Melanoma , Humans , Endoplasmic Reticulum Stress/genetics , Endoplasmic Reticulum Stress/drug effects , Melanoma/genetics , Melanoma/metabolism , Melanoma/pathology , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/genetics , Cell Death/genetics , Apoptosis/genetics , Apoptosis/drug effects , Cell Proliferation/genetics , Cell Proliferation/drug effects , Membrane Proteins
20.
Photodiagnosis Photodyn Ther ; 48: 104237, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38871017

ABSTRACT

PURPOSE: To report the use of anterior segment optical coherence tomography (AS-OCT) for superficial keratectomy (SK) in anterior corneal opacity. METHODS: The characteristics of 43 eyes (39 patients) with various lesions responsible for anterior corneal opacity were included in this retrospective non-comparative study. AS-OCT was performed on all eyes before surgery. The thickness of corneal opacity and the underlying healthy stroma were measured. SK was performed on each individual. RESULTS: Four types of anterior corneal opacity were evaluated, including corneal degeneration (26/43), Reis-Bücklers corneal dystrophy (8/43), alkali burn (1/43) and corneal tumors (8/43). Based on AS-OCT images, all eyes showed abnormal hyper-reflective signals in the superficial cornea to less than one-third of the normal corneal thickness in the deepest corneal opacity. All 43 eyes underwent an SK procedure. In addition, 1 eye with alkali burns and 7 eyes with corneal tumors were combined with amniotic membrane transplantation. All eyes restored transparency without significant complications. CONCLUSION: AS-OCT is a valuable method for objective preoperative and noninvasive assessments of anterior corneal opacities and is useful for guiding SK.

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