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1.
J Environ Sci (China) ; 147: 50-61, 2025 Jan.
Article in English | MEDLINE | ID: mdl-39003066

ABSTRACT

With the increasing severity of arsenic (As) pollution, quantifying the environmental behavior of pollutant based on numerical model has become an important approach to determine the potential impacts and finalize the precise control strategies. Taking the industrial-intensive Jinsha River Basin as typical area, a two-dimensional hydrodynamic water quality model coupled with Soil and Water Assessment Tool (SWAT) model was developed to accurately simulate the watershed-scale distribution and transport of As in the terrestrial and aquatic environment at high spatial and temporal resolution. The effects of hydro-climate change, hydropower station construction and non-point source emissions on As were quantified based on the coupled model. The result indicated that higher As concentration areas mainly centralized in urban districts and concentration slowly decreased from upstream to downstream. Due to the enhanced rainfall, the As concentration was significantly higher during the rainy season than the dry season. Hydro-climate change and the construction of hydropower station not only affected the dissolved As concentration, but also affected the adsorption and desorption of As in sediment. Furthermore, As concentration increased with the input of non-point source pollution, with the maximum increase about 30%, resulting that non-point sources contributed important pollutant impacts to waterways. The coupled model used in pollutant behavior analysis is general with high potential application to predict and mitigate water pollution.


Subject(s)
Arsenic , Environmental Monitoring , Rivers , Water Pollutants, Chemical , Arsenic/analysis , China , Water Pollutants, Chemical/analysis , Rivers/chemistry , Environmental Monitoring/methods , Models, Chemical , Models, Theoretical
2.
Commun Biol ; 7(1): 795, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38951640

ABSTRACT

The peroxisome is a versatile organelle that performs diverse metabolic functions. PEX3, a critical regulator of the peroxisome, participates in various biological processes associated with the peroxisome. Whether PEX3 is involved in peroxisome-related redox homeostasis and myocardial regenerative repair remains elusive. We investigate that cardiomyocyte-specific PEX3 knockout (Pex3-KO) results in an imbalance of redox homeostasis and disrupts the endogenous proliferation/development at different times and spatial locations. Using Pex3-KO mice and myocardium-targeted intervention approaches, the effects of PEX3 on myocardial regenerative repair during both physiological and pathological stages are explored. Mechanistically, lipid metabolomics reveals that PEX3 promotes myocardial regenerative repair by affecting plasmalogen metabolism. Further, we find that PEX3-regulated plasmalogen activates the AKT/GSK3ß signaling pathway via the plasma membrane localization of ITGB3. Our study indicates that PEX3 may represent a novel therapeutic target for myocardial regenerative repair following injury.


Subject(s)
Cell Membrane , Integrin beta3 , Mice, Knockout , Regeneration , Animals , Mice , Integrin beta3/metabolism , Integrin beta3/genetics , Cell Membrane/metabolism , Myocytes, Cardiac/metabolism , Male , Plasmalogens/metabolism , Signal Transduction , Myocardium/metabolism , Myocardium/pathology , Mice, Inbred C57BL , Heart Injuries/metabolism , Heart Injuries/pathology , Heart Injuries/genetics , Cell Proliferation , Membrane Proteins/metabolism , Membrane Proteins/genetics
3.
Int J Surg ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38959095

ABSTRACT

BACKGROUND: Non-malignant upper gastrointestinal diseases, including peptic ulcer disease (PUD), gastritis and duodenitis (GD), and gastroesophageal reflux disease (GERD), significantly challenge global healthcare. These conditions not only impact patient health but also highlight socio-economic development issues and healthcare system accessibility and efficiency. Utilizing the Global Burden of Disease (GBD) database, this study aims to assess the global burden of PUD, GD, and GERD comprehensively, examining their association with the sociodemographic index (SDI). METHODS: Employing data from the GBD 2019 database, this study analyzed the disability-adjusted life years (DALYs) for PUD, GD, and GERD. We integrated the SDI with the inequality slope index and concentration index for an international health inequality analysis, assessing disparities in the burden of these non-malignant upper gastrointestinal diseases. Decomposition analysis was conducted to determine the effects of population growth, aging, and epidemiological shifts on disease burden. Frontier analysis was performed to identify potential improvement areas and disparities among countries by development status. Disease time trends were depicted using a Joinpoint regression model, and the Bayesian age-period-cohort (BAPC) model projected the disease burden up to 2030. RESULTS: Between 1990 and 2019, the age-standardized DALYs rates (ASDR) for non-malignant upper gastrointestinal diseases declined. However, global geographic heterogeneity remained evident, closely linked to the SDI. Notably, low-SDI countries experienced higher disease burdens. Population growth and aging emerged as principal contributors to the increasing disease burden. Despite development levels, many countries have considerable potential for reducing the burden of these diseases. Furthermore, significant variations in the time trends of non-malignant upper gastrointestinal diseases were observed among countries and regions with different SDI levels, a pattern expected to continue through 2030. CONCLUSION: Non-malignant upper gastrointestinal diseases demonstrate notable heterogeneity across age, gender, and geography, with the disparities most marked in underdeveloped regions or countries. Consequently, it is imperative to focus research on policy development and to enact prevention and treatment strategies tailored to high-risk groups. This targeted approach is essential for mitigating the disease burden effectively.

4.
J Sep Sci ; 47(13): e2400154, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38948935

ABSTRACT

Glycosylation and phosphorylation rank as paramount post-translational modifications, and their analysis heavily relies on enrichment techniques. In this work, a facile approach was developed for the one-step simultaneous enrichment and stepwise elution of glycoproteins and phosphoproteins. The core of this approach was the application of the novel titanium (IV) ion immobilized poly(glycidyl methacrylate) microparticles functionalized with dendrimer polyethylenimine and phytic acid. The microparticles possessed dual enrichment capabilities due to their abundant titanium ions and hydroxyl groups on the surface. They demonstrate rapid adsorption equilibrium (within 30 min) and exceptional adsorption capacity for ß-casein (1107.7 mg/g) and horseradish peroxidase (438.6 mg/g), surpassing that of bovine serum albumin (91.7 mg/g). Furthermore, sodium dodecyl sulfate-polyacrylamide gel electrophoresis was conducted to validate the enrichment capability. Experimental results across various biological samples, including standard protein mixtures, non-fat milk, and human serum, demonstrated the remarkable ability of these microparticles to enrich low-abundance glycoproteins and phosphoproteins from biological samples.


Subject(s)
Dendrimers , Glycoproteins , Phosphoproteins , Polyethyleneimine , Polymethacrylic Acids , Titanium , Glycoproteins/chemistry , Phosphoproteins/chemistry , Polyethyleneimine/chemistry , Dendrimers/chemistry , Humans , Titanium/chemistry , Polymethacrylic Acids/chemistry , Hydrophobic and Hydrophilic Interactions , Surface Properties , Animals , Particle Size , Adsorption , Cattle
5.
J Chem Inf Model ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38949724

ABSTRACT

Ameliorating microglia-mediated neuroinflammation is a crucial strategy in developing new drugs for neurodegenerative diseases. Plant compounds are an important screening target for the discovery of drugs for the treatment of neurodegenerative diseases. However, due to the spatial complexity of phytochemicals, it becomes particularly important to evaluate the effectiveness of compounds while avoiding the mixing of cytotoxic substances in the early stages of compound screening. Traditional high-throughput screening methods suffer from high cost and low efficiency. A computational model based on machine learning provides a novel avenue for cytotoxicity determination. In this study, a microglia cytotoxicity classifier was developed using a machine learning approach. First, we proposed a data splitting strategy based on the molecule murcko generic scaffold, under this condition, three machine learning approaches were coupled with three kinds of molecular representation methods to construct microglia cytotoxicity classifier, which were then compared and assessed by the predictive accuracy, balanced accuracy, F1-score, and Matthews Correlation Coefficient. Then, the recursive feature elimination integrated with support vector machine (RFE-SVC) dimension reduction method was introduced to molecular fingerprints with high dimensions to further improve the model performance. Among all the microglial cytotoxicity classifiers, the SVM coupled with ECFP4 fingerprint after feature selection (ECFP4-RFE-SVM) obtained the most accurate classification for the test set (ACC of 0.99, BA of 0.99, F1-score of 0.99, MCC of 0.97). Finally, the Shapley additive explanations (SHAP) method was used in interpreting the microglia cytotoxicity classifier and key substructure smart identified as structural alerts. Experimental results show that ECFP4-RFE-SVM have reliable classification capability for microglia cytotoxicity, and SHAP can not only provide a rational explanation for microglia cytotoxicity predictions, but also offer a guideline for subsequent molecular cytotoxicity modifications.

6.
Front Neurosci ; 18: 1360459, 2024.
Article in English | MEDLINE | ID: mdl-38966761

ABSTRACT

Objective: SWI image signal is related to venous reflux disorder and perfusion defect. Computed tomography perfusion (CTP) contains perfusion information in space and time. There is a complementary basis between them to affect the prognosis of cerebral infarction. Methods: Sixty-six patients included in the retrospective study were designated as the training set. Effective perfusion indicator features and imaging radiomic features of the peri-infarction area on Susceptibility weighted imaging (SWI) and CTP modality images were extracted from each case. Thirty-three patients from the prospectively included group were designated as the test set of the machine learning model based on a sparse representation method. The predicted results were compared with the DWI results of the patients' 7-10 days review to assess the validity and accuracy of the prediction. Results: The AUC of the SWI + CTP integrated model was 0.952, the ACC was 0.909, the SEN was 0.889, and the SPE was 0.933. The prediction performance is the highest. Compared with the value of AUC: the SWI model is 0.874, inferior to the performance of the SWI + CTP model, and the CTP model is 0.715. Conclusion: The prediction efficiency of the changing trend of infarction volume is further improved by the correlation between the combination of the two image features.

7.
Sci Rep ; 14(1): 15198, 2024 07 02.
Article in English | MEDLINE | ID: mdl-38956154

ABSTRACT

Early prognostic assessment of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is important for guiding clinical management and reducing mortality. The aim of this study was to dynamically monitor the clinical characteristics of HBV-ACLF patients, thereby allowing the construction of a novel prognostic scoring model to predict the outcome of HBV-ACLF patients. Clinical data was prospectively collected for 518 patients with HBV-ACLF and randomly divided into training and validation sets. We constructed day-1, day-2, and day-(1 + 3) prognostic score models based on dynamic time points. The prognostic risk score constructed for day-3 was found to have the best predictive ability. The factors included in this scoring system, referred to as DSM-ACLF-D3, were age, hepatic encephalopathy, alkaline phosphatase, total bilirubin, triglycerides, very low-density lipoprotein, blood glucose, neutrophil count, fibrin, and INR. ROC analysis revealed the area under the curve predicted by DSM-ACLF-D3 for 28-day and 90-day mortality (0.901 and 0.889, respectively) was significantly better than those of five other scoring systems: COSSH-ACLF IIs (0.882 and 0.836), COSSH-ACLFs (0.863 and 0.832), CLIF-C ACLF (0.838 and 0.766), MELD (0.782 and 0.762) and MELD-Na (0.756 and 0.731). Dynamic monitoring of the changes in clinical factors can therefore significantly improve the accuracy of scoring models. Evaluation of the probability density function and risk stratification by DSM-ACLF-D3 also resulted in the best predictive values for mortality. The novel DSM-ACLF-D3 prognostic scoring model based on dynamic data can improve early warning, prediction and clinical management of HBV-ACLF patients.


Subject(s)
Acute-On-Chronic Liver Failure , Humans , Male , Female , Prognosis , Acute-On-Chronic Liver Failure/mortality , Acute-On-Chronic Liver Failure/diagnosis , Middle Aged , Adult , Hepatitis B virus , ROC Curve , Hepatitis B/complications , Prospective Studies , Aged
8.
Sci Total Environ ; 946: 174440, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38960182

ABSTRACT

Despite the increasing use of motor vehicles, the impact of airborne pollutants and their health risks inside public transportation, such as commuter buses, is not well understood. This study assessed air quality inside an urban commuter bus by continuously monitoring PM10, PM2.5, and CO concentrations during both driving and parking periods. Our findings revealed that the ventilation system of the bus significantly reduced the infiltration of outdoor particulate matter and water vapor. However, CO concentrations were considerably higher inside the bus than outside, primarily due to vehicular self-emission. The ineffection of the ventilation system to remove CO potentially increases long-term exposure risks for passengers. The study identified ozone as a key oxidant in the cabin. Besides vehicle emissions, C3-C10 saturated aldehydes and carbonyl compounds were detected, including acetone, propanal, and hexanal. The presence of 6-MHO, an oxidation product of squalene, suggests that passengers contribute to VOCs load through direct emissions or skin surface reactions. Additionally, human respiration was found to significantly contribute to isoprene levels, estimated at 81.7 %. This research underscores the need for further investigation into the cumulative effects of stable compounds in cabin air and provides insights for developing healthier public transportation systems.

9.
ACS Nano ; 18(26): 16867-16877, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38952328

ABSTRACT

Suppressing Sn2+ oxidation and rationally controlling the crystallization process of tin-lead perovskite (Sn-Pb PVK) films by suitable bonding methods have emerged as key approaches to achieving efficient and stable Sn-Pb perovskite solar cells (PSCs). Herein, the chelating coordination is performed at the top and bottom interfaces of Sn-Pb PVK films. The chelation strength is stronger toward Sn2+ than Pb2+ by introducing oligomeric proanthocyanidins (OPC) at the bottom interface. This difference in chelation strength resulted in a spontaneous gradient distribution of Sn/Pb within the perovskite layer during crystallization, particularly enhancing the enrichment of Sn2+ at the bottom interface and facilitating the extraction and separation of photogenerated charge carriers in PSCs. Simultaneously, this top-down distribution of gradually increasing Sn content slowed down the crystallization rate of Sn-Pb PVK films, forming higher-quality films. On the top interface of the PVK, trifluoroacetamidine (TFA) was used to inhibit the generation of iodine vacancies (VI) through chelating with surface-uncoordinated Pb2+/Sn2+, further passivating defects while suppressing the oxidation of Sn2+. Ultimately, the PSCs with simultaneous chelation at both top and bottom interfaces achieved a power conversion efficiency (PCE) of 23.31% and an open-circuit voltage (VOC) exceeding 0.90 V. The stability of unencapsulated target devices in different environments also improved.

10.
Heliyon ; 10(12): e33076, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38948034

ABSTRACT

Oresitrophe is monotypic, with the only species, Oresitrophe rupifraga Bunge, which is exclusive to China, having special growth and developmental traits due to its habitat. Furthermore, it has bright flowers and medicinal benefits. This study investigated the metabolites present in various tissues of Oresitrophe rupifraga Bunge. Using a widely targeted metabolomics approach, 1965 different metabolites were identified in Oresitrophe rupifraga Bunge. Based on principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA), the aboveground and underground metabolites of Oresitrophe rupifraga differed significantly. The comparison between bulblets and leaves revealed the differential expression of 461 metabolites, whereas the comparison between rhizomes and leaves showed the differential expression of 423 metabolites, and the comparison between bulblets and rhizomes showed the differential expression of 249 metabolites. The bulblets exhibited 49 metabolites that were higher and 412 metabolites that were lower than those of the leaves, whereas the rhizomes showed 123 upregulated and 300 downregulated metabolites. Bulblets showed an increase in 18 metabolites and a decrease in 231 metabolites compared to the rhizomes. Leaves contain more phenolic acids than the rhizomes and bulblets, whereas the rhizomes and bulblets contain more terpenoids than the leaves. KEGG pathway analysis showed an association between metabolites and metabolic pathways, as well as their effect on the progression and maturation of Oresitrophe rupifraga Bunge. The research findings can provide some insight into the growth and developmental traits of Oresitrophe rupifraga Bunge, thus providing a theoretical foundation for cultivating and utilising this plant.

11.
Front Microbiol ; 15: 1367630, 2024.
Article in English | MEDLINE | ID: mdl-38952444

ABSTRACT

Purpose: To investigate the therapeutic efficiency of a novel drink termed "Ferment" in cases of ulcerative colitis (UC) and its influence on the gut microbiota. Method: In this study, we developed a complex of mixed fruit juice and lactic acid bacteria referred to as Ferment. Ferment was fed to mice for 35 days, before inducing UC with Dextran Sulfate Sodium Salt. We subsequently investigated the gut microbiome composition using 16S rRNA sequencing. Result: After Ferment treatment, mouse body weight increased, and animals displayed less diarrhea, reduced frequency of bloody stools, and reduced inflammation in the colon. Beneficial bacteria belonging to Ileibacterium, Akkermansia, and Prevotellacea were enriched in the gut after Ferment treatment, while detrimental organisms including Erysipelatoclostridium, Dubosiella, and Alistipes were reduced. Conclusion: These data place Ferment as a promising dietary candidate for enhancing immunity and protecting against UC.

12.
Small Methods ; : e2400258, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38962863

ABSTRACT

Nanoengineering polar oxide films have attracted great attention in energy storage due to their high energy density. However, most of them are deposited on thick and rigid substrates, which is not conducive to the integration of capacitors and applications in flexible electronics. Here, an alternative strategy using van der Waals epitaxial oxide dielectrics on ultra-thin flexible mica substrates is developed and increased the disorder within the system through high laser flux. The introduction of defects can efficiently weaken or destroy the long-range ferroelectric ordering, ultimately leading to the emergence of a large numbers of weak-coupling regions. Such polarization configuration ensures fast polarization response and significantly improves energy storage characteristics. A flexible BiFeO3-BaTiO3 (BF-BT) capacitor exhibits a total energy density of 43.5 J cm-3 and an efficiency of 66.7% and maintains good energy storage performance over a wide temperature range (20-200 °C) and under large bending deformation (bending radii ≈ 2 mm). This study provides a feasible approach to improve the energy storage characteristics of dielectric oxide films and paves the way for their practical application in high-energy density capacitors.

13.
Article in Chinese | MEDLINE | ID: mdl-38973048

ABSTRACT

Objective:To investigate the therapeutic effect of ß-tricalcium phosphate in mastoid cavity obliteration for middle ear cholesteatoma under endoscope. Methods:Sixty patients with middle ear cholesteatoma admitted to our department from September 2021 to March 2022 were included in this study. The observation group(n=30) received ß-tricalcium phosphate during mastoid cavity obliteration. The control group(n=30) received autologous tissue during mastoid cavity obliteration. Pure tone audiometry was performed before surgery and after surgery in both groups, and the air conduction thresholds of 500, 1 000, 2 000 and 4 000 Hz were recorded. The external acoustic meatus cross-sectional area within 1 cm of the external acoustic meatus opening was measured during the operation and after the operation. The differences of postoperative ear drying time, hearing change and mastoid cavity healing were compared between the two groups. Results:The duration of postoperative dry ear in the observation group was 2-14 weeks, with an average of (9.4±2.7) weeks, while that in the control group was 4-26 weeks, with an average of(16.0±5.7) weeks. The difference in dry ear time between the two groups was statistically significant(P<0.05). In the observation group, the threshold change was -19-27 dB, with an average of(6.4±10.7) dB, and in the control group, the threshold change was -9-17 dB, with an average of (4.7±7.1) dB. There was no significant difference in hearing change between the two groups(P>0.05). In the observation group, the cross-sectional area of 1 cm inside the ear canal opening was -5.9-8.2 mm², with an average of (-0.6±2.6) mm², and in the control group, the cross-sectional area of 1 cm inside the ear canal opening was -5.5-5.2 mm², with an average of (-0.4±2.3) mm². There was no significant difference in intraoperative cavity changes between the two groups(P>0.05). Conclusion:The application of ß-tricalcium phosphate to fill the mastoid cavity during the operation of endoscopic middle ear cholesteatoma has no adverse effect on the hearing of patients, can shorten the postoperative dry ear time, and results in good postoperative healing, which is worth promoting.


Subject(s)
Calcium Phosphates , Cholesteatoma, Middle Ear , Mastoid , Humans , Calcium Phosphates/therapeutic use , Mastoid/surgery , Cholesteatoma, Middle Ear/surgery , Male , Female , Adult , Endoscopy/methods , Middle Aged , Audiometry, Pure-Tone , Treatment Outcome , Endoscopes
14.
J Nanobiotechnology ; 22(1): 394, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38965594

ABSTRACT

DNA nanostructures have long been developed for biomedical purposes, but their controlled delivery in vivo proposes a major challenge for disease theranostics. We previously reported that DNA nanostructures on the scales of tens and hundreds nanometers showed preferential renal excretion or kidney retention, allowing for sensitive evaluation and effective protection of kidney function, in response to events such as unilateral ureter obstruction or acute kidney injury. Encouraged by the positive results, we redirected our focus to the liver, specifically targeting organs noticeably lacking DNA materials, to explore the interaction between DNA nanostructures and the liver. Through PET imaging, we identified SDF and M13 as DNA nanostructures exhibiting significant accumulation in the liver among numerous candidates. Initially, we investigated and assessed their biodistribution, toxicity, and immunogenicity in healthy mice, establishing the structure-function relationship of DNA nanostructures in the normal murine. Subsequently, we employed a mouse model of liver ischemia-reperfusion injury (IRI) to validate the nano-bio interactions of SDF and M13 under more challenging pathological conditions. M13 not only exacerbated hepatic oxidative injury but also elevated local apoptosis levels. In contrast, SDF demonstrated remarkable ability to scavenge oxidative responses in the liver, thereby mitigating hepatocyte injury. These compelling results underscore the potential of SDF as a promising therapeutic agent for liver-related conditions. This aimed to elucidate their roles and mechanisms in liver injury, providing a new perspective for the biomedical applications of DNA nanostructures.


Subject(s)
DNA , Liver , Nanostructures , Reperfusion Injury , Animals , Reperfusion Injury/drug therapy , Mice , Liver/metabolism , DNA/chemistry , Nanostructures/chemistry , Male , Tissue Distribution , Mice, Inbred C57BL , Apoptosis/drug effects , Oxidative Stress/drug effects
15.
Pharmgenomics Pers Med ; 17: 319-336, 2024.
Article in English | MEDLINE | ID: mdl-38952778

ABSTRACT

Background: Lung cancer is the leading cause of cancer deaths worldwide, primarily due to lung adenocarcinoma (LUAD). However, the heterogeneity of programmed cell death results in varied prognostic and predictive outcomes. This study aimed to develop an LUAD evaluation marker based on cuproptosis-related lncRNAs. Methods: First, transcriptome data and clinical data related to LUAD were downloaded from the Cancer Genome Atlas (TCGA), and cuproptosis-related genes were analyzed to identify cuproptosis-related lncRNAs. Univariate, LASSO, and multivariate Cox regression analyses were conducted to construct cuproptosis-associated lncRNA models. LUAD patients were categorized into high-risk and low-risk groups using prognostic risk values. Kaplan-Meier analysis, PCA, GSEA, and nomograms were employed to evaluate and validate the results. Results: 7 cuproptosis-related lncRNAs were identified, and a risk model was created. High-risk tumors exhibited cuproptosis-related gene alterations in 95.54% of cases, while low-risk tumors showed alterations in 85.65% of cases, mainly involving TP53. The risk value outperformed other clinical variables and tumor mutation burden as a predictor of 1-, 3-, and 5-year overall survival. The cuproptosis-related lncRNA-based risk model demonstrated high validity for LUAD evaluation, potentially influencing individualized treatment approaches. Expression analysis of four candidate cuproptosis-related lncRNAs (AL606834.1, AL161431.1, AC007613.1, and LINC02835) in LUAD tissues and adjacent normal tissues revealed significantly higher expression levels of AL606834.1 and AL161431.1 in LUAD tissues, positively correlating with tumor stage, lymph node metastasis, and histopathological grade. Conversely, AC007613.1 and LINC02835 exhibited lower expression levels, negatively correlating with these factors. High expression of AL606834.1 and AL161431.1 indicated poor prognosis, while low expression of AC007613.1 and LINC02835 was associated with unfavorable outcomes. Univariate and multivariate analyses confirmed these lncRNAs as independent risk factors for LUAD prognosis. Conclusion: The 4 cuproptosis-related (lncRNAsAL606834.1, AL161431.1, AC007613.1, and LINC02835) can accurately predict the prognosis of patients with LUAD and may provide new insights into clinical applications and immunotherapy.

16.
BMC Microbiol ; 24(1): 246, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38970013

ABSTRACT

Previous studies have shown that antimicrobial photodynamic inactivation (aPDI) can be strongly potentiated by the addition of the non-toxic inorganic salt, potassium iodide (KI). This approach was shown to apply to many different photosensitizers, including the xanthene dye Rose Bengal (RB) excited by green light (540 nm). Rose Bengal diacetate (RBDA) is a lipophilic RB derivative that is easily taken up by cells and hydrolyzed to produce an active photosensitizer. Because KI is not taken up by microbial cells, it was of interest to see if aPDI mediated by RBDA could also be potentiated by KI. The addition of 100 mM KI strongly potentiated the killing of Gram-positive methicillin-resistant Staphylocccus aureus, Gram-negative Eschericia coli, and fungal yeast Candida albicans when treated with RBDA (up to 15 µM) for 2 hours followed by green light (540 nm, 10 J/cm2). Both RBDA aPDI regimens (400 µM RBDA with or without 400 mM KI followed by 20 J/cm2 green light) accelerated the healing of MRSA-infected excisional wounds in diabetic mice, without damaging the host tissue.


Subject(s)
Candida albicans , Methicillin-Resistant Staphylococcus aureus , Photosensitizing Agents , Potassium Iodide , Rose Bengal , Staphylococcal Infections , Wound Healing , Animals , Rose Bengal/pharmacology , Methicillin-Resistant Staphylococcus aureus/drug effects , Wound Healing/drug effects , Potassium Iodide/pharmacology , Mice , Candida albicans/drug effects , Photosensitizing Agents/pharmacology , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Escherichia coli/drug effects , Diabetes Mellitus, Experimental/microbiology , Diabetes Mellitus, Experimental/drug therapy , Photochemotherapy/methods , Drug Synergism , Light , Male
17.
Int Med Case Rep J ; 17: 647-650, 2024.
Article in English | MEDLINE | ID: mdl-38974881

ABSTRACT

Neurosyphilis is a central nervous system infection caused by Treponema pallidum that imitates various neurological and mental disorders. Therefore, patients with this disease are prone to misdiagnoses. Here, we report a case of neurosyphilis with a psychotic disorder as the main manifestation. A young girl exhibited mental and behavioural abnormalities after a heartbreak, which manifested as alternating low mood, emotional irritability, and a lack of interest in social relations, followed by memory loss. The cerebrospinal fluid protein - Treponema pallidum particle agglutination test was positive, the toluidine red unheated serum test titre was 1:4, the white blood cell count was 5 × 10^6/L, the cerebrospinal fluid protein level was 0.97 g/L, and the brain CT was abnormal. After admission, the possibility of neurosyphilis was considered and the patient received intravenous penicillin G treatment. The patient's clinical symptom ms improved. This case emphasises that doctors should maintain clinical suspicion of Treponema pallidum infection in adolescent patients with mental abnormalities.

18.
Proc Natl Acad Sci U S A ; 121(30): e2405160121, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-38976765

ABSTRACT

Due to the scarcity of rock samples, the Hadean Era predating 4 billion years ago (Ga) poses challenges in understanding geological processes like subaerial weathering and plate tectonics that are critical for the evolution of life. The Jack Hills zircon from Western Australia, the primary Hadean samples available, offer valuable insights into magma sources and tectonic genesis through trace element signatures. However, a consensus on these signatures has not been reached. To address this, we developed a machine learning classifier capable of deciphering the geochemical fingerprints of zircon. This allowed us to identify the oldest detrital zircon originating from sedimentary-derived "S-type" granites. Our results indicate the presence of S-type granites as early as 4.24 Ga, persisting throughout the Hadean into the Archean. Examining global detrital zircon across Earth's history reveals consistent supercontinent-like cycles from the present back to the Hadean. These findings suggest that a significant amount of Hadean continental crust was exposed, weathered into sediments, and incorporated into the magma sources of Jack Hills zircon. Only the early operation of both subaerial weathering and plate subduction can account for the prevalence of S-type granites we observe. Additionally, the periodic evolution of S-type granite proportions implies that subduction-driven tectonic cycles were active during the Hadean, at least around 4.2 Ga. The evidence thus points toward an early Earth resembling the modern Earth in terms of active tectonics and habitable surface conditions. This suggests the potential for life to originate in environments like warm ponds rather than extreme hydrothermal settings.

19.
Int J Biol Macromol ; : 133715, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38977048

ABSTRACT

The fundamental binding of single-stranded (ssDNA) and double-stranded DNA (dsDNA) with graphene oxide-Ag nanocomposites (GO-AgNCPs) has been systematically investigated by multi spectroscopic methods, i.e. ultraviolet-visible (UV-vis) absorption, fluorescence spectroscopy, and circular dichroism (CD). The experimental and theoretical results demonstrate that both ssDNA and dsDNA can be adsorbed onto the GO-AgNCPs surface. All of the evidence indicated that there were relatively strong binding of ssDNA/dsDNA with GO-AgNCPs. The article compares the differences in binding between the two types of DNA and the nanomaterials using spectroscopic and thermodynamic data. UV-vis absorption spectroscopy experiments indicate that the characteristic absorbance intensity of both ss DNA and ds DNA increases, but the rate of change in absorbance is different. The fluorescence results revealed that ss/dsDNA could interact with the GO-AgNCPs surface, in spite of the different binding affinities. The Ka value of ssDNA binding with GO-AgNCPs is greater than that of dsDNA at each constant temperature, indicating that the affinity of dsDNA toward GO-AgNCPs is comparatively weak. Molecular docking studies have corroborated the mentioned experimental results. The calculated thermodynamic parameters showed that the binding process was thermodynamically spontaneous, van der Waals force and hydrogen bonding played predominant roles in the binding process. The mechanism of ss/ds DNA binding with GO-AgNCPs was also investigated, and the results indicated that GO-AgNCPs directly binds to the minor groove of ss/ds DNA by replacing minor groove binders.

20.
Nat Chem Biol ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38977786

ABSTRACT

Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems are prokaryotic adaptive immune systems against invading phages and other mobile genetic elements. Notably, some phages, including the Vibrio cholerae-infecting ICP1 (International Center for Diarrheal Disease Research, Bangladesh cholera phage 1), harbor CRISPR-Cas systems to counteract host defenses. Nevertheless, ICP1 Cas8f lacks the helical bundle domain essential for recruitment of helicase-nuclease Cas2/3 during target DNA cleavage and how this system accomplishes the interference stage remains unknown. Here, we found that Cas1, a highly conserved component known to exclusively work in the adaptation stage, also mediates the interference stage through connecting Cas2/3 to the DNA-bound CRISPR-associated complex for antiviral defense (Cascade; CRISPR system yersinia, Csy) of the ICP1 CRISPR-Cas system. A series of structures of Csy, Csy-dsDNA (double-stranded DNA), Cas1-Cas2/3 and Csy-dsDNA-Cas1-Cas2/3 complexes reveal the whole process of Cas1-mediated target DNA cleavage by the ICP1 CRISPR-Cas system. Together, these data support an unprecedented model in which Cas1 mediates the interference stage in a phage-encoded CRISPR-Cas system and the study also sheds light on a unique model of primed adaptation.

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