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1.
Nat Chem Biol ; 19(12): 1492-1503, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37500770

ABSTRACT

Enolase 1 (ENO1) is a glycolytic enzyme that plays essential roles in various pathological activities including cancer development. However, the mechanisms underlying ENO1-contributed tumorigenesis are not well explained. Here, we uncover that ENO1, as an RNA-binding protein, binds to the cytosine-uracil-guanine-rich elements of YAP1 messenger RNA to promote its translation. ENO1 and YAP1 positively regulate alternative arachidonic acid (AA) metabolism by inverse regulation of PLCB1 and HPGD (15-hydroxyprostaglandin dehydrogenase). The YAP1/PLCB1/HPGD axis-mediated activation of AA metabolism and subsequent accumulation of prostaglandin E2 (PGE2) are responsible for ENO1-mediated cancer progression, which can be retarded by aspirin. Finally, aberrant activation of ENO1/YAP1/PLCB1 and decreased HPGD expression in clinical hepatocellular carcinoma samples indicate a potential correlation between ENO1-regulated AA metabolism and cancer development. These findings underline a new function of ENO1 in regulating AA metabolism and tumorigenesis, suggesting a therapeutic potential for aspirin in patients with liver cancer with aberrant expression of ENO1 or YAP1.


Subject(s)
Carcinogenesis , Liver Neoplasms , Humans , Arachidonic Acid , Cell Line, Tumor , Cell Proliferation , Carcinogenesis/genetics , Cell Transformation, Neoplastic , Phosphopyruvate Hydratase/genetics , Phosphopyruvate Hydratase/metabolism , Liver Neoplasms/genetics , Aspirin/pharmacology , DNA-Binding Proteins/genetics , Biomarkers, Tumor , Tumor Suppressor Proteins/genetics
2.
FASEB J ; 38(18): e70061, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39305120

ABSTRACT

Indole is a microbial metabolite produced by the gut microbiota through the degradation of dietary tryptophan, known for its well-established anti-inflammatory and antioxidant properties. In this study, we collected fecal samples from mice fed a high-fat diet (HFD) and those on a standard diet (SD), then conducted 16S rRNA sequencing to analyze their gut microbiota. The analysis revealed distinct differences in the dominant bacterial species between the two groups, with a significant decrease in indole-producing probiotics in the HFD mice compared to the SD group. Then we administered oral indole treatment to male C57BL/6J mice with HFD-induced NAFLD and observed a significant improvement in hepatic steatosis and inflammation. Notably, indole alleviated the HFD-induced decline in serum Angiotensin-(1-7) [Ang-(1-7)] levels and Angiotensin-Converting Enzyme 2 (ACE2) expression. To further investigate the role of indole and ACE2 in NAFLD, we conducted experiments using ACE2 knockout (ACE2KO) mice that were also induced with HFD-induced NAFLD and treated with indole. Interestingly, the protective effects of indole were compromised in the absence of ACE2. In HepG2 cells, indole similarly stimulated ACE2 expression and, in an ACE2-dependent manner, reduced ROS generation, maintained mitochondrial membrane potential stability, and increased SIRT3 expression. In summary, our results highlight the formation of a biologically active gut-liver axis between the gut microbiota and the liver through the tryptophan metabolite indole, which mitigates NAFLD in an ACE2-dependent manner. Elevating dietary tryptophan and increasing indole levels may represent an effective approach for preventing and treating NAFLD.


Subject(s)
Angiotensin-Converting Enzyme 2 , Diet, High-Fat , Gastrointestinal Microbiome , Indoles , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/drug therapy , Animals , Angiotensin-Converting Enzyme 2/metabolism , Angiotensin-Converting Enzyme 2/genetics , Mice , Male , Indoles/pharmacology , Gastrointestinal Microbiome/drug effects , Humans , Diet, High-Fat/adverse effects , Mice, Knockout , Liver/metabolism , Liver/drug effects , Peptide Fragments/metabolism , Angiotensin I
3.
Crit Rev Immunol ; 44(4): 79-89, 2024.
Article in English | MEDLINE | ID: mdl-38505923

ABSTRACT

Community-acquired pneumonia (CAP) is a leading cause of hospitalization and mortality in the elderly. The peripheral blood neutrophil CD64 (nCD64) index is increasingly recognized for its association with poor pneumonia prognosis. A comprehensive investigation involving 128 elderly patients diagnosed with CAP, including 96 with non-severe CAP and 32 with severe CAP, from January 2020 to January 2021 was performed. The nCD64 index, CD4+, CD8+, C-reactive protein (CRP), white blood cell (WBC) count, procalcitonin (PCT), neutrophil (NEUT), and B lymphocyte count were determined using flow cytometry. Our findings reveal that patients with severe CAP exhibited significantly higher levels of nCD64 index, NEUT, WBC, CRP, and PCT. Intriguingly, lower CRP, nCD64 index, CURB-65 score, and PCT were associated with a higher survival rate. Notably, the nCD64 index demonstrated remarkable predictive efficiency for 28-d survival in CAP patients [area under the curve (AUC) = 0.907], surpassing other markers and even showing enhanced predictive power when combined with the CURB-65 score (AUC = 0.905). Furthermore, a negative association was observed between the nCD64 index and both CD4+, CD4+/CD8+ ratios, and B lymphocytes, highlighting its potential role in immune dysregulation. These findings underscore the critical importance of the nCD64 index in the early diagnosis, risk stratification, and prognostic evaluation of infections and immune responses in elderly CAP patients.


Subject(s)
Community-Acquired Infections , Pneumonia , Humans , Aged , Prognosis , Neutrophils , C-Reactive Protein/analysis , Pneumonia/diagnosis , Leukocyte Count , Community-Acquired Infections/diagnosis
4.
Stroke ; 55(1): 92-100, 2024 01.
Article in English | MEDLINE | ID: mdl-38018834

ABSTRACT

BACKGROUND: Both genetic factors and environmental air pollution contribute to the risk of stroke. However, it is unknown whether the association between air pollution and stroke risk is influenced by the genetic susceptibilities of stroke and its risk factors. METHODS: This prospective cohort study included 40 827 Chinese adults without stroke history. Satellite-based monthly fine particulate matter (PM2.5) estimation at 1-km resolution was used for exposure assessment. Based on 534 identified genetic variants from genome-wide association studies in East Asians, we constructed 6 polygenic risk scores for stroke and its risk factors, including atrial fibrillation, blood pressure, type 2 diabetes, body mass index, and triglyceride. The Cox proportional hazards model was applied to evaluate the hazard ratios and 95% CIs for the associations of PM2.5 and polygenic risk score with incident stroke and the potential effect modifications. RESULTS: Over a median follow-up of 12.06 years, 3147 incident stroke cases were documented. Compared with the lowest quartile of PM2.5 exposure, the hazard ratio (95% CI) for stroke in the highest quartile group was 2.72 (2.42-3.06). Among individuals at high genetic risk, the relative risk of stroke was 57% (1.57; 1.40-1.76) higher than those at low genetic risk. Although no statistically significant interaction was found, participants with both the highest PM2.5 and high genetic risk showed the highest risk of stroke, with ≈4× that of the lowest PM2.5 and low genetic risk group (hazard ratio, 3.55 [95% CI, 2.84-4.44]). Similar upward gradients were observed in the risk of stroke when assessing the joint effects of PM2.5 and genetic risks of blood pressure, type 2 diabetes, body mass index, atrial fibrillation, and triglyceride. CONCLUSIONS: Long-term exposure to PM2.5 was associated with a higher risk of incident stroke across different genetic susceptibilities. Our findings highlighted the great importance of comprehensive assessment of air pollution and genetic risk in the prevention of stroke.


Subject(s)
Air Pollutants , Air Pollution , Atrial Fibrillation , Diabetes Mellitus, Type 2 , Stroke , Adult , Humans , Particulate Matter/adverse effects , Particulate Matter/analysis , Prospective Studies , Atrial Fibrillation/complications , Genome-Wide Association Study , Environmental Exposure/adverse effects , Incidence , Stroke/epidemiology , Stroke/genetics , Stroke/chemically induced , Air Pollution/adverse effects , Risk Factors , Genetic Predisposition to Disease , Triglycerides , Air Pollutants/adverse effects
5.
Stroke ; 55(8): 2066-2074, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39038095

ABSTRACT

BACKGROUND: Previous studies focusing on assessing the effects of remnant cholesterol (RC) and low-density lipoprotein cholesterol (LDL-C) on stroke may not consider their mutual influence. We aimed to explore the associations of RC and discordant high RC with LDL-C with stroke, ischemic stroke (IS), and hemorrhagic stroke. METHODS: This prospective cohort study was conducted based on 3 cohorts of the China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) project. RC was calculated as non-high-density lipoprotein cholesterol minus LDL-C estimated by Martin/Hopkins equations. Concordant/discordant categories for RC versus LDL-C were determined based on cut-points of 130 mg/dL for LDL-C and equivalent percentile (32.50 mg/dL) for RC. Cox models were used to estimate adjusted hazard ratios and 95% CIs for incident stroke. RESULTS: Among 113 448 participants recruited at baseline, a total of 98 967 participants were eligible for the final analysis (mean age of 51.44 years; 40.45% were men). During 728 776.87 person-years of follow-up, 2859 stroke cases, 1811 IS cases, and 849 hemorrhagic stroke cases were observed. RC was positively associated with stroke and IS, but not hemorrhagic stroke, with adjusted hazard ratios (95% CIs) of 1.06 (1.02-1.10), 1.09 (1.04-1.13), and 0.95 (0.88-1.03) for per SD increase in RC. Compared with low LDL-C/low RC group, low LDL-C/high RC group had higher risks of stroke (adjusted hazard ratio, 1.15 [95% CI, 1.02-1.30]) and IS (1.19, 1.03-1.38), while high LDL-C/low RC group had no increased risk of stroke (1.07 [0.95-1.20]) and IS (1.09 [0.94-1.25]). CONCLUSIONS: Higher RC was associated with increased risks of stroke and IS but not hemorrhagic stroke. Discordantly high RC, not discordantly high LDL-C, conferred higher risks of stroke and IS. Our findings support further lowering RC by interventions to reduce residual IS risk.


Subject(s)
Cholesterol, LDL , Cholesterol , Stroke , Humans , Male , Middle Aged , Female , Cholesterol, LDL/blood , Prospective Studies , China/epidemiology , Stroke/epidemiology , Stroke/blood , Cholesterol/blood , Adult , Risk Factors , Cohort Studies , Aged , Ischemic Stroke/epidemiology , Ischemic Stroke/blood , Hemorrhagic Stroke/epidemiology , Hemorrhagic Stroke/blood , Triglycerides/blood , East Asian People
6.
J Am Chem Soc ; 146(1): 1185-1195, 2024 01 10.
Article in English | MEDLINE | ID: mdl-38148611

ABSTRACT

Patients treated with Pt-based anticancer drugs (PtII) often experience severe side effects and are susceptible to cancer recurrence due to the limited bioavailability of PtII and tumor-induced immunosuppression. The exposure of phosphatidylserine on the cell's outer surface induced by PtII results in profound immunosuppression through the binding of phosphatidylserine to its receptors on immune cells. Here, we report a novel approach for enhanced cancer chemoimmunotherapy, where a novel nuclear-targeting lipid PtIV prodrug amphiphile was used to deliver a small interfering RNA (siXkr8) to simultaneously amplify Pt-DNA adducts and reduce the level of exposure of phosphatidylserine. This drug delivery vehicle is engineered by integrating the PtIV prodrug with self-assembly performance and siXkr8 into a lipid nanoparticle, which shows tumor accumulation, cancer cell nucleus targeting, and activatable in a reduced microenvironment. It is demonstrated that nuclear-targeting lipid PtIV prodrug increases the DNA cross-linking, resulting in increased Pt-DNA adduct formation. The synergistic effects of the PtIV prodrug and siXkr8 contribute to the improvement of the tumor immune microenvironment. Consequently, the increased Pt-DNA adducts and immunogenicity effectively inhibit primary tumor growth and prevent tumor recurrence. These results underscore the potential of utilizing the nuclear-targeting lipid PtIV prodrug amphiphile to enhance Pt-DNA adduct formation and employing siXkr8 to alleviate immunosuppression during chemotherapy.


Subject(s)
Antineoplastic Agents , Neoplasms , Prodrugs , Humans , Prodrugs/pharmacology , DNA Adducts , Phosphatidylserines , RNA, Small Interfering , Antineoplastic Agents/pharmacology , Neoplasms/drug therapy , RNA, Double-Stranded , Cell Line, Tumor , Cisplatin , Tumor Microenvironment
7.
Anal Chem ; 96(36): 14560-14570, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39197159

ABSTRACT

Deep vein thrombosis (DVT) is a serious health issue that often leads to considerable morbidity and mortality. Diagnosis of DVT in a clinical setting, however, presents considerable challenges. The fusion of metabolomics techniques and machine learning methods has led to high diagnostic and prognostic accuracy for various pathological conditions. This study explored the synergistic potential of dual-platform metabolomics (specifically, gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS)) to expand the detection of metabolites and improve the precision of DVT diagnosis. Sixty-one differential metabolites were identified in serum from DVT patients: 22 from GC-MS and 39 from LC-MS. Among these, five key metabolites were highlighted by SHapley Additive exPlanations (SHAP)-guided feature engineering and then used to develop a stacking diagnostic model. Additionally, a user-friendly interface application system was developed to streamline and automate the application of the diagnostic model, enhancing its practicality and accessibility for clinical use. This work showed that the integration of dual-platform metabolomics with a stacking machine learning model enables faster and more accurate diagnosis of DVT in clinical environments.


Subject(s)
Machine Learning , Metabolomics , Venous Thrombosis , Humans , Venous Thrombosis/diagnosis , Venous Thrombosis/metabolism , Venous Thrombosis/blood , Metabolomics/methods , Gas Chromatography-Mass Spectrometry , Chromatography, Liquid , Male , Middle Aged , Female
8.
Small ; : e2405992, 2024 Sep 26.
Article in English | MEDLINE | ID: mdl-39324289

ABSTRACT

Tribovoltaic nanogenerator (TVNG) is an emerging energy device with the advantages of direct current and high power density. At present, many TVNGs are based on single-crystal materials, which are expensive and fragile during structural processing. Here, a polysilicon-based TVNG for bearing in situ rotational speed sensing is developed, which has the same level of performance and lower cost compared to monocrystalline silicon. The defects in polysilicon can provide additional carriers, but the grain boundaries can suppress the transport process of carriers, resulting in almost the same electrical output as single crystals. The oiled sliding mode TVNG has an impressive durability of up to 1 million cycles. The friction coefficient of rolling mode TVNG is as low as 0.14. Based on rolling mode polysilicon TVNG, the tapered roller bearing, thrust ball bearing, and deep groove ball bearing are manufactured by cutting and engraving processes. Moreover, their short-circuit current and open-circuit voltage are linear with speed, and the fitting coefficient is as high as 0.99, providing favorable conditions for in situ rotational speed sensing. This work presents a structure-function integrated bearing design methodology, demonstrating the considerable potential of in situ sensing for intelligent components in the industrial Internet of Things.

9.
Plant Biotechnol J ; 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38861663

ABSTRACT

The length of hypocotyl affects the height of soybean and lodging resistance, thus determining the final grain yield. However, research on soybean hypocotyl length is scarce, and the regulatory mechanisms are not fully understood. Here, we identified a module controlling the transport of sucrose, where sucrose acts as a messenger moved from cotyledon to hypocotyl, regulating hypocotyl elongation. This module comprises four key genes, namely MYB33, SWEET11, SWEET21 and GA2ox8c in soybean. In cotyledon, MYB33 is responsive to sucrose and promotes the expression of SWEET11 and SWEET21, thereby facilitating sucrose transport from the cotyledon to the hypocotyl. Subsequently, sucrose transported from the cotyledon up-regulates the expression of GA2ox8c in the hypocotyl, which ultimately affects the length of the hypocotyl. During the domestication and improvement of soybean, an allele of MYB33 with enhanced abilities to promote SWEET11 and SWEET21 has gradually become enriched in landraces and cultivated varieties, SWEET11 and SWEET21 exhibit high conservation and have undergone a strong purified selection and GA2ox8c is under a strong artificial selection. Our findings identify a new molecular pathway in controlling soybean hypocotyl elongation and provide new insights into the molecular mechanism of sugar transport in soybean.

10.
Opt Express ; 32(2): 1246-1256, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38297680

ABSTRACT

Optical zoom is an essential function for many imaging systems including consumer electronics, biomedical microscopes, telescopes, and projectors. However, most optical zoom imaging systems have discrete zoom rates or narrow zoom ranges. In this work, a continuous optical zoom imaging system with a wide zoom range is proposed. It consists of a solid lens, two Alvarez lenses, and a camera with an objective. Each Alvarez lens is composed of two cubic phase plates, which have inverted freeform surfaces concerning each other. The movement of the cubic phase masks perpendicular to the optical axis is realized by the actuation of the dielectric elastomer. By applying actuation voltages to the dielectric elastomer, cubic phase masks are moved laterally and then the focal lengths of the two Alvarez lenses are changed. By adjusting the focal lengths of these two Alvarez lenses, the optical magnification is tuned. The proposed continuous optical zoom imaging system is built and the validity is verified by the experiments. The experimental results demonstrate that the zoom ratio is up to 10×, i.e., the magnification continuously changes from 1.58× to 15.80× when the lateral displacements of the cubic phase masks are about 1.0 mm. The rise and fall response times are 150 ms and 210 ms, respectively. The imaging resolution can reach 114 lp/mm during the optical zoom process. The proposed continuous optical imaging system is expected to be used in the fields of microscopy, biomedicine, virtual reality, etc.

11.
Opt Express ; 32(5): 7119-7135, 2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38439401

ABSTRACT

Ghost imaging (GI) has been widely used in the applications including spectral imaging, 3D imaging, and other fields due to its advantages of broad spectrum and anti-interference. Nevertheless, the restricted sampling efficiency of ghost imaging has impeded its extensive application. In this work, we propose a novel foveated pattern affine transformer method based on deep learning for efficient GI. This method enables adaptive selection of the region of interest (ROI) by combining the proposed retina affine transformer (RAT) network with minimal computational and parametric quantities with the foveated speckle pattern. For single-target and multi-target scenarios, we propose RAT and RNN-RAT (recurrent neural network), respectively. The RAT network enables an adaptive alteration of the fovea of the variable foveated patterns spot to different sizes and positions of the target by predicting the affine matrix with a minor number of parameters for efficient GI. In addition, we integrate a recurrent neural network into the proposed RAT to form an RNN-RAT model, which is capable of performing multi-target ROI detection. Simulations and experimental results show that the method can achieve ROI localization and pattern generation in 0.358 ms, which is a 1 × 105 efficiency improvement compared with the previous methods and improving the image quality of ROI by more than 4 dB. This approach not only improves its overall applicability but also enhances the reconstruction quality of ROI. This creates additional opportunities for real-time GI.

12.
J Exp Bot ; 75(13): 4038-4051, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38490694

ABSTRACT

Chilling stress caused by extreme weather is threatening global rice (Oryza sativa L.) production. Identifying components of the signal transduction pathways underlying chilling tolerance in rice would advance molecular breeding. Here, we report that OsMST6, which encodes a monosaccharide transporter, positively regulates the chilling tolerance of rice seedlings. mst6 mutants showed hypersensitivity to chilling, while OsMST6 overexpression lines were tolerant. During chilling stress, OsMST6 transported more glucose into cells to modulate sugar and abscisic acid signaling pathways. We showed that the transcription factor OsERF120 could bind to the DRE/CRT element of the OsMST6 promoter and activate the expression of OsMST6 to positively regulate chilling tolerance. Genetically, OsERF120 was functionally dependent on OsMST6 when promoting chilling tolerance. In summary, OsERF120 and OsMST6 form a new downstream chilling regulatory pathway in rice in response to chilling stress, providing valuable findings for molecular breeding aimed at achieving global food security.


Subject(s)
Cold Temperature , Monosaccharide Transport Proteins , Oryza , Plant Proteins , Seedlings , Transcription Factors , Oryza/genetics , Oryza/metabolism , Oryza/physiology , Plant Proteins/metabolism , Plant Proteins/genetics , Seedlings/physiology , Seedlings/genetics , Seedlings/metabolism , Monosaccharide Transport Proteins/metabolism , Monosaccharide Transport Proteins/genetics , Transcription Factors/metabolism , Transcription Factors/genetics , Gene Expression Regulation, Plant
13.
Opt Lett ; 49(18): 5296-5299, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39270289

ABSTRACT

Computational ghost imaging (CGI) allows two-dimensional (2D) imaging by using spatial light modulators and bucket detectors. However, most CGI methods attempt to obtain 2D images through measurements with a single sampling ratio. Here, we propose a CGI method enhanced by degradation models for under-sampling, which can be reflected by results from measurements with different sampling ratios. We utilize results from low-sampling-ratio measurements and normal-sampling-ratio measurements to train the neural network for the degradation model, which is fitted through self-supervised learning. We obtain final results by importing normal-sampling-ratio results into the neural network with optimal parameters. We experimentally demonstrate improved results from the CGI method using degradation models for under-sampling. Our proposed method would promote the development of CGI in many applications.

14.
Respir Res ; 25(1): 217, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38783236

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic interstitial lung disease characterized by progressive dyspnea and decreased lung function, yet its exact etiology remains unclear. It is of great significance to discover new drug targets for IPF. METHODS: We obtained the cis-expression quantitative trait locus (cis-eQTL) of druggable genes from eQTLGen Consortium as exposure and the genome wide association study (GWAS) of IPF from the International IPF Genetics Consortium as outcomes to simulate the effects of drugs on IPF by employing mendelian randomization analysis. Then colocalization analysis was performed to calculate the probability of both cis-eQTL of druggable genes and IPF sharing a causal variant. For further validation, we conducted protein quantitative trait locus (pQTL) analysis to reaffirm our findings. RESULTS: The expression of 45 druggable genes was significantly associated with IPF susceptibility at FDR < 0.05. The expression of 23 and 15 druggable genes was significantly associated with decreased forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLco) in IPF patients, respectively. IPF susceptibility and two significant genes (IL-7 and ABCB2) were likely to share a causal variant. The results of the pQTL analysis demonstrated that high levels of IL-7 in plasma are associated with a reduced risk of IPF (OR = 0.67, 95%CI: 0.47-0.97). CONCLUSION: IL-7 stands out as the most promising potential drug target to mitigate the risk of IPF. Our study not only sheds light on potential drug targets but also provides a direction for future drug development in IPF.


Subject(s)
Genome-Wide Association Study , Idiopathic Pulmonary Fibrosis , Mendelian Randomization Analysis , Humans , Idiopathic Pulmonary Fibrosis/genetics , Idiopathic Pulmonary Fibrosis/drug therapy , Idiopathic Pulmonary Fibrosis/diagnosis , Mendelian Randomization Analysis/methods , Genome-Wide Association Study/methods , Quantitative Trait Loci , Genetic Predisposition to Disease , Female , Molecular Targeted Therapy/methods , Male
15.
Int J Legal Med ; 138(1): 197-206, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37804331

ABSTRACT

Given that combination with multiple biomarkers may well raise the predictive value of wound age, it appears critically essential to identify new features under the limited cost. For this purpose, the present study explored whether the gene expression ratios provide unique time information as an additional indicator for wound age estimation not requiring the detection of new biomarkers and allowing full use of the available data. The expression levels of four wound-healing genes (Arid5a, Ier3, Stom, and Lcp1) were detected by real-time polymerase chain reaction, and a total of six expression ratios were calculated among these four genes. The results showed that the expression levels of four genes and six ratios of expression changed time-dependent during wound repair. The six expression ratios provided additional temporal information, distinct from the four genes analyzed separately by principal component analysis. The overall performance metrics for cross-validation and external validation of four typical prediction models were improved when six ratios of expression were added as additional input variables. Overall, expression ratios among genes provide temporal information and have excellent potential as predictive markers for wound age estimation. Combining the expression levels of genes with ratio-expression of genes may allow for more accurate estimates of the time of injury.


Subject(s)
Contusions , Rats , Animals , Humans , Rats, Sprague-Dawley , Contusions/genetics , Contusions/metabolism , Muscle, Skeletal/metabolism , Wound Healing/genetics , Biomarkers/metabolism
16.
Int J Legal Med ; 138(4): 1629-1644, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38532207

ABSTRACT

The present study is aimed to address the challenge of wound age estimation in forensic science by identifying reliable genetic markers using low-cost and high-precision second-generation sequencing technology. A total of 54 Sprague-Dawley rats were randomly assigned to a control group or injury groups, with injury groups being further divided into time points (4 h, 8 h, 12 h, 16 h, 20 h, 24 h, 28 h, and 32 h after injury, n = 6) to establish rat skeletal muscle contusion models. Gene expression data were obtained using second-generation sequencing technology, and differential gene expression analysis, weighted gene co-expression network analysis (WGCNA) and time-dependent expression trend analysis were performed. A total of six sets of biomarkers were obtained: differentially expressed genes at adjacent time points (127 genes), co-expressed genes most associated with wound age (213 genes), hub genes exhibiting time-dependent expression (264 genes), and sets of transcription factors (TF) corresponding to the above sets of genes (74, 87, and 99 genes, respectively). Then, random forest (RF), support vector machine (SVM) and multilayer perceptron (MLP), were constructed for wound age estimation from the above gene sets. The results estimated by transcription factors were all superior to the corresponding hub genes, with the transcription factor group of WGCNA performed the best, with average accuracy rates of 96% for three models' internal testing, and 91.7% for the highest external validation. This study demonstrates the advantages of the indicator screening system based on second-generation sequencing technology and transcription factor level for wound age estimation.


Subject(s)
Contusions , Muscle, Skeletal , Rats, Sprague-Dawley , Animals , Muscle, Skeletal/injuries , Muscle, Skeletal/metabolism , Contusions/genetics , Time Factors , Support Vector Machine , High-Throughput Nucleotide Sequencing , Rats , Gene Expression Profiling , Genetic Markers , Male , Forensic Genetics/methods
17.
Environ Sci Technol ; 58(26): 11649-11660, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38872439

ABSTRACT

Brominated byproducts and toxicity generation are critical issues for ozone application to wastewater containing bromide. This study demonstrated that ultraviolet/ozone (UV/O3, 100 mJ/cm2, 1 mg-O3/mg-DOC) reduced the cytotoxicity of wastewater from 14.2 mg of pentol/L produced by ozonation to 4.3 mg of pentol/L (1 mg/L bromide, pH 7.0). The genotoxicity was also reduced from 1.65 to 0.17 µg-4-NQO/L by UV/O3. Compared with that of O3 alone, adsorbable organic bromine was reduced from 25.8 to 5.3 µg/L by UV/O3, but bromate increased from 32.9 to 71.4 µg/L. The UV/O3 process enhanced the removal of pre-existing precursors (highly unsaturated and phenolic compounds and poly aromatic hydrocarbons), while new precursors were generated, yet the combined effect of UV/O3 on precursors did not result in a significant change in toxicity. Instead, UV radiation inhibited HOBr concentration through both rapid O3 decomposition to reduce HOBr production and decomposition of the formed HOBr, thus suppressing the AOBr formation. However, the hydroxyl radical-dominated pathway in UV/O3 led to a significant increase of bromate. Considering both organic bromine and bromate, the UV/O3 process effectively controlled both cytotoxicity and genotoxicity of wastewater to mammalian cells, even though an emphasis should be also placed on managing elevated bromate. Futhermore, other end points are needed to evaluate the toxicity outcomes of the UV/O3 process.


Subject(s)
Bromine , Wastewater , Bromine/chemistry , Bromine/toxicity , Bromates/chemistry , Photochemical Processes , Ultraviolet Rays , Ozone/chemistry , Water Purification/methods , Wastewater/toxicity , Mammals , Animals , CHO Cells , Cricetulus
18.
Acta Pharmacol Sin ; 45(8): 1715-1726, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38684798

ABSTRACT

Colorectal cancer (CRC) is a prevalent form of gastrointestinal malignancy with challenges in chemotherapy resistance and side effects. Effective and low toxic drugs for CRC treatment are urgently needed. Ferroptosis is a novel mode of cell death, which has garnered attention for its therapeutic potential against cancer. Baicalein (5, 6, 7-trihydroxyflavone) is the primary flavone extracted from the dried roots of Scutellaria baicalensis that exhibits anticancer effects against several malignancies including CRC. In this study, we investigated whether baicalein induced ferroptosis in CRC cells. We showed that baicalein (1-64 µM) dose-dependently inhibited the viability of human CRC lines HCT116 and DLD1. Co-treatment with the ferroptosis inhibitor liproxstatin-1 (1 µM) significantly mitigated baicalein-induced CRC cell death, whereas autophagy inhibitor chloroquine (25 µM), necroptosis inhibitor necrostatin-1 (10 µM), or pan-caspase inhibitor Z-VAD-FMK (10 µM) did not rescue baicalein-induced CRC cell death. RNA-seq analysis confirmed that the inhibitory effect of baicalein on CRC cells is associated with ferroptosis induction. We revealed that baicalein (7.5-30 µM) dose-dependently decreased the expression levels of GPX4, key regulator of ferroptosis, in HCT116 and DLD1 cells by blocking janus kinase 2 (JAK2)/STAT3 signaling pathway via direct interaction with JAK2, ultimately leading to ferroptosis in CRC cells. In a CRC xenograft mouse model, administration of baicalein (10, 20 mg/kg, i.g., every two days for two weeks) dose-dependently inhibited the tumor growth with significant ferroptosis induced by inhibiting the JAK2/STAT3/GPX4 axis in tumor tissue. This study demonstrates that ferroptosis contributes to baicalein-induced anti-CRC activity through blockade of the JAK2/STAT3/GPX4 signaling pathway, which provides evidence for the therapeutic application of baicalein against CRC.


Subject(s)
Colorectal Neoplasms , Ferroptosis , Flavanones , Janus Kinase 2 , Phospholipid Hydroperoxide Glutathione Peroxidase , STAT3 Transcription Factor , Flavanones/pharmacology , Flavanones/therapeutic use , Humans , Ferroptosis/drug effects , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , STAT3 Transcription Factor/metabolism , STAT3 Transcription Factor/antagonists & inhibitors , Animals , Janus Kinase 2/metabolism , Janus Kinase 2/antagonists & inhibitors , Mice , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , Phospholipid Hydroperoxide Glutathione Peroxidase/antagonists & inhibitors , Mice, Nude , Mice, Inbred BALB C , Signal Transduction/drug effects , Cell Line, Tumor , HCT116 Cells , Xenograft Model Antitumor Assays , Cell Survival/drug effects , Dose-Response Relationship, Drug
19.
Support Care Cancer ; 32(10): 653, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39259369

ABSTRACT

OBJECTIVE: To evaluate the application of a rehabilitation management protocol for urinary incontinence after robot-assisted laparoscopic prostatectomy (RALP). METHODS: We conducted a retrospective cohort study of 114 patients who underwent RALP between August 2021 and November 2021 as the control group and a prospective analysis of 114 patients who underwent RALP between May 2022 and August 2022 as the experimental group. The rehabilitation management protocol focused on preoperative stage, postoperative care, day of catheter removal, 1 month postoperative, 3 months postoperative, 6 months postoperative, and 12 months or more postoperative. RESULTS: The 24-h pad test was significantly lower in the experimental group compared with the control group at 2 and 6 months after RALP (both P < 0.01). The scores of the international consultation on incontinence questionnaire-short form (ICIQ-SF) in the experimental group were significantly lower than those in the control group at 1 month after RALP (P < 0.01).The scores of quality of life in the experimental group were significantly higher than those of the control group at 1, 2, and 6 months after RALP (all P < 0.01).The scores of Broome Pelvic Muscle Self-efficacy Scale (BPMSES) were lower than those of the control group at 1, 2, 3, and 6 months after RALP (all P < 0.01). CONCLUSION: The application of the rehabilitation management protocol had significant beneficial effects on urinary functions and quality of life in patients with prostate cancer after RALP.


Subject(s)
Laparoscopy , Prostatectomy , Prostatic Neoplasms , Quality of Life , Robotic Surgical Procedures , Urinary Incontinence , Humans , Male , Prostatectomy/adverse effects , Prostatectomy/methods , Prostatectomy/rehabilitation , Urinary Incontinence/etiology , Urinary Incontinence/rehabilitation , Middle Aged , Retrospective Studies , Robotic Surgical Procedures/methods , Robotic Surgical Procedures/adverse effects , Laparoscopy/methods , Laparoscopy/adverse effects , Aged , Prospective Studies , Prostatic Neoplasms/surgery , Prostatic Neoplasms/rehabilitation , Surveys and Questionnaires , Postoperative Complications/etiology , Postoperative Complications/rehabilitation , Treatment Outcome
20.
Network ; : 1-29, 2024 Mar 03.
Article in English | MEDLINE | ID: mdl-38433470

ABSTRACT

As the number of patients increases, physicians are dealing with more and more cases of degenerative spine pathologies on a daily basis. To reduce the workload of healthcare professionals, we propose a modified Swin-UNet network model. Firstly, the Swin Transformer Blocks are improved using a residual post-normalization and scaling cosine attention mechanism, which makes the training process of the model more stable and improves the accuracy. Secondly, we use the log-space continuous position biasing method instead of the bicubic interpolation position biasing method. This method solves the problem of performance loss caused by the large difference between the resolution of the pretraining image and the resolution of the spine image. Finally, we introduce a segmentation smooth module (SSM) at the decoder stage. The SSM effectively reduces redundancy, and enhances the segmentation edge processing to improve the model's segmentation accuracy. To validate the proposed method, we conducted experiments on a real dataset provided by hospitals. The average segmentation accuracy is no less than 95%. The experimental results demonstrate the superiority of the proposed method over the original model and other models of the same type in segmenting the spinous processes of the vertebrae and the posterior arch of the spine.

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