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Many diseases are associated with genetic mutation and expression of mutated proteins, such as cancers. Therapeutic approaches that selectively target the synthesis process of multiple proteins show greater potential compared to single-protein approaches in oncological diseases. However, conventional agents to regulate the synthesis of multiple protein still suffer from poor spatiotemporal selectivity and stability. Here, a new method using a dye-peptide conjugate, PRFK, for multi-protein interference with spatiotemporal selectivity and reliable stability, is reported. By using the peptide sequence that targets tumor cells, PRFK can be efficiently taken up, followed by specific binding to the KDELR (KDEL receptor) protein located in the endoplasmic reticulum (ER). The dye generates 1O2 under light irradiation, enabling photodynamic therapy. This process converts the furan group into a cytidine-reactive intermediate, which covalently binds to mRNA, thereby blocking protein synthesis. Upon treating 4T1 cells, the proteomics data show alterations in apoptosis, ferroptosis, proliferation, migration, invasion, and immune infiltration, suggesting that multi-protein interference leads to the disruption of cellular physiological activities, ultimately achieving tumor treatment. This study presents a multi-protein interference probe with the potential for protein interference within various subcellular organelles in the future.
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Intelligent food packaging has recently gained significant attention due to the heightened consumer awareness regarding food quality. Although anthocyanins avoid safety issues, the instability and leakage of anthocyanins restrict their utilization in freshness indicator labels. In this study, we introduced an innovative metal-organic framework (UiO-66-NH2) synergistic pH-colorimetric label with fast ammonia-responsive, incorporating sodium alginate, red cabbage anthocyanin, and UiO-66-NH2. The cross-linked sodium alginate substrate enabled the label to possess superior insolubility. The microscopic morphology of the labels was intricately analyzed, while their sensitivity was rigorously tested utilizing ammonia as a representative gas. Due to the remarkable UV absorption capability of UiO-66-NH2 and various molecular interactions with anthocyanins, the label exhibited good UV absorption, enhanced stability, and optimized performance in reducing anthocyanin leakage, ensuring the stability and effectiveness of the labels in practical applications. The prepared label exhibited good specificity for volatile amines and ammonia gases, and robust anti-interference properties, enabling visualization and early detection of shrimp spoilage during storage at different temperatures. The strategy employed in this study presents promising new possibilities for developing intelligent packaging solutions for food products.
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Objectives: To assess the effectiveness of auricular acupressure (AA) in managing pain and disability in individuals with chronic musculoskeletal pain. Materials and Methods: A systematic search on six electronic databases was performed from their inception to May 7, 2023, to identified relevant randomized controlled trials (RCTs). Two independent reviewers screened the abstracts and full texts, extracted data, and assessed risk of bias using RoB 2. The primary outcomes were pain intensity and disability. The secondary outcomes were pain pressure thresholds, pain catastrophizing level, and fear avoidance beliefs. A random-effects model was used for meta-analyses. The certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation. Sensitivity analyses were conducted after removing low-quality papers. Results: Of 633 identified records, six studies involving 496 participants were included. All included studies compared the effectiveness of AA with sham controls in treating various chronic musculoskeletal pain. Four meta-analyses were conducted to compare the effectiveness of AA with sham controls. Low-quality evidence supported that AA had a large effect size on postintervention subjective pain reduction (standardized mean difference [SMD] = -0.95; 95% confidence interval [CI]: -1.36 to -0.54; p = 0.00; I2 = 52.61%); moderate-quality evidence substantiated that AA had a large effect size on enhancing postintervention pressure pain threshold (SMD = -0.55; 95% CI: -0.88 to -0.23; p = 0.00; I2 = 0%). There was low-quality evidence that AA had a large effect on reducing postintervention disability (SMD = -0.68; 95% CI: -1.24 to -0.12; p = 0.02; I2 = 51.33%). Our sensitivity analysis reaffirmed the same conclusion regarding pain reduction immediately after the intervention. Fourteen participants reported minimal adverse events, including soreness, tenderness, irritation, and redness, which disappeared within 1-7 days. Discussion: Our systematic review revealed that AA significantly improved pain, pressure pain thresholds, and disability in individuals with various chronic musculoskeletal pain conditions immediately post-treatment compared with sham treatment. Given the paucity of studies and inconsistent protocols, future RCTs are warranted to evaluate the effectiveness of AA in people with chronic musculoskeletal pain at a longer follow-up with detailed protocols, which allows researchers and clinicians to optimize AA intervention. Conclusion: AA has immediate post-treatment benefits for chronic musculoskeletal pain, whereas its effects at the 1- or 6-month follow-up remain uncertain.
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Two important plant enzymes are 4-hydroxyphenylpyruvate dioxygenase (HPPD; EC 1.13.11.27), which is necessary for biosynthesis of plastoquinone and tocopherols, and phytoene dehydrogenase (PDS; EC 1.3.99.26), which plays an important role in colour rendering. Dual-target proteins that inhibit pigment synthesis will prevent resistant weeds and improve the spectral characteristics of herbicides. This study introduces virtual screening of pharmacophores based on the complex structure of the two targets. A three-dimensional database was established by screening 1,492,858 compounds based on the Lipinski principle. HPPD&PDS dual-target receptor-ligand pharmacophore models were then constructed, and nine potential dual-target inhibitors were obtained through pharmacophore modeling, molecular docking, and molecular dynamics simulations. Ultimately, ADMET prediction software yielded three compounds with high potential as dual-target herbicides. The obtained nine inhibitors were stable when combined with both HPPD and PDS proteins. This study offers guidance for the development of HPPD&PDS dual-target inhibitors with novel skeletons.
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Sex role differentiation is a widespread phenomenon. Sex pheromones are often associated with sex roles and convey sex-specific information. In Lepidoptera, females release sex pheromones to attract males, which evolve sophisticated olfactory structures to relay pheromone signals. However, in some primitive moths, sex role differentiation becomes diverged. Here, we introduce the chromosome-level genome assembly from ancestral Himalaya ghost moths, revealing a unique olfactory evolution pattern and sex role parity among Lepidoptera. These olfactory structures of the ghost moths are characterized by a dense population of trichoid sensilla, both larger male and female antennal entry parts of brains, compared to the evolutionary later Lepidoptera. Furthermore, a unique tandem of 34 odorant receptor 19 homologs in Thitarodes xiaojinensis (TxiaOr19) has been identified, which presents overlapped motifs with pheromone receptors (PRs). Interestingly, the expanded TxiaOr19 was predicted to have unconventional tuning patterns compared to canonical PRs, with nonsexual dimorphic olfactory neuropils discovered, which contributes to the observed equal sex roles in Thitarodes adults. Additionally, transposable element activity bursts have provided traceable loci landscapes where parallel diversifications occurred between TxiaOr19 and PRs, indicating that the Or19 homolog expansions were diversified to PRs during evolution and thus established the classic sex roles in higher moths. This study elucidates an olfactory prototype of intermediate sex communication from Himalaya ghost moths.
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Mariposas Nocturnas , Animales , Mariposas Nocturnas/genética , Mariposas Nocturnas/fisiología , Masculino , Femenino , Atractivos Sexuales/metabolismo , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Receptores de Feromonas/genética , Receptores de Feromonas/metabolismo , Filogenia , Conducta Sexual AnimalRESUMEN
Anaerobic digestion (AD) has the great potential to treat organic waste and achieve remarkable results effectively. However, it is very tough to establish an accurate mechanistic model for this process. Data-driven modeling technology has opened a new door to solving this problem. While when the sample set is small, traditional data-driven modeling methods are often powerless. In this paper, an effective method is proposed for data-driven high-precision modeling in small sample scenarios. A time series generative adversarial network (TimeGAN) is first utilized to augment the original high-quality small-sample data collected during the AD methane production. A novel hybrid kernel extreme learning machine (HKELM) is then designed to form a better structure of the data-driven model, whose regularization coefficient C0 is optimized by the sparrow search algorithm (SSA). Finally, this semi-finished model (SSA-HKELM) is trained by the augmented data to form the final mathematical model (TimeGAN-SSA-HKELM) for the AD methane generation process. Comparative experiments of the methane daily production prediction error have verified the effectiveness of the method, which can be extended to other similar small sample data-driven modeling scenarios.
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Metano , Anaerobiosis , Modelos Teóricos , AlgoritmosRESUMEN
This study aimed to investigate the potential protective effects of Dexmedetomidine (DEX) against acute kidney injury (AKI) induced by acute stress (AS). Wistar rats were divided into five groups: Control, DEX, AS, AS + DEX, and AS + A438079. The results showed that AS led to AKI by increasing inflammatory biomarkers and oxidative stress-related indicators. The acute stress model in rats was successfully established. Renal function, histopathology, oxidative stress, and inflammation were assessed. Localization of P2X7 receptor (P2X7R) was determined by immunofluorescence. Additionally, the key inflammatory proteins of the P2X7R/NF-κB/NLRP3 signaling pathway were measured by Western blotting. DEX significantly improved kidney function, alleviated kidney injury, and reduced oxidative stress and inflammation. DEX inhibited the activation of the P2X7R, decreased the expression of NF-κB, NLRP3 inflammasome, and Caspase-1, and inhibited the expression of interleukin-1ß (IL-1ß) and tumor necrosis factor α (TNFα). Furthermore, DEX also alleviated AS-induced AKI by inhibiting the excessive production of reactive oxygen species (ROS) and reducing oxidative stress. In conclusion, DEX attenuates AS-induced AKI by mitigating inflammation and oxidative stress through the inhibition of the P2X7R/NF-κB/NLRP3 pathway in rats.
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PFOS is a ubiquitous pollutant garnering considerable attention due to its deleterious effects on both human and animal health. Given the poultry industry's intimate link with human health, investigating PFOS's impact on quails is crucial. PFOS readily accumulates in the liver, causing hepatotoxicity, yet its molecular mechanisms remain elusive. In our study, we fed quail diets contaminated with varying PFOS concentrations (12.5, 25, and 50 mg/kg) and observed dose-dependent liver damage in quails. The results show that PFOS damages mitochondrial structure, increases ROS levels, and downregulates antioxidants to promote oxidative stress damage in hepatocytes. PFOS also upregulated pro-inflammatory molecules (TNF-α, IL-1ß, and IL-6) while downregulating the anti-inflammatory factor IL-10, activating the TLR4//MyD88/NF-κB signaling pathway, thereby potentiating liver inflammation. Then, oxidative stress and inflammation by PFOS induce apoptosis in quail hepatocytes through the mitochondrial pathway, with severity closely related to hepatotoxicity. In conclusion, PFOS induces mitochondrial apoptosis by exacerbating oxidative stress and inflammation by activating the TLR4/MyD88/NF-κB signaling pathway, ultimately leading to hepatotoxicity in quails.
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AIMS: MicroRNA-126 (miR-126), one of the most abundant microRNAs in platelets, is involved in the regulation of platelet activity and the circulating miR-126 is reduced during antiplatelet therapy. However, whether intraplatelet miR-126 plays a role in thrombosis and platelet inhibition remains unclear. METHODS AND RESULTS: Here, using tissue-specific knockout mice, we reported that the deficiency of miR-126 in platelets and vascular endothelial cells significantly prevented thrombosis and prolonged bleeding time. Using chimeric mice, we identified that the lack of intraplatelet miR-126 significantly prevented thrombosis. Ex vivo experiments further demonstrated that miR-126-deficient platelets displayed impaired platelet aggregation, spreading and secretory functions. Next, miR-126 was confirmed to target phosphoinositol-3 kinase regulatory subunit 2 (PIK3R2) in platelet, which encodes a negative regulator of the PI3 K/AKT pathway, enhancing platelet activation through activating the integrin αIIbß3-mediated outside-in signaling. After undergoing myocardial infarction (MI), chimeric mice lacking intraplatelet miR-126 displayed reduced microvascular obstruction and prevented MI expansion in vivo. In contrast, overexpression of miR-126 by the administration of miR-126 agonist (agomiR-126) in wild-type mice aggravated microvascular obstruction and promoted MI expansion, which can be almost abolished by aspirin administration. In patients with cardiovascular diseases, antiplatelet therapies, either aspirin alone or combined with clopidogrel, decreased the level of intraplatelet miR-126. The reduction of intraplatelet miR-126 level was associated with the decrease of platelet activity. CONCLUSIONS: Our murine and human data reveal that (i) intraplatelet miR-126 contributes to platelet activity and promotes thrombus formation, and (ii) the reduction of intraplatelet miR-126 contributes to platelet inhibition during antiplatelet therapy.
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ETHNOPHARMACOLOGICAL RELEVANCE: Taohong Siwu Decoction (TSD), a classic traditional Chinese medicine formula, is used for the treatment of vascular diseases, including vascular dementia (VD). However, the mechanisms remain unclear. AIM OF STUDY: This study aimed to investigate whether TSD has a positive effect on cognitive impairment in VD rats and to confirm that the mechanism of action is related to the Endoplasmic Reticulum stress (ERs) and cell apoptosis signaling pathway. MATERIALS AND METHODS: A total of 40 male adult Sprague-Dawley rats were divided into four groups: sham-operated group (Sham), the two-vessel occlusion group (2VO), the 2VO treated with 4.5 g/kg/d TSD group (2VO + TSD-L), the 2VO treated with 13.5 g/kg/d TSD group (2VO + TSD-H). The rats underwent either 2VO surgery or sham surgery. Postoperative TSD treatment was given for 4 consecutive weeks. Behavioral tests were initiated at the end of gastrulation. Open-field test (OFT) was used to detect the activity level. The New Object Recognition test (NOR) was used to test long-term memory. The Morris water maze (MWM) test was used to examine the foundation of spatial learning and memory. As a final step, the hippocampus was taken for molecular testing. The protein levels of GRP78 (Bip), p-PERK, PERK, IRE1α, p-IRE1α, ATF6, eIF2α, p-eIF2α, ATF4, XBP1, Bcl-2 and Bax were determined by Western blot. Immunofluorescence visualizes molecular expression. RESULTS: In the OFT, residence time in the central area was significantly longer in both TSD treatment groups compared to the 2VO group. In the NOR, the recognition index was obviously elevated in both TSD treatment groups. The 2VO group had a significantly longer escape latency and fewer times in crossing the location of the platform compared with the Sham group in MWM. TSD treatment reversed this notion. Pathologically, staining observations confirmed that TSD inhibited hippocampal neuronal loss and alleviated the abnormal reduction of the Nissl body. In parallel, TUNEL staining illustrated that TSD decelerated neuronal apoptosis. Western Blot demonstrated that TSD reduces the expression of ERs and apoptotic proteins. CONCLUSION: In this study, the significant ameliorative effect on cognitive impairment of TSD has been determined by comparing the behavioral data of the 4 groups of rats. Furthermore, it was confirmed that this effect of TSD was achieved by suppressing the ERs-mediated apoptosis signaling pathway.
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Apoptosis , Disfunción Cognitiva , Demencia Vascular , Medicamentos Herbarios Chinos , Estrés del Retículo Endoplásmico , Ratas Sprague-Dawley , Transducción de Señal , Animales , Estrés del Retículo Endoplásmico/efectos de los fármacos , Masculino , Medicamentos Herbarios Chinos/farmacología , Apoptosis/efectos de los fármacos , Demencia Vascular/tratamiento farmacológico , Demencia Vascular/metabolismo , Disfunción Cognitiva/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Ratas , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Modelos Animales de Enfermedad , Aprendizaje por Laberinto/efectos de los fármacosRESUMEN
In this paper, a novel 4H-SiC deep-trench super-junction MOSFET (Metal-Oxide-Semiconductor Field-Effect Transistor) with a split-gate is proposed and theoretically verified by Sentaurus TCAD simulations. A deep trench filled with P-poly-Si combined with the P-SiC region leads to a charge balance effect. Instead of a full-SiC P region in conventional super-junction MOSFET, this new structure reduces the P region in a super-junction MOSFET, thus helping to lower the specific on-resistance. As a result, the figure of merit (FoM, BV2/Ron,sp) of the proposed new structure is 642% and 39.65% higher than the C-MOS and the SJ-MOS, respectively.
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BACKGROUND: Kawasaki disease (KD) is an immune vasculitis of unknown origin, characterized by transient inflammation. The activation of the cGAS-STING pathway, triggered by mitochondrial DNA (mtDNA) release, has been implicated in the onset of KD. However, its specific role in the progression of inflammation during KD's acute phase remains unclear. METHODS: We measured mtDNA and 2'3'-cGAMP expression in KD patient serum using RT-qPCR and ELISA. A murine model of KD was induced by injecting Lactobacillus casei cell wall extract (LCWE), after which cGAS-STING pathway activation and inflammatory markers were assessed via immunohistochemistry, western blot, and RT-qPCR. Human umbilical vein endothelial cells (HUVECs) were treated with KD serum and modulators of the cGAS-STING pathway for comparative analysis. Mitochondrial function was evaluated using Mitosox staining, mPTP opening was quantified by fluorescence microscopy, and mitochondrial membrane potential (MMP) was determined with JC-1 staining. RESULTS: KD patient serum exhibited increased mtDNA and 2'3'-cGAMP expression, with elevated levels of pathway-related proteins and inflammatory markers observed in both in vivo and in vitro models. TEM confirmed mitochondrial damage, and further studies demonstrated that inhibition of mPTP opening reduced mtDNA release, abrogated cGAS-STING pathway activation, and mitigated inflammation. CONCLUSION: These findings indicate that mtDNA released through the mPTP is a critical activator of the cGAS-STING pathway, contributing significantly to KD-associated inflammation. Targeting mtDNA release or the cGAS-STING pathway may offer novel therapeutic approaches for KD management.
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ADN Mitocondrial , Inflamación , Proteínas de la Membrana , Poro de Transición de la Permeabilidad Mitocondrial , Síndrome Mucocutáneo Linfonodular , Nucleotidiltransferasas , Transducción de Señal , Síndrome Mucocutáneo Linfonodular/metabolismo , Síndrome Mucocutáneo Linfonodular/patología , Síndrome Mucocutáneo Linfonodular/genética , ADN Mitocondrial/genética , ADN Mitocondrial/metabolismo , Nucleotidiltransferasas/metabolismo , Nucleotidiltransferasas/genética , Humanos , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Inflamación/patología , Inflamación/metabolismo , Inflamación/genética , Animales , Poro de Transición de la Permeabilidad Mitocondrial/metabolismo , Masculino , Ratones , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Femenino , Enfermedad Aguda , Ratones Endogámicos C57BL , PreescolarRESUMEN
Objective. Closed-loop deep brain stimulation (DBS) is a promising therapy for Parkinson's disease (PD) that works by adjusting DBS patterns in real time from the guidance of feedback neural activity. Current closed-loop DBS mainly uses threshold-crossing on-off controllers or linear time-invariant (LTI) controllers to regulate the basal ganglia (BG) Parkinsonian beta band oscillation power. However, the critical cortex-BG-thalamus network dynamics underlying PD are nonlinear, non-stationary, and noisy, hindering accurate and robust control of Parkinsonian neural oscillatory dynamics.Approach. Here, we develop a new robust adaptive closed-loop DBS method for regulating the Parkinsonian beta oscillatory dynamics of the cortex-BG-thalamus network. We first build an adaptive state-space model to quantify the dynamic, nonlinear, and non-stationary neural activity. We then construct an adaptive estimator to track the nonlinearity and non-stationarity in real time. We next design a robust controller to automatically determine the DBS frequency based on the estimated Parkinsonian neural state while reducing the system's sensitivity to high-frequency noise. We adopt and tune a biophysical cortex-BG-thalamus network model as an in-silico simulation testbed to generate nonlinear and non-stationary Parkinsonian neural dynamics for evaluating DBS methods.Main results. We find that under different nonlinear and non-stationary neural dynamics, our robust adaptive DBS method achieved accurate regulation of the BG Parkinsonian beta band oscillation power with small control error, bias, and deviation. Moreover, the accurate regulation generalizes across different therapeutic targets and consistently outperforms current on-off and LTI DBS methods.Significance. These results have implications for future designs of closed-loop DBS systems to treat PD.
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Simulación por Computador , Estimulación Encefálica Profunda , Enfermedad de Parkinson , Estimulación Encefálica Profunda/métodos , Humanos , Enfermedad de Parkinson/terapia , Enfermedad de Parkinson/fisiopatología , Ganglios Basales/fisiopatología , Ganglios Basales/fisiología , Ritmo beta/fisiología , Modelos Neurológicos , Corteza Cerebral/fisiopatología , Corteza Cerebral/fisiología , Tálamo/fisiología , Tálamo/fisiopatología , Dinámicas no LinealesRESUMEN
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected many people around the world; fast and accurate detection of the virus can help control the spread of the virus. Reverse transcription-polymerase chain reaction (RT-PCR) is the gold standard method for SARS-CoV-2 detection. In this study, we improved the RT-PCR by proposing a novel method using dual double-quenched fluorescence probes. We used the improved probes to detect the plasmid DNA and RNA reference materials of SARS-CoV-2, respectively. The results show that, the background fluorescence intensity reduced by 50%, the fluorescence increment increased to 2.8 folds, and the Ct value significantly reduced by 3 or more, indicating that the detection sensitivity increased at least 8 times. In addition, we demonstrated that the improved probes have well performance in detecting SARS-CoV-2, with the minimum concentration of 6.2 copies/µL. This study will help biological companies develop better products for SARS-CoV-2 and other clinical pathogen infection.
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COVID-19 , Colorantes Fluorescentes , ARN Viral , SARS-CoV-2 , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/genética , Colorantes Fluorescentes/química , Humanos , COVID-19/diagnóstico , COVID-19/virología , ARN Viral/análisis , ARN Viral/genética , Sensibilidad y Especificidad , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Prueba de Ácido Nucleico para COVID-19/métodos , Límite de DetecciónRESUMEN
The karyotype of an organism is the set of gross features that characterize the way the genome is packaged into separate chromosomes. It has been known for decades that different taxonomic groups often have distinct karyotypic features, but whether selective forces act to maintain these differences over evolutionary timescales is an open question. In this paper we analyze a database of karyotype features and sperm head morphology in 103 mammal species with spatulate sperm heads and 90 sauropsid species (birds and non-avian reptiles) with vermiform heads. We find that mammal species with a larger head area have more chromosomes, while sauropsid species with longer heads have a wider range of chromosome lengths. These results remain significant after controlling for genome size, so sperm head morphology is the relevant variable. This suggest that post-copulatory sexual selection, by acting on sperm head shape, can influence genome architecture.
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Metabolic abnormalities represent one of the pathological features of chronic obstructive pulmonary disease (COPD). Glutamic pyruvate transaminase 2 (GPT2) is involved in glutamate metabolism and lipid synthesis pathways, whilst the exact roles of GPT2 in the occurrence and development of COPD remains uncertain. This study aims at investigating how GPT2 and the associated genes modulate smoking-induced airway epithelial metabolism and damage by reprogramming lipid synthesis. The circulating or human airway epithelial metabolomic and lipidomic profiles of COPD patients or cell-lines explored with smoking were assessed to elucidate the pivotal roles of GPT2 in reprogramming processes. We found that GPT2 regulate the reprogramming of lipid metabolisms caused by smoking, especially phosphatidylcholine (PC) and triacylglycerol (TAG), along with changes in the expression of lipid metabolism-associated genes. GPT2 modulated cell sensitivities and survival in response to smoking by enhancing mitochondrial functions and maintaining lipid and energy homeostasis. Our findings provide evidence for the involvement of GPT2 in the reprogramming of airway epithelial lipids following smoking, as well as the molecular mechanisms underlying GPT2-mediated regulation, which may offer an alternative of therapeutic strategies for chronic lung diseases.
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Lipidómica , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/genética , Lipidómica/métodos , Fumar/efectos adversos , Fumar/metabolismo , Metabolismo de los Lípidos/genética , Masculino , Femenino , Metabolómica/métodos , Persona de Mediana EdadRESUMEN
Background: Allied disorders of Hirschsprung's disease (ADHD) exhibit symptoms akin to those of Hirschsprung's disease, primarily characterized by intestinal obstruction, bowel dilatation, and chronic constipation. The occurrence of amyloid complications in patients with ADHD is infrequent. In this report, we present a case of ADHD with intestinal ulcers as the initial gastrointestinal manifestation, and subsequent pathological examination revealed the presence of amyloid deposits in the colonic mucosa. Case Report: A male patient, aged 20, exhibited recurring abdominal distension and intestinal obstruction for a duration of three years. Multiple colonoscopies revealed the presence of recurrent colonic ulcers, with pathological examination indicating the existence of amyloid deposits within the mucosal layer of the colon. Abdominal CT scans suggested colonic dilatation. Following a multidisciplinary consultation, a subtotal resection of the colon was performed, and subsequent postoperative pathology confirmed a decrease and absence of myenteric plexus ganglion cells. Considering the patient's symptoms and the findings from the postoperative pathology, a diagnosis of ADHD was made. The patient's symptoms resolved postoperatively and he was discharged from the hospital and followed up for 1 year in stable condition. Conclusion: Our study highlights the potential association between ADHD and the initial presentation of recurrent colonic ulcers, accompanied by amyloid deposition in the intestinal mucosa. This finding suggests a possible pathogenic mechanism for ADHD and offers a novel perspective on its diagnosis.
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Introduction: Deep learning-based methods can promote and save critical time for the diagnosis of pneumonia from computed tomography (CT) images of the chest, where the methods usually rely on large amounts of labeled data to learn good visual representations. However, medical images are difficult to obtain and need to be labeled by professional radiologists. Methods: To address this issue, a novel contrastive learning model with token projection, namely CoTP, is proposed for improving the diagnostic quality of few-shot chest CT images. Specifically, (1) we utilize solely unlabeled data for fitting CoTP, along with a small number of labeled samples for fine-tuning, (2) we present a new Omicron dataset and modify the data augmentation strategy, i.e., random Poisson noise perturbation for the CT interpretation task, and (3) token projection is utilized to further improve the quality of the global visual representations. Results: The ResNet50 pre-trained by CoTP attained accuracy (ACC) of 92.35%, sensitivity (SEN) of 92.96%, precision (PRE) of 91.54%, and the area under the receiver-operating characteristics curve (AUC) of 98.90% on the presented Omicron dataset. On the contrary, the ResNet50 without pre-training achieved ACC, SEN, PRE, and AUC of 77.61, 77.90, 76.69, and 85.66%, respectively. Conclusion: Extensive experiments reveal that a model pre-trained by CoTP greatly outperforms that without pre-training. The CoTP can improve the efficacy of diagnosis and reduce the heavy workload of radiologists for screening of Omicron pneumonia.
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The government's environmental protection policy can significantly contribute to alleviating resource shortages and curbing environmental pollution, but the impact of various policy instruments implemented by the government on energy efficiency is unclear. Based on the panel data of 30 provinces in China from 2005 to 2021, this paper analyses the impact of environmental regulation and the industrial structure on energy efficiency from the perspective of resource taxes. The U-shaped relationship between environmental regulation and energy efficiency and between the optimization of industrial structure can significantly improve energy efficiency, and the optimization of industrial structure is conducive to weakening the initial inhibitory effect of environmental regulation. In addition, the analysis of regional heterogeneity showed that the impact of environmental regulation was stronger in the central and western regions, while the impact of industrial structure was stronger in the eastern and western regions. The conclusions of this study can help to expand the understanding of the relationship between environmental regulation and industrial structure on energy efficiency, provide policy enlightenment for the realization of green development and high-quality development, and provide Chinese examples and experiences for developing countries to improve energy efficiency.
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Industrias , China , Contaminación Ambiental/prevención & control , Política Ambiental/legislación & jurisprudencia , Conservación de los Recursos Energéticos , Conservación de los Recursos Naturales/métodosRESUMEN
Ferroptosis, a type of programmed cell death that relies on iron, is distinct in terms of its morphological, biochemical and genetic features. Unlike other forms of cell death, such as autophagy, apoptosis, necrosis, and pyroptosis, ferroptosis is primarily caused by lipid peroxidation. Cells that die due to iron can potentially trigger an immune response which intensifies inflammation and causes severe inflammatory reactions that eventually lead to multiple organ failure. In recent years, ferroptosis has been identified in an increasing number of medical fields, including neurological pathologies, chronic liver diseases and sepsis. Ferroptosis has the potential to cause an inflammatory tempest, with many of the catalysts and pathological indications of respiratory ailments being linked to inflammatory reactions. The growing investigation into ferroptosis in respiratory disorders has also garnered significant interest to better understand the mechanism of ferroptosis in these diseases. In this review, the recent progress in understanding the molecular control of ferroptosis and its mechanism in different respiratory disorders is examined. In addition, this review discusses current challenges and prospects for understanding the link between respiratory diseases and ferroptosis.