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Memories about sensory experiences are tightly linked to the context in which they were formed. Memory contextualization is fundamental for the selection of appropriate behavioral reactions needed for survival, yet the underlying neuronal circuits are poorly understood. By combining trans-synaptic viral tracing and optogenetic manipulation, we found that the ventral hippocampus (vHC) and the amygdala, two key brain structures encoding context and emotional experiences, interact via multiple parallel pathways. A projection from the vHC to the basal amygdala mediates fear behavior elicited by a conditioned context, whereas a parallel projection from a distinct subset of vHC neurons onto midbrain-projecting neurons in the central amygdala is necessary for context-dependent retrieval of cued fear memories. Our findings demonstrate that two fundamentally distinct roles of context in fear memory retrieval are processed by distinct vHC output pathways, thereby allowing for the formation of robust contextual fear memories while preserving context-dependent behavioral flexibility.
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Amígdala del Cerebelo/fisiología , Hipocampo/fisiología , Memoria , Vías Nerviosas , Animales , Condicionamiento Psicológico , Fenómenos Electrofisiológicos , Miedo , Ratones , Ratones Endogámicos C57BL , Neuronas/citología , Neuronas/fisiología , Optogenética , Virus de la Rabia/genética , SinapsisRESUMEN
The bone marrow microenvironment (BMM) can regulate leukemia stem cells (LSCs) via secreted factors. Increasing evidence suggests that dissecting the mechanisms by which the BMM maintains LSCs may lead to the development of effective therapies for the eradication of leukemia. Inhibitor of DNA binding 1 (ID1), a key transcriptional regulator in LSCs, previously identified by us, controls cytokine production in the BMM, but the role of ID1 in acute myeloid leukemia (AML) BMM remains obscure. Here, we report that ID1 is highly expressed in the BMM of patients with AML, especially in BM mesenchymal stem cells, and that the high expression of ID1 in the AML BMM is induced by BMP6, secreted from AML cells. Knocking out ID1 in mesenchymal cells significantly suppresses the proliferation of cocultured AML cells. Loss of Id1 in the BMM results in impaired AML progression in AML mouse models. Mechanistically, we found that Id1 deficiency significantly reduces SP1 protein levels in mesenchymal cells cocultured with AML cells. Using ID1-interactome analysis, we found that ID1 interacts with RNF4, an E3 ubiquitin ligase, and causes a decrease in SP1 ubiquitination. Disrupting the ID1-RNF4 interaction via truncation in mesenchymal cells significantly reduces SP1 protein levels and delays AML cell proliferation. We identify that the target of Sp1, Angptl7, is the primary differentially expression protein factor in Id1-deficient BM supernatant fluid to regulate AML progression in mice. Our study highlights the critical role of ID1 in the AML BMM and aids the development of therapeutic strategies for AML.
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Proteína 7 Similar a la Angiopoyetina , Proteína 1 Inhibidora de la Diferenciación , Leucemia Mieloide Aguda , Animales , Ratones , Proteína 7 Similar a la Angiopoyetina/genética , Proteína 7 Similar a la Angiopoyetina/metabolismo , Médula Ósea/metabolismo , Modelos Animales de Enfermedad , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Microambiente Tumoral , Humanos , Proteína 1 Inhibidora de la Diferenciación/metabolismoRESUMEN
Abundant evidence demonstrates that mechanical stress could induce an inflammatory response in periodontal tissue, but the precise mechanism remains unclear. In the past few years, periodontal ligament cells (PDLCs), as the most force-sensitive cells, have been investigated in depth as local immune cells, associated with activation of inflammasomes and secretion of inflammatory cytokines in response to mechanical stimuli. However, this study innovatively inspected the effect of PDLCs on the other immune cells after stretch loading to reveal the detailed mechanism by which mechanical stimuli initiate immunoreaction in periodontium. In the present study, we found that cyclic stretch could stimulate human PDLCs to secret exosomes and that these exosomes could further induce the increase of phagocytic cells in the periodontium in Sprague-Dawley rats and the M1 polarization of the cultured macrophages (including the mouse macrophage cell line RAW264.7 and the bone marrow-derived macrophages from C57BL/6 mice). Furthermore, the exosomal miR-9-5p was detected to be overexpressed after mechanical stimuli in both in vivo and in vitro experiments and could trigger M1 polarization via the SIRT1/NF-κB signaling pathway in the cultured macrophages. In summary, this study revealed that PDLCs could transmit the mechanobiological signals to immune cells by releasing exosomes and simultaneously enhance periodontal inflammation through the miR-9-5p/SIRT1/NF-κB pathway. We hope that our research can improve understanding of force-related periodontal inflammatory diseases and lead to new targets for treatment.
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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.
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Antineoplásicos , Neoplasias , Profármacos , Humanos , Profármacos/farmacología , Aductos de ADN , Fosfatidilserinas , ARN Interferente Pequeño , Antineoplásicos/farmacología , Neoplasias/tratamiento farmacológico , ARN Bicatenario , Línea Celular Tumoral , Cisplatino , Microambiente TumoralRESUMEN
BACKGROUND: The dysfunction of secretory pathways may represent biomarkers or therapeutic targets of cancer. The hepatocellular carcinoma (HCC) phenotype was studied in relation to the genes in the secretory pathway and to screen for a combination of genes that may be a viable therapeutic target for HCC and connected to the pathophysiological features of the tumor. METHODS: Using the HCC information from The Cancer Genome Atlas, somatic mutation and prognostic association analysis were performed on the secretory pathway genes. Based on prognostic genes in the secretory pathway, the samples were consensus clustered, and a Random Forest model was built. The clinical characteristics, tumor mutation burden, functional status and potential responses to immunotherapy and tumor suppressor medications of various subtypes and risk groups were discussed. RESULTS: Of the 84 genes for secretory pathway, 32 were prognostic genes related to HCC, which divided HCC into two categories: C1 and C2. By comparing the two types of HCC samples, it was found that the survival outcome of C1 was inferior, with stronger adaptive and innate immunity, but less sensitive to immunotherapy than C2. The constructed prognostic signature included seven of the 32 prognostic genes in the secretory pathway, which showed significant correlation with the prognosis, somatic mutation, biological pathway status, potential response to immunotherapy and sensitivity of 72 tumor suppressor drugs from different HCC cohorts, and had a feasible prognostic effect for 31 types of cancer and immunotherapy cohorts. CONCLUSIONS: In this study, HCC was divided into two molecular subtypes according to prognostic genes in the secretory pathway, and seven of them were combined into one signature, which produced significant results in evaluating the prognosis of different HCC cohorts, pan-cancer cohorts and immunotherapy cohorts, and had potential guiding significance for prophylactic immunotherapy in patients with HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Bosques Aleatorios , Vías Secretoras , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , InmunoterapiaRESUMEN
Immunotherapy has emerged as a potent strategy in cancer treatment, with many approved drugs and modalities in the development stages. Despite its promise, immunotherapy is not without its limitations, including side effects and suboptimal efficacy. Using nanoparticles (NPs) as delivery vehicles to target immunotherapy to lymph nodes (LNs) can improve the efficacy of immunotherapy drugs and reduce side effects in patients. In this context, this paper reviews the development of LN-targeted immunotherapeutic NP strategies, the mechanisms of NP transport during LN targeting, and their related biosafety risks. NP targeting of LNs involves either passive targeting, influenced by NP physical properties, or active targeting, facilitated by affinity ligands on NP surfaces, while alternative methods, such as intranodal injection and high endothelial venule (HEV) targeting, have uncertain clinical applicability and require further research and validation. LN targeting of NPs for immunotherapy can reduce side effects and increase biocompatibility, but risks such as toxicity, organ accumulation, and oxidative stress remain, although strategies such as biodegradable biomacromolecules, polyethylene glycol (PEG) coating, and impurity addition can mitigate these risks. Additionally, this work concludes with a future-oriented discussion, offering critical insights into the field.
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Inmunoterapia , Ganglios Linfáticos , Nanopartículas , Neoplasias , Inmunoterapia/métodos , Humanos , Neoplasias/terapia , Neoplasias/inmunología , Nanopartículas/química , AnimalesRESUMEN
BACKGROUND: Molecularly targeted therapies have recently become a hotspot in the treatment of LUAD, with ongoing efforts to identify new effective targets due to individual variability. Among these potential targets, the mitochondrial transcription elongation factor (TEFM) stands out as a crucial molecule involved in mitochondrial synthetic transcriptional processing. Dysregulation of TEFM has been implicated in the development of various diseases; however, its specific role in LUAD remains unclear. METHODS: We conducted a comprehensive analysis of TEFM expression in LUAD, leveraging data from the TCGA database. Subsequently, we validated these findings using clinical specimens obtained from the First Affiliated Hospital of Soochow University, employing western blotting and qRT-PCR techniques. Further experimental validation was performed through the transfection of cells with TEFM overexpression, knockdown, and knockout lentiviruses. The effects of TEFM on LUAD were evaluated both in vitro and in vivo using a range of assays, including CCK-8, colony formation, EdU incorporation, Transwell migration, Tunel assay, flow cytometry, JC-1 staining, and xenograft tumour models. RESULTS: Our investigation uncovered that TEFM exhibited elevated expression levels in LUAD and exhibited co-localization with mitochondria. Overexpression of TEFM facilitated malignant processes in LUAD cells, whereas its silencing notably curbed these behaviors and induced mitochondrial depolarization, along with ROS production, culminating in apoptosis. Moreover, the absence of TEFM substantially influenced the expression of mitochondrial transcripts and respiratory chain complexes. Results from nude mouse xenograft tumors further validated that inhibiting TEFM expression markedly hindered tumor growth. CONCLUSION: TEFM promotes LUAD malignant progression through the EMT pathway and determines apoptosis by affecting the expression of mitochondrial transcripts and respiratory chain complexes, providing a new therapeutic direction for LUAD-targeted therapy.
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Apoptosis , Mitocondrias , Factores de Elongación Transcripcional , Humanos , Animales , Mitocondrias/metabolismo , Línea Celular Tumoral , Factores de Elongación Transcripcional/metabolismo , Factores de Elongación Transcripcional/genética , Apoptosis/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/terapia , Ratones Desnudos , Regulación Neoplásica de la Expresión Génica , Proliferación Celular , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/terapia , Movimiento Celular , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones , Especies Reactivas de Oxígeno/metabolismo , Terapia Molecular Dirigida , Femenino , MasculinoRESUMEN
RATIONALE & OBJECTIVE: The life expectancy of patients treated with maintenance hemodialysis (MHD) is heterogeneous. Knowledge of life-expectancy may focus care decisions on near-term versus long-term goals. The current tools are limited and focus on near-term mortality. Here, we develop and assess potential utility for predicting near-term mortality and long-term survival on MHD. STUDY DESIGN: Predictive modeling study. SETTING & PARTICIPANTS: 42,351 patients contributing 997,381 patient months over 11 years, abstracted from the electronic health record (EHR) system of midsize, nonprofit dialysis providers. NEW PREDICTORS & ESTABLISHED PREDICTORS: Demographics, laboratory results, vital signs, and service utilization data available within dialysis EHR. OUTCOME: For each patient month, we ascertained death within the next 6 months (ie, near-term mortality) and survival over more than 5 years during receipt of MHD or after kidney transplantation (ie, long-term survival). ANALYTICAL APPROACH: We used least absolute shrinkage and selection operator logistic regression and gradient-boosting machines to predict each outcome. We compared these to time-to-event models spanning both time horizons. We explored the performance of decision rules at different cut points. RESULTS: All models achieved an area under the receiver operator characteristic curve of≥0.80 and optimal calibration metrics in the test set. The long-term survival models had significantly better performance than the near-term mortality models. The time-to-event models performed similarly to binary models. Applying different cut points spanning from the 1st to 90th percentile of the predictions, a positive predictive value (PPV) of 54% could be achieved for near-term mortality, but with poor sensitivity of 6%. A PPV of 71% could be achieved for long-term survival with a sensitivity of 67%. LIMITATIONS: The retrospective models would need to be prospectively validated before they could be appropriately used as clinical decision aids. CONCLUSIONS: A model built with readily available clinical variables to support easy implementation can predict clinically important life expectancy thresholds and shows promise as a clinical decision support tool for patients on MHD. Predicting long-term survival has better decision rule performance than predicting near-term mortality. PLAIN-LANGUAGE SUMMARY: Clinical prediction models (CPMs) are not widely used for patients undergoing maintenance hemodialysis (MHD). Although a variety of CPMs have been reported in the literature, many of these were not well-designed to be easily implementable. We consider the performance of an implementable CPM for both near-term mortality and long-term survival for patients undergoing MHD. Both near-term and long-term models have similar predictive performance, but the long-term models have greater clinical utility. We further consider how the differential performance of predicting over different time horizons may be used to impact clinical decision making. Although predictive modeling is not regularly used for MHD patients, such tools may help promote individualized care planning and foster shared decision making.
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Fallo Renal Crónico , Diálisis Renal , Humanos , Diálisis Renal/mortalidad , Diálisis Renal/métodos , Masculino , Femenino , Persona de Mediana Edad , Fallo Renal Crónico/terapia , Fallo Renal Crónico/mortalidad , Anciano , Esperanza de Vida , Tasa de Supervivencia/tendencias , Factores de Tiempo , Medición de Riesgo/métodos , Estudios RetrospectivosRESUMEN
INTRODUCTION: This study aim to analyzed the main pollen allergen components that cause allergic asthma and/or rhinitis and the cross-reactions between the allergen components. METHODS: Twenty one allergic rhinitis patients and 23 allergic asthma patients with pollen sensitization from the China Biological Information Repository of Respiratory Diseases were included. All the patients were detected serum pollen allergens components specific immunoglobulin E (sIgE) including Betula verrucosa (Bet v 1, Bet v 2, Bet v 4), Quercus alba (Pla a 1, Pla a 2), Ambrosia elatior (Amb a 1), Artemisia vulgaris (Art v 1, Art v 3, Art v 4), Bermuda grass (Cyn d 1, Cyn d 12), Phleum pratense (Phl p 5, Phl p 1, Phl p 4, Phl p 7, Phl p 12), and cross-reactive carbohydrate determinants. RESULTS: In patients with asthma, Phl p 4 had the highest positive rate (60.9%), followed by Phl p 1 (43.5%) and Pla a 2 (34.8%), while in patients with rhinitis, Amb a 1 had the highest positive rate (71.4%), followed by Phl p 4 (61.9%) and Pla a 2 (42.9%). Meanwhile, Phl p 1 (43.5%) in asthma patients was higher than that in rhinitis (4.7%, p = 0.03), while Amb a 1 (71.4%) in rhinitis patients was higher than that in asthma (26.1%, p = 0.03). Interestingly, optimal scale analysis show that the severity of both asthma and rhinitis is related to Bet v 4 (Cronbach's Alpha = 95.0%). CONCLUSIONS: In general, Phl p 4 is the main allergenic component in pollen sensitized asthma patients, while Amb a 1 is the main allergenic component in pollen sensitized rhinitis patients. Sensitization to Bet v 4 may lead to more severe symptoms, and this result may be applied in future clinical precise diagnosis.
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Due to the sustained proliferative potential of cancer cells, inducing cell death is a potential strategy for cancer therapy. Paraptosis is a mode of cell death characterized by endoplasmic reticulum (ER) and/or mitochondrial swelling and cytoplasmic vacuolization, which is less investigated. Considerable evidence shows that paraptosis can be triggered by various chemical compounds, particularly in cancer cells, thus highlighting the potential application of this non-classical mode of cell death in cancer therapy. Despite these findings, there remain significant gaps in our understanding of the role of paraptosis in cancer. In this review, we summarize the current knowledge on chemical compound-induced paraptosis. The ER and mitochondria are the two major responding organelles in chemical compound-induced paraptosis, which can be triggered by the reduction of protein degradation, disruption of sulfhydryl homeostasis, overload of mitochondrial Ca2+, and increased generation of reactive oxygen species. We also discuss the stumbling blocks to the development of this field and the direction for further research. The rational use of paraptosis might help us develop a new paradigm for cancer therapy.
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Neoplasias , Paraptosis , Línea Celular Tumoral , Muerte Celular , Especies Reactivas de Oxígeno/metabolismo , Retículo Endoplásmico/metabolismo , Apoptosis , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismoRESUMEN
Spinal cord injury (SCI) often results in motor and sensory deficits, or even paralysis. Due to the role of the cascade reaction, the effect of excessive reactive oxygen species (ROS) in the early and middle stages of SCI severely damage neurons, and most antioxidants cannot consistently eliminate ROS at non-toxic doses, which leads to a huge compromise in antioxidant treatment of SCI. Selenium nanoparticles (SeNPs) have excellent ROS scavenging bioactivity, but the toxicity control problem limits the therapeutic window. Here, we propose a synergistic therapeutic strategy of SeNPs encapsulated by ZIF-8 (SeNPs@ZIF-8) to obtain synergistic ROS scavenging activity. Three different spatial structures of SeNPs@ZIF-8 were synthesized and coated with ferrostatin-1, a ferroptosis inhibitor (FSZ NPs), to achieve enhanced anti-oxidant and anti-ferroptosis activity without toxicity. FSZ NPs promoted the maintenance of mitochondrial homeostasis, thereby regulating the expression of inflammatory factors and promoting the polarization of macrophages into M2 phenotype. In addition, the FSZ NPs presented strong abilities to promote neuronal maturation and axon growth through activating the WNT4-dependent pathways, while prevented glial scar formation. The current study demonstrates the powerful and versatile bioactive functions of FSZ NPs for SCI treatment and offers inspiration for other neural injury diseases.
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Antioxidantes , Nanopartículas , Especies Reactivas de Oxígeno , Selenio , Traumatismos de la Médula Espinal , Traumatismos de la Médula Espinal/tratamiento farmacológico , Animales , Antioxidantes/farmacología , Antioxidantes/química , Nanopartículas/química , Ratones , Especies Reactivas de Oxígeno/metabolismo , Selenio/química , Selenio/farmacología , Neuronas/efectos de los fármacos , Ferroptosis/efectos de los fármacos , Ratas , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Células RAW 264.7 , Regeneración Nerviosa/efectos de los fármacosRESUMEN
The deployment of imaging examinations has evolved into a robust approach for the diagnosis of lymph node metastasis (LNM). The advancement of technology, coupled with the introduction of innovative imaging drugs, has led to the incorporation of an increasingly diverse array of imaging techniques into clinical practice. Nonetheless, conventional methods of administering imaging agents persist in presenting certain drawbacks and side effects. The employment of controlled drug delivery systems (DDSs) as a conduit for transporting imaging agents offers a promising solution to ameliorate these limitations intrinsic to metastatic lymph node (LN) imaging, thereby augmenting diagnostic precision. Within the scope of this review, we elucidate the historical context of LN imaging and encapsulate the frequently employed DDSs in conjunction with a variety of imaging techniques, specifically for metastatic LN imaging. Moreover, we engage in a discourse on the conceptualization and practical application of fusing diagnosis and treatment by employing DDSs. Finally, we venture into prospective applications of DDSs in the realm of LNM imaging and share our perspective on the potential trajectory of DDS development.
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Sistemas de Liberación de Medicamentos , Ganglios Linfáticos , Humanos , Metástasis Linfática/patología , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patologíaRESUMEN
BACKGROUND: The Apolipoprotein E (APOE) ε4 allele is a risk factor for late-onset Alzheimer's disease (AD). However, no investigation has focused on racial differences in the longitudinal effect of APOE genotypes on CSF amyloid beta (Aß42) and tau levels in AD. METHODS: This study used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI): 222 participants with AD, 264 with cognitive normal (CN), and 692 with mild cognitive impairment (MCI) at baseline and two years follow-up. We used a linear mixed model to investigate the effect of APOE-ε4-genotypes on longitudinal changes in the amyloid beta and tau levels. RESULTS: Individuals with 1 or 2 APOE ε4 alleles revealed significantly higher t-Tau and p-Tau, but lower amyloid beta Aß42 compared with individuals without APOE ε4 alleles. Significantly higher levels of log-t-Tau, log-p-Tau, and low levels of log-Aß42 were observed in the subjects with older age, being female, and the two diagnostic groups (AD and MCI). The higher p-Tau and Aß42 values are associated with poor Mini-Mental State Examination (MMSE) performance. Non-Hispanic Africa American (AA) and Hispanic participants were associated with decreased log-t-Tau levels (ß = - 0.154, p = 0.0112; ß = - 0.207, and p = 0.0016, respectively) as compared to those observed in Whites. Furthermore, Hispanic participants were associated with a decreased log-p-Tau level (ß = - 0.224, p = 0.0023) compared to those observed in Whites. There were no differences in Aß42 level for non-Hispanic AA and Hispanic participants compared with White participants. CONCLUSION: Our study, for the first time, showed that the APOE ε4 allele was associated with these biomarkers, however with differing degrees among racial groups.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Femenino , Humanos , Masculino , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/diagnóstico , Péptidos beta-Amiloides , Apolipoproteína E4/genética , Apolipoproteínas E/genética , Biomarcadores , Disfunción Cognitiva/genética , Disfunción Cognitiva/diagnóstico , Fragmentos de Péptidos , Factores Raciales , Proteínas tauRESUMEN
A novel approach, to the best of our knowledge, is presented for assessing silicon wafer surface profiles using an interferometer and vertically rotatable wafer holder. This approach significantly enhances precision and reduces costs, and outperforms traditional techniques in measurement consistency and accuracy. It effectively reduces sample distortion and positional shifts owing to the removal and reinstallation of the wafers. Using this method, a global backsurface-referenced ideal range of 0.385 µm, warp of 0.193 µm, and other parameters were obtained, demonstrating its practicality in efficiently capturing key surface profile metrics for silicon wafers. This innovation promises substantial improvements in high-volume wafer surface profile testing, overcoming prevalent technological challenges in this industry.
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Noninvasive optical imaging with deep tissue penetration depth and high spatiotemporal resolution is important to longitudinally studying the biology at the single-cell level in live mammals, but has been challenging due to light scattering. Here, we developed near-infrared II (NIR-II) (1,000 to 1,700 nm) structured-illumination light-sheet microscopy (NIR-II SIM) with ultralong excitation and emission wavelengths up to â¼1,540 and â¼1,700 nm, respectively, suppressing light scattering to afford large volumetric three-dimensional (3D) imaging of tissues with deep-axial penetration depths. Integrating structured illumination into NIR-II light-sheet microscopy further diminished background and improved spatial resolution by approximately twofold. In vivo oblique NIR-II SIM was performed noninvasively for 3D volumetric multiplexed molecular imaging of the CT26 tumor microenvironment in mice, longitudinally mapping out CD4, CD8, and OX40 at the single-cell level in response to immunotherapy by cytosine-phosphate-guanine (CpG), a Toll-like receptor 9 (TLR-9) agonist combined with OX40 antibody treatment. NIR-II SIM affords an additional tool for noninvasive volumetric molecular imaging of immune cells in live mammals.
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Imagenología Tridimensional , Imagen Óptica/métodos , Análisis de la Célula Individual , Receptor Toll-Like 9/aislamiento & purificación , Animales , Línea Celular Tumoral , Microambiente Celular/genética , Ratones , Microscopía Fluorescente/métodos , Receptor Toll-Like 9/genéticaRESUMEN
INTRODUCTION: Diagnostic procedures for pulp vitality assessment are a crucial aspect of routine dental practice. This review aims to provide a comprehensive overview of nontraditional techniques and methodologies for assessing pulp vitality, specifically exploring promising approaches that are currently not used in dental practice. METHODS: The study protocol was registered a priori (https://osf.io/3m97z/). An extensive electronic search was conducted across multiple databases, including MEDLINE via PubMed, Scopus, Web of Science, and Embase. Inclusion criteria were guided by the research question based on the PCC model as follows: "What are the potential nontraditional techniques (Concept) for assessing pulp vitality (Population) in the field of endodontics or clinical practice (Context)?" Studies were included that explored possible approaches to pulp vitality assessment, utilizing a range of techniques, whilst any studies using traditional pulp tests (cold, heat, and electric stimulation) or well-known methods (pulse oximetry and laser Doppler flowmetry) were excluded. Reviewers independently screened articles and extracted data. A patent search was also performed. RESULTS: Of 3062 studies, 65 were included that described nontraditional approaches for assessing pulp vitality. These included a range of optical diagnostic methods, ultrasound Doppler flowmetry (UDF), magnetic resonance imaging (MRI), terahertz imaging, tooth temperature measurements, as well as invasive methodologies, including 133xenon washout, radioisotope-labelled tracers, hydrogen gas desaturation, intravital microscopy and fluorescent microspheres isotope clearance. The patent search included artificial intelligence and biomarkers methods. CONCLUSIONS: This review provides details for potential innovative tests that may directly describe pulp vitality. Importantly, these methods range from clinically impractical through to promising methods that may transform clinical practice. Several nontraditional techniques have the potential to enhance diagnostic accuracy and could provide valuable insights into the assessment of pulp vitality in challenging clinical scenarios.
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Pulpa Dental , Humanos , Pulpa Dental/irrigación sanguínea , Pulpa Dental/fisiología , Pulpa Dental/diagnóstico por imagen , Prueba de la Pulpa Dental/métodos , Flujometría por Láser-Doppler/métodosRESUMEN
Land subsidence induced by coal mining (MLS) has posed a huge threat to the ecological environment, buildings, roads, and other infrastructure safety in mining areas. However, the prediction and evaluation of MLS is relatively complex, and the reliability of the prediction results is closely related to factors such as the professional knowledge and engineering experience of researchers. This paper aims to combine intelligent optimization algorithms: ant lion optimizer (ALO), bald eagle search (BES), bird swarm algorithm (BSA), harris hawks optimization (HHO), and sparrow search algorithm (SSA), with machine learning model of gradient boosting with categorical features support algorithm (CatBoost) to predict MLS. To achieve this goal, five hybrid models based CatBoost were developed and the prediction accuracy and reliability of the models were compared and analyzed. The prediction performance of the hybrid models has been significantly improved on the basis of a single model, of which the SSA-CatBoost model has the most obvious improvement (from R2 = 0.927 to 0.965, RMSE = 0.541 to 0.377, MAE = 0.386 to 0.297, VAF = 92.720 to 95.837). The importance and predictive contribution of all input features to predictive labels were studied with the Shapley method. The research results indicate that hybrid model technology is a reliable MLS prediction method. This study can help mining technicians use machine learning methods to study the degree of MLS damage to the surface environment and provide scientific advanced prediction and evaluation for the protection and management of the ecological environment in mining areas and the formulation of safety production measures.
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Algoritmos , Ingeniería , Reproducibilidad de los Resultados , Ambiente , ConocimientoRESUMEN
OBJECTIVES: To assess the performance of deep learning (DL) in the detection, classification, and segmentation of maxillary sinus diseases. MATERIALS AND METHODS: An electronic search was conducted by two reviewers on databases including PubMed, Scopus, Cochrane, and IEEE. All English papers published no later than February 7, 2024, were evaluated. Studies related to DL for diagnosing maxillary sinus diseases were also searched in journals manually. RESULTS: 14 of 1167 studies were eligible according to the inclusion criteria. All studies trained DL models based on radiographic images. Six studies applied to detection tasks, one focused on classification, two segmented lesions, and five studies made a combination of 2 types of DL models. The accuracy of the DL algorithms ranged from 75.7% to 99.7%, and the area under curves (AUC) varied between 0.7 and 0.997. CONCLUSION: DL can accurately deal with the tasks of diagnosing maxillary sinus diseases. Students, residents, and dentists could be assisted by DL algorithms to diagnose and make rational decisions on implant treatment related to maxillary sinuses.
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The main purpose of vital pulp therapy (VPT) is to preserve the integrity and function of the pulp. A wide variety of materials and techniques have been proposed to improve treatment outcomes, and among them, the utilization of lasers has gained significant attention. The application of lasers in different stages of VPT has witnessed remarkable growth in recent years, surpassing previous approaches.This study aimed to review the applications of lasers in different steps of VPT and evaluate associated clinical and radiographic outcomes. An electronic search using Scopus, MEDLINE, Web of Science and Google Scholar databases from 2000 to 2023 was carried out by two independent researchers. The focus was on human studies that examined the clinical and/or radiographic effects of different laser types in VPT. A total of 4243 studies were included in this narrative review article. Based on the compiled data, it can be concluded that although current literature suggests laser may be proposed as an adjunct modality for some procedural steps in VPT, more research with standardized methodologies and criteria is needed to obtain more reliable and conclusive results.
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Terapia por Láser , Humanos , Terapia por Láser/métodos , Resultado del TratamientoRESUMEN
As the global prevalence of obesity and the elderly population continues to increase,the incidence of sarcopenic obesity is also on the rise and becoming a global public health concern.Sarcopenic obesity not only increases the incidence of cancer,but is also associated with poor clinical outcomes in various cancers,such as surgical complications,increased risk of death,and possibly even an impact on chemotherapy as well.Therefore,sarcopenic obesity is emerging as an important indicator of prognosis in cancer patients.However,there are limited relevant studies on the association between sarcopenic obesity and cancer in China.This article reviews the definition and diagnosis of sarcopenic obesity,the clinical correlation between sarcopenic obesity and cancer,and the potential mechanisms,with a view to providing a reference for future clinical practice in China.