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Hepatocyte growth factor (HGF) and its receptor, c-Met, play important roles in the occurrence, development, and treatment of gastric cancer (GC). This review explored the function of the HGF/c-Met signaling pathway in GC and its potential targeted therapeutic mechanisms. As one of the most common malignant tumors worldwide, GC has a complex pathogenesis and limited therapeutic options. Therefore, a thorough understanding of the molecular mechanism of GC is very important for the development of new therapeutic methods. The HGF/c-Met signaling pathway plays an important role in the proliferation, migration, and invasion of GC cells and has become a new therapeutic target. This review summarizes the current research progress on the role of HGF/c-Met in GC and discusses targeted therapeutic strategies targeting this signaling pathway, providing new ideas and directions for the treatment of GC.
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Molecular materials possessing switchable magneto-optical properties are of great interest due to their potential applications in spintronics and molecular devices. However, switching their photoluminescence (PL) and single-molecule magnet (SMM) behavior via light-induced structural changes still constitutes a formidable challenge. Here, a series of cubane structures were synthesized via self-assembly of 9-anthracene carboxylic acid (HAC) and rare-earth ions. All complexes exhibited obvious photochromic phenomena and complete PL quenching upon Xe lamp irradiation, which were realized via the synergistic effect of photogenerated radicals and [4 + 4] photocycloaddition of the AC components. The quenched PL showed the largest fluorescence intensity change (99.72%) in electron-transfer photochromic materials. A reversible decoloration process was realized via mechanical grinding, which is unexpectedly in the electron-transfer photochromic materials. Importantly, an SMM behavior of the Dy analog was observed after room-temperature irradiation due to the photocycloaddition of AC ligands and the photogenerated stable radicals changed the electrostatic ligand field and magnetic coupling. Moreover, based on the remarkably photochromic and photoluminescent properties of these compounds, 2 demos were applied to support their application in information anti-counterfeiting and inkless printing. This work, for the first time utilizing the simultaneous modulation of photocycloaddition and photogenerated radicals in one system, realizes complete PL quenching and light-induced SMM behavior, providing a dynamical switch for the construction of multifunctional polymorphic materials with optical response and optical storage devices.
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PURPOSE: Our study aimed to develop and validate a homologous recombination deficiency (HRD) scoring algorithm in the Chinese breast cancer population. METHODS AND MATERIALS: Ninety-six in-house breast cancer (BC) samples and 6 HRD-positive standard cells were analyzed by whole-genome sequencing (WGS). Besides, 122 BCs from the TCGA database were down-sampled to ~ 1X WGS. We constructed an algorithm named AcornHRD for HRD score calculated based on WGS at low coverage as input data to estimate large-scale copy number alteration (LCNA) events on the genome. A clinical cohort of 50 BCs (15 cases carrying BRCA mutation) was used to assess the association between HRD status and anthracyclines-based neoadjuvant treatment outcomes. RESULTS: A 100-kb window was defined as the optimal size using 41 in-house cases and the TCGA dataset. HRD score high threshold was determined as HRD score ≥ 10 using 55 in-house BCs with BRCA mutation to achieve a 95% BRCA-positive agreement rate. Furthermore, the HRD status agreement rate of AcornHRD is 100%, while the ShallowHRD is 60% in standard cells. BRCA mutation was significantly associated with a high HRD score evaluated by AcornHRD and ShallowHRD (p = 0.008 and p = 0.003, respectively) in the TCGA dataset. However, AcornHRD showed a higher positive agreement rate than did the ShallowHRD algorithm (70% vs 60%). In addition, the BRCA-positive agreement rate of AcornHRD was superior to that of ShallowHRD (87% vs 13%) in the clinical cohort. Importantly, the high HRD score assessed by AcornHRD was significantly correlated with a residual cancer burden score of 0 or 1 (RCB0/1). Besides, the HRD-positive group was more likely to respond to anthracycline-based chemotherapy than the HRD-negative group (pCR [OR = 9.5, 95% CI 1.11-81.5, p = 0.040] and RCB0/1 [OR = 10.29, 95% CI 2.02-52.36, p = 0.005]). CONCLUSION: Using the AcornHRD algorithm evaluation, our analysis demonstrated the high performance of the LCNA genomic signature for HRD detection in breast cancers.
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Algoritmos , Antraciclinas , Neoplasias da Mama , Terapia Neoadjuvante , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Feminino , Antraciclinas/uso terapêutico , Antraciclinas/administração & dosagem , Terapia Neoadjuvante/métodos , Pessoa de Meia-Idade , China/epidemiologia , Adulto , Recombinação Homóloga , Mutação , Idoso , Variações do Número de Cópias de DNA , Proteína BRCA1/genéticaRESUMO
BACKGROUND: Due to cardiotoxicity concerns, the concurrent use of epirubicin and trastuzumab has not been fully studied. This study aimed to examine the cardiotoxicity and pathological complete response (pCR) rate associated with the concurrent regimens in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC). METHODS: We conducted a systematic search for relevant literature in the NCBI/PubMed, the Cochrane database, and international conference abstracts for phase II or III randomized controlled trials between January 1, 2000, and February 28, 2021, focusing on the concurrent regimens in patients with HER2-positive EBC. To compare the risk of cardiotoxicity and the odds of the pCR rate, we performed linear meta-regression analyses to investigate the effects of multiple covariates. RESULTS: We analyzed 7 neoadjuvant trials involving the concurrent use of epirubicin and trastuzumab with 1797 patients. The median cumulative dose of epirubicin used was 300 mg/m2, with a total of 96 reported adverse cardiac events. The concurrent regimens did not result in a significant increase in cardiotoxicity compared to nonconcurrent regimens (risk ratio [RR] = 1.18, 95% confidence interval [CI] = 0.68-2.05). Compared with nonconcurrent or non-anthracycline-containing regimens, concurrent regimens were associated with a significant increase in the pCR rate (odds ratio = 1.48, 95% CI = 1.04-2.12). The linear fixed-effects meta-regression analysis indicated that in trials including more patients with hormone receptor-positive EBC, the RR of cardiotoxicity significantly increased with concurrent regimens, and the pCR rate became less significant. CONCLUSIONS: The combination of trastuzumab and a low dose of epirubicin positively impacted the pCR rate without a significant increase in cardiotoxicity. We recommend exploring concurrent regimens for HR-negative, HER2-positive tumors to enhance pCR rates, with caution advised for HR-positive tumors due to potential cardiotoxicity.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama , Cardiotoxicidade , Epirubicina , Receptor ErbB-2 , Trastuzumab , Humanos , Epirubicina/efeitos adversos , Epirubicina/administração & dosagem , Trastuzumab/efeitos adversos , Trastuzumab/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Feminino , Receptor ErbB-2/metabolismo , Cardiotoxicidade/etiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
Controlling the optical activity of halide perovskite materials through modulation of the coordination configurations of the metal ions is important. Herein, a novel manganese-based halide, specifically diaquatetrakis(methyldiphenylphosphine oxide)manganese(II) tetrachloridomanganate(II), [Mn(C13H13OP)4(H2O)2][MnCl4] or [Mn(MDPPO)4(H2O)2][MnCl4] (MDPPO is methyldiphenylphosphine oxide), was synthesized through the solvothermal reaction of MnCl2 with the neutral molecule MDPPO. In this compound, [Mn(MDPPO)4(H2O)2]2+ acts as the cation, while [MnCl4]2- serves as the anion, enabling the co-existence of tetrahedral and octahedral structures within the same system. Remarkably, the compound exhibits efficient red-light emission at 662â nm, distinct from the green-light emission typically observed in MnX4-based halides. Theoretical calculations show that the red emission comes from the charge transfer from the MDPPO to the Mn2+ of [MnCl4]2-. This work provides a new perspective for the design and synthesis of red-light-emitting manganese-based halides with unique structures.
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BACKGROUND: Cysticercosis is a zoonotic parasitic disease that poses a serious threat to public health. It is widely distributed and has a high incidence rate in China. Reports of disseminated cysticercosis worldwide are rare. This article presents a case of disseminated cysticercosis in the Guangxi Zhuang Autonomous Region of southwestern China. CASE PRESENTATION: The patient, a 46-year-old male belonging to the Miao ethnic group, hailed from a region in Guangxi Zhuang Autonomous Region known for its high incidence of cysticercosis. He had a habit of consuming raw pork and beef. With a history of recurrent consciousness disturbances and limb convulsions for five years, he presented with headaches and dizziness nine days prior. Comprehensive examinations were conducted on the patient. Ultimately, based on epidemiological history, imaging findings, pathogen testing, and pathological results, he was diagnosed with disseminated cysticercosis. Following anthelmintic treatment, the patient was discharged with clear consciousness, free from headaches, dizziness, nausea, vomiting, and seizures. The patient is currently under follow-up care. CONCLUSION: It is crucial to enhance public awareness, promote health education, and cultivate good hygiene habits, as these are essential measures in reducing the incidence of cysticercosis.
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Cisticercose , Humanos , Masculino , Pessoa de Meia-Idade , China/epidemiologia , Cisticercose/epidemiologia , Cisticercose/tratamento farmacológico , Cisticercose/diagnóstico , Animais , Anti-Helmínticos/uso terapêuticoRESUMO
This paper proposes a novel adaptive variable power sliding mode observer-based model predictive control (AVPSMO-MPC) method for the trajectory tracking of a Mecanum-wheeled mobile robot (MWMR) with external disturbances and model uncertainties. First, in the absence of disturbances and uncertainties, a model predictive controller that considers various physical constraints is designed based on the nominal dynamics model of the MWMR, which can transform the tracking problem into a constrained quadratic programming (QP) problem to solve the optimal control inputs online. Subsequently, to improve the anti-jamming ability of the MWMR, an AVPSMO is designed as a feedforward compensation controller to suppress the effects of external disturbances and model uncertainties during the actual motion of the MWMR, and the stability of the AVPSMO is proved via Lyapunov theory. The proposed AVPSMO-MPC method can achieve precise tracking control while ensuring that the constraints of MWMR are not violated in the presence of disturbances and uncertainties. Finally, comparative simulation cases are presented to demonstrate the effectiveness and robustness of the proposed method.
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PURPOSE OF REVIEW: There are numerous sarcoma subtypes and vary widely in terms of epidemiology, clinical characteristics, genetic profiles, and pathophysiology. They also differ widely between ethnic groups. This review focuses on the different incidence rates of sarcomas in different regions and the potential explanations for these disparities. RECENT FINDINGS: In an intercontinental study using national cancer registry databases from France and Taiwan, the French population had a higher risk of liposarcomas, leiomyosarcomas, and synovial sarcomas, whereas the Taiwanese population had a higher incidence of angiosarcomas and malignant peripheral nerve sheath tumors. The anatomical distribution of these sarcomas also varied between these two regions. In France, most angiosarcoma cases occurred in the extremities and trunk, whereas in Taiwan, angiosarcoma cases in the abdomen and pelvis were more common. Another international study showed that in addition to the common known TP53 and NF1 germline mutations, genes involved in centromere and telomere maintenance were also involved in sarcomagenesis. We reviewed factors related to genetics, environmental effects, chemical exposure, and radiation exposure that could explain the differences in sarcoma incidence among different geographical or ethnic regions. SUMMARY: Our understanding of the potential cause of sarcomas with different subtypes is limited. Establishing a comprehensive global database for patients with sarcomas from all ethnic groups is essential to deepen our understanding of the potential risk factors and the pathophysiology of all sarcoma subtypes.
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Sarcoma , Humanos , Saúde Global , Incidência , Sarcoma/epidemiologia , Sarcoma/genética , Sarcoma/patologia , Taiwan/epidemiologia , França/epidemiologiaRESUMO
Epithelioid hemangioendothelioma (EHE) is a rare vascular neoplasm with a clinical behaviour that falls between a benign hemangioma and a high-grade angiosarcoma. Pleural EHE is exceptionally rare, and its prognosis is grim, with most patients experiencing survival of less than 1 year. Here, we present a case of pleural EHE in a 45-year-old woman with a month-long history of right-sided pleuritic chest pain. Chest computed tomography revealed consolidation, atelectasis of the right lung, right pleural thickening, and pleural effusion. She underwent video-assisted thoracoscopic surgery for decortication and was diagnosed with conclusively pleural EHE, showing a CAMTA1 rearrangement. Paclitaxel treatment, administered once weekly on days 1, 8 and 15 of a 28-day cycle, resulted in a stable disease after 12 cycles. Managing patients with pleural EHE is challenging because there are still no established standard treatments. Our case achieved 11-month progression-free survival following paclitaxel treatment.
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The Al-Mn alloy heat exchanger fin production process includes a brazing treatment at s high temperature of 600 °C, in which coarse grains are preferred for their high resistance to deformation at elevated temperatures by decreasing the grain boundary sliding. In this study, Al-1.57Mn-1.57Zn-0.58Si-0.17Fe alloy foils cold rolled by 81.7% (1.1 mm in thickness) and 96.5% (0.21 mm in thickness) were annealed at 100-550 °C for 1 h to investigate their recrystallization behavior, grain sizes, and precipitates by increasing the annealing temperature, using micro-hardness measurement, electron back-scattered diffraction (EBSD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) techniques. The micro-hardness results showed that the recrystallization finishing temperatures for the two samples were almost the same, 323 ± 2 °C. The EBSD results showed that when the annealing temperature decreased from 550 to 400 °C, the recrystallized grain sizes of the two samples were nearly identical-both increased slightly. Further decreasing the annealing temperature from 400 to 330 °C caused the grain sizes to increase more, with the thinner foil sample having a more significant increase. The SEM and TEM observations showed that the micron-sized primary-phase remained unchanged during the annealing process. The nano-sized secondary phase precipitates formed during the hot-rolling process experienced a coarsening and dissolving process upon annealing. The particle size of the secondary phase increased from 32 nm to 44 nm and the area fraction decreased from 4.2% to 3.8%. The nucleation analysis confirmed that the large primary-phase could act as a nucleation site through particle stimulated nucleation (PSN) mode. The relatively dense secondary phase precipitates with small sizes at lower temperatures could provide higher Zener drag to the grain boundaries, leading to fewer nuclei and thereafter coarser grains. The coarsening of the recrystallized grains in the foils could be implemented through thickness reduction and/or precipitation processes to form densely distributed nano-sized precipitates.
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BACKGROUND: Gut microbes and age are both factors that influence the development of disease. The community structure of gut microbes is affected by age. OBJECTIVE: To plot time-dependent gut microbe profiles in individuals over 45 years old and explore the correlation between age and gut microbes. METHODS: Fecal samples were collected from 510 healthy individuals over 45 years old. Shannon index, Simpson index, Ace index, etc. were used to analyze the diversity of gut microbes. The beta diversity analysis, including non-metric multidimensional scaling (NMDS), was used to analyze community distribution. Linear discriminant analysis (LDA) and random forest (RF) algorithm were used to analyze the differences of gut microbes. Trend analysis was used to plot the abundances of characteristic gut microbes in different ages. RESULTS: The individuals aged 45-49 had the highest richness of gut bacteria. Fifteen characteristic gut microbes, including Siphoviridae and Bifidobacterium breve, were screened by RF algorithm. The abundance of Ligiactobacillus and Microviridae were higher in individuals older than 65 years. Moreover, the abundance of Blautia_A massiliensis, Lubbockvirus and Enterocloster clostridioformis decreased with age and the abundance of Klebsiella variicola and Prevotella increased with age. The functional genes, such as human diseases and aging, were significantly different among different aged individuals. CONCLUSIONS: The individuals in different ages have characteristic gut microbes. The changes in community structure of gut microbes may be related to age-induced diseases.
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Envelhecimento , Fezes , Microbioma Gastrointestinal , Humanos , Pessoa de Meia-Idade , Envelhecimento/fisiologia , Idoso , Masculino , Feminino , Fezes/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Fatores Etários , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: In patients with advanced soft tissue sarcoma (STS), surgery had been reported to be associated with superior overall survival (OS). Chemotherapy details for such patients were less reported, and whether multimodal treatment with surgery and chemotherapy provides extra survival benefit remains unclear. METHODS: We retrospectively reviewed patients with newly diagnosed advanced STS treated at National Taiwan University Hospital from January 1, 2011, to December 31, 2017. OS was calculated from the day of diagnosis of advanced STS to the day of death or last follow-up. Baseline patient characteristics and details regarding surgery and chemotherapy were recorded. RESULTS: A total of 545 patients were diagnosed with STS from 2011 to 2017, of which 226 patients had advanced STS. The median age was 54.7 years, and 54% of patients were women. Approximately 38% of patients with advanced STS underwent surgery and exhibited a trend of longer OS compared with who did not (median = 18.6 vs. 11.9 months, p = 0.083). In the chemotherapy subgroup, the benefit of surgery was more prominent (median = 21.9 vs. 16.5 months, p = 0.037). Patients who received chemotherapy prior to surgery exhibited numerically longer OS than those who underwent surgery first (median = 33.9 vs. 18.3 months, p = 0.155). After adjusting other clinical factors, chemotherapy remained an independent factor associated with favourable OS. CONCLUSION: Surgery may be more beneficial for the patients who receive chemotherapy. Our results support evaluation of sequential multimodal treatments strategy including surgery and chemotherapy in patients with advanced STS.
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BACKGROUND: The clinical outcomes of chemotherapy (CT) for the treatment of metastatic triple-negative (TN) and hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) have proven to be disappointing. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway, a tumor-promoting signaling cascade frequently mutated in breast cancer (BC), has been implicated in chemoresistance. In this study, our objective is to investigate the efficacy and safety of combining everolimus with chemotherapy in mBC patients exhibiting mutations in the PI3K/AKT/mTOR pathway. METHODS: We conducted a retrospective analysis to characterize the efficacy, safety, and their association with clinical and molecular characteristics of metastatic lesions in 14 patients with HER2- mBC. These patients harbored at least one altered member of the PI3K/AKT/mTOR signaling pathway and were treated with a combination of a chemotherapy agent and the mTOR inhibitor everolimus (CT+EVE). RESULTS: The majority of patients belonged to the triple-negative (TN) subtype (9/14, 64.3%), having already undergone 2 lines of chemotherapy (CT) in the metastatic setting (11, 78.6%). These patients carried altered phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and were administered a vinorelbine-containing regimen (10, 71.4%). The objective response rate (ORR) was 42.9%, with a disease control rate of 92.9%. The median progression-free survival (PFS) and overall survival (OS) were 5.9 (95% confidence interval (CI): 4.9-13.6) months and 14.3 (95% CI: 8.5-not reached (NR)) months, respectively. Patients with fewer prior treatment lines tended to exhibit longer PFS. OS, PFS, and ORR were comparable between hormone receptor-positive (HR+) and triple-negative breast cancer (TNBC) patients, but numerical improvements were noted in patients with a single PI3K pathway alteration compared to those with more than one alteration. Genomic alterations that surfaced upon progression on CT+EVE included cyclin dependent kinase 4 (CDK4) and epidermal growth factor receptor (EGFR) amplification, as well as neurofibromin 1 (NF1) mutation, suggesting potential mechanisms of acquired resistance. An analysis of adverse events indicated manageable toxicities. CONCLUSIONS: The findings of this study suggest both activity and safety for the combination of chemotherapy and the mTOR inhibitor everolimus (CT+EVE) in patients with HER2- mBC who have alterations in the PI3K pathway, particularly those who have received fewer prior chemotherapy. However, it is crucial to note that large-scale, randomized control studies are warranted to more comprehensively characterize the efficacy and safety of this combination therapy.
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Neoplasias da Mama , Everolimo , Humanos , Feminino , Everolimo/uso terapêutico , Neoplasias da Mama/patologia , Proteínas Proto-Oncogênicas c-akt/uso terapêutico , Fosfatidilinositol 3-Quinases , Estudos Retrospectivos , Receptor ErbB-2/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Serina-Treonina Quinases TORRESUMO
Pericytes and endothelial cells (ECs) constitute the fundamental components of blood vessels. While the role of ECs in tumor angiogenesis and the tumor microenvironment is well appreciated, pericyte function in tumors remains underexplored. In this study, we used pericyte-specific deletion of the nitric oxide (NO) receptor, soluble guanylate cyclase (sGC), to investigate via single-cell RNA sequencing how pericytes influence the vascular niche and the tumor microenvironment. Our findings demonstrate that pericyte sGC deletion disrupts EC-pericyte interactions, impairing Notch-mediated intercellular communication and triggering extensive transcriptomic reprogramming in both pericytes and ECs. These changes further extended their influence to neighboring cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) through paracrine signaling, collectively suppressing tumor growth. Inhibition of pericyte sGC has minimal impact on quiescent vessels but significantly increases the vulnerability of angiogenic tumor vessels to conventional anti-angiogenic therapy. In conclusion, our findings elucidate the role of pericytes in shaping the tumor vascular niche and tumor microenvironment and support pericyte sGC targeting as a promising strategy for improving anti-angiogenic therapy for cancer treatment.
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Neoplasias , Pericitos , Humanos , Pericitos/patologia , Pericitos/fisiologia , Guanilil Ciclase Solúvel , Células Endoteliais/fisiologia , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Neoplasias/genética , Neoplasias/patologia , Guanilato Ciclase , Microambiente TumoralRESUMO
Deciphering patterns of connectivity between neurons in the brain is a critical step toward understanding brain function. Imaging-based neuroanatomical tracing identifies area-to-area or sparse neuron-to-neuron connectivity patterns, but with limited throughput. Barcode-based connectomics maps large numbers of single-neuron projections, but remains a challenge for jointly analyzing single-cell transcriptomics. Here, we established a rAAV2-retro barcode-based multiplexed tracing method that simultaneously characterizes the projectome and transcriptome at the single neuron level. We uncovered dedicated and collateral projection patterns of ventromedial prefrontal cortex (vmPFC) neurons to five downstream targets and found that projection-defined vmPFC neurons are molecularly heterogeneous. We identified transcriptional signatures of projection-specific vmPFC neurons, and verified Pou3f1 as a marker gene enriched in neurons projecting to the lateral hypothalamus, denoting a distinct subset with collateral projections to both dorsomedial striatum and lateral hypothalamus. In summary, we have developed a new multiplexed technique whose paired connectome and gene expression data can help reveal organizational principles that form neural circuits and process information.
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Neuritos , Neurônios , Neurônios/metabolismo , Encéfalo , Córtex Pré-Frontal , Vias Neurais/fisiologiaRESUMO
Adenine base editors (ABEs) and cytosine base editors (CBEs) enable the single nucleotide editing of targeted DNA sites avoiding generation of double strand breaks, however, the genomic features that influence the outcomes of base editing in vivo still remain to be characterized. High-throughput datasets from lentiviral integrated libraries were used to investigate the sequence features affecting base editing outcomes, but the effects of endogenous factors beyond the DNA sequences are still largely unknown. Here the base editing outcomes of ABE and CBE were evaluated in mammalian cells for 5012 endogenous genomic sites and 11,868 genome-integrated target sequences, with 4654 genomic sites sharing the same target sequences. The comparative analyses revealed that the editing outcomes of ABE and CBE at endogenous sites were substantially different from those obtained using genome-integrated sequences. We found that the base editing efficiency at endogenous target sites of both ABE and CBE was influenced by endogenous factors, including epigenetic modifications and transcriptional activity. A deep-learning algorithm referred as BE_Endo, was developed based on the endogenous factors and sequence information from our genomic datasets, and it yielded unprecedented accuracy in predicting the base editing outcomes. These findings along with the developed computational algorithms may facilitate future application of BEs for scientific research and clinical gene therapy.
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Background: Delayed neuropsychiatric sequelae (DNS), which seriously affect the daily lives of patients, are the most common complications of carbon monoxide (CO) poisoning. No uniform screening tool is available for identifying high-risk groups. Therefore, in this study, we aimed to explore whether conventional laboratory indicators and imaging data from primary hospitals could predict the occurrence of DNS. Methods: This retrospective observational study was conducted in a single-center primary hospital from January 1, 2021 to May 31, 2023. Participants included patients aged >18 years with acute CO poisoning. Patients with complete recovery in the acute phase were followed up by telephone and outpatient visits, and the presence of DNS was determined according to the occurrence of new neurological symptoms within 6 weeks after discharge. We obtained demographic, laboratory, and imaging data from the medical records and performed a univariate analysis. A multivariate logistic regression model was used to identify independent clinical predictors of DNS. Results: A total of 73 patients were included in the study, of whom 25 (34.2%) developed DNS. Multivariate logistic regression analysis revealed that a longer duration of CO exposure (adjusted odds ratio (AOR): 1.262, 95% confidence interval (CI): 1.069-1.490) and the presence of acute brain lesions on diffusion-weighted imaging (DWI) (AOR: 5.117, 95% CI: 1.430-18.315) were independent risk factors for DNS. Receiver operating characteristic analyses of the duration of CO exposure were performed (area under the curve (AUC): 0.825; 95% CI: 0.731-0.918) with a cut-off value of 5.5 h, and DNS was predicted with a sensitivity of 96% and a specificity of 66.7%. Conclusion: High cranial DWI signal within 24 h and duration of poisoning longer than 5.5 h are independent predictors of DNS. The predictive effects of conventional laboratory indicators require further standardized and large-sample studies.
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BACKGROUND: Clusters, a novel hierarchical material structure that emerges from atoms or molecules, possess unique reactivity and catalytic properties, crucial in catalysis, biomedicine, and optoelectronics. Predicting cluster energy provides insights into electronic structure, magnetism, and stability. However, the structure of clusters and their potential energy surface is exceptionally intricate. Searching for the global optimal structure (the lowest energy) among these isomers poses a significant challenge. Currently, modelling cluster energy predictions with traditional machine learning methods has several issues, including reliance on manual expertise, slow computation, heavy computational resource demands, and less efficient parameter tuning. RESULTS: This paper introduces a predictive model for the energy of a gold cluster comprising twenty atoms (referred to as Au20 cluster). The model integrates the Multiple Strategy Fusion Whale Optimization Algorithm (MSFWOA) with the Light Gradient Boosting Machine (LightGBM), resulting in the MSFWOA-LightGBM model. This model employs the Coulomb matrix representation and eigenvalue solution methods for feature extraction. Additionally, it incorporates the Tent chaotic mapping, cosine convergence factor, and inertia weight updating strategy to optimize the Whale Optimization Algorithm (WOA), leading to the development of MSFWOA. Subsequently, MSFWOA is employed to optimize the parameters of LightGBM for supporting the energy prediction of Au20 cluster. CONCLUSIONS: The experimental results show that the most stable Au20 cluster structure is a regular tetrahedron with the lowest energy, displaying tight and uniform atom distribution, high geometric symmetry. Compared to other models, the MSFWOA-LightGBM model excels in accuracy and correlation, with MSE, RMSE, and R2 values of 0.897, 0.947, and 0.879, respectively. Additionally, the MSFWOA-LightGBM model possesses outstanding scalability, offering valuable insights for material design, energy storage, sensing technology, and biomedical imaging, with the potential to drive research and development in these areas.