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1.
Proc Natl Acad Sci U S A ; 120(46): e2308670120, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37939085

RESUMO

Understanding the neurobiological mechanisms underlying consciousness remains a significant challenge. Recent evidence suggests that the coupling between distal-apical and basal-somatic dendrites in thick-tufted layer 5 pyramidal neurons (L5PN), regulated by the nonspecific-projecting thalamus, is crucial for consciousness. Yet, it is uncertain whether this thalamocortical mechanism can support emergent signatures of consciousness, such as integrated information. To address this question, we constructed a biophysical network of dual-compartment thick-tufted L5PN, with dendrosomatic coupling controlled by thalamic inputs. Our findings demonstrate that integrated information is maximized when nonspecific thalamic inputs drive the system into a regime of time-varying synchronous bursting. Here, the system exhibits variable spiking dynamics with broad pairwise correlations, supporting the enhanced integrated information. Further, the observed peak in integrated information aligns with criticality signatures and empirically observed layer 5 pyramidal bursting rates. These results suggest that the thalamocortical core of the mammalian brain may be evolutionarily configured to optimize effective information processing, providing a potential neuronal mechanism that integrates microscale theories with macroscale signatures of consciousness.


Assuntos
Neurônios , Células Piramidais , Animais , Neurônios/fisiologia , Células Piramidais/fisiologia , Dendritos/fisiologia , Tálamo/fisiologia , Mamíferos
2.
Proc Natl Acad Sci U S A ; 120(39): e2218501120, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37722049

RESUMO

While an array of ecological mechanisms has been shown to stabilize natural community dynamics, how the effectiveness of these mechanisms-including both their direction (stabilizing vs. destabilizing) and strength-shifts under a changing climate remains unknown. Using a 35-y dataset (1985 to 2019) from a desert stream in central Arizona (USA), we found that as annual mean air temperature rose 1°C and annual mean precipitation reduced by 40% over the last two decades, macroinvertebrate communities experienced dramatic changes, from relatively stable states during the first 15 y of this study to wildly fluctuating states highly sensitive to climate variability in the last 10 y. Asynchronous species responses to climatic variability, the primary mechanism historically undergirding community stability, greatly weakened. The emerging climate regime-specifically, concurrent warming and prolonged multiyear drought-resulted in community-wide synchronous responses and reduced taxa richness. Diversity loss and new establishment of competitors reorganized species interactions. Unlike manipulative experiments that often suggest stabilizing roles of species interactions, we found that reorganized species interactions switched from stabilizing to destabilizing influences, further amplifying community fluctuations. Our study provides evidence of climate change-induced modifications of mechanisms underpinning long-term community stability, resulting in an overall destabilizing effect.


Assuntos
Mudança Climática , Secas , Arizona , Análise por Conglomerados , Rios
3.
Brief Bioinform ; 24(5)2023 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-37544661

RESUMO

With the development of chromosome conformation capture technology, the genome-wide investigation of higher-order chromatin structure by using high-throughput chromatin conformation capture (Hi-C) technology is emerging as an important component for understanding the mechanism of gene regulation. Considering genetic and epigenetic differences are typically used to explore the pathological reasons on the chromosome and gene level, visualizing multi-omics data and performing an intuitive analysis by using an interactive browser become a powerful and welcomed way. In this paper, we develop an effective sequence and chromatin interaction data display browser called HiBrowser for visualizing and analyzing Hi-C data and their associated genetic and epigenetic annotations. The advantages of HiBrowser are flexible multi-omics navigation, novel multidimensional synchronization comparisons and dynamic interaction system. In particular, HiBrowser first provides an out of the box web service and allows flexible and dynamic reconstruction of custom annotation tracks on demand during running. In order to conveniently and intuitively analyze the similarities and differences among multiple samples, such as visual comparisons of normal and tumor tissue samples, and pan genomes of multiple (consanguineous) species, HiBrowser develops a clone mode to synchronously display the genome coordinate positions or the same regions of multiple samples on the same page of visualization. HiBrowser also supports a pluralistic and precise search on correlation data of distal cis-regulatory elements and navigation to any region on Hi-C heatmap of interest according to the searching results. HiBrowser is a no-build tool, and could be easily deployed in local server. The source code is available at https://github.com/lyotvincent/HiBrowser.


Assuntos
Visualização de Dados , Software , Genoma , Cromossomos , Cromatina
4.
Genes Chromosomes Cancer ; 63(3): e23231, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38459936

RESUMO

Lynch syndrome-associated endometrial cancer patients often present multiple synchronous tumors and this assessment can affect treatment strategies. We present a case of a 27-year-old woman with tumors in the uterine corpus, cervix, and ovaries who was diagnosed with endometrial cancer and exhibited cervical invasion and ovarian metastasis. Her family history suggested Lynch syndrome, and genetic testing identified a variant of uncertain significance, MLH1 p.L582H. We conducted immunohistochemical staining, microsatellite instability analysis, and Sanger sequencing for Lynch syndrome-associated cancers in three generations of the family and identified consistent MLH1 loss. Whole-exome sequencing for the corpus, cervical, and ovarian tumors of the proband identified a copy-neutral loss of heterozygosity (LOH) occurring at the MLH1 position in all tumors. This indicated that the germline variant and the copy-neutral LOH led to biallelic loss of MLH1 and was the cause of cancer initiation. All tumors shared a portion of somatic mutations with high mutant allele frequencies, suggesting a common clonal origin. There were no mutations shared only between the cervix and ovary samples. The profiles of mutant allele frequencies shared between the corpus and cervix or ovary indicated that two different subclones originating from the corpus independently metastasized to the cervix or ovary. Additionally, all tumors presented unique mutations in endometrial cancer-associated genes such as ARID1A and PIK3CA. In conclusion, we demonstrated clonal origin and genomic diversity in a Lynch syndrome-associated endometrial cancer, suggesting the importance of evaluating multiple sites in Lynch syndrome patients with synchronous tumors.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias do Endométrio , Proteína 1 Homóloga a MutL , Neoplasias Primárias Múltiplas , Adulto , Feminino , Humanos , Neoplasias Colorretais Hereditárias sem Polipose/complicações , Neoplasias Colorretais Hereditárias sem Polipose/genética , Reparo de Erro de Pareamento de DNA , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Genômica , Instabilidade de Microssatélites , Proteína 1 Homóloga a MutL/genética , Neoplasias Primárias Múltiplas/genética
5.
Proteins ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38687146

RESUMO

An explicit analytic solution is given for the Langevin equation applied to the Gaussian Network Model of a protein subjected to both a random and a deterministic periodic force. Synchronous and asynchronous components of time correlation functions are derived and an expression for phase differences in the time correlations of residue pairs is obtained. The synchronous component enables the determination of dynamic communities within the protein structure. The asynchronous component reveals causality, where the time correlation function between residues i and j differs depending on whether i is observed before j or vice versa, resulting in directional information flow. Driver and driven residues in the allosteric process of cyclophilin A and human NAD-dependent isocitrate dehydrogenase are determined by a perturbation-scanning technique. Factors affecting phase differences between fluctuations of residues, such as network topology, connectivity, and residue centrality, are identified. Within the constraints of the isotropic Gaussian Network Model, our results show that asynchronicity increases with viscosity and distance between residues, decreases with increasing connectivity, and decreases with increasing levels of eigenvector centrality.

6.
Small ; 20(26): e2311377, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38299746

RESUMO

Developing inventive approaches to control crystallization and suppress trap defects in perovskite films is crucial for achieving efficient perovskite photovoltaics. Here, a synchronous regulation strategy is developed that involves the infusion of a zwitterionic ionic liquid additive, pyrrolidinium thiocyanate (PySCN), into the perovskite precursor to optimize the subsequent crystallization and defects. PySCN modification not only orchestrates the crystallization process but also deftly addresses trap defects in perovskite films. Within this, SCN- compensates for positively charged defects, while Py+ plays the role of passivating negatively charged defects. Based on the vacuum flash evaporation without anti-solvent, the air-processed perovskite solar cells (PSCs) with PySCN modification can achieve an extraordinary champion efficiency of 22.46% (0.1 cm2) and 21.15% (1.0 cm2) with exceptional stability surpassing 1200 h. Further, the self-powered photodetector goes above and beyond, showcasing an ultra-low dark current of 2.13 × 10-10 A·cm-2, a specific detection rate of 6.12 × 1013 Jones, and an expansive linear dynamic range reaching an astonishing 122.49 dB. PySCN modification not only signifies high efficiency but also ushers in a new era for crystallization regulation, promising a transformative impact on the optoelectronic performance of perovskite-based devices.

7.
Small ; 20(11): e2305688, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37922529

RESUMO

Developing a facile strategy for constructing oriented mixed matrix membranes (MMMs) with uniformly dispersed and high-loading metal-organic frameworks (MOFs) is a crucial scientific challenge in probing the enhanced capability and potential applications of MOF-polymer MMMs. Herein, a novel synchronous synthetic method for constructing oriented CuBDC/poly(m-phenylenediamine) (CuBDC/PmPD) MMM with uniform MOF dispersion at high loading at the air-solution interface via the dual function of metal ions is reported. The resulting MMM exhibits excellent separation performance in ion sieving and seawater desalination due to the structural integrity of the proposed membrane and the highly interconnected channels created through the oriented distribution of MOF in a polymer matrix. Such a cutting-edge approach may provide promising insights into the development of advanced MMMs with optimized structure and superior performances.

8.
Small ; : e2401167, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528426

RESUMO

Covalent organic frameworks (COFs) are promising iodine adsorbents. For improved performances, it is critical and essential to fundamentally understand the underlying mechanism. Here, using the operando dark-field optical microscopy (DFM) imaging technique, the observation of an extraordinary structure shrinkage of 2D triphenylbenzene (TPB)-dimethoxyterephthaldehyde (DMTP)-COF upon the adsorption of I2 vapor at the single-particle resolution is reported. Combining single-particle DFM imaging with other experimental and theoretical methods, it is revealed that the shrinkage mechanism of the TPB-DMTP-COF is attributed to the I2 sorption-induced synchronous skeleton-pore interactions. The redox reaction of I2 and TPB-DMTP-COF yields some cationic skeletons and I3 - species, which triggers the multi-directional halogen-bonding interactions of I2 and I3 - as well as strong cation-π interactions between neutral and cationic skeletons, accompanying the synchronous in-plane skeleton shrinking in the xy plane and compact out-of-plane layer packing in the z-direction. This understanding of the synchronous action between the skeleton and pore breaks the perspective on the structure robustness of 2D COFs with excellent stability during the I2 uptake, which offers pivotal guidance for the rational design and creation of advanced microporous adsorbents.

9.
Proc Biol Sci ; 291(2021): 20232335, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38628129

RESUMO

Many animals and plants have species-typical annual cycles, but individuals vary in their timing of life-history events. Individual variation in fur replacement (moult) timing is poorly understood in mammals due to the challenge of repeated observations and longitudinal sampling. We examined factors that influence variation in moult duration and timing among elephant seals (Mirounga angustirostris). We quantified the onset and progression of fur loss in 1178 individuals. We found that an exceptionally rapid visible moult (7 days, the shortest of any mammals or birds), and a wide range of moult start dates (spanning 6-10× the event duration) facilitated high asynchrony across individuals (only 20% of individuals in the population moulting at the same time). Some of the variation was due to reproductive state, as reproductively mature females that skipped a breeding season moulted a week earlier than reproductive females. Moreover, individual variation in timing and duration within age-sex categories far outweighed (76-80%) variation among age-sex categories. Individuals arriving at the end of the moult season spent 50% less time on the beach, which allowed them to catch up in their annual cycles and reduce population-level variance during breeding. These findings underscore the importance of individual variation in annual cycles.


Assuntos
Aves , Focas Verdadeiras , Animais , Feminino , Muda , Reprodução , Mamíferos , Estações do Ano
10.
Ann Surg Oncol ; 31(5): 3437-3447, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38300405

RESUMO

BACKGROUND: The standard treatment for advanced esophageal cancer with synchronous distant metastasis is systemic chemotherapy or immunotherapy. Conversion surgery is not established for esophageal cancer with synchronous distant metastasis. This study aimed to investigate the clinical impact of conversion surgery for esophageal cancer with synchronous distant metastasis after induction therapy. METHODS: This multi-institutional retrospective study enrolled 66 patients with advanced esophageal cancer, including synchronous distant metastasis, who underwent induction chemotherapy or chemoradiotherapy followed by conversion surgery between 2005 and 2021. Short- and long-term outcomes were investigated. RESULTS: Distant lymph node (LN) metastasis occurred in 51 patients (77%). Distant organ metastasis occurred in 15 (23%) patients. There were 41 patients with metastatic para-aortic LNs, and 10 patients with other metastatic LNs. Organs with distant metastasis included the lung in seven patients, liver in seven patients, and liver and lung in one patient. For 61 patients (92%), R0 resection was achieved. The postoperative complication rate was 47%. The in-hospital mortality rate was 1%, and the 3- and 5-year overall survival (OS) rates for all the patients were 32.4% and 24.4%, respectively. The OS rates were similar between the patients with distant LN metastasis and the patients with distant organ metastasis (3-year OS: 34.9% vs. 26.7%; P = 0.435). Multivariate analysis showed that pathologic nodal status is independently associated with a poor prognosis (hazard ratio, 2.43; P = 0.005). CONCLUSIONS: Conversion surgery after chemotherapy or chemoradiotherapy for esophageal cancer with synchronous distant metastasis is feasible and promising. It might be effective for improving the long-term prognosis for patients with controlled nodal status.


Assuntos
Neoplasias Esofágicas , Quimioterapia de Indução , Humanos , Estudos Retrospectivos , Neoplasias Esofágicas/patologia , Prognóstico , Linfonodos/cirurgia , Linfonodos/patologia , Metástase Linfática/patologia , Taxa de Sobrevida , Estadiamento de Neoplasias
11.
J Cardiovasc Electrophysiol ; 35(6): 1115-1120, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38534012

RESUMO

INTRODUCTION: Few studies have demonstrated a high degree of atrioventricular (AV) synchrony with a new leadless pacemaker called Micra AV. Our group previously reported a new and unique sensing method. We believe that this novel sensing method, "Simplified A3 method," might facilitate better AV synchrony than a conventional sensing method in almost all cases with Micra AV implantation. METHODS: We conducted a non-randomized retrospective study comparing the two pacing methods at two centers. From December 1, 2021 to October 31, 2022, Micra AV was implanted for 32 patients at the two centers. Twenty of the 32 patients with sinus rhythm and complete AV block were included in this study. In Group 1, the conventional setting was programmed as follows: auto A3 threshold, auto A3 window-end (WE), and auto A4 threshold turned on during hospitalization. In Group 2, the "Simplified A3 method" was programmed as follows: auto A3 threshold and auto A3WE turned off. Instead, an intentionally prolonged A3WE (850-1000 ms) and low A3 threshold (A3 signal amplitude + 0.5-1.0 m/s2) were programmed. RESULTS: Twenty patients were analyzed. In Group 2, AV synchrony (%AMVp) was significantly higher at the first outpatient clinic (63.0 ± 5.7% vs 81.0 ± 4.2%, p = .03). A3 threshold was significantly lower in Group 2 (5.9 ± 0.7 m/s2, p < .05 vs 2.3 ± 0.5 m/s2, p < .05). CONCLUSION: Our novel sensing method might be a more feasible sensing method for obtaining higher AV synchrony than the conventional algorithm.


Assuntos
Potenciais de Ação , Bloqueio Atrioventricular , Estimulação Cardíaca Artificial , Estudos de Viabilidade , Frequência Cardíaca , Marca-Passo Artificial , Humanos , Masculino , Feminino , Estimulação Cardíaca Artificial/métodos , Estudos Retrospectivos , Idoso , Bloqueio Atrioventricular/terapia , Bloqueio Atrioventricular/fisiopatologia , Bloqueio Atrioventricular/diagnóstico , Resultado do Tratamento , Desenho de Equipamento , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Fatores de Tempo , Valor Preditivo dos Testes , Nó Atrioventricular/fisiopatologia , Processamento de Sinais Assistido por Computador
12.
Artigo em Inglês | MEDLINE | ID: mdl-38923693

RESUMO

INTRODUCTION: Pacemaker-mediated tachycardia is a known arrhythmia in patients with dual chamber pacemakers and defibrillators and intact ventriculoatrial (VA) conduction. We report a case of pacemaker-mediated reentrant arrhythmia (PMRA) in a patient with an atrioventricular (AV) synchronous leadless pacemaker. METHODS AND RESULTS: A 91-year-old female presented with 2:1 AV conduction and received an AV synchronous leadless pacemaker. She had atrial mechanical sense-ventricular paced beats between heart rates of 80-100 bpm more than 80% of the time. She was found to have a new cardiomyopathy and was referred for placement of biventricular pacemaker. At the time of device implantation, her electrocardiogram showed ventricular pacing with a short RP interval and superiorly directed P waves. Changes in the ventricular pacing rate resulted in changes in the atrial rate. Following device placement, her heart rate decreased to the lower rate limit of her pacemaker. The atrial mechanical sense impulse most likely was generated by a retrograde conducted P wave resulting in near incessant PMRA. CONCLUSION: PMRA may occur in patients who receive an AV synchronous leadless pacemaker with intact VA conduction and sinoatrial node dysfunction. Due to the lower rates of PMRA, this arrhythmia may be underrecognized. Interventions for and implications of PMRA need further investigation.

13.
Cancer Invest ; 42(3): 212-225, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38527848

RESUMO

This study aimed to develop prognostic prediction models for patients diagnosed with synchronous thyroid and breast cancer (TBC). Utilizing the SEER database, key predictive factors were identified, including T stage of thyroid cancer, T stage of breast cancer, M stage of breast cancer, patient age, thyroid cancer surgery type, and isotope therapy. A nomogram predicting 5-year and 10-year survival rates was constructed and validated, exhibiting strong performance (C-statistic: 0.79 in the development cohort (95% CI: 0.74-0.84), and 0.82 in the validation cohort (95% CI: 0.77-0.89)). The area under the Receiver Operator Characteristic (ROC) curve ranged from 0.798 to 0.883 for both cohorts. Calibration and decision curve analyses further affirmed the model's clinical utility. Stratifying patients into high-risk and low-risk groups using the nomogram revealed significant differences in survival rates (P < 0.0001). The successful development and validation of this nomogram for predicting 5-year and 10-year survival rates in patients with synchronous TBC hold promise for similar patient populations, contributing significantly to cancer research.


Assuntos
Neoplasias da Mama , Nomogramas , Programa de SEER , Neoplasias da Glândula Tireoide , Humanos , Feminino , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Pessoa de Meia-Idade , Prognóstico , Idoso , Neoplasias Primárias Múltiplas/mortalidade , Neoplasias Primárias Múltiplas/patologia , Adulto , Taxa de Sobrevida , Estadiamento de Neoplasias , Curva ROC
14.
BMC Cancer ; 24(1): 260, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38402173

RESUMO

BACKGROUND: Primary tumor removal by cytoreductive nephrectomy in synchronous metastatic renal cell carcinoma patients has been investigated in the context of various treatment regimens. Two randomized controlled trials investigated the role and timing of cytoreductive nephrectomy in the era of targeted therapy and demonstrated that upfront nephrectomy should no longer be performed when patients require systemic therapy. Superiority of checkpoint immunotherapy agents has led to a paradigm change from targeted therapies to immunotherapy-based first-line treatment in patients with primary metastatic disease; thus, deferred cytoreductive nephrectomy needs to be verified in the immunotherapy setting. Furthermore, a need exists for personalizing treatment choices for the individual patient to avoid unnecessary overtreatment. METHODS/DESIGN: To explore the impact of cytoreductive nephrectomy in this patient group receiving checkpoint immunotherapy, we initiated a randomized, controlled trial comparing deferred cytoreductive nephrectomy with no surgery. The trial integrates a comprehensive translational research program with specimen sampling for biomarker analysis. DISCUSSION: The trial aims to show that deferred cytoreductive nephrectomy improves overall survival in patients with synchronous metastatic renal cell carcinoma, and furthermore, to identify relevant biomarkers for personalized renal cancer management. TRIAL REGISTRATION: ClinicalTrials.gov NCT03977571 June 6, 2019.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/cirurgia , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/cirurgia , Nefrectomia
15.
Exp Eye Res ; 239: 109783, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38199262

RESUMO

Form deprivation (FD) is a widely employed experimental paradigm, typically used to induce unilateral myopia in animal models. This model is weakened by potential influence upon the FD eye from vision in the freely-viewing contralateral eye, which could be eliminated by imposing FD in both eyes; but while a few previous studies have explored the feasibility of inducing bilateral FD in chicks, substantial discrepancies in treatment outcomes were noted. Consequently, this study aimed to establish a bilateral FD myopia model in chicks, with validation by investigating the associated ocular growth patterns, feeding, and social behavior. Six-day-old chicks were treated with bilateral (n = 21) or unilateral (n = 10) FD for 12 days; the fellow untreated eyes in the unilateral FD group served as controls. Refractive error, corneal power, and ocular axial dimensions were measured at 4-day intervals after the onset of form deprivation, with a Hartinger refractometer, a custom-made videokeratography system, and a high-resolution A-scan ultrasonographer, respectively. Body weight was monitored to assess the chick's physical development. Our results showed that birds treated with bilateral FD grew as robustly as the unilaterally form-deprived chicks, with similar or slightly heavier body weights and mortalities. Unilateral FD induced significantly higher myopia in the treated eye, with stronger corneal power, deeper anterior and vitreous chambers, and longer axial length. Moreover, either bilaterally or unilaterally FD eyes developed similar refractive error (bilateral FD, left: -28.03 ± 9.06 D, right: -28.44 ± 9.45 D; unilateral FD: -29.48 ± 8.26 D) and ocular biometric changes; but choroidal thickness was thicker in bilaterally FD eyes, rather than thinner as in unilaterally FD eyes. In addition to the highly synchronized (symmetrical, parallel) development reported previously in bilateral FD, we found in this study that the correlations between bilaterally form-deprived eyes were highest for ocular biometric parameters directly contributing to myopia development, including corneal power (r = 0.74 to 0.93), anterior chamber depth (r = 0.60 to 0.85), vitreous chamber depth (r = 0.92 to 0.94), and axial length (r = 0.90 to 0.96). The remarkably synchronized growth pattern confirmed the feasibility of the bilateral FD paradigm for future research on myopia.


Assuntos
Miopia , Erros de Refração , Animais , Miopia/etiologia , Olho , Galinhas , Córnea , Corioide , Privação Sensorial , Refração Ocular
16.
Pharm Res ; 41(3): 513-529, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38383935

RESUMO

BACKGROUND: Panax notoginseng saponins (PNS) are commonly used first-line drugs for treating cerebral thrombosis and stroke in China. However, the synchronized and targeted delivery of active ingredients in traditional Chinese medicine (TCM) poses a significant challenge for modern TCM formulations. METHODS: Bovine serum albumin (BSA) was modified using 2-methacryloyloxyethyl phosphorylcholine (MPC), an analog of acetylcholine, and subsequently adsorbed the major PNS onto the modified albumin to produce MPC-BSA@PNS nanoparticles (NPs). This novel delivery system facilitated efficient and synchronized transport of PNS across the blood-brain barrier (BBB) through active transport mediated by nicotinic acetylcholine receptors. RESULTS: In vitro experiments demonstrated that the transport rates of R1, Rg1, Rb1, and Rd across the BBB were relatively synchronous in MPC-BSA@PNS NPs compared to those in the PNS solution. Additionally, animal experiments revealed that the brain-targeting efficiencies of R1 + Rg1 + Rb1 in MPC-BSA@PNS NPs were 2.02 and 7.73 times higher than those in BSA@PNS NPs and the free PNS group, respectively. CONCLUSIONS: This study presents a simple and feasible approach for achieving the targeted delivery of complex active ingredient clusters in TCM.


Assuntos
Panax notoginseng , Saponinas , Animais , Acetilcolina , Encéfalo , Albuminas
17.
BMC Neurol ; 24(1): 118, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600450

RESUMO

BACKGROUND: Syncope is a common condition that increases the risk of injury and reduces the quality of life. Abdominal pain as a precursor to vasovagal syncope (VVS) in adults is rarely reported and is often misdiagnosed.​. METHODS: We present three adult patients with VVS and presyncopal abdominal pain diagnosed by synchronous multimodal detection (transcranial Doppler [TCD] with head-up tilt [HUT]) and discuss the relevant literature. RESULTS: Case 1: A 52-year-old man presented with recurrent decreased consciousness preceded by six months of abdominal pain. Physical examinations were unremarkable. Dynamic electrocardiography, echocardiography, head and neck computed tomography angiography, magnetic resonance imaging (MRI), and video electroencephalogram showed no abnormalities. Case 2: A 57-year-old woman presented with recurrent syncope for 30 + years, accompanied by abdominal pain. Physical examination, electroencephalography, and MRI showed no abnormalities. Echocardiography showed large right-to-left shunts. Case 3: A 30-year-old woman presented with recurrent syncope for 10 + years, with abdominal pain as a precursor. Physical examination, laboratory analysis, head computed tomography, electrocardiography, and echocardiography showed no abnormalities. Syncope secondary to abdominal pain was reproduced during HUT. Further, HUT revealed vasovagal syncope, and synchronous TCD showed decreased cerebral blood flow; the final diagnosis was VVS in all cases. CONCLUSIONS: Abdominal pain may be a precursor of VVS in adults, and our findings enrich the clinical phenotypic spectrum of VVS. Prompt recognition of syncopal precursors is important to prevent incidents and assist in treatment decision-making. Abdominal pain in VVS may be a sign of sympathetic overdrive. Synchronous multimodal detection can help in diagnosing VVS and understanding hemodynamic mechanisms.


Assuntos
Síncope Vasovagal , Masculino , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Síncope Vasovagal/diagnóstico , Síncope Vasovagal/diagnóstico por imagem , Teste da Mesa Inclinada/métodos , Qualidade de Vida , Frequência Cardíaca , Síncope/complicações
18.
Curr Oncol Rep ; 26(7): 791-803, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38776011

RESUMO

PURPOSE OF REVIEW: This review addresses the current landscape of colorectal cancer (CRC) with a focus on liver metastases, the third most common cancer globally. It explores recent findings in treatment strategies, emphasizing the dynamic interplay between surgery, systemic chemotherapy, and local therapies for synchronous colorectal liver metastases (CRLMs). RECENT FINDINGS: Highlighting the role of advanced imaging, the review underscores the significance of contrast-enhanced MRI in surgical planning for CRLMs. Surgical resection remains a primary choice for resectable cases, with considerations for oncologic scoring systems and tumor biology. Perioperative systemic chemotherapy plays a pivotal role, especially in conversion therapy for initially unresectable CRLMs. The review also explores various local therapies, including radiofrequency ablation, microwave ablation, stereotactic body radiotherapy, hepatic arterial infusional chemotherapy, selective internal radiation therapy, and transarterial chemoembolization for unresectable cases. A comprehensive approach, integrating surgery, systemic chemotherapy, and local therapies, is crucial for managing synchronous CRLMs. Surgical resection and perioperative chemotherapy are key players, guided by considerations of tumor biology and scoring systems. For unresectable cases, local therapies offer viable alternatives, emphasizing the need for tailored treatments. Multidisciplinary collaboration among medical oncologists, surgeons, and radiologists is essential. Ongoing research will refine treatment approaches, while emerging technologies hold promise for further advancements in managing colorectal liver metastases.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/cirurgia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Terapia Combinada
19.
J Fluoresc ; 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38319520

RESUMO

A green developed spectrofluorimetric method has been applied for Antazoline (ANT) and Xylometazoline (XLO) determination in both pharmaceutical formulation and pure form. The developed method is synchronous spectrofluorimetry coupled with the second derivative mathematical tool for the determination of antazoline and xylometazoline in their dosage form. The developed method depends on reacting the cited drugs with dansyl chloride, a suitable derivatizing agent, to generate highly fluorescent derivatives. The products formed were measured at emission wavelengths; 703.0 and 712.0 nm after being excited at wavelengths; 350.0 and 355.0 nm for antazoline and xylometazoline, respectively. Synchronous spectrofluorimetry coupled with second derivative mathematical tool was developed and optimized using fluorescence data manager software generating second derivative peak amplitudes at 556.5 nm for antazoline and 598.0 nm for xylometazoline. Linear responses have been represented over a wide range of concentration 0.5-12.0 µg/mL for antazoline and 0.1-10.0 µg/mL for xylometazoline, correspondingly. Method validation was successfully applied. Additionally, statistical comparison of developed method with official ones has been carried out where no significant difference was found. Evaluation of the method's greenness was proven using several assessment tools. Indeed, the method developed is found to be precise, sensitive, and discriminating to assess the cited drugs for regular analysis.

20.
J Fluoresc ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38717648

RESUMO

Fuel fraud has proliferated due to underlying economic advantage in nearly every nation. For the purpose of detecting adulteration and providing real-time quality assurance, non-destructive oil analysis is crucial. This paper reports the simple approach for fingerprinting undiluted petroleum products including gasoline from various brands, diesel, and kerosene oil in comparison with organic solvents using synchronous fluorescence spectroscopy and hierarchical cluster analysis. Fluorescence-based successful detection of adulterated samples is demonstrated in imported RON 92 gasoline, synthetically adulterated with kerosene oil (KO) in proportions up to 70%. Compared to gasoline, kerosene oil has a lower relative poly aromatic hydrocarbons, as the amount of kerosene oil (KO) increases, the KO peak at 352 nm rises, but the gasoline's peak intensity decreases in the range of 371-500 nm. It is noteworthy that imported fuel grades RON 92 and RON 95 are comparable to each other and surprisingly clustered with RON 91 from the Attock refinery presenting concerns about quality. Similarly, the Shell website mentions that Shell V-Power is RON 99 but interestingly it clusters with retail fuel samples acquired from PSO filling stations and PSO RON 95 showing disagreement with the claim that the fuel is high octane. Another use for this technique in oil exploration was the detection of adulterants and successfully spotted methanol, ethanol, and kerosene oil in the tainted samples. These findings suggest SFS as an accurate, and low-cost testing tool for gasoline fingerprinting and contamination screening.

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