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1.
Pharmaceuticals (Basel) ; 17(7)2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39065801

RESUMEN

Diabetes is a widespread chronic disease that occurs mainly in the elderly population. Due to the difference in pathophysiology between elderly and young patients, the current clinical practice to treat elderly patients with anti-diabetes medications still faces some challenges and dilemmas, such as the urgent need for early diagnosis and prevention, and an imbalance between restricted dietary intake and the risk of undernutrition. Traditional Chinese medicine (TCM) offers various treatment regimens that are actively utilized in the field of diabetes management. Through multiple targets and multiple pathways, TCM formulas, medicinal herbs, and active natural products enhance the efficacy of diabetes prevention and diabetes control measures, simplify complex medication management, and improve common symptoms and common diabetic complications in elderly people. Historically, natural products have played a key role in material composition analysis of TCM and mechanism interpretation to enable drug discovery. However, there have been few conclusions on this topic. This review summarizes the development of TCM for the prevention and management of diabetes in elderly people, existing evidence-based clinical practices, and prospects for future development.

2.
Neural Netw ; 179: 106527, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-39029298

RESUMEN

A novel coronavirus discovered in late 2019 (COVID-19) quickly spread into a global epidemic and, thankfully, was brought under control by 2022. Because of the virus's unknown mutations and the vaccine's waning potency, forecasting is still essential for resurgence prevention and medical resource management. Computational efficiency and long-term accuracy are two bottlenecks for national-level forecasting. This study develops a novel multivariate time series forecasting model, the densely connected highly flexible dendritic neuron model (DFDNM) to predict daily and weekly positive COVID-19 cases. DFDNM's high flexibility mechanism improves its capacity to deal with nonlinear challenges. The dense introduction of shortcut connections alleviates the vanishing and exploding gradient problems, encourages feature reuse, and improves feature extraction. To deal with the rapidly growing parameters, an improved variation of the adaptive moment estimation (AdamW) algorithm is employed as the learning algorithm for the DFDNM because of its strong optimization ability. The experimental results and statistical analysis conducted across three Japanese prefectures confirm the efficacy and feasibility of the DFDNM while outperforming various state-of-the-art machine learning models. To the best of our knowledge, the proposed DFDNM is the first to restructure the dendritic neuron model's neural architecture, demonstrating promising use in multivariate time series prediction. Because of its optimal performance, the DFDNM may serve as an important reference for national and regional government decision-makers aiming to optimize pandemic prevention and medical resource management. We also verify that DFDMN is efficiently applicable not only to COVID-19 transmission prediction, but also to more general multivariate prediction tasks. It leads us to believe that it might be applied as a promising prediction model in other fields.

3.
BMC Emerg Med ; 24(1): 113, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38982343

RESUMEN

OBJECTIVES: The purpose of this study was to investigate the preferred modes of transportation to the hospital among patients with acute stroke and acute myocardial infarction (AMI), as well as to identify the factors that influence the utilization of ambulances. METHODS: We conducted a cross-sectional study, including patients who were diagnosed with acute stroke and AMI, at the people's hospital of Zhongjiang, from September 30th, 2022 to August 30th, 2023. All patients were divided into emergency medical service (EMS)-activation group and self-transportation group. Chi-square and t-tests were utilized to discern differences between groups at baseline. To screen relevant variables, we employed the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis using R package glmnet. Subsequently, we performed a logistic regression analysis to identify predictors of EMS activation according the results of LASSO regression. RESULTS: we collected 929 valid questionnaires. 26.16% of the patients required the services of EMS. 90.9% of individuals have not received any formal first aid education. 42.1% of them reported that they had no understanding of cardiovascular and cerebrovascular diseases. Diagnosed as AMI (OR 0.22, 95%CI 0.06 to 0.88) or acute cerebral infarction (OR 0.26, 0.10 to 0.68), the distance between the patient and the nearest 120 network hospital when the patient had these symptoms (OR 0.97, 0.94 to 0.99), the patient's son or daughter was there when the patient was symptomatic (OR 0.58, 0.37 to 0.94), the patient (OR 0.19, 0.05 to 0.72) and the patient's partner (wife or husband) (OR 0.36, 0.16 to 0.85) had decided that the patient needed further medical help, Among patients who did not seek immediate help after symptom onset, thinking that the symptoms will disappear spontaneously (OR 0.34, 0.13 to 0.92) or not wanting to disturb others (OR 0.06, 0.01 to 0.66) or believing that they are not important symptoms (OR 0.15, 0.05 to 0.42) were factors independently associated with less ambulance use. Age (OR 1.02, 1.00 to 1.04), Stroke patients have experienced symptoms of disturbance of consciousness or convulsions (OR 2.99, 1.72 to 5.2) were independent factors associated with increased ambulance use. CONCLUSION: There is still ambulance underutilization among patients with acute stroke and AMI in county territory of China. Moreover, it is needed to raise the level of first aid education and awareness about EMS. Additionally, private clinic doctors and the public should gain adequate understanding of the severity of acute stroke and AMI, as well as their common symptoms, the crucial importance of prompt medical intervention. Finally, we propose that all township hospitals should be integrated into the 120 emergency networks and equipped with emergency first aid capabilities, pre-hospital care, and transportation abilities.


Asunto(s)
Servicios Médicos de Urgencia , Infarto del Miocardio , Accidente Cerebrovascular , Humanos , Estudios Transversales , Masculino , Femenino , China , Infarto del Miocardio/terapia , Persona de Mediana Edad , Accidente Cerebrovascular/terapia , Anciano , Servicios Médicos de Urgencia/estadística & datos numéricos , Transporte de Pacientes/estadística & datos numéricos , Encuestas y Cuestionarios , Ambulancias/estadística & datos numéricos
4.
J Econ Entomol ; 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38966881

RESUMEN

Cadra cautella (Walker) (Lepidoptera: Pyralidae) is a pest in barn, and its eggs are often utilized as an alternative prey or as hosts for mass production of insect predators and parasitoids. To aid in developing a mass-rearing system for C. castella, the suitability of using an artificial diet based on brown rice flour and whole brown rice was compared using the age-stage, 2-sex life table. Compared with those reared on brown rice, the insects reared on an artificial diet had a shorter preadult period (32.08 vs 37.38 d), higher fecundity (468.14 vs 356.20 eggs/female), greater intrinsic rate of increase (0.1509 vs 0.1145 d-1), and higher net reproductive rate (199.28 vs 103.52 offspring). Small populations were required to rear the moth on an artificial diet to achieve the same daily production of C. cautella. Still, the food expense was only 60.2% of that of C. cautella reared on brown rice. Approximately 99.44% of the eggs in each rearing procedure could be supplied as alternative prey for predators, with the remainder served to maintain the colonies for subsequent batches. Only eggs laid within 6 d would be utilized to ensure the high quality of alternative prey for the mass production of predacious bugs. Additionally, a multifunctional device was designed for moth rearing and egg collection, reducing labor input and minimizing health risks for workers coping with inhaled scales. To encourage the production of natural enemies, a cost-effective diet for maintaining a sustainable colony, and a system for daily egg-harvesting of alternative prey were proposed.

5.
Rev Cardiovasc Med ; 25(2): 38, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-39077341

RESUMEN

Background: Percutaneous radiofrequency catheter ablation (RFA) in hypertrophic obstructive cardiomyopathy (HOCM) with intracardiac echocardiography (ICE) guidance is a novel method that has been proven to be safe and effective in a small sample size study. RFA of the interventricular septum through a trans-atrial septal approach in HOCM patients with a longer follow-up has not been reported. Methods: 62 consecutive patients from March 2019 to February 2022 were included in this study. The area between the hypertrophied septum and anterior mitral valve (MV) leaflet was established using the three-dimensional system (CARTO 3 system), and all patients received atrial septal puncture under the guidance of intracardiac echocardiography (ICE). Point-by-point ablation was performed to cover the contact area. After ablation, the patients were followed up for 1, 3, 6, and 12 months. Transthoracic echocardiography was performed at 1, 3, 6, and 12 months, and resting and exercise-provoked left ventricular outflow tract (LVOT) gradients were obtained. Results: During the 1-year follow-up, most patients' symptoms improved. The NYHA grading of the patient decreased from 2 (2, 3) at baseline to 2 (1, 2) (p < 0.001). LVOT peak gradient at rest was decreased from 59 ( ± 27) mmHg to 30 ( ± 24) mmHg (p < 0.001), and the provoked peak gradient was decreased from 99 ( ± 33) mmHg to 59 ( ± 34) mmHg (p < 0.001). The average maximum septal thickness was reduced from 21 ( ± 4) mm to 19 ( ± 4) mm (p < 0.001). Conclusions: After a 1-year follow-up, ice-guided radiofrequency ablation for HOCM might be a safe, accurate, and effective method. The catheter might be reliably attached to the ablation target area via trans-atrial septal access.

6.
Econom Stat ; 30: 124-132, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38919505

RESUMEN

The instrumental variable approaches have been demonstrated effective for semiparametrically modeling the propensity function in analyzing data that may be missing not at random. A model specification test is considered for a class of parsimonious semiparametric propensity models. The test is constructed based on assessing an over-identification so as to detect possible incompatibility in the moment conditions when the model and/or instrumental variables are misspecified. Validity of the test under the null hypothesis is established; and its power is studied when the model is misspecified. A data analysis and simulations are presented to demonstrate the effectiveness of our methods.

7.
Front Endocrinol (Lausanne) ; 15: 1364028, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38863925

RESUMEN

Background: The aim of this cross-sectional study was to elucidate the associations between various domains of physical activity, such as occupation-related (OPA), transportation-related (TPA), leisure-time (LTPA) and overall physical activity (PA), and diabetic kidney disease. Methods: Our study encompassed 2,633 participants, drawn from the cross-sectional surveys of the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018, and employed survey-weighted logistic regression, generalized linear regression, and restricted cubic spline (RCS) analyses to ascertain the relationship between different domains of physical activity and diabetic kidney disease. Results: After controlling for all confounders, multivariate logistic regression analyses revealed a lack of correlation between the various domains of physical activity and the prevalence of diabetic kidney disease. Multiple generalized linear regression analyses showed that durations of PA (ß = 0.05, 95% CI, 0.01-0.09, P = 0.012) and TPA (ß = 0.32, 95% CI, 0.10-0.55, P = 0.006) were positively associated with eGFR levels; and LTPA durations were inversely associated with UACR levels (ß = -5.97, 95% CI, -10.50 - -1.44, P = 0.011). The RCS curves demonstrated a nonlinear relationship between PA, OPA, and eGFR, as well as a nonlinear correlation between PA and ACR. Subgroup and sensitivity analyses largely aligned with the outcomes of the multivariate generalized linear regression, underscoring the robustness of our findings. Conclusion: Our population-based study explored the association between different domains of physical activity and diabetic kidney disease. Contrary to our expectations, we found no significant association between the duration of physical activity across all domains and the prevalence of diabetic nephropathy. Nonetheless, renal function markers, including eGFR and UACR, exhibited significant correlations with the duration of total physical activity (TPA) and leisure-time physical activity (LTPA), respectively, among diabetic patients. Interestingly, our findings suggest that diabetic patients engage in physical activity to preserve renal function, ensuring moderate exercise durations not exceeding 35 hours per week.


Asunto(s)
Nefropatías Diabéticas , Ejercicio Físico , Encuestas Nutricionales , Humanos , Masculino , Femenino , Estudios Transversales , Persona de Mediana Edad , Nefropatías Diabéticas/epidemiología , Nefropatías Diabéticas/fisiopatología , Adulto , Actividades Recreativas , Anciano , Tasa de Filtración Glomerular , Prevalencia
8.
Small ; : e2402613, 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38850186

RESUMEN

Methanol is not only a promising liquid hydrogen carrier but also an important feedstock chemical for chemical synthesis. Catalyst design is vital for enabling the reactions to occur under ambient conditions. This study reports a new class of van der Waals heterojunction photocatalyst, which is synthesized by hot-injection method, whereby carbon dots (CDs) are grown in situ on ZnSe nanoplatelets (NPLs), i.e., metal chalcogenide quantum wells. The resultant organic-inorganic hybrid nanoparticles, CD-NPLs, are able to perform methanol dehydrogenation through CH splitting. The heterostructure has enabled light-induced charge transfer from the CDs into the NPLs occurring on a sub-nanosecond timescale, with charges remaining separated across the CD-NPLs heterostructure for longer than 500 ns. This resulted in significantly heightened H2 production rate of 107 µmole·g-1·h-1 and enhanced photocurrent density up to 34 µA cm-2 at 1 V bias potential. EPR and NMR analyses confirmed the occurrence of α-CH splitting and CC coupling. The novel CD-based organic-inorganic semiconductor heterojunction is poised to enable the discovery of a host of new nano-hybrid photocatalysts with full tunability in the band structure, charge transfer, and divergent surface chemistry for guiding photoredox pathways and accelerating reaction rates.

9.
PNAS Nexus ; 3(6): pgae222, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38894876

RESUMEN

S-palmitoylation, a reversible lipid post-translational modification, regulates the functions of numerous proteins. Voltage-gated sodium channels (NaVs), pivotal in action potential generation and propagation within cardiac cells and sensory neurons, can be directly or indirectly modulated by S-palmitoylation, impacting channel trafficking and function. However, the role of S-palmitoylation in modulating NaV1.7, a significant contributor to pain pathophysiology, has remained unexplored. Here, we addressed this knowledge gap by investigating if S-palmitoylation influences NaV1.7 channel function. Acyl-biotin exchange assays demonstrated that heterologously expressed NaV1.7 channels are modified by S-palmitoylation. Blocking S-palmitoylation with 2-bromopalmitate resulted in reduced NaV1.7 current density and hyperpolarized steady-state inactivation. We identified two S-palmitoylation sites within NaV1.7, both located in the second intracellular loop, which regulated different properties of the channel. Specifically, S-palmitoylation of cysteine 1126 enhanced NaV1.7 current density, while S-palmitoylation of cysteine 1152 modulated voltage-dependent inactivation. Blocking S-palmitoylation altered excitability of rat dorsal root ganglion neurons. Lastly, in human sensory neurons, NaV1.7 undergoes S-palmitoylation, and the attenuation of this post-translational modification results in alterations in the voltage-dependence of activation, leading to decreased neuronal excitability. Our data show, for the first time, that S-palmitoylation affects NaV1.7 channels, exerting regulatory control over their activity and, consequently, impacting rodent and human sensory neuron excitability. These findings provide a foundation for future pharmacological studies, potentially uncovering novel therapeutic avenues in the modulation of S-palmitoylation for NaV1.7 channels.

10.
Mar Environ Res ; 199: 106613, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38905867

RESUMEN

Coastal hypoxia (low dissolved oxygen in seawater) is a cumulative result of many physical and biochemical processes. However, it is often difficult to determine the key drivers of hypoxia due to the lack of frequent observational oceanographic and meteorological data. In this study, high-frequency time-series observational data of dissolved oxygen (DO) and related parameters in the coastal waters of Muping, China, were used to analyze the temporal pattern of hypoxia and its key drivers. Two complete cycles with the formation and destruction of hypoxia were captured over the observational period. Persistent thermal stratification, high winds and phytoplankton blooms are identified as key drivers of hypoxia in this region. Hypoxia largely occurs due to persistent thermal stratification in summer, and hypoxia can be noticeably relieved when strong wind mixing weakens thermal stratification. Furthermore, we found that northerly high winds are more efficient at eroding stratification than southerly winds and thus have a greater ability to relieve hypoxia. This study revealed an episodic hypoxic event driven by a phytoplankton bloom that was probably triggered by terrestrial nutrient loading, confirming the causal relationship between phytoplankton blooms and hypoxia. In addition, we found that the lag time between nutrient loading, phytoplankton blooms and hypoxia can be as short as one week. This study could help better understand the development of hypoxia and forecast phytoplankton and hypoxia, which are beneficial for aquaculture in this region.


Asunto(s)
Monitoreo del Ambiente , Eutrofización , Oxígeno , Fitoplancton , Agua de Mar , China , Fitoplancton/fisiología , Agua de Mar/química , Oxígeno/análisis , Viento , Estaciones del Año
11.
J Ethnopharmacol ; 333: 118440, 2024 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-38885916

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Jiedu Tongluo Tiaogan Formula (JTTF), a traditional Chinese herbal decoction, exhibits the potential to treat type 2 diabetes mellitus (T2DM) by inhibiting endoplasmic reticulum stress (ERS) and excessive autophagy, which are the risk factors for the abnormal development and progression of ß cells. AIM OF THE STUDY: We aimed to assess the effect of JTTF on pancreatic glucotoxicity by inhibiting ERS and excessive autophagy, for which db/db mice and INS-1 insulinoma cells were used. MATERIALS AND METHODS: The chemical composition of the JTTF was analyzed by UPLC-Q/TOF-MS. Diabetic (db/db) mice were treated with distilled water or JTTF (2.4 and 7.2 g/kg/day) for 8 weeks. Furthermore, INS-1 cells induced by high glucose (HG) levels were treated with or without JTTF (50, 100, and 200 µg/mL) for 48 h to elucidate the protective mechanism of JTTF on glucose toxicity. The experimental methods included an oral glucose tolerance test, hematoxylin-eosin staining, immunohistochemistry, western blotting, RT-qPCR, and acridine orange staining. RESULT: 28 chemical components of JTTF were identified. Additionally, treatment with JTTF significantly decreased the severity of glycemic symptoms in the db/db mice. Moreover, the treatment partially restored glucose homeostasis in the db/db mice and protected the pancreatic ß-cell function. JTTF protected INS-1 cells from HG injury by upregulating GSIS and PDX1, MafA mRNA expression. Further, treatment with JTTF downregulated GRP78 and ATF6 expression, whereas it inhibited Beclin-1 and LC3 activation. The treatment protected the cells from HG-induced ERS and excessive autophagy by downregulating the CaMKKß/AMPK pathway. CONCLUSIONS: The present study findings show that JTTF may protects ß-cells by inhibiting the CaMKKß/AMPK pathway, which deepens our understanding of the effectiveness of JTTF as a treatment strategy against T2DM.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Autofagia , Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina , Medicamentos Herbarios Chinos , Estrés del Retículo Endoplásmico , Células Secretoras de Insulina , Transducción de Señal , Animales , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Autofagia/efectos de los fármacos , Ratones , Masculino , Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina/metabolismo , Transducción de Señal/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/metabolismo , Ratas , Chaperón BiP del Retículo Endoplásmico , Ratones Endogámicos C57BL , Línea Celular Tumoral , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Experimental/tratamiento farmacológico
12.
J Med Virol ; 96(6): e29755, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38922896

RESUMEN

Throughout the COVID-19 pandemic, rhinovirus (RV) remained notable persistence, maintaining its presence while other seasonal respiratory viruses were largely suppressed by pandemic restrictions during national lockdowns. This research explores the epidemiological dynamics of RV infections among pediatric populations on Hainan Island, China, specifically focusing on the impact before and after the zero-COVID policy was lifted. From January 2021 to December 2023, 19 680 samples were collected from pediatric patients hospitalized with acute lower respiratory tract infections (ARTIs) at the Hainan Maternal and Child Health Hospital. The infection of RV was detected by tNGS. RV species and subtypes were identified in 32 RV-positive samples representing diverse time points by analyzing the VP4/VP2 partial regions. Among the 19 680 pediatric inpatients with ARTIs analyzed, 21.55% were found to be positive for RV infection, with notable peaks observed in April 2021 and November 2022. A gradual annual decline in RV infections was observed, alongside a seasonal pattern of higher prevalence during the colder months. The highest proportion of RV infections was observed in the 0-1-year age group. Phylogenetic analysis on 32 samples indicated a trend from RV-A to RV-C in 2022. This observation suggests potential evolving dynamics within the RV species although further studies are needed due to the limited sample size. The research emphasizes the necessity for ongoing surveillance and targeted management, particularly for populations highly susceptible to severe illnesses caused by RV infections.


Asunto(s)
COVID-19 , Variación Genética , Filogenia , Infecciones por Picornaviridae , Infecciones del Sistema Respiratorio , Rhinovirus , Humanos , Rhinovirus/genética , Rhinovirus/clasificación , Rhinovirus/aislamiento & purificación , China/epidemiología , Lactante , Preescolar , Infecciones por Picornaviridae/epidemiología , Infecciones por Picornaviridae/virología , Niño , Femenino , Masculino , COVID-19/epidemiología , COVID-19/virología , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/epidemiología , Recién Nacido , Estaciones del Año , Adolescente , Prevalencia , Niño Hospitalizado/estadística & datos numéricos , SARS-CoV-2/genética , Hospitalización/estadística & datos numéricos
13.
Yi Chuan ; 46(5): 408-420, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38763775

RESUMEN

Lesch-Nyhan syndrome (LNS) is a congenital defect disease that results in defective purine metabolism. It is caused by pathogenic variants of the HPRT gene. Its clinical symptoms mainly include high uric acid levels, gout, and kidney stones and damage. The mechanism of LNS has not been fully elucidated, and no cure exists. Animal models have always played an important role in exploring causative mechanisms and new therapies. This study combined CRISPR/Cas9 and microinjection to knock out the HPRT gene to create an LNS rabbit model. A sgRNA targeting exon 3 of HPRT gene was designed. Subsequently, Cas9 mRNA and sgRNA were injected into rabbit zygotes, and injected embryos were transferred to the uterus. The genotype and phenotype of rabbits were analyzed after birth. Four infant rabbits (named R1, R2, R3 and R4), which showed varying levels of gene modification, were born. The gene-editing efficiency was 100%. No wild-type sequences at the target HPRT gene were detected in R4 rabbit. Next, 6-thioguanine drug testing confirmed that HPRT enzymatic activity was deficient in R4 infant rabbit. HE staining revealed kidney abnormalities in all infant rabbits. Overall, an sgRNA capable of knocking out the HPRT gene in rabbits was successfully designed, and HPRT gene-modified rabbits were successfully constructed by using CRISPR/Cas9 technology and microinjection. This study provides a new nonrodent animal model for studying LNS syndrome.


Asunto(s)
Sistemas CRISPR-Cas , Modelos Animales de Enfermedad , Hipoxantina Fosforribosiltransferasa , Síndrome de Lesch-Nyhan , Animales , Conejos , Síndrome de Lesch-Nyhan/genética , Hipoxantina Fosforribosiltransferasa/genética , Hipoxantina Fosforribosiltransferasa/metabolismo , Femenino , Edición Génica , ARN Guía de Sistemas CRISPR-Cas/genética , Masculino , Fenotipo
14.
bioRxiv ; 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38766071

RESUMEN

Paraneoplastic neurological syndromes arise from autoimmune reactions against nervous system antigens due to a maladaptive immune response to a peripheral cancer. Patients with small cell lung carcinoma or malignant thymoma can develop an autoimmune response against the CV2/collapsin response mediator protein 5 (CRMP5) antigen. For reasons that are not understood, approximately 80% of patients experience painful neuropathies. Here, we investigated the mechanisms underlying anti-CV2/CRMP5 autoantibodies (CV2/CRMP5-Abs)-related pain. We found that patient-derived CV2/CRMP5-Abs can bind to their target in rodent dorsal root ganglia (DRG) and superficial laminae of the spinal cord. CV2/CRMP5-Abs induced DRG neuron hyperexcitability and mechanical hypersensitivity in rats that were abolished by preventing binding to their cognate autoantigen CRMP5. The effect of CV2/CRMP5-Abs on sensory neuron hyperexcitability and mechanical hypersensitivity observed in patients was recapitulated in rats using genetic immunization providing an approach to rapidly identify possible therapeutic choices for treating autoantibody-induced pain including the repurposing of a monoclonal anti-CD20 antibody that selectively deplete B-lymphocytes. These data reveal a previously unknown neuronal mechanism of neuropathic pain in patients with paraneoplastic neurological syndromes resulting directly from CV2/CRMP5-Abs-induced nociceptor excitability. CV2/CRMP5-Abs directly sensitize pain responses by increasing sensory neuron excitability and strategies aiming at either blocking or reducing CV2/CRMP5-Abs can treat pain as a comorbidity in patients with paraneoplastic neurological syndromes.

15.
Mamm Genome ; 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38816661

RESUMEN

Prostatitis represents a common disease of the male genitourinary system, significantly impacting the physical and mental health of male patients. While numerous studies have suggested a potential link between immune cell activity and prostatitis, the exact causal role of immune cells in prostatitis remains uncertain. This study aims to explore the causal relationship between immune cell characteristics and prostatitis using a bidirectional Mendelian randomization approach. This study utilizes data from the public GWAS database and employs bidirectional Mendelian randomization analysis to investigate the causal relationship between immune cells and prostatitis. The causal relationship between 731 immune cell features and prostatitis was primarily investigated through inverse variance weighting (IVW), complemented by MR-Egger regression, a simple model, the weighted median method, and a weighted model. Ultimately, the results underwent sensitivity analysis to assess the heterogeneity, horizontal pleiotropy, and stability of Single Nucleotide Polymorphisms (SNPs) in immune cells and prostatitis. MR analysis revealed 17 immune cells exhibiting significant causal effects on prostatitis. In contrast, findings from reverse MR indicated a significant causal relationship between prostatitis and 13 immune cells. Our study utilizes bidirectional Mendelian Randomization to establish causal relationships between specific immune cell phenotypes and prostatitis, highlighting the reciprocal influence between immune system behavior and the disease. Our findings suggest targeted therapeutic approaches and the importance of including diverse populations for broader validation and personalized treatment strategies.

16.
Materials (Basel) ; 17(9)2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38730891

RESUMEN

The simultaneous increase in strength and plasticity of aluminum and its alloys at cryogenic temperatures has been shown in previous research, but the deformation mechanism was still unclear. Therefore, the purpose of this investigation was to reveal the relationship between slip behavior and mechanical response at low temperatures. A quasi-in situ scanning electron microscope was used to observe the evolution of slip bands in the selected aluminum single crystals with two typical orientations at 25 °C, -100 °C, and -180 °C. The results showed that irrespective of orientation, the density of the slip plane was increased with the decline in temperature, which inhibited slip localization and significantly improved plasticity and work hardening. In detail, at RT, the slip bands were widening until the micro-cracks were generated, causing early failure during deformation. When the temperature was decreased to -180 °C, the slip plane density was increased, and the deformation was more homogenous. Moreover, the slip mode was influenced by orientation and temperature. In particular, a single slip system was activated in the sample with the [112] orientation at all the temperatures investigated. Multiple slip systems were found to activate at 25 °C and -100 °C, and only the primary slip system was activated in the sample with [114] orientation at -180 °C. These findings deepen the understanding of slip behavior at cryogenic temperatures, providing new insights into the deformation mechanism of aluminum and its alloys.

17.
Chemosphere ; 358: 142186, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38701860

RESUMEN

Fluorinated compounds (FCs) such as sulfur hexafluoride (SF6) and nitrogen trifluoride (NF3) have garnered attention due to their environmental impact. This study investigates the mineralization and removal of two potent FCs: SF6 and NF3. The results confirm that utilizing various oxalate salts leads to the formation of corresponding metallic fluorides: lithium fluoride (LiF), sodium fluoride (NaF), and potassium fluoride (KF), validating the occurrence of mineralization reactions. Among the oxalate salts, sodium oxalate demonstrates the highest mineralization efficiency in both SF6 and NF3 removal. Real-time Fourier transform infrared spectroscopy (FT-IR) gas-phase analysis confirms rapid and complete gas removal within a short reaction time using the selected oxalate salts. Meticulous mass balance calculations revealed that oxalates (LiF, NaF, and KF) yielded sulfur (S) at rates of 92.09%, 91.85%, and 84.98% following SF6 mineralization. Additionally, the conversion rates of oxalates to the corresponding metallic fluorides (LiF, NaF, and KF) after SF6 mineralization were 98.18%, 95.82%, and 95.21%, respectively. Similarly, after NF3 mineralization, these conversion rates stood at 92.18%, 90.67%, and 90.02%, respectively. The removal efficiencies for SF6 (1000 ppm) were 4.98, 12.01, and 7.23 L/g, while those for NF3 (1000 ppm) were 14.1, 12.6, and 11.7 L/g, respectively. Notably, sodium oxalate exhibits superior effectiveness, achieving 100% SF6 conversion within 30 min and 100% NF3 conversion within 50 min. This work underscores the potential of oxalate mineralization as a promising strategy for efficient and rapid removal of potent fluorinated compounds, paving the way for environmentally benign FC remediation techniques with broader implications for sustainable gas treatment technologies.


Asunto(s)
Fluoruros , Gases de Efecto Invernadero , Oxalatos , Hexafluoruro de Azufre , Oxalatos/química , Hexafluoruro de Azufre/química , Fluoruros/química , Gases de Efecto Invernadero/análisis , Espectroscopía Infrarroja por Transformada de Fourier , Restauración y Remediación Ambiental/métodos
18.
Stem Cells Dev ; 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38814826

RESUMEN

The prognosis of fracture is directly related to several factors. Due to the limitations of existing treatment strategies, there are still many fractures with poor healing. Bone marrow mesenchymal stem cells (BMSCs) have the potential to differentiate into osteoblasts and chondrocytes. Therefore, BMSC transplantation is promised as an effective method for treating bone fractures. We aim to explore whether silently expressing sclerostin gene (SOST) can promote bone formation through the SOST/Wnt/ß-catenin signal pathway. We isolated rat BMSCs and the target gene (SOST shRNA) was transduced into them for osteogenic induction. The results showed that SOST significantly inhibited the proliferation and osteogenic differentiation of BMSCs during osteogenic induction, whereas silently expressing SOST not only increased the number of surviving BMSCs but also promoted the expression of osteogenesis-related proteins RUNX2, osteoprotegerin, Collagen I (COL-I), and bone morphogenetic protein-2 during osteogenic induction. The results of imaging examination in rats show that downregulating the expression of SOST can promote the formation of bony callus and the transformation of cartilage tissue into normal bone tissue, and then accelerate the healing of osteoporotic fracture. In addition, we also found that SOST silencing can activate the Wnt/ß-catenin pathway to achieve these effects. In conclusion, SOST silencing can promote the proliferation and osteogenic differentiation of BMSCs in situ, and therefore may enhance the therapeutic efficiency of BMSC transplantation in OPF.

19.
Pancreatology ; 24(4): 600-607, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38565467

RESUMEN

BACKGROUND/OBJECTIVES: Liposomal irinotecan plus 5-fluorouracil and leucovorin (nal-IRI + 5-FU/LV) provides survival benefits for metastatic pancreatic adenocarcinoma (mPDAC) refractory to gemcitabine-based treatment, mainly gemcitabine plus nab-paclitaxel (GA), in current practice. Gemcitabine plus S-1 (GS) is another commonly administered first-line regimen before nab-paclitaxel reimbursement; however, the efficacy and safety of nal-IRI + 5-FU/LV for mPDAC after failed GS treatment has not been reported and was therefore explored in this study. METHODS: In total, 177 patients with mPDAC received first-line GS or GA treatment, followed by second-line nal-IRI + 5-FU/LV treatment (identified from a multicenter retrospective cohort in Taiwan from 2018 to 2020); 85 and 92 patients were allocated to the GS and GA groups, respectively. Overall survival (OS), time-to-treatment failure (TTF), and adverse events were compared between the two groups. RESULTS: The baseline characteristics of the two groups were generally similar; however, a higher median age (67 versus 62 years, p < 0.001) and fewer liver metastases (52% versus 78%, p < 0.001) were observed in the GS versus GA group. The median OS was 15.0 and 15.9 months in the GS and GA groups, respectively (p = 0.58). The TTF (3.1 versus 2.8 months, p = 0.36) and OS (7.6 versus 6.7 months, p = 0.83) after nal-IRI treatment were similar between the two groups. More patients in the GS group developed mucositis during nal-IRI treatment (15% versus 4%, p = 0.02). CONCLUSIONS: The efficacy of second-line nal-IRI +5-FU/LV treatment was unaffected by prior S-1 exposure. GS followed by nal-IRI treatment is an alternative treatment sequence for patients with mPDAC.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Combinación de Medicamentos , Fluorouracilo , Irinotecán , Leucovorina , Ácido Oxónico , Neoplasias Pancreáticas , Tegafur , Humanos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Leucovorina/uso terapéutico , Leucovorina/administración & dosificación , Persona de Mediana Edad , Masculino , Femenino , Fluorouracilo/uso terapéutico , Fluorouracilo/administración & dosificación , Anciano , Irinotecán/uso terapéutico , Irinotecán/administración & dosificación , Tegafur/administración & dosificación , Tegafur/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios Retrospectivos , Ácido Oxónico/administración & dosificación , Ácido Oxónico/uso terapéutico , Liposomas , Resultado del Tratamiento , Metástasis de la Neoplasia , Adulto , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico
20.
ACS Sens ; 9(4): 2183-2193, 2024 04 26.
Artículo en Inglés | MEDLINE | ID: mdl-38588327

RESUMEN

Sensitive and selective acetone detection is of great significance in the fields of environmental protection, industrial production, and individual health monitoring from exhaled breath. To achieve this goal, bimetallic Au@Pt core-shell nanospheres (BNSs) functionalized-electrospun ZnFe2O4 nanofibers (ZFO NFs) are prepared in this work. Compared to pure NFs-650 analogue, the ZFO NFs/BNSs-2 sensor exhibits a stronger mean response (3.32 vs 1.84), quicker response/recovery speeds (33 s/28 s vs 54 s/42 s), and lower operating temperature (188 vs 273 °C) toward 0.5 ppm acetone. Note that an experimental detection limit of 30 ppb is achieved, which ranks among the best cases reported thus far. Besides the demonstrated excellent repeatability, humidity-enhanced response, and long-term stability, the selectivity toward acetone is remarkably improved after BNSs functionalization. Through material characterizations and DFT calculations, all these improvements could be attributed to the boosted oxygen vacancies and abundant Schottky junctions between ZFO NFs and BNSs, and the synergistic catalytic effect of BNSs. This work offers an alternative strategy to realize selective subppm acetone under high-humidity conditions catering for the future requirements of noninvasive breath diabetes diagnosis in the field of individual healthcare.


Asunto(s)
Acetona , Pruebas Respiratorias , Oro , Nanofibras , Nanosferas , Platino (Metal) , Acetona/análisis , Acetona/química , Nanofibras/química , Oro/química , Pruebas Respiratorias/métodos , Nanosferas/química , Platino (Metal)/química , Humanos , Límite de Detección , Oxígeno/química , Técnicas Electroquímicas/métodos
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