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1.
Nature ; 633(8029): 344-350, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39261614

RESUMEN

Reliable control of the conductivity and its polarity in semiconductors is at the heart of modern electronics1-7, and has led to key inventions including diodes, transistors, solar cells, photodetectors, light-emitting diodes and semiconductor lasers. For archetypal semiconductors such as Si and GaN, positive (p)- and negative (n)-type conductivities are achieved through the doping of electron-accepting and electron-donating elements into the crystal lattices, respectively1-6. For halide perovskites, which are an emerging class of semiconductors, mechanisms for reliably controlling charge conduction behaviours while maintaining high optoelectronic qualities are yet to be discovered. Here we report that the p- and n-type characteristics in a wide-bandgap perovskite semiconductor can be adjusted by incorporating a phosphonic acid molecular dopant with strong electron-withdrawing abilities. The resultant carrier concentrations were more than 1013 cm-3 for the p- and n-type samples, with Hall coefficients ranging from -0.5 m3 C-1 (n-type) to 0.6 m3 C-1 (p-type). A shift of the Fermi level across the bandgap was observed. Importantly, the transition from n- to p-type conductivity was achieved while retaining high photoluminescence quantum yields of 70-85%. The controllable doping in the emissive perovskite semiconductor enabled the demonstration of ultrahigh brightness (more than 1.1 × 106 cd m-2) and exceptional external quantum efficiency (28.4%) in perovskite light-emitting diodes with a simple architecture.

2.
Adv Sci (Weinh) ; : e2406529, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39303163

RESUMEN

Recently, unconventional antiferromagnets that enable the spin splitting (SS) of electronic states have been theoretically proposed and experimentally realized, where the magnetic sublattices containing moments pointing at different directions are connected by a novel set of symmetries. Such SS is substantial, k-dependent, and independent of the spin-orbit coupling (SOC) strength, making these magnets promising materials for antiferromagnetic spintronics. Here, combined with angle-resolved photoemission spectroscopy (ARPES) and density functional theory (DFT) calculations, a systematic study on CrSb, a metallic spin-split antiferromagnet candidate with Néel temperature TN = 703 K, is conducted. The data reveal the electronic structure of CrSb along both out-of-plane and in-plane momentum directions, rendering an anisotropic k-dependent SS that agrees well with the calculational results. The magnitude of such SS reaches up to at least 0.8 eV at non-high-symmetry momentum points, which is significantly higher than the largest known SOC-induced SS. This compound expands the choice of materials in the field of antiferromagnetic spintronics and is likely to stimulate subsequent investigations of high-efficiency spintronic devices that are functional at room temperature.

3.
FEBS J ; 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39298503

RESUMEN

Stromal interaction molecule 1 (STIM1) is the endoplasmic reticulum Ca2+ sensor for store-operated calcium entry and is closely associated with carcinogenesis and tumor progression. Previously, we found that STIM1 is upregulated in melanoma cells resistant to the serine/threonine-protein kinase B-raf inhibitor vemurafenib, although the mechanism underlying this upregulation is unknown. Here, we show that vemurafenib resistance upregulates STIM1 through an epidermal growth factor (EGF)/epidermal growth factor receptor (EGFR)-Yes-associated protein 1 (YAP1)/TEA domain transcription factor 2 (TEAD2) signaling axis. Vemurafenib resistance can lead to an increase in EGF and EGFR levels, causing activation of the EGFR signaling pathway, which promotes YAP1 nuclear localization to increase the expression of STIM1. Our findings not only reveal the mechanism by which vemurafenib resistance promotes STIM1 upregulation, but also provide a rationale for combined targeting of the EGF/EGFR-YAP1/TEAD2-STIM1 axis to improve the therapeutic efficacy of BRAF inhibitor in melanoma patients.

5.
Front Neurosci ; 18: 1440975, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39176382

RESUMEN

The global recognition of the importance of physical exercise (PE) for human health has resulted in increased research on its effects on cortical activity. Neural oscillations, which are prominent features of brain activity, serve as crucial indicators for studying the effects of PE on brain function. Existing studies support the idea that PE modifies various types of neural oscillations. While EEG-related literature in exercise science exists, a comprehensive review of the effects of exercise specifically in healthy populations has not yet been conducted. Given the demonstrated influence of exercise on neural plasticity, particularly cortical oscillatory activity, it is imperative to consolidate research on this phenomenon. Therefore, this review aims to summarize numerous PE studies on neuromodulatory mechanisms in the brain over the past decade, covering (1) effects of resistance and aerobic training on brain health via neural oscillations; (2) how mind-body exercise affects human neural activity and cognitive functioning; (3) age-Related effects of PE on brain health and neurodegenerative disease rehabilitation via neural oscillation mechanisms; and (4) conclusion and future direction. In conclusion, the effect of PE on cortical activity is a multifaceted process, and this review seeks to comprehensively examine and summarize existing studies' understanding of how PE regulates neural activity in the brain, providing a more scientific theoretical foundation for the development of personalized PE programs and further research.

6.
Biomacromolecules ; 25(9): 5758-5770, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39145523

RESUMEN

Lanthanide-containing luminescent hydrogels have shown potential for sensing and imaging applications. Nonetheless, integrating lanthanide ions or complexes into the polymer matrix often results in the poor stability and mechanical strength of the hydrogels. This work presents an innovative approach to fabricating luminescent hydrogels with three dynamic cross-links: imine bond, boronate ester bond, and metal-ligand coordination. Europium(III) (Eu3+) ions are incorporated into a dual-cross-linked matrix composed of phenylboronic acid-polyethylenimine-modified gelatin (PPG) and alginate dialdehyde (ADA) through a combined treatment involving freeze-drying-swelling (FDS) and freeze-thawing (FT) processes. The FDS process facilitates the formation of additional europium-carboxylate cross-links within the polymeric network to enhance its luminescence and stability, while the FT process strengthens the network physically. The impact of the FDS-FT cycle number on the microstructures and properties of PPG/ADA-Eu3+ hydrogels is thoroughly investigated, and their potential for monitoring bacterial growth and detecting copper(II) ions is also demonstrated.


Asunto(s)
Alginatos , Gelatina , Hidrogeles , Alginatos/química , Hidrogeles/química , Gelatina/química , Europio/química , Reactivos de Enlaces Cruzados/química , Liofilización/métodos , Luminiscencia , Congelación , Ácido Glucurónico/química , Ácidos Hexurónicos/química
7.
Enzyme Microb Technol ; 180: 110480, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39067324

RESUMEN

(S)-equol, the most influential metabolite of daidzein in vivo, has aroused great attention due to the excellent biological activities. Although existing studies have accomplished the construction of its heterologous synthetic pathway in the context of anaerobicity and inefficiency of natural strains, the low productivity of (S)-equol limits its industrial application. Here, rational design strategies based on decreasing the pocket steric hindrance and fine-tuning the pocket microenvironment to systematically redesign the binding pocket of enzyme were developed and processed to the rate-limiting enzyme dihydrodaidzein reductase in (S)-equol synthesis. After iterative combinatorial mutagenesis, an effective mutant S118G/T169A capable of significantly increasing (S)-equol yield was obtained. Computational analyses illustrated that the main reason of the increased activity relied on the decreased critical distance and more stable interacting conformation. Then, the reaction optimization was performed, and the recombinant Escherichia coli whole-cell biocatalyst harboring S118G/T169A enabled the efficient conversion of 2 mM daidzein to (S)-equol, achieving conversion rate of 84.5 %, which was 2.9 times higher than that of the parental strain expressing wide type dihydrodaidzein reductase. This study provides an effective idea and a feasible method for enzyme modification and whole-cell catalytic synthesis of (S)-equol, and will greatly accelerate the process of industrial production.


Asunto(s)
Equol , Escherichia coli , Escherichia coli/genética , Escherichia coli/enzimología , Escherichia coli/metabolismo , Equol/biosíntesis , Equol/metabolismo , Deshidrogenasas-Reductasas de Cadena Corta/metabolismo , Deshidrogenasas-Reductasas de Cadena Corta/genética , Isoflavonas/metabolismo , Isoflavonas/biosíntesis , Ingeniería de Proteínas , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Simulación del Acoplamiento Molecular
8.
Aging Clin Exp Res ; 36(1): 140, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38965150

RESUMEN

BACKGROUND: Sarcopenia has been reported to play an important role in frailty syndrome. The serum creatinine/serum cystatin C ratio (Scr/Cys C ratio) has recently been recognized as a valuable indicator for assessing sarcopenia. However, few studies have examined the association between serum creatinine/serum cystatin C ratio and frailty. The objective of this study is to investigate the relationship between the serum creatinine/serum cystatin C ratio and frailty among older adults residing in the community. METHODS AND MATERIALS: A Total of 1926 community-dwelling older adults aged ≥ 60 years in the 2011 waves of the China Health and Retirement Longitudinal Study (CHARLS) were included. The participants' frailty status was determined using a 39 item frailty index (FI), which classified individuals as "robust" (FI ≤ 0.1), "pre-frailty" (0.1 < FI < 0.25), or "frailty" (FI ≥ 0.25). The Scr/Cys C ratio was determined by dividing the serum creatinine level (mg/dL) by the cystatin C level (mg/L). The one-way analysis of variance(ANOVA) and Chi-squared test (χ2)were applied to compare the differences between the 3 groups. Both linear regression and logistic regression models were used to further investigate the relationship between Scr/Cys C ratio and frailty. RESULTS: After adjusting for potential confounding factors, the study revealed that participants in the Q1 quartile of Scr/Cys C ratio had increased odds of frailty (Q1vs.Q4: OR = 1.880, 95% CI 1.126-3.139, p = 0.016) compared with those in the Q4 quartile group. In fully adjusted logistic regression models, male participants in the Q2 quartile of Scr/Cys C ratio were significantly correlated with higher odds of pre-frailty (Q2 vs.Q4: OR = 1.693, 95%CI 1.040-2.758, p = 0.034). However, this correlation was not observed in females (OR = 0.984, 95% CI 0.589-1.642, p = 0.950,). Additionally, the study observed an increase in both the frailty index and the incidence of frailty as age increased in both males and females. CONCLUSION: Among community-dwelling older adults, lower Serum creatinine to cystatin C ratio were found to be associated with increased odds of frailty prevalence in males.


Asunto(s)
Creatinina , Cistatina C , Fragilidad , Vida Independiente , Humanos , Cistatina C/sangre , Masculino , Anciano , Creatinina/sangre , Femenino , Fragilidad/sangre , Fragilidad/epidemiología , Anciano de 80 o más Años , Incidencia , Persona de Mediana Edad , Anciano Frágil/estadística & datos numéricos , China/epidemiología , Estudios Longitudinales , Sarcopenia/sangre , Sarcopenia/epidemiología , Factores Sexuales , Biomarcadores/sangre , Evaluación Geriátrica/métodos
9.
Biomolecules ; 14(6)2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38927136

RESUMEN

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes and the main cause of end-stage renal disease around the world. Mitochondria are the main organelles responsible for producing energy in cells and are closely involved in maintaining normal organ function. Studies have found that a high-sugar environment can damage glomeruli and tubules and trigger mitochondrial dysfunction. Meanwhile, animal experiments have shown that DKD symptoms are alleviated when mitochondrial damage is targeted, suggesting that mitochondrial dysfunction is inextricably linked to the development of DKD. This article describes the mechanisms of mitochondrial dysfunction and the progression and onset of DKD. The relationship between DKD and mitochondrial dysfunction is discussed. At the same time, the progress of DKD treatment targeting mitochondrial dysfunction is summarized. We hope to provide new insights into the progress and treatment of DKD.


Asunto(s)
Nefropatías Diabéticas , Mitocondrias , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/patología , Humanos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Animales
10.
J Phys Chem Lett ; 15(26): 6705-6711, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38900573

RESUMEN

Self-assembled monolayers (SAMs) have shown great potential as hole injection materials for perovskite light-emitting diodes due to their low parasitic absorption and ability to adjust energy level alignment. However, the head and anchoring groups on SAM molecules with significant differences in polarity can lead to the formation of micelles in the commonly used alcoholic processing solvent, inhibiting the formation of an intact SAM. In this work, the introduction of methyl groups on carbazole in the phosphonic-acid-based SAM materials is found to facilitate energy level alignment and promote the formation of compact SAMs. The alternative molecular structure also enhances the solvent resistance of poly(9-vinylcarbazole), suppressing interfacial defect densities and nonradiative recombination processes in the emissive perovskites. PeLEDs based on the methyl-containing SAMs exhibit ∼30% enhancement in efficiency. These findings contribute to a better understanding of the design of SAM materials for PeLED applications.

11.
Int J Biol Macromol ; 275(Pt 1): 133376, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38917924

RESUMEN

In this work, a straightforward approach utilizing distillers' grains (DG) waste and sodium alginate (SA) was developed to prepare functional and bioactive packaging films. Deep eutectic solvents (DESs) were initially synthesized from choline chloride (CO), betaine (BO), glycerol (GO), and oxalic acid. Composite films were then prepared from DES-treated DG slurry and SA at different ratios. Characterization and analysis revealed that adding 75 % CO-treated DG slurry reduced the water vapor permeability (WVP) by over 66 % compared to that of the SA film. Composite films containing CO/BO-treated DG slurry had an ultraviolet light barrier rate exceeding 99 %, while those with 75 % DES-treated DG slurry demonstrated excellent antioxidant activity, with a 2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) free radical scavenging rate of 80.14 %-88.35 %, representing a 322.45 %-365.73 % increase compared to that of the pure SA film. These composite films also exhibited favorable mechanical properties (31.58 MPa, 5.53 % EB), thermal stability, and biodegradability, extending the shelf life of grapes by 1.8 times. In conclusion, bioactive composite films derived from DES-treated DG are expected to replace petroleum-based plastics, enhancing sustainable biomass use and environmental responsibility.


Asunto(s)
Alginatos , Antioxidantes , Disolventes Eutécticos Profundos , Permeabilidad , Alginatos/química , Antioxidantes/química , Antioxidantes/farmacología , Disolventes Eutécticos Profundos/química , Vapor , Colina/química , Glicerol/química
12.
Hum Gene Ther ; 35(11-12): 401-411, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38717948

RESUMEN

Currently, adeno-associated virus (AAV) is one of the primary gene delivery vectors in gene therapy, facilitating long-term in vivo gene expression. Despite being imperative, it is incredibly challenging to precisely assess AAV particle distribution according to the sedimentation coefficient and identify impurities related to capsid structures. This study performed the systematic methodological validation of quantifying the AAV empty and full capsid ratio. This includes specificity, accuracy, precision, linearity, and parameter variables involving the sedimentation velocity analytical ultracentrifugation (SV-AUC) method. Specifically, SV-AUC differentiated among the empty, partial, full, and high sedimentation coefficient substance (HSCS) AAV particles while evaluating their sedimentation heterogeneity. The intermediate precision analysis of HE (high percentage of empty capsid) and HF (high percentage of full capsid) samples revealed that the specific species percentage, such as empty or full, was more significant than 50%. Moreover, the relative standard deviation (RSD) could be within 5%. Even for empty or partially less than 15%, the RSD could be within 10%. The accuracy recovery rates of empty capsid were between 103.9% and 108.7% across three different mixtures. When the measured percentage of specific species was more significant than 14%, the recovery rate was between 77.9% and 106.6%. Linearity analysis revealed an excellent linear correlation between the empty, partial, and full in the HE samples. The AAV samples with as low as 7.4 × 1011 cp/mL AAV could be accurately quantified with SV-AUC. The parameter variable analyses revealed that variations in cell alignment significantly affected the overall results. Still, the detection wavelength of 235 nm slightly influenced the empty, partial, and full percentages. Minor detection wavelength changes showed no impact on the sedimentation coefficient of these species. However, the temperature affected the measured sedimentation coefficient. These results validated the SV-AUC method to quantify AAV. This study provides solutions to AAV empty and full capsid ratio quantification challenges and the subsequent basis for calibrating the AAV empty capsid system suitability substance. Because of the AAV structure and potential variability complexity in detection, we jointly calibrated empty capsid system suitability substance with three laboratories to accurately detect the quantitative AAV empty and full capsid ratio. The empty capsid system suitability substance could be used as an external reference to measure the performance of the instrument. The results could be compared with multiple QC (quality control) laboratories based on the AAV vector and calibration accuracy. This is crucial for AUC to be used for QC release and promote gene therapy research worldwide.


Asunto(s)
Dependovirus , Vectores Genéticos , Ultracentrifugación , Dependovirus/genética , Ultracentrifugación/métodos , Humanos , Vectores Genéticos/genética , Vectores Genéticos/química , Calibración , Terapia Genética/métodos , Cápside/química , Células HEK293
13.
Chemosphere ; 359: 142271, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38734248

RESUMEN

Acinetobacter sp. AL-6 combining with biochar was adapted in activated sludge (AS & co-system) to decontaminate Mn2+, Fe2+ and NH4+-N, and treat activated sludge (AS) for its activity and settling performance improvement. Specifically, the co-system promoted the growth of bacteria in the activated sludge, thus increasing its ability to nitrify and adsorb Mn2+ and Fe2+, resulting in the removal of high concentrations of NH4+-N, Mn2+, Fe2+ and COD in the reactor by 100%, 100%, 100%, and 96.8%, respectively. And the pH of wastewater was increased from 4 to 8.5 by co-system also facilitated the precipitation of Mn2+ and Fe2+. The MLVSS/MLSS ratio increased from 0.64 to 0.95 and SVI30 decreased from 92.54 to 1.54 after the addition of co-system, which indicated that biochar helped to improve the activity and settling performance of activated sludge and prevented it from being damaged by the compound Mn2+ and Fe2+. In addition, biochar promoted the increase of the tyrosine-like protein substance and humic acid-like organic matter in the sludge EPS, thus enhanced the ability of sludge to adsorb Mn2+ and Fe2+. Concretely, compared with AS group, the proteins content and polysaccharides content of the AS & co-system group were increased by 13.14 times and 6.30 times respectively. Further, microbial diversity analysis showed that more resistant bacteria and dominant bacteria Acinetobacter sp. AL-6 in sludge enhanced the nitrification and adsorption of manganese and iron under the promotion of biochar. Pre-eminently, the more effective AS & co-system were applied to the removal of actual electrolytic manganese slag leachate taken from the contaminated site, and the removal of NH4+-N, Mn2+, Fe2+ and COD remained high at 100%, 100%, 71.82% and 94.72%, respectively, revealing advanced value for high engineering applications of AS & co-system.


Asunto(s)
Carbón Orgánico , Hierro , Manganeso , Aguas del Alcantarillado , Eliminación de Residuos Líquidos , Aguas Residuales , Carbón Orgánico/química , Aguas del Alcantarillado/microbiología , Aguas del Alcantarillado/química , Aguas Residuales/química , Aguas Residuales/microbiología , Hierro/química , Eliminación de Residuos Líquidos/métodos , Adsorción , Acinetobacter/metabolismo , Compuestos de Amonio , Contaminantes Químicos del Agua/metabolismo , Nitrógeno , Nitrificación
15.
J Agric Food Chem ; 72(20): 11331-11340, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38721769

RESUMEN

Research on mesoionic structures in pesticide design has gained significant attention in recent years. However, the 1-position of pyridino[1,2-a]pyrimidine is usually designed with 2-chlorothiazole, 2-chloropyridine, or cyano moieties commonly found in neonicotinoid insecticides. In order to enrich the available pharmacophore library, here, we disclose a series of new pyridino[1,2-a]pyrimidine mesoionics bearing indole-containing substituents at the 1-position. Most of these target compounds are confirmed to have good insecticidal activity against aphids through bioevaluation. In addition, a three-dimensional structure-activity relationship model is established to allow access to optimal compound F45 with an LC50 value of 2.97 mg/L. This value is comparable to the property achieved by the positive control triflumezopyrim (LC50 = 2.94 mg/L). Proteomics and molecular docking analysis suggest that compound F45 has the potential to modulate the functioning of the aphid nervous system through its interaction with neuronal nicotinic acetylcholine receptors. This study expands the existing pharmacophore library for the future development of new mesoionic insecticides based on 1-position modifications of the pyridino[1,2-a]pyrimidine scaffold.


Asunto(s)
Áfidos , Diseño de Fármacos , Indoles , Insecticidas , Simulación del Acoplamiento Molecular , Pirimidinas , Insecticidas/química , Insecticidas/síntesis química , Insecticidas/farmacología , Animales , Pirimidinas/química , Pirimidinas/farmacología , Pirimidinas/síntesis química , Áfidos/efectos de los fármacos , Indoles/química , Indoles/farmacología , Indoles/síntesis química , Relación Estructura-Actividad , Estructura Molecular , Receptores Nicotínicos/metabolismo , Receptores Nicotínicos/química , Receptores Nicotínicos/efectos de los fármacos
16.
J Hazard Mater ; 472: 134425, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38691998

RESUMEN

Soil health is a crucial aspect of sustainable agriculture and food production, necessitating attention to the ecological risks associated with substantial amounts of mulch film residues. Biodegradable mulch films (BDMs) carry the same risk of mulch film residues formation as low-density polyethylene (LDPE) mulch films during actual use. More information is needed to elucidate the specific impacts of mulch film residues on the soil environment. Integrated 16S rRNA gene sequencing and non-targeted metabolomics, this study revealed the response patterns of bacterial communities, metabolites, and metabolic functions in the soil from three different agricultural regions to the presence of mulch film residues. LDPE mulch film residues negatively impacted the bacterial communities in the soils of Heilongjiang (HLJ) and Yunnan (YN) and had a lesser impact on the metabolic spectrum in the soils of HLJ, YN, and Xinjiang (XJ). BDM residues had a greater negative impact on all three soils in terms of both the bacterial communities and metabolites. The impact of BDM treatment on the soils of HLJ, YN, and XJ increased sequentially in that order. It is recommended that, when promoting the use of biodegradable mulch films, a fuller assessment should be made, accounting for local soil properties.


Asunto(s)
Agricultura , Bacterias , ARN Ribosómico 16S , Microbiología del Suelo , Contaminantes del Suelo , Bacterias/metabolismo , Bacterias/genética , Contaminantes del Suelo/metabolismo , Biodegradación Ambiental , Polietileno/química , Suelo/química , Poliésteres/metabolismo , Poliésteres/química , Plásticos Biodegradables/química , Plásticos Biodegradables/metabolismo
17.
Urol Int ; : 1-13, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38657590

RESUMEN

BACKGROUND: Urine storage and excretion require a network of interactions in the urinary tract and the central nervous system, which is mediated by a reservoir of water in the bladder and the outlet to the bladder neck, urethra, and external urethral sphincter. Through communicating and coordinating each other, micturition system eventually showed a switch-like activity pattern. SUMMARY: At cervicothoracic and lumbosacral spine, the spinal reflex pathway of the lower urinary tract (LUT) received mechanosensory input from the urothelium to regulate the bladder contraction activity, thereby controlled urination voluntarily. Impairment of above-mentioned any level could result in lower urinary tract dysfunction, placed a huge burden on patients and society. Specific expression of purinergic receptors and transient receptor potential (TRP) channels are thought to play an important role in urinary excretion in the LUT. KEY MESSAGES: This article reviewed the knowledge about the voiding reflex and described the role and function of TRP channels during voiding.

18.
Nat Med ; 30(5): 1309-1319, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38627559

RESUMEN

Cancer of unknown primary (CUP) site poses diagnostic challenges due to its elusive nature. Many cases of CUP manifest as pleural and peritoneal serous effusions. Leveraging cytological images from 57,220 cases at four tertiary hospitals, we developed a deep-learning method for tumor origin differentiation using cytological histology (TORCH) that can identify malignancy and predict tumor origin in both hydrothorax and ascites. We examined its performance on three internal (n = 12,799) and two external (n = 14,538) testing sets. In both internal and external testing sets, TORCH achieved area under the receiver operating curve values ranging from 0.953 to 0.991 for cancer diagnosis and 0.953 to 0.979 for tumor origin localization. TORCH accurately predicted primary tumor origins, with a top-1 accuracy of 82.6% and top-3 accuracy of 98.9%. Compared with results derived from pathologists, TORCH showed better prediction efficacy (1.677 versus 1.265, P < 0.001), enhancing junior pathologists' diagnostic scores significantly (1.326 versus 1.101, P < 0.001). Patients with CUP whose initial treatment protocol was concordant with TORCH-predicted origins had better overall survival than those who were administrated discordant treatment (27 versus 17 months, P = 0.006). Our study underscores the potential of TORCH as a valuable ancillary tool in clinical practice, although further validation in randomized trials is warranted.


Asunto(s)
Aprendizaje Profundo , Neoplasias Primarias Desconocidas , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ascitis/patología , Citodiagnóstico/métodos , Neoplasias Primarias Desconocidas/patología , Curva ROC
19.
Front Genet ; 15: 1367434, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38660677

RESUMEN

Background: Tumor mutational burden (TMB) is a promising biomarker for immunotherapy. The challenge of spatial and temporal heterogeneity and high costs weaken its power in clinical routine. The aim of this study is to estimate TMB preoperatively using a volumetric CT-based radiomic signature (rMB). Methods: Seventy-one patients with resectable lung adenocarcinoma (LUAD) who underwent whole-exome sequencing (WXS) from 2011 to 2014 were enrolled from the institutional biobank of Tianjin Medical University Cancer Institute and Hospital (TMUCIH). Forty-nine LUAD patients with WXS from the Cancer Genome Atlas Program (TCGA) served as the external validation cohort. Computed tomography (CT) volumes were resampled to 1-mm isotropic, semi-automatically segmented, and manually adjusted by two radiologists. A total of 3,108 radiomic features were extracted via PyRadiomics and then harmonized across cohorts by ComBat. Features with inter-segmentation intra-class correlation coefficient (ICC) > 0.8, low collinearity, and significant univariate power were passed to the least absolute shrinkage and selection operator (LASSO)-logistic classifier to discriminate TMB-high/TMB-low at a threshold of 10 mut/Mb. The receiver operating characteristic (ROC) curve analysis and calibration curve were used to determine its efficiency. Shapley values (SHAP) attributed individual predictions to feature contributions. Clinical variables and circulating biomarkers were collected to find potential associations with TMB and rMB. Results: The top frequently mutated genes significantly differed between the Chinese and TCGA cohorts, with a median TMB of 2.20 and 3.46 mut/Mb and 15 (21.12%) and 9 (18.37%) cases of TMB-high, respectively. After dimensionality reduction, rMB comprised 21 features, which reached an AUC of 0.895 (sensitivity = 0.867, specificity = 0.875, and accuracy = 0.873) in the discovery cohort and 0.878 (sensitivity = 1.0, specificity = 0.825, and accuracy = 0.857 in a consist cutoff) in the validation cohort. rMB of TMB-high patients was significantly higher than rMB of TMB-low patients in both cohorts (p < 0.01). rMB was well-calibrated in the discovery cohort and validation cohort (p = 0.27 and 0.74, respectively). The square-filtered gray-level concurrence matrix (GLCM) correlation was of significant importance in prediction. The proportion of circulating monocytes and the monocyte-to-lymphocyte ratio were associated with TMB, whereas the circulating neutrophils and lymphocyte percentage, original and derived neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio were associated with rMB. Conclusion: rMB, an intra-tumor radiomic signature, could predict lung adenocarcinoma patients with higher TMB. Insights from the Shapley values may enhance persuasiveness of the purposed signature for further clinical application. rMB could become a promising tool to triage patients who might benefit from a next-generation sequencing test.

20.
Heliyon ; 10(3): e25041, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38352758

RESUMEN

Mitigating heat is a vital ecosystem service of trees, particularly with climate change. Land surface temperature measures captured at a single time of day (in the morning) dominate the urban heat island literature. Less is known about how local tree canopy and impervious surface regulate air temperature throughout the day, and/or across many days with varied weather conditions, including cloud cover. We use bike-mounted air temperature sensors throughout the day in New Haven, Connecticut, USA, from 2019 to 2021 and generalized additive mixed models across 156 rides to estimate the daily variation in cooling benefits associated with tree canopy cover, and warming from impervious surface cover in 90 m buffers surrounding bike observations. Cooling is inferred by subtracting the bicycle-observed temperature from a reference station. The cooling benefits from tree canopy cover were strongest in the midday (11:00-14:00, -1.62 °C), afternoon (14:00-17:00, -1.19 °C), and morning (8:00-11:00, -1.15 °C) on clear days. The cooling effect was comparatively smaller on cloudy mornings -0.92 °C and afternoons -0.51 °C. Warming from impervious surfaces was most pronounced in the evening (17:00-20:00, 1.11 °C) irrespective of clouds, and during cloudy nights (20:00-23:00) and cloudy mornings 1.03 °C 95 % CI [1.03, 1.04]. Among the hottest observed days (top 25th percentile of reference station daily maxima), tree canopy was associated with lower temperatures on clear afternoons -1.78 °C [-1.78, -1.78], cloudy midday -1.17 °C [-1.19, -1.15], clear midday -1.12 °C [-1.12, -1.11]. We add a broader spectrum of weather conditions by explicitly including clouds, and greater temporal resolution by measuring throughout the day to bike-based urban heat research. Future mobile sampling campaigns may broaden the spatial extent with more environmental variation, representing an opportunity for public science and engagement.

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