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A novel approach is proposed leveraging surface-enhanced Raman spectroscopy (SERS) combined with machine learning (ML) techniques, principal component analysis (PCA)-centroid displacement-based nearest neighbor (CDNN). This label-free approach can identify slight abnormalities between SERS spectra of gastric lesions at different stages, offering a promising avenue for detection and prevention of precancerous lesion of gastric cancer (PLGC). The agaric-shaped nanoarray substrate was prepared using gas-liquid interface self-assembly and reactive ion etching (RIE) technology to measure SERS spectra of serum from mice model with gastric lesions at different stages, and then a SERS spectral recognition model was trained and constructed using the PCA-CDNN algorithm. The results showed that the agaric-shaped nanoarray substrate has good uniformity, stability, cleanliness, and SERS enhancement effect. The trained PCA-CDNN model not only found the most important features of PLGC, but also achieved satisfactory classification results with accuracy, area under curve (AUC), sensitivity, and specificity up to 100%. This demonstrated the enormous potential of this analysis platform in the diagnosis of PLGC.
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Aprendizaje Automático , Lesiones Precancerosas , Espectrometría Raman , Neoplasias Gástricas , Neoplasias Gástricas/diagnóstico , Espectrometría Raman/métodos , Animales , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/sangre , Ratones , Análisis de Componente PrincipalRESUMEN
BACKGROUND: This study aimed to investigate the influence of CYP2D6 polymorphisms on risperidone plasma concentrations in patients with schizophrenia. Based on pharmacogenomics, we examined whether plasma concentration of risperidone is associated with clinical response and adverse side-effects. METHODS: We recruited patients with chronic schizophrenia who were then treated with risperidone. The CYP2D6 genotypes were determined using targeted sequencing. All high-frequency mutation sites of the nine exons of the gene were assayed in the present study. Plasma concentrations of risperidone and 9-hydroxyrisperidone (9-OH-RIS) were measured using high-performance liquid chromatography (HPLC). Psychiatric symptoms were monitored using The Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impression (CGI). Adverse effects were evaluated using the Barnes Akathisia Scale (BAS) and Extrapyramidal Symptom Rating Scale (ESRS). Follow-up visits were scheduled at weeks 2,4, and 8 after treatment initiation. RESULTS: Among the 76 patients, 100 C > T (rs1065852), 1038 C > T (rs1081003), 1662 G > C (rs1058164), 2851 C > T (rs16947), and 4181G > C (rs1135840) variants were detected. The most common allele was CYP2D6*10 (81.6%), whereas CYP2D6*2 (9.2%) and CYP2D6*5 (17.1%) were relatively rare. Plasma levels of risperidone and the risperidone/9-OH risperidone ratio (R/9-OH) were significantly increased in individuals with CYP2D6*10 (P < 0.05). The change in PANSS score, weight, high-density lipoprotein (HDL) level, prolactin (PRL) level, and ESRS were significantly different from baseline, between the different genotypes (P < 0.01). Moreover, individuals with CYP2D6*10 homozygous (TT) mutations were associated with higher risperidone concentration and R/9-OH ratio than those with heterozygous mutations (CT) (P < 0.01). A change from baseline in BPRS scores was observed only during week 8 and was different between heterozygous and homozygous mutations. As for the C2851T polymorphism, the incidence of adverse metabolic effects was significantly different between the C/C and C/T genotypes (P < 0.01). Regarding the G4181C polymorphisms, the changes from baseline in GLU and TG, were different between the C/C and C/G genotypes (P < 0.01). CONCLUSIONS: The genotype of CYP2D6 significantly influences the plasma concentration of risperidone and may subsequently influence the adverse side-effects following risperidone treatment, while also exerting a slight influence on clinical outcomes.
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Antipsicóticos , Risperidona , Antipsicóticos/uso terapéutico , Citocromo P-450 CYP2D6/genética , Humanos , Isoxazoles , Palmitato de Paliperidona , Plasma , Pirimidinas , Risperidona/uso terapéuticoRESUMEN
Using velocity map ion imaging, the photodissociation of chlorobromomethane (CH2BrCl) at 233-234 nm has been studied. The total translational energy distributions and the anisotropy parameters have been determined from the ion images of the photofragments Br ((2)P1/2) (denoted as Br(*)) and Br ((2)P3/2) (denoted as Br) for the dominant CH2BrCl + hv â CH2Cl + Br(*) and CH2BrCl + hv â CH2Cl + Br channels. Using an impulsive model invoking angular momentum conservation, the vibrational energy distributions of the chloromethyl radicals have been derived from the total translational energy distributions for the two channels. The study suggests that there are a number of vibrational modes of the chloromethyl radical to be excited in both of the two photodissociation channels. In the Br* channel, the CH2 s-stretch mode v1 has the most probability of excitation. While in the Br channel, the CH2 scissors mode ν2 is attributed to the highest peak of the vibrational energy curve of the chloromethyl radical. The results further imply that, following absorption of one UV photon of 234 nm, other vibrational modes besides v5 (C-Br stretch mode) are also excited in the parent molecule.
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Second-generation antipsychotics are widely used to treat schizophrenia but their use could induce metabolic dysfunction. To balance efficacy and side effects, various guidelines recommend the use of therapeutic drug monitoring. Given the controversial relationship between olanzapine serum concentration and metabolic dysfunction, its use in clinical practice is still debated. To address this issue, we conducted a prospective cohort study to explore the associations in patients with schizophrenia. Specifically, first-episode drug-naive patients and patients with chronic schizophrenia were recruited. All participants received olanzapine monotherapy for 8 weeks. Anthropometric parameters and metabolic indices were tested at baseline and at week 8, and olanzapine serum concentration was tested at week 4. After 8 weeks of observation, body weight and BMI increased significantly in drug-naive patients. Moreover, triglycerides and LDL increased significantly in both drug-naive and chronic patients. Among chronic patients, those who have never used olanzapine/clozapine before had a significantly higher increase in weight and BMI than those who have previously used olanzapine/clozapine. Furthermore, olanzapine concentration was associated with changes in weight, BMI, and LDL levels in the drug-naive group and glucose, triglyceride and LDL levels in chronic patients who have not used olanzapine/clozapine previously. In conclusion, the metabolic dysfunction induced by olanzapine is more severe and dose-dependent in drug-naive patients but independent in patients with chronic schizophrenia. Future studies with a longer period of observation and a larger sample are warranted.
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2H-NbSe2 single crystal flake (ca. 2 × 2 × 0.5 mm in size) by chemical vapor transport is employed as the precursor for a top-down preparation of NbSe2 micro/nanoparticles by two kinds of processes, i.e. (1) mechanical exfoliation; (2) ultrasonic-assisted exfoliation in ethanol without ageing and with ageing for 210 days. NbSe2 micro/nanoparticles are applied on top of a Cu disk by a drop-casting process and the tribological property in sliding against a Cu pin under sliding electrical contact is investigated at room temperature. Mechanical exfoliation produces NbSe2 microplatets with typical sizes of 1 µm to 30 µ m with a thickness less than 2 µm. Ultrasonic-assisted exfoliation without aging facilitates the formation of NbSe2 micro/nanoplatets with sizes of 0.1 µm to 25 µm and nano-whiskers with 100 nm in diameter and 1 ~ 3 µm in length, but Nb2O5 and Se are also found on the basis of XPS results. Prolonged aging of the suspensions modifies the morphology by converting platets and whiskers into corrugated floccules (hybrid material), which are composed of Nb2O5, Se, NbSe2, and graphene. Notably, NbSe2 micro/nanoparticles by ultrasonic-assisted exfoliation without ageing exhibit an excellent lubricating property with low friction coefficient (0.3), mild wear, and longer wear lifetime (120 min) than that of mechanical exfoliated NbSe2 microplatets (10 min). The wear lifetime for the aged NbSe2 micro/nanoparticles can be as long as 504 min and are 4.2 times of the sample without aging, which can be a good solid lubricant for sliding electrical contact.
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Developing low-cost and highly active bifunctional electrocatalysts for water splitting is very important but still remains a challenge. Herein, a novel bifunctional electrocatalyst composed of CoP and Ni2P nanoparticles implanted in a hollow porous N-doped carbon polyhedron (CoP/Ni2P@HPNCP) is synthesized by carbonization of Co/Ni-layered double hydroxide@zeolitic imidazolate framework-67 (Co/Ni-LDH@ZIF-67) followed by an oxidation and phosphorization strategy. The introduction of LDH can not only promote the formation of a hollow porous structure to supply more active sites, but also generate the CoP/Ni2P nanoheterostructure to afford extra active sites and modulate the electronic structure of the catalyst. As a result, CoP/Ni2P@HPNCP exhibits excellent pH universal hydrogen evolution reaction activity and alkaline oxygen evolution reaction activity. Furthermore, the electrolytic cell assembled from bifunctional CoP/Ni2P@HPNCP requires a cell voltage of 1.59 V in 1.0 M KOH at 10 mA cm-2, revealing its potential as a high performance bifunctional electrocatalyst.
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Rational design and construction of high-efficiency and low-cost non-noble metal-based electrocatalysts for the hydrogen evolution reaction (HER) is critical for future renewable energy systems. Herein, a multi-channel V-doped CoP (MC-V-CoP) hollow nanofiber is fabricated via electrospinning and a subsequent oxidation/phosphorization process. The formation of a multi-channel hollow structure and V doping can enlarge the exposure of active sites, facilitate the electron transfer and tune the electronic structure of the active sites, resulting in the enhancement of the HER performance. As a result, the MC-V-CoP hollow nanofiber exhibits excellent HER activity with a low overpotential of 65 and 189 mV at 10 and 300 mA cm-2 in alkaline medium, respectively. This is superior to the commercial 20 wt% Pt/C catalyst at a high current density (212 mV at 300 mA cm-2), manifesting its outstanding performance toward the HER at a high current density. In addition, the MC-V-CoP hollow nanofiber also exhibits outstanding HER activity in neutral medium. The proposed strategy for fabricating multi-channel hollow nanofibers can also be used to prepare other transition metal phosphides for advanced electrochemical applications.
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Thermal behavior of biological apatite is the object of several studies. Crystal size, carbonate content, phase composition, and other parameters change during annealing up to 900 °C in biological minerals with apatite structure. The way these parameters change reflects the specific properties of the initial bioapatite. This work presents data on thermal transformations of pathological bioapatite from the human cardiovascular system, namely aortic wall deposits. Some minor elements, foreign to calcium hydroxyapatite (e.g., Na and Mg), can be both incorporated in the apatite structure and localized in the surface layers of crystals, modifying functions of the mineral. A new approach was proposed to determine the predominant location of minor elements, such as Mg, Na, and K, in the mineral of pathological deposits. Mg and Na in pathological apatite can be in both structurally bound (substituting calcium in lattice) and labile (localized on the crystal surface) states, while K is not able to join the apatite structure in significant amount or be chemically bound to it. This approach, based on atomic spectrometry, can be used effectively in combination with a set of traditional techniques, such as like EDS, IRS, and XRD.
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Orthodenticle homolog 1 (OTX1) has previously been revealed to be tightly associated with the development and progression of several human tumors. However, the functional roles and underlying molecular mechanisms of OTX1 in gastric cancer (GC) remain poorly understood. In the present study, we observed that OTX1 was highly expressed in GC tissues compared with adjacent nontumor tissues based on a large cohort of samples from The Cancer Genome Atlas (TCGA) database. An immunohistochemical analysis indicated that OTX1 levels were increased in tumors that became metastatic compared with those in tumors that did not. This finding was significantly associated with patients who had shorter overall survival times. The knockdown of OTX1 significantly inhibited the proliferation, migration and invasion of SGC7901 and MGC803 cells. Furthermore, the knockdown of OTX1 induced cell cycle arrest in the G0/G1 phase and reduced the expression of cyclin D1. In addition, the inhibition of OTX1 led to increased GC cell apoptosis by upregulating cleaved PARP, cleaved caspase3 and Bax. In conclusion, our data indicated that OTX1 functions as a key regulator in tumor growth and metastasis of GC cells. Thus, OTX1 may be a promising novel target for molecular therapy directed toward GC.
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Biomarcadores de Tumor/metabolismo , Movimiento Celular , Proliferación Celular , Factores de Transcripción Otx/metabolismo , Neoplasias Gástricas/patología , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis , Biomarcadores de Tumor/genética , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Factores de Transcripción Otx/genética , Pronóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Tasa de Supervivencia , Células Tumorales CultivadasRESUMEN
Idiopathic segmental infraction of the greater omentum (ISIGO) is a rare cause of acute abdomen. One of the main symptoms is right-side abdominal pain, while its etiology is still unclear. Until now, ISIGO simultaneously with spontaneous splenic rupture (SSR) has not been reported. Here, we presented a case of a 35-year old man, who was admitted with an acute abdomen, and the clinical diagnosis was ISIGO with SSR. He had a significant previous medical history of the vein thrombosis of lower limbs. Partial omental resection and splenectomy were performed, and the postoperative recovery of the patient was excellent. We also highlighted several possible theories to explain the etiology of the ISIGO, and emphasized that surgical methods, including laparoscopic surgery and laparotomy, are still the best way to treat the ISIGO at the emergency condition.
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Two precursors of ribbon-like anhydrous dicalcium phosphate (DCPA) and calcium phosphate fibres were successfully synthesized at 85 °C through a simple and mild pathway from Ca(NO(3))(2)·4H(2)O and (NH(4))(2)HPO(4) upon the hydrolysis of urea. Different molar concentrations of urea resulted in different precursors, including precursor I (DCPA phase) and precursor II (calcium phosphate with DCPA, octacalcium phosphate (OCP) and hydroxyapatite (HAp) phase). By immersing the two precursors in ammonium hydroxide solution (pH = 12), the transformation from precursors to hydroxyapatite could be achieved. X-ray diffraction (XRD) results combined with transmission electron microscopy (TEM) indicated that DCPA fibres (precursor I) were transformed to HAp nanorods in transformation I. In transformation II, dandelion-like spheres assembled by HAp nanorods were obtained from calcium phosphate (precursor II). The mechanisms of transformations I and II are also proposed and discussed based on the XRD and TEM results.