Molecular, biological characterization and drug sensitivity of chidamide-resistant MCF7 cells.

Background: Chidamide (CHI) is a subtype-selective histone deacetylase inhibitor (HDACI) developed in China and approved as a second-line treatment combined with the aromatase inhibitor for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. However, drug resistance is commonly occurred after a long period of medication. This study aimed to investigate the characterization of induced resistance to CHI and explore the potential cross-resistance to chemotherapeutic agents. Methods: CHI with gradually increasing concentrations was added to breast cancer MCF7 cells to establish a CHI-resistant MCF7 (MCF7-CHI-R) cell line. Cell counting kit-8 (CCK-8) assays were performed to detect half-maximal inhibitory concentration (IC50) of CHI. Colony formation was used to determine the proliferation inhibition rate. Western blot analysis was conducted to detect expressions of protein related with cell cycle, apoptosis, ferroptosis, and histone deacetylase (HDAC). Flow cytometry was used to analyze apoptosis and cell cycle. Results: The IC50 value of CHI of MCF7-CHI-R cells was increased in comparison with MCF7 cells. And CHI led to cell cycle arrest and ferroptosis, which were not exhibited in MCF7-CHI-R cells. Moreover, HDAC activity decreased in MCF7-CHI-R cells in comparison with MCF7 cells, and HDAC1 and HDAC10 might be involved in the resistance to CHI. In addition, MCF7-CHI-R cells were resistant to gemcitabine (GEM), doxorubicin (ADM), docetaxel (DXT), albumin-bound paclitaxel (nab-PTX) and paclitaxel (PTX). Conclusions: The MCF7-CHI-R was established and the anti-ferroptosis pathway activation was involved in the resistance of MCF-CHI-R cells. Also, MCF7-CHI-R cells were resistant to GEM, ADM, DXT, nab-PTX and PTX.

Mechanisms of low nighttime temperature promote oil accumulation in Brassica napus L. based on in-depth transcriptome analysis.

Rape (Brassica napus L.; AACC) is an important oil-bearing crop worldwide. Temperature significantly affects the production of oil crops; however, the mechanisms underlying temperature-promoted oil biosynthesis remain largely unknown. In this study, we found that a temperature-sensitive cultivar (O) could accumulate higher seed oil content under low nighttime temperatures (LNT,13°C) compared with a temperature-insensitive cultivar (S). We performed an in-depth transcriptome analysis of seeds from both cultivars grown under different nighttime temperatures. We found that low nighttime temperatures induced significant changes in the transcription patterns in the seeds of both cultivars. In contrast, the expression of genes associated with fatty acid and lipid pathways was higher in the O cultivar than in the S cultivar under low nighttime temperatures. Among these genes, we identified 14 genes associated with oil production, especially BnLPP and ACAA1, which were remarkably upregulated in the O cultivar in response to low nighttime temperatures compared to S. Further, a WGCNA analysis and qRT-PCR verification revealed that these genes were mainly regulated by five transcription factors, WRKY20, MYB86, bHLH144, bHLH95, and NAC12, whose expression was also increased in O compared to S under LNT. These results allowed the elucidation of the probable molecular mechanism of oil accumulation under LNT conditions in the O cultivar. Subsequent biochemical assays verified that BnMYB86 transcriptionally activated BnLPP expression, contributing to oil accumulation. Meanwhile, at LNT, the expression levels of these genes in the O plants were higher than at high nighttime temperatures, DEGs (SUT, PGK, PK, GPDH, ACCase, SAD, KAS II, LACS, FAD2, FAD3, KCS, KAR, ECR, GPAT, LPAAT, PAP, DGAT, STERO) related to lipid biosynthesis were also upregulated, most of which are used in oil accumulation.

Detection of optical properties of chiral substances by a photoconductive THz polarization detector.

Chiral enantiomers have significant differences in biochemical functions. The use of THz wave polarization detection to characterize the optical properties of chiral substances is of great significance to the development of life science and the identification and application of chiral substances. However, the traditional polarization detection procedures of THz waves are complex, which limits the study of chiral substances. Herein, we proposed a high-sensitivity THz polarization detector, which can simultaneously obtain the change information of amplitude, phase, and polarization state through a single measurement. The optical rotation and elliptical angle of solid and liquid D/L-Glutamic acid 5-methyl ester in the THz band are studied. Then it is verified that anisotropic interference may occur in the preparation of solid samples. Finally, the effects of sample content and thickness on polarization are obtained. The experimental results show that different chirality has the opposite effect on the state of polarization, and the difference between chiral enantiomers can be detected by this method. This work is of great significance for understanding the optical properties of chiral substances and promoting the development of chiral recognition.

Efficacy and safety of gemcitabine plus raltitrexed or S-1 versus standard third-line therapies in metastatic colorectal cancer: a retrospective cohort study.

Background: After the failure of standard first- and second-line treatments, including oxaliplatin, irinotecan, and 5-fluorouracil (5-FU) combined with targeted drugs, the currently recommended third-line regimens for metastatic colorectal cancer (mCRC) include TAS-102, regorafenib, and fruquintinib. However, these regimens have the drawbacks of mediocre efficacy, substantive side effects, and high cost. Therefore, more effective, economical regimens with fewer side effects are needed in clinical practice. In this study, we assessed the efficacy and safety of gemcitabine plus raltitrexed or S-1 as a third- or later-line treatment in comparison to those of standard third-line therapies for patients with mCRC. Methods: Patients with previous failures of at least two lines of standard therapy with oxaliplatin, 5-FU, irinotecan, or capecitabine combined with targeted drugs were included. The participants received standard third-line therapies (including TAS-102, regorafenib, and fruquintinib) or gemcitabine plus raltitrexed or S-1 until disease progression, death, or intolerable toxicity arose. Imaging follow-up was performed every 3 months during their treatment. Progression-free survival (PFS) and overall survival (OS) were recorded. Cox regression analysis was used to investigate the potential predictors of survival. Results: From April 2018 to October 2022, 60 patients with mCRC were enrolled in our study. The numbers of patients in the chemotherapy, fruquintinib, regorafenib, and TAS-102 groups were 13, 15, 17, and 15, respectively; the median OS of the four groups was 7.4, 6.1, 8.3, and 6.7 months (P=0.384), respectively; the median PFS was 4.1, 3.4, 4.4, and 2.3 months (P=0.656), respectively; the overall response rate was 7.69%, 6.67%, 0.00%, and 13.33%, respectively; and the disease control rate was 61.54%, 60.00%, 70.59%, and 60.00%, respectively. Additionally, multivariate analysis revealed that primary lesion located in the rectum was adverse independent prognostic factors for OS. A typical case is presented in this article. Conclusions: The gemcitabine plus raltitrexed or S-1 regimen is a potential regimen with tolerable adverse reactions and low cost for patients with mCRC.

Insights into the hierarchical structure and physicochemical properties of starch isolated from fermented dough.

Understanding the hierarchical structure and physicochemical properties of starch isolated from fermented dough with different times (0-120 min) is valuable for improving the quality of fermented dough-based products. The results indicate that fermentation disrupted the starch granule surface and decreased the average particle size from 19.72 µm to 18.45 µm. Short-term fermentation (< 60 min) disrupted the crystalline, lamellar, short-range ordered molecular and helical structures of starch, while long-term fermentation (60-120 min) elevated the ordered degree of these structures. For example, relative crystallinity and double helix contents increased from 23.7 % to 26.8 % and 34.4 % to 37.2 %, respectively. During short-term fermentation, the structural amorphization facilitated interactions between starch molecular chains and water molecules, which increased the peak viscosity from 275.4 to 320.6 mPa·s and the swelling power from 7.99 to 8.52 g/g. In contrast, starches extracted from long-term fermented dough displayed the opposite results. Interestingly, the hardness and springiness of starch gels gradually decreased as fermentation time increased. These findings extend our understanding of the starch structure-property relationship during varied fermentation stages, potentially benefiting the production of better-fermented foods.

Chemometrics combined with comprehensive two-dimensional gas chromatography-mass spectrometry for the identification of Baijiu vintage.

The identification of baijiu vintage is crucial for quality assessment and economic value determination. However, its complex composition and multifaceted influences pose significant technical challenges, necessitating research into its aging mechanisms and the development of related identification methods. This study utilized Chemometrics in conjunction with GC × GC-TOFMS for Baijiu Vintage identification. Data compression achieved a reduction of over 1000-fold without compromising key information, enabling analysis on many samples and get their changing regular in a big matrix by MCR. Subsequently, MCR-ALS facilitated the extraction of physical and chemical meaningful information related to baijiu vintage. Key MCR principal components suitable for qualitative and quantitative assessments were selected using CARS-PLS. The regression model demonstrated errors of less than one year. Furthermore, a PLS-DA model provided 30 MCR principal components as potential markers. The research results provide technical support for baijiu vintage identification and lay the groundwork for studying the changing patterns of flavor compounds in baijiu.

Effect of cerebral small vessel disease on the integrity of cholinergic system in mild cognitive impairment patients: a longitudinal study.

We aimed to investigate the effect of cerebral small vessel disease (SVD) on cholinergic system integrity in mild cognitive impairment (MCI) patients. Nucleus basalis of Meynert (NBM) volume and cholinergic pathways integrity was evaluated at baseline, 1-, 2-, and 4-year follow-ups in 40 cognitively unimpaired (CU) participants, 29 MCI patients without SVD, and 23 MCI patients with SVD. We compared cholinergic markers among three groups and examined their associations with SVD burden in MCI patients. We used linear mixed models to assess longitudinal changes in cholinergic markers over time among groups. Mediation analysis was employed to investigate the mediating role of cholinergic system degeneration between SVD and cognitive impairment. Increased mean diffusivity (MD) in medial and lateral pathways was observed in MCI patients with SVD compared to those without SVD and CU participants. Both MCI groups showed decreased NBM volume compared to CU participants, while there was no significant difference between the two MCI groups. Longitudinally, compared to CU participants, MCI patients with SVD displayed a more rapid change in MD in both pathways, but not in NBM volume. Furthermore, SVD burden was associated with cholinergic pathway disruption and its faster rate of change in MCI patients. However, mediation analyses showed that cholinergic pathways did not mediate significant indirect effects of SVD burden on cognitive impairment. Our findings suggest that SVD could accelerate the degeneration of cholinergic pathways in MCI patients. However, they do not provide evidence to support that SVD could contribute to cognitive impairment through cholinergic system injury.

Establishment and verification of a prognostic risk score model based on immune genes for hepatocellular carcinoma in an Asian population.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, with the highest incidence in East Asia, and hepatitis B virus (HBV) infection is the most common cause of HCC in Asian population. The immune system is closely related to the development of HCC and plays an important role in the treatment of this disease. In this study, we analyzed the data of HCC from The Cancer Genome Atlas (TCGA) database and constructed a risk-score prognostic model based on immune genes of an Asian HCC population, aiming to provide new perspectives for clinical treatment and management of HCC in Asian population. Methods: Data concerning clinical attributes and transcriptomic profiles of individuals in the Asian population diagnosed with HCC were retrieved from the TCGA database. Concurrently, immune-related genes were sourced from the Immport database for incorporation into our analysis. A total of 265 immune-related genes displaying differential expression were identified through wilcoxTest analysis in R. Further refinement using univariate and multivariate Cox regression analysis led to the identification of 15 genes that exhibited strong associations with prognosis. MICB/PSMD14/TRAF3/SP1/NDRG1/HDAC1/HRAS/NRAS/SEMA5B/GMFB/ACVR2B/BRD8/MMP12/KITLG/DCK, and a prognostic risk score model was constructed based on the above genes. Results: The findings demonstrated notable differences in survival rates between the low-risk and high-risk groups, as depicted by the Kaplan-Meier (K-M) survival curves (P<0.001). Furthermore, the model's predictive capability was evidenced by receiver operating characteristic (ROC) curves, with area under the curve (AUC) =0.901. Finally, the relationship of the model with each clinical trait and immune cells was assessed by correlation analysis. Conclusions: The prognostic risk score model constructed by immune genes based on the Asian HCC population has certain predictive capacity.

MiR-122 knockdown regulates vascular smooth muscle cells phenotypic switching through enhanced FOXO3 expression.

Vascular smooth muscle cells (VSMCs) phenotypic switching is identified as enhanced dedifferentiation, proliferation, and migration ability of VSMCs, in which microRNAs have been identified as important regulators of the process. The present study is aimed to explore the pathophysiological effect of miR-122 on VSMC phenotypic modulation. Here, the result showed that the decreased miR-122 expression was found in VSMCs subjected to platelet-derived growth factor-BB (PDGF-BB) treatment. Next, we investigated the response of miR-122 knockdown in VSMCs with PDGF-BB stimulation. MiR-122 silencing showed increased proliferation and migration capability, whereas attenuated the differentiation markers expression. The above results were reversed by miR-122 overexpression. Finally, we further demonstrated that FOXO3 was an important target for miR-122. Collectively, we demonstrated that miR-122 silencing promoted VSMC phenotypic modulation partially through upregulated FOXO3 expression that indicated miR-122 may be a novel therapeutic target for neointimal formation.

Upregulated Mitochondrial Dynamics Is Responsible for the Procatabolic Changes of Chondrocyte Induced by α2-Adrenergic Signal Activation.

OBJECTIVE: Activation of sympathetic tone is important for cartilage degradation in osteoarthritis (OA). Recent studies reported that sympathetic signals can affect the mitochondrial function of target cells. It is unknown whether this effect exits in chondrocytes and affects chondrocyte catabolism. The contribution of mitochondrial dynamics in the activation of α2-adrenergic signal-mediated chondrocyte catabolism was investigated in this study. DESIGN: Primary chondrocytes were stimulated with norepinephrine (NE) alone, or pretreated with an α2-adrenergic receptor (Adra2) antagonist (yohimbine) and followed by stimulation with NE. Changes in chondrocyte metabolism and their mitochondrial dynamics were investigated. RESULTS: We demonstrated that NE stimulation induced increased gene and protein expressions of matrix metalloproteinase-3 and decreased level of aggrecan by chondrocytes. This was accompanied by upregulated mitochondriogenesis and the number of mitochondria, when compared with the vehicle-treated controls. Mitochondrial fusion and fission, and mitophagy also increased significantly in response to NE stimulation. Inhibition of Adra2 attenuated chondrocyte catabolism and mitochondrial dynamics induced by NE. CONCLUSIONS: The present findings indicate that upregulation of mitochondrial dynamics through mitochondriogenesis, fusion, fission, and mitophagy is responsible for activation of α2-adrenergic signal-mediated chondrocyte catabolism. The hypothesis that "α2-adrenergic signal activation promotes cartilage degeneration in temporomandibular joint osteoarthritis (TMJ-OA) by upregulating mitochondrial dynamics in chondrocytes" is validated. This represents a new regulatory mechanism in the chondrocytes of TMJ-OA that inhibits abnormal activation of mitochondrial fusion and fission is a potential regulator for improving mitochondrial function and inhibiting chondrocyte injury and contrives a potentially innovative therapeutic direction for the prevention of TMJ-OA.

Primary microcephaly gene CENPE is a novel biomarker and potential therapeutic target for non-WNT/non-SHH medulloblastoma.

Background: Non-WNT/non-SHH medulloblastoma (MB) is one of the subtypes with the highest genetic heterogeneity in MB, and its current treatment strategies have unsatisfactory results and significant side effects. As a member of the centromere protein (CENP) family, centromeric protein E (CENPE) is a microtubule plus-end-directed kinetochore protein. Heterozygous mutations in CENPE can leads to primary microcephaly syndrome. It has been reported that CENPE is upregulated in MB, but its role in MB development is still unknown. Methods: We downloaded the relevant RNA seq data and matched clinical information from the GEO database. Bioinformatics analysis includes differential gene expression analysis, Kaplan-Meier survival analysis, nomogram analysis, ROC curve analysis, immune cell infiltration analysis, and gene function enrichment analysis. Moreover, the effects of CENPE expression on cell proliferation, cell cycle, and p53 signaling pathway of non-WNT/non-SHH MB were validated using CENPE specific siRNA in vitro experiments. Results: Compared with normal tissues, CENPE was highly expressed in MB tissues and served as an independent prognostic factor for survival in non-WNT/non-SHH MB patients. The nomogram analysis and ROC curve further confirmed these findings. At the same time, immune cell infiltration analysis showed that CENPE may participate in the immune response and tumor microenvironment (TME) of non-WNT/non-SHH MB. In addition, gene enrichment analysis showed that CENPE was closely related to the cell cycle and p53 pathway in non-WNT/non-SHH MB. In vitro experimental validation showed that knockdown of CENPE inhibited cell proliferation by activating the p53 signaling pathway and blocking the cell cycle. Conclusion: The expression of CENPE in non-WNT/non-SHH MB was positively correlated with poor prognosis. CENPE may affect tumor progression by regulating cell cycle, p53 pathway, and immune infiltration. Hence, CENPE is highly likely a novel biomarker and potential therapeutic target for non-WNT/non-SHH MB.

[Optimization of parameters for stir-frying of Kansui Radix with vinegar based on conversion of toxic components].

This study aims to optimize the parameters for stir-frying of Kansui Radix with vinegar based on the conversion of representative toxic diterpenes, which is expected to serve as a reference for the standardized production of Kansui Radix stir-fried with vinegar. To be specific, the toxic components [3-O-(2'E,4'Z-decadienoyl)-20-O-acetylingenol(3-O-EZ), kansuiphorin C(KPC)] in Kansui Radix and the products(ingenol, 20-deoxyingenol) after the stir-frying with vinegar were selected. The toxicity to intestine and water-draining activity were evaluated with NCM460(normal human colon mucosal epithelial cell line) and HT-29(a human colorectal adenocarcinoma cell line). An HPLC method was then developed to assess the conversion of toxic components. On this basis, temperature, time, and amount of vinegar for the processing of Kansui Radix were optimized with the Box-Behnken design and the content of ingenol and 20-deoxyingenol as evaluation index. The results showed that after the stir-frying of Kansui Radix with vinegar, 3-O-EZ and KPC were first converted to monoester 3-O-(2'E,4'Z-decadienoyl)ingenol(3-EZ) and 5-O-benzoyl-20-deoxyingenol(5-O-Ben) and finally to almost non-toxic ingenol and 20-deoxyingenol, respectively. Meanwhile, the water-draining activity was retained. Six compounds had a good linear relationship with the peak area in the corresponding concentration ranges(R~2≥0.999 8), and the average recovery fell in the range of 98.20%-102.3%(RSD≤2.4%). The content of representative diterpenes and intermediate products was 14.78%-24.67% lower in the Kansui Radix stir-fried with vinegar than in the Kansui Radix, while the content of the conversed products was 14.37%-71.37% higher. Among the process parameters, temperature had significant influence on the total content of products, followed by time. The optimal parameters were 210 ℃, 15 min, and 30% vinegar. The relative error between the experimental results and the predicted values was 1.68%, indicating that the process was stable and reproducible. The strategy of screening optimal parameters for stir-frying of Kansui Radix with vinegar based on the transformation of toxic components can help improve the production stability, reduce the toxicity, and ensure the efficacy of Kansui Radix stir-fried with vinegar, which can serve as a reference for the process optimization of similar toxic Chinese medicinals.

Construction and validation of a prognostic model based on autophagy-related genes for hepatocellular carcinoma in the Asian population.

BACKGROUND AND OBJECTIVE: Hepatocellular carcinoma (HCC), which has a complex pathogenesis and poor prognosis, is one of the most common malignancies worldwide. Hepatitis virus B infection is the most common cause of HCC in Asian patients. Autophagy is the process of digestion and degradation, and studies have shown that autophagy-associated effects are closely related to the development of HCC. In this study, we aimed to construct a prognostic model based on autophagy-related genes (ARGs) for the Asian HCC population to provide new ideas for the clinical management of HCC in the Asian population. METHODS: The clinical information and transcriptome data of Asian patients with HCC were downloaded from The Cancer Genome Atlas (TCGA) database, and 206 ARGs were downloaded from the human autophagy database (HADB). We performed differential and Cox regression analyses to construct a risk score model. The accuracy of the model was validated by using the Kaplan-Meier (K-M) survival curve, receiver operating characteristic (ROC) curve, and univariate and multivariate Cox independent prognostic analyses. The results Thirteen ARGs that were significantly associated with prognosis were finally identified by univariate and multivariate Cox regression analyses. The K-M survival curves showed that the survival rate of the low-risk group was significantly higher than that of the high-risk group (p < 0.001), and the multi-indicator ROC curves further demonstrated the predictive ability of the model (AUC = 0.877). CONCLUSION: The risk score model based on ARGs was effective in predicting the prognosis of Asian patients with HCC.

Detection of the minimum concentrations of α-lactose solution using high-power THz-ATR spectroscopy.

Terahertz (THz) technology has emerged as a promising tool for the qualitative and quantitative identification of markers containing major diseases, enabling early diagnosis and staged treatment of diseases. Nevertheless, the detection of water-containing biological samples is facing significant challenges due to limitations in high-power THz radiation sources and high-sensitivity detection devices. In this paper, we present a designed and constructed set of Terahertz-Attenuated Total Reflection (THz-ATR) spectrometer for high-sensitivity detection of liquid biological samples, which can dynamically maintain the signal-to-noise ratio (SNR) of THz detection signal of liquid biological samples at 40-60 dB. Our high-power THz-ATR spectroscopy can identify and quantitatively detect α-lactose aqueous solution with a minimum concentration of 0.292 mol/L. Moreover, we observed that the rate of change in the absorption peak position varied greatly between high and low concentration samples. Our high-power, high-sensitivity THz-ATR spectroscopy detection provides a rapid, accurate, and low-cost method for detecting disease markers such as blood and urine indicators. Additionally, this approach offers new perspectives for the refinement and in-depth detection of biomedical samples.

Soy Protein Isolate Interacted with Acrylamide to Reduce the Release of Acrylamide in the In Vitro Digestion Model.

Acrylamide (AA), a common carcinogen, has been found in many dietary products.. This study aimed to explore the interaction of soybean protein isolate (SPI) with AA and further research the different effects of SPI on the AA release due to interactions in the in vitro digestion model. Analysis of variance was used to analyze the data. The results suggested that AA could bind with SPI in vitro, leading to the variation in SPI structure. The intrinsic fluorescence of SPI was quenched by AA via static quenching. The non-covalent (van der Waals forces and hydrogen bonding) and covalent bonds were the main interaction forces between SPI and AA. Furthermore, the release of AA significantly decreased due to its interaction with SPI under simulated gastrointestinal conditions. SPI had different effects on the AA release rate after different treatments. The thermal (80, 85, 90, and 95 °C for either 10 or 20 min) and ultrasound (200, 300, and 400 W for either 15, 30, or 60 min) treatments of SPI were useful in reducing the release of AA. However, the high pressure-homogenized (30, 60, 90, and 120 MPa once, twice, or thrice) treatments of SPI were unfavorable for reducing the release of AA.

Plasma metabolomics for the assessment of the progression of non-small cell lung cancer.

OBJECTIVES: Non-small cell lung cancer (NSCLC) is a leading type of lung cancer with a high mortality rate worldwide. Although many procedures for the diagnosis and prognosis assessment of lung cancer exist, they are often laborious, expensive, and invasive. This study aimed to develop an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)-based analysis method for the plasma biomarkers of NSCLC with the potential to indicate the stages and progression of this malignancy conveniently and reliably. METHODS: A total of 53 patients with NSCLC in early stages (I-III) and advanced stage (IV) were classified into the early and advanced groups based on the tumor node metastasis staging system. A comprehensive metabolomic analysis of plasma from patients with NSCLC was performed via UPLC-MS/MS. Principal component analysis and partial least squares-discriminant analysis were conducted for statistical analysis. Potential biomarkers were evaluated and screened through receiver operating characteristic analyses and correlation analysis. Main differential metabolic pathways were also identified by utilizing metaboanalyst. RESULTS: A total of 129 differential metabolites were detected in accordance with the criteria of VIP ≥ 1 and a P-value of ≤ 0.05. The receiver operating characteristic curves indicated that 11 of these metabolites have the potential to be promising markers of disease progression. Apparent correlated metabolites were also filtered out. Furthermore, the 11 most predominant metabolic pathways with alterations involved in NSCLC were identified. CONCLUSION: Our study focused on the plasma metabolomic changes in patients with NSCLC. These changes may be used for the prediction of the stage and progression of NSCLC. Moreover, we discussed the metabolic pathways wherein the altered metabolites were mainly enriched.

Effects of Five-Step Nutritional Interventions Conducted by a Multidisciplinary Care Team on Gastroenteric Cancer Patients Undergoing Chemotherapy: A Randomized Clinical Trial.

The present study aims to report a five-step nutritional intervention conducted by a multidisciplinary care team as well as to investigate its effects on the nutritional status and quality of life of gastroenteric cancer patients undergoing chemotherapy. A total of 176 patients with newly diagnosed gastroenteric cancer were enrolled in the observational study. The nutritional status of the patients was assessed using Patient-Generated Subjective Global Assessment (PG-SGA) and Nutritional Risk Screening-2002 (NRS-2002), and anthropometry and biological tests were performed. Patients were randomly divided into intervention group (n = 40) and control group (n = 38). Patients in the intervention group received five-step nutrition intervention, while the control group received routine nutrition management. In the newly diagnosed patients with gastroenteric cancer, 50% presented mild to moderate malnutrition, 29.5% presented severe malnutrition, while only 20.5% of patients were in good nutritional status. Nutritional interventions reduced the progression of malnutrition after 10 weeks. Anthropometric parameters increased as well as function and symptoms improved; therefore, controlled the decline in quality of life. To sum up, five-step nutritional interventions conducted by a multidisciplinary care team improved the nutritional status of patients with gastroenteric cancer undergoing chemotherapy, and showed positive impacts on quality of life.

High-performance visible-near-infrared photodetector based on the N2200/Sb2Se3 nanorod arrays organic-inorganic hybrid heterostructure.

Antimony selenide (Sb2Se3) is a suitable candidate for a broadband photodetector owing to its remarkable optoelectronic properties. Achieving a high-performance self-powered photodetector through a desirable heterojunction still needs more efforts to explore. In this work, we demonstrate a broadband photodetector based on the hybrid heterostructure of Sb2Se3 nanorod arrays (NRAs) absorber and polymer acceptor (P(NDI2OD-T2), N2200). Owing to the well-matched energy levels between N2200 and Sb2Se3, the recombination of photogenerated electrons and holes in N2200/Sb2Se3 hybrid heterostructure is greatly inhibited. The photodetector can detect the wavelength from 405 to 980 nm, and exhibit high responsivity of 0.39 A/W and specific detectivity of 1.84 × 1011 Jones at 780 nm without bias voltage. Meanwhile, ultrafast response rise time (0.25 ms) and fall time (0.35 ms) are obtained. Moreover, the time-dependent photocurrent of this heterostructure-based photodetector keeps almost the same value after the storge for 40 days, indicating the excellent stability and reproducibility. These results demonstrate the potential application of a N2200/Sb2Se3 NRAs heterojunction in visible-near-infrared photodetectors.

Altered functional connectivity pattern of hippocampal subfields in individuals with objectively-defined subtle cognitive decline and its association with cognition and cerebrospinal fluid biomarkers.

Recent studies have shown that in the preclinical phase of Alzheimer's disease (AD), subtle cognitive changes can be detected using sensitive neuropsychological measures, and have proposed the concept of objectively-defined subtle cognitive decline (Obj-SCD). We aimed to assess the functional alteration of hippocampal subfields in individuals with Obj-SCD and its association with cognition and pathological biomarkers. Forty-two participants with cognitively normal (CN), 29 with Obj-SCD, and 55 with mild cognitive impairment (MCI) were retrospectively collected from the ADNI database. Neuropsychological performance, functional MRI, and cerebrospinal fluid (CSF) data were obtained. We calculated the seed-based functional connectivity (FC) of hippocampal subfields (cornu ammonis1 [CA1], CA2/3/dentate gyrus [DG], and subiculum) with whole-brain voxels. Additionally, we analyzed the correlation between FC values of significantly altered regions and neuropsychological performance and CSF biomarkers. The Obj-SCD group showed lower FC between left CA1-CA2/3/DG and right thalamus and higher FC between right subiculum and right superior parietal gyrus (SPG) compared with the CN and MCI groups. In the Obj-SCD group, FC values between left CA2/3/DG and right thalamus were positively associated with Auditory Verbal Learning Test (AVLT) recognition (r = 0.395, p = 0.046) and CSF Aß1-42 levels (r = 0.466, p = 0.019), and FC values between left CA1 and right thalamus were positively correlated with CSF Aß1-42 levels (r = 0.530, p = 0.006). Taken together, dysfunction in CA1-CA2/3/DG subregions suggests subtle cognitive impairment and AD-specific pathological changes in individuals with Obj-SCD. Additionally, increased subiculum connectivity may indicate early functional compensation for subtle cognitive changes.

Safety and Viral Shedding of Live Attenuated Influenza Vaccine (LAIV) in Chinese Healthy Juveniles and Adults: A Phase â Randomized, Double-Blind, Placebo-Controlled Study.

This study was a randomized, double-blind, placebo-controlled study to evaluate the safety and viral shedding of live attenuated influenza vaccine (LAIV) in Chinese healthy juveniles and adults. A total of 80 Eligible volunteers were divided into two age groups (≥18 and 3-17 years old). Volunteers were randomly and equally assigned to the experimental group and placebo-controlled group by ratio of 3:1 in each age group. Vaccination was carried out in steps. Totally, 34 (56.67%) adverse events and 24 (40.00%) adverse reactions of the LAIV group were reported. Most adverse reactions were grade 1 and grade 2, and the incidence of adverse reactions that grade 3 was 5%. The most common local reaction was runny nose/nasal congestion (n = 4, 6.67%). And the most common general reaction was fever (n = 10, 16.67%). There were no statistically significant differences in the incidence of total adverse reactions, different grades of adverse reactions, and symptoms between the experimental group and placebo-controlled group. No severe adverse events were reported. Three subjects (5.00%) had been detected vaccine strains on the 3rd day after LAIV vaccination; one was type B and the other two were H3N2. Four subjects (6.67%) had been detected with vaccine strains on the 7th day after LAIV vaccination, all were H3N2. There were no subjects detected carrying the influenza virus on the 15th day after vaccination. There were no statistically significant differences in the positive rate of vaccine strains of influenza virus between the experimental group and placebo-controlled group. The vaccine was well tolerated and not associated with increased rates in adverse reactions or the occurrence of severe adverse events. Pathogenicity of shed vaccine virus to surrounding people was not observed. Thus, Phase Ⅱ study can be carried out as scheduled.