Spectrum-effect relationship study between ultra-high-performance liquid chromatography fingerprints and anti-hepatoma effect in vitro of Cnidii Fructus.

Cnidii Fructus, derived from the dried ripe fruit of Cnidium monnieri (L.) Cuss, has the effect of warming kidneys and invigorating Yang. This study established the spectrum-effect relationships between ultra-high-performance liquid chromatography (UHPLC) fingerprints and the antitumor activities of Cnidii Fructus on human hepatocellular carcinoma (HepG2) cells. In UHPLC fingerprints, 19 common peaks were obtained, and 17 batches of herbs had similarity >0.948. In Cell Counting Kit-8 (CCK-8) test, 17 batches of Cnidii Fructus extract significantly inhibited the proliferation of HepG2 cells to different degrees, showing different half-maximal inhibitory concentration (IC50) values. Furthermore, gray correlation analysis, Pearson's analysis, and orthogonal partial least squares discriminant analysis were performed to screen out eight components. The analysis of mass spectrum data and a comparison with standards revealed that the eight components were methoxsalen, isopimpinellin, osthenol, imperatorin, osthole, ricinoleic acid, linoleic acid, and oleic acid. The verification experiments by testing single compounds indicated that these eight compounds were the major anti-hepatoma compounds in Cnidii Fructus. This work provides a model combining UHPLC fingerprints and antitumor activities to study the spectrum-effect relationships of Cnidii Fructus, which can be used to determine the principal components responsible for the bioactivity.

Delivery of paclitaxel by carboxymethyl chitosan-functionalized dendritic fibrous nano-silica: Fabrication, characterization, controlled release performance and pharmacokinetics.

In this study, carboxymethyl chitosan (CMCS) with excellent biocompatibility was used as the "gatekeeper" to design and fabricate a pH-responsive drug delivery system (CMCS-DFNS) as paclitaxel carriers. Characterization results showed that CMCS-DFNS was successfully prepared and the nanocarriers displayed excellent drug loading efficiency of 19.8 %, and the results of the adsorption mechanism revealed that the adsorption of PTX was consistent with the Freundlich isotherm and pseudo-second-order kinetic model. Furthermore, the pH-responsive controlled release behavior at different pH (pH = 7.4, 6.5, and 5.0) was evaluated, and the results demonstrated that the cumulative release at pH 5.0 was 58.8 %, which was 2.7 times higher than that at pH 7.4, suggesting that the carrier exhibited a good pH sensitivity. The results of in vitro cellular experiments further indicated that CMCS-DFNS significantly improved the drug uptake efficiency in breast cancer MCF-7 cells. Importantly, the results of in vivo and cellular pharmacokinetic revealed that CMCS-DFNS can improve the circulation time and enhance the relative bioavailability of paclitaxel. Therefore, the fabricated pH-responsive drug delivery system has potential applications in the delivery of anti-tumor drugs, and provides a new delivery pathway for other compounds with low bioavailability.

Visualized and Nondestructive Quality Identification of Two-Dimensional MoS2 Based on Principal Component Analysis.

To date, the common quality characterizations for MoS2 are inefficient or cause irreversible damage to the samples, which have limited scalability and low throughput. Here, we propose a visualized and nondestructive approach to evaluate the quality of MoS2 based on the PCA machine learning method. Through PCA processing of PL mapping, the CVD grown MoS2 with different edge defect densities can be well distinguished. Furthermore, six twin GBs along the sulfur zigzag direction of the six pointed MoS2 stars are also successfully identified. To verify the correctness of the identification results, we measured the lifetime mapping and thermal expansion coefficient of the synthesized MoS2 samples. It is found that the high quality MoS2 samples have a shorter carrier lifetime (∼0.291 ns) and lower thermal expansion coefficient (∼2.03 × 10-5K-1). Therefore, our work offers a new approach to evaluate the quality of MoS2 to drive their practical application.

Qualitative identification and quantitative comparison of Physochlainae Radix from different regions based on chemometric methods.

Physochlainae Radix (PR) is an essential herbal medicine that has been generally applied for treating cough and asthma. In this study, a comprehensive strategy for quality evaluation of PR from different origins was established by integrating qualitative identification, quantitative analysis, and chemometric methods. A total of 58 chemical components were identified by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS/MS), and a sensitive and rapid UHPLC-QqQ-MS/MS method was established for the simultaneous determination of 12 compounds. In addition, multivariate statistical analysis was applied for discriminant analysis to compare the differences among 30 batches of PR samples. The results showed that the 30 batches of PR collected from four provinces could be clustered into three categories, in which scoparone, protocatechuic acid, tropic acid, and scopolin were important components to distinguish the primary and non-primary producing areas, as well as superior and inferior products of PR. Chemometric results were consistent and validated each other, and systematically explained the intrinsic quality characteristics of PR. This study first demonstrated that LC-MS combined with multivariate statistical analysis, provided a comprehensive and effective means for quality evaluation of PR.

Comparative analysis of chemical components in fruits of Chebulae Fructus and its pulp based on chromatographic technology coupled with multivariate chemometric methods.

Chebulae Fructus, was extensively used as a food supplement and medicinal herb, which contained two medicinal forms corresponding to the mature fruit of Chebulae Fructus (CF) and CF pulp. They were widely used in the Chinese clinical medicine and it played a significant role in the Mongolian and Tibetan medicine for the treatment of sore throat, asthma, diarrhea and other diseases. Both of them were recorded in the 2020 Edition (Volume I) of the Chinese Pharmacopoeia. However, the chemical components of CF and CF pulp have not been holistically explored, which seriously hindered its quality evaluation. This study investigated the overall chemical profile of the CF and CF pulp using ultra high-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UHPLC-Q-TOF/MS) and ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Sixty-four chemical components were tentatively identified, and 13 components were quantified in Chebulae Fructus. Furthermore, multivariate chemometric methods were applied to compare the differences among CF samples, and all samples were classified by orthogonal partial least squares-discriminant analysis (OPLS-DA) based on the 13 quantified compounds. The results showed that CF and CF pulp were clustered in two different areas. Ellagic acid, chebulagic acid, chebulinic acid, corilagin and pentagalloyl glucose were selected as the significant constituents to different of CF and CF pulp. LC-MS coupled with chemometrics strategy analysis could comprehensively evaluate the holistic quality of CF, which provided a necessary information for the rational development and utilization of CF and CF pulp resource.

Pharmacokinetics of active compounds of a Terminalia chebula Retz. Ethanolic extract after oral administration rats using UPLC-MS/MS.

Terminalia chebula Retz. (TC) is a well-known Chinese herbal medicine and rich in chemical components with multiple pharmacological effects. In this study, an ultra-performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) method was developed and used to determine the blood concentrations of nine active compounds (chebulic acid, gallic acid, protocatechuic acid, corilagin, chebulagic acid, chebulinic acid, 1,2,3,4,6-O-pentagalloylglucose, ellagic acid and ethyl gallate) after oral administration of TC extracts in rats. Pretreatment of plasma samples with protein precipitate with methanol was carried out, and caffeic acid was used as the internal standard (IS). Compounds precisions of intra- and inter-day were less than 14.6%, and the accuracy ranged from -11.7% to 13.5%. The extraction recoveries of compounds were between 84.9% and 108.4%, while matrix effects occurred between 86.4% and 115.9%. Stability tests showed that all nine analytes had been stable under four storage conditions, and statistically significant the relative standard deviations were under 13.7%. The validated UPLC-MS/MS method was applied with great success to plasma pharmacokinetics analysis of the TC extracts, and the pharmacokinetic results showed that among the nine components, the area under the concentration-time curve (AUC(0-tn), 231112.38 ± 64555.20 h ng/mL) and maximum concentration (Cmax, 4,983.57 ± 1721.53 ng/mL) of chebulagic acid were relatively large, which indicated that it had a higher level of plasma exposure. The half-life of elimination (T1/2) of chebulinic acid, corilagin and chebulagic acid were 43.30, 26.39 and 19.98 h, respectively, suggesting that these analytes showed prolonged retention and metabolize more slowly in vivo. This study would deliver a theoretical foundation for the further application of TC in clinical practice.

Long non-coding RNA XIST promotes the malignant features of oral squamous cell carcinoma (OSCC) cells through regulating miR-133a-5p/VEGFB.

OBJECTIVE: Oral squamous cell carcinoma (OSCC) represents a frequently seen oral cavity malignancy, and the mechanisms of its occurrence and development remain unclear. The present work examined the expression and biological function of long non-coding RNA (lncNRA) XIST (X-inactive specific transcript) in OSCC cells and tissues. STUDY DESIGN: A total number of 50 OSCC and paired non-carcinoma tissue samples were collected in this study. Gene expression levels in cancer tissues and cells were quantified by RT-qPCR. In addition, gain- and loss-of-function experiments were conducted to investigate the biological roles of XIST as well as its downstream targets in OSCC cells. RESULTS: XIST was upregulated in OSCC cells and tissues, which predicted a poorer prognostic outcome in OSCC patients. Silencing XIST inhibited the growth and invasion of OSCC cells and triggered apoptosis. miR-133a-5p was identified as a downstream target of XIST, which was downregulated in OSCC tissues. miR-133a-5p mediated the effect of XIST by targeting VEGFB. VEGFB overexpression rescued the inhibitory effects of XIST silencing on cell growth, invasion and migration. CONCLUSION: Taken together, the above data indicates that XIST serves as an oncogenic factor to enhance the growth and invasion of OSCC cells by targeting the miR-133a/VEGFB axis.

Strong Anisotropic Optical Properties by Rolling up MoS2 Nanoflake.

Although anisotropic two-dimensional materials have attracted great scientific interest, the anisotropy of those materials is limited to particular crystallographic directions. Herein, with dimension confining, MoS2 nanoscrolls are successfully fabricated by a rolling-up process after dropping an ethanol-water solution on a chemical vapor deposition-grown MoS2 monolayer. The anisotropic vibrational and optical properties are systematically studied by angle-resolved polarized spectroscopy, including Raman, photoluminescence, and reflection measurements. Upon comparing the photoluminescence results between MoS2 nanoscrolls and nanosheets, an obvious PL quenching phenomenon is observed, indicating the efficient separation of photon-induced carriers. Moreover, the time-resolved PL test identifying the lifetime of the carriers is decreased to 303 ps in the nanoscrolls, indicating a higher carrier-transfer efficiency. In summary, our work demonstrates the strong anisotropic optical properties of MoS2 nanorolls, showing the nanoscrolls are a promising candidate for the fabrication of multifunctional devices.

Low vitamin D levels and the long-term functional outcome of stroke up to 5 years.

BACKGROUND AND PURPOSE: Previous studies have established that vitamin D was associated with stroke. The purpose of this study was to investigate the relationship between vitamin D and 5-year outcome of patients with stroke including acute ischemic stroke (AIS) and intracranial hemorrhage (ICH) stroke. METHODS: Serum 25-hydroxyvitamin D levels were prospectively analyzed in patients admitted to the First Affiliated Hospital of Wenzhou Medical University from 2013 to 2015. Modified Rankin scale (mRS) was used to evaluate their 5-year functional outcome, and univariate and multivariate logistic regressions were applied to evaluate the effects of vitamin D on stroke outcome. RESULTS: In total, 668 patients diagnosed with stroke were recruited, and 420 completed the 5-year follow-up. Ninety-five patients experienced poor outcome in the 5 years since stroke onset. Vitamin D levels in patients with poor outcome showed significant differences compared to good outcome patients (p < .001). In multivariable logistic regression analysis, after adjusting the potential confounders, the 5-year functional outcome was significantly associated with vitamin D levels. Stroke patients with vitamin D levels less than 38.4 nmol/L had a higher risk for poor outcome compared with those with vitamin D level over 71.4 nmol/L at 5-year (odds ratio [OR] = 3.66, 95% confidence interval [CI] = 1.42-9.45, p = .007), which was consistent with AIS patients (OR = 6.36, 95% CI = 1.89-21.44, p = .003). CONCLUSION: Vitamin D level less than 38.4 nmol/L at admission is a potential risk biomarker for poor functional outcome at 5-year prognosis in AIS patients, which might provide new ideas for the prognostic assessment of stroke.

Corrigendum: Early-Onset Depression in Stroke Patients: Effects on Unfavorable Outcome 5 Years Post-stroke.

[This corrects the article DOI: 10.3389/fpsyt.2021.556981.].

Early-Onset Depression in Stroke Patients: Effects on Unfavorable Outcome 5 Years Post-stroke.

Background: Post-stroke depression (PSD) constitutes an essential complication of stroke and is associated with high-risk unfavorable outcome after stroke. The main objective of this prospective study was to determine the relationship between early-onset PSD (1 month after stroke) and functional outcomes 5 years after baseline enrollment. Methods: Four hundred thirty-six patients who met the criteria were included in this study from October 2013 to February 2015. The follow-up time for each patient was ~5 years, with follow-up every 3 months. Patients received questionnaires including the 17-item Hamilton Depression Scale (HAMD), the Mini-Mental State Examination (MMSE), the National Institutes of Health Stroke Scale (NIHSS), the modified Rankin Scale (mRS), and the Barthel Index (BI). Results: Of the 436 patients, 154 (35.3%) patients with the prevalence of PSD status at baseline, 26 (7.2%) patients with the prevalence of PSD status, and 73 (20.1%) had an unfavorable outcome 5 years after stroke. The odds ratio (OR) for unfavorable outcome at 5 years in the PSD group was ~2.2 relative to the non-PSD group after adjusting for potential risk factors [OR = 2.217, 95% confidence interval (CI) = 1.179-4.421, P = 0.015]. In the early-onset PSD group, HAMD scores were independently associated with 5-year unfavorable outcome rates (OR = 1.168, 95% CI = 1.015-1.345, P = 0.031). Conclusions: Our findings indicate that early-onset PSD status in Chinese patients is an independent risk factor for unfavorable outcome 5 years after stroke, and that the severity of PSD is also related to unfavorable outcome.

Weaker Braking Force, A New Marker of Worse Gait Stability in Alzheimer Disease.

Background: Braking force is a gait marker associated with gait stability. This study aimed to determine the alteration of braking force and its correlation with gait stability in Alzheimer disease (AD). Methods: A total of 32 AD patients and 32 healthy controls (HCs) were enrolled in this study. Gait parameters (braking force, gait variability, and fall risk) in the walking tests of Free walk, Barrier, and Count backward were measured by JiBuEn® gait analysis system. Gait variability was calculated by the coefficient of variation (COV) of stride time, stance time, and swing time. Results: The braking force of AD was significantly weaker than HCs in three walking tests (P < 0.001, P < 0.001, P = 0.007). Gait variability of AD showed significant elevation than HCs in the walking of Count backward (COVstride: P = 0.013; COVswing: P = 0.006). Fall risk of AD was significantly higher than HCs in three walking tests (P = 0.001, P = 0.001, P = 0.001). Braking force was negatively associated with fall risks in three walking tests (P < 0.001, P < 0.001, P < 0.001). There were significant negative correlations between braking force and gait variability in the walking of Free walk (COVstride: P = 0.018; COVswing: P = 0.013) and Barrier (COVstride: P = 0.002; COVswing: P = 0.001), but not Count backward (COVstride: P = 0.888; COVswing: P = 0.555). Conclusion: Braking force was weaker in AD compared to HCs, reflecting the worse gait stability of AD. Our study suggests that weakening of braking force may be a new gait marker to indicate cognitive and motor impairment and predict fall risk in AD.

Vulnerability to fraud among Chinese older adults: do personality traits and loneliness matter?

This study examined correlates of the vulnerability to fraud among a group of urban Chinese older adults, focusing on the influence of personality traits and loneliness. A non-probability sample of 321 older participants recruited from six urban communities in Tianjin, China participated in a survey. Key measures included the Elder Risk for Fraud Scale, the short Big Five Inventory, and the Emotional-Social Loneliness Inventory. Regression analyses found that agreeableness personality was associated with lower risks for fraud while social loneliness was associated with higher risks for fraud. Older participants who needed medical assistance with their daily living were found at higher risks for fraud than their counterparts without medical needs. It is recommendded that policymakers and helping professionals in China should assess psychosocial risk factors for fraud. Great attention needs to be paid to older adults who demonstrate low levels of agreeableness and high levels of social loneliness.