SF3A2 promotes progression and cisplatin resistance in triple-negative breast cancer via alternative splicing of MKRN1.

Triple-negative breast cancer (TNBC) is the deadliest subtype of breast cancer owing to the lack of effective therapeutic targets. Splicing factor 3a subunit 2 (SF3A2), a poorly defined splicing factor, was notably elevated in TNBC tissues and promoted TNBC progression, as confirmed by cell proliferation, colony formation, transwell migration, and invasion assays. Mechanistic investigations revealed that E3 ubiquitin-protein ligase UBR5 promoted the ubiquitination-dependent degradation of SF3A2, which in turn regulated UBR5, thus forming a feedback loop to balance these two oncoproteins. Moreover, SF3A2 accelerated TNBC progression by, at least in part, specifically regulating the alternative splicing of makorin ring finger protein 1 (MKRN1) and promoting the expression of the dominant and oncogenic isoform, MKRN1-T1. Furthermore, SF3A2 participated in the regulation of both extrinsic and intrinsic apoptosis, leading to cisplatin resistance in TNBC cells. Collectively, these findings reveal a previously unknown role of SF3A2 in TNBC progression and cisplatin resistance, highlighting SF3A2 as a potential therapeutic target for patients with TNBC.

Relationship between leaf vein traits of three dominant Quercus species and ecological factors in the Qinling Mountains, China.

We investigated the inter- and intra-species differences of leaf vein traits of three dominant Quercus species, Q. wutaishanica, Q. aliena var. acutiserrata, and Q. variabilis of Niubeiling (subtropical humid climate) and Taohuagou (warm temperate semi-humid climate), located in the eastern and western Qinling Mountains. The nine examined leaf vein traits included primary leaf vein width, secondary leaf vein width, mean fine vein width, primary vein density, fine vein density, vein areole diameter, areole density, 3D fine vein surface area, and fine vein volume. We further elucidated the influencing mechanisms and regulatory pathways of biotic and abiotic factors on leaf vein traits. The results showed that species identity had significant effects on eight out of nine leaf vein traits except 3D fine vein surface area, while habitat had significant effects on primary leaf vein width, secondary leaf vein width, vein areole diameter, fine vein density, and areole density. Altitude had significant effects on primary vein density, mean fine vein width, vein areole diameter, fine vein density and areole density. Habitat, tree species identity, and altitude had significantly interactive effects on primary leaf vein density, 3D fine vein surface area, and fine vein volume. There were significant differences in primary leaf vein width, mean fine vein width, areole density, 3D fine vein surface area, fine vein volume, primary vein density of Q. wutaishanica between the two studied habitats, but the differences were only found in secondary leaf vein width and areole density of Q. aliena var. acutiserrata and Q. variabilis. The examined leaf vein traits were influenced both by biotic and abiotic factors, with varying effect sizes. Among the biotic factors, petiole length, leaf length and width ratio had strong effect on leaf vein traits. Among the abiotic factors, climatic and soil factors had high effect size on vein traits, with the former being higher than the latter. Leaf vein traits were affected directly by biotic factors, but indirectly by abiotic factors (soil and climatic factors) via regulating biotic factors (leaf stoichiometry and leaf phenotypic traits).

Growth hormone promotes myelin repair after chronic hypoxia via triggering pericyte-dependent angiogenesis.

White matter injury (WMI) causes oligodendrocyte precursor cell (OPC) differentiation arrest and functional deficits, with no effective therapies to date. Here, we report increased expression of growth hormone (GH) in the hypoxic neonatal mouse brain, a model of WMI. GH treatment during or post hypoxic exposure rescues hypoxia-induced hypomyelination and promotes functional recovery in adolescent mice. Single-cell sequencing reveals that Ghr mRNA expression is highly enriched in vascular cells. Cell-lineage labeling and tracing identify the GHR-expressing vascular cells as a subpopulation of pericytes. These cells display tip-cell-like morphology with kinetic polarized filopodia revealed by two-photon live imaging and seemingly direct blood vessel branching and bridging. Gain-of-function and loss-of-function experiments indicate that GHR signaling in pericytes is sufficient to modulate angiogenesis in neonatal brains, which enhances OPC differentiation and myelination indirectly. These findings demonstrate that targeting GHR and/or downstream effectors may represent a promising therapeutic strategy for WMI.

The rat as a novel model for chronic rotator cuff injuries.

Chronic rotator cuff injuries (CRCIs) still present a great challenge for orthopaedics surgeons. Many new therapeutic strategies are developed to facilitate repair and improve the healing process. However, there is no reliable animal model for chronic rotator cuff injury research. To present a new valuable rat model for future chronic rotator cuff injuries (CRCIs) repair studies, and describe the changes of CRCIs on the perspectives of histology, behavior and MRI. Sixty male Wistar rats were enrolled and underwent surgery of the left shoulder joint for persistent subacromial impingement. They were randomly divided into experimental group (n = 30, a 3D printed PEEK implant shuttled into the lower surface of the acromion) and sham operation group (n = 30, insert the same implant, but remove it immediately). Analyses of histology, behavior, MRI and inflammatory pain-related genes expression profiles were performed to evaluate the changes of CRCIs. After 2-weeks running, the rats in the experimental group exhibited compensatory gait patterns to protect the injured forelimb from loading after 2-weeks running. After 8-weeks running, the rats in the experimental group showed obvious CRCIs pathological changes: (1) acromion bone hyperplasia and thickening of the cortical bone; (2) supraspinatus muscle tendon of the humeral head: the bursal-side tendon was torn and layered with disordered structure, forming obvious gaps; the humeral-side tendon is partially broken, and has a neatly arranged collagen. Partial fat infiltration is found. The coronal T2-weighted images showed that abnormal tendon-to-bone junctions of the supraspinatus tendon. The signal intensity and continuity were destroyed with contracted tendon. At the nighttime, compared with the sham operation group, the expression level of IL-1ß and COX-2 increased significantly (P = 0063, 0.0005) in the experimental group. The expression of COX-2 in experimental group is up-regulated about 1.5 times than that of daytime (P = 0.0011), but the expression of IL-1ß, TNF-a, and NGF are all down-regulated (P = 0.0146, 0.0232, 0.0161). This novel rat model of chronic rotator cuff injuries has the similar characteristics with that of human shoulders. And it supplies a cost-effective, reliable animal model for advanced tissue engineered strategies and future therapeutic strategies.

Homocysteine-potentiated Kelch-like ECH-associated protein 1 promotes senescence of neuroblastoma 2a cells via inhibiting ubiquitination of ß-catenin.

Elevated serum homocysteine (Hcy) level is a risk factor for Alzheimer's disease (AD) and accelerates cell aging. However, the mechanism by which Hcy induces neuronal senescence remains largely unknown. In this study, we observed that Hcy significantly promoted senescence in neuroblastoma 2a (N2a) cells with elevated ß-catenin and Kelch-like ECH-associated protein 1 (KEAP1) levels. Intriguingly, Hcy promoted the interaction between KEAP1 and the Wilms tumor gene on the X chromosome (WTX) while hampering the ß-catenin-WTX interaction. Mechanistically, Hcy attenuated the methylation level of the KEAP1 promoter CpG island and activated KEAP1 transcription. However, a slow degradation rate rather than transcriptional activation contributed to the high level of ß-catenin. Hcy-upregulated KEAP1 competed with ß-catenin to bind to WTX. Knockdown of both ß-catenin and KEAP1 attenuated Hcy-induced senescence in N2a cells. Our data highlight a crucial role of the KEAP1-ß-catenin pathway in Hcy-induced neuronal-like senescence and uncover a promising target for AD treatment.

Experimental Ischemic Stroke Induces Secondary Bihemispheric White Matter Degeneration and Long-Term Cognitive Impairment.

Clinical studies have identified widespread white matter degeneration in ischemic stroke patients. However, contemporary research in stroke has predominately focused on the infarct and periinfarct penumbra regions. The involvement of white matter degeneration after ischemic stroke and its contribution to post-stroke cognitive impairment and dementia (PSCID) has remained less explored in experimental models. In this study, we examined the progression of locomotor and cognitive function up to 4 months after inducing ischemic stroke by middle cerebral artery occlusion in young adult rats. Despite evident ongoing locomotor recovery, long-term cognitive and affective impairments persisted after ischemic stroke, as indicated by Morris water maze, elevated plus maze, and open field performance. At 4 months after stroke, multimodal MRI was conducted to assess white matter degeneration. T2-weighted MRI (T2WI) unveiled bilateral cerebroventricular enlargement after ischemic stroke. Fluid Attenuated Inversion Recovery MRI (FLAIR) revealed white matter hyperintensities in the corpus callosum and fornix across bilateral hemispheres. A positive association between the volume of white matter hyperintensities and total cerebroventricular volume was noted in stroke rats. Further evidence of bilateral white matter degeneration was indicated by the reduction of fractional anisotropy and quantitative anisotropy at bilateral corpus callosum in diffusion-weighted MRI (DWI) analysis. Additionally, microglia and astrocyte activation were identified in the bilateral corpus callosum after stroke. Our study suggests that experimental ischemic stroke induced by MCAO in young rat replicate long-term cognitive impairment and bihemispheric white matter degeneration observed in ischemic stroke patients. This model provides an invaluable tool for unraveling the mechanisms underlying post-stroke secondary white matter degeneration and its contribution to PSCID.

Lipid metabolism-related long noncoding RNA RP11-817I4.1 promotes fatty acid synthesis and tumor progression in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common types of tumors. The influence of lipid metabolism disruption on the development of HCC has been demonstrated in published studies. AIM: To establish an HCC prognostic model for lipid metabolism-related long non-coding RNAs (LMR-lncRNAs) and conduct in-depth research on the specific role of novel LMR-lncRNAs in HCC. METHODS: Correlation and differential expression analyses of The Cancer Genome Atlas data were used to identify differentially expressed LMR-lncRNAs. Quantitative real-time polymerase chain reaction analysis was used to evaluate the expression of LMR-lncRNAs. Nile red staining was employed to observe intracellular lipid levels. The interaction between RP11-817I4.1, miR-3120-3p, and ATP citrate lyase (ACLY) was validated through the performance of dual-luciferase reporter gene and RIP assays. RESULTS: Three LMR-lncRNAs (negative regulator of antiviral response, RNA transmembrane and coiled-coil domain family 1 antisense RNA 1, and RP11-817I4.1) were identified as predictive markers for HCC patients and were utilized in the construction of risk models. Additionally, proliferation, migration, and invasion were reduced by RP11-817I4.1 knockdown. An increase in lipid levels in HCC cells was significantly induced by RP11-817I4.1 through the miR-3120-3p/ACLY axis. CONCLUSION: LMR-lncRNAs have the capacity to predict the clinical characteristics and prognoses of HCC patients, and the discovery of a novel LMR-lncRNAs, RP11-817I4.1, revealed its role in promoting lipid accumulation, thereby accelerating the onset and progression of HCC.

Short time effects of two radiofrequency ablation methods on hypertrophic obstructive cardiomyopathy.

BACKGROUND: Radiofrequency ablation has been applied for the treatment of hypertrophic obstructive cardiomyopathy (HOCM). The two known procedures are percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) and endocardial radiofrequency septal ablation (ERSA). METHODS: This study presents a retrospective analysis of the PIMSRA and ERSA procedures in patients with drug-refractory HOCM. A total of 28 patients participated in the study, with 12 receiving PIMSRA and 16 receiving ERSA. The objective of our study was to compare the short-term effects of these two radiofrequency ablation procedures. RESULTS: At the 30-day follow-up, the PIMSRA group demonstrated a greater reduction in left ventricular outflow tract peak gradient at rest compared to the ERSA group (22.25 [16.72] mmHg versus 47.75 [21.94] mmHg) (p < .01). The values for the PIMSRA group decreased from 99.33 (32.00) mmHg to 22.25 (16.72) mmHg (p < .01), while the ERSA group decreased from 97.75 (30.24) mmHg to 47.75 (21.94) mmHg (p < .01). Only the PIMSRA group exhibited a decrease in mitral regurgitation (MR). The area of MR decreased from 10.13 (4.12) mm2 to 3.65 (2.80) mm2 in the PIMSRA group (p < .01). Additionally, the PIMSRA group experienced reductions in left atrial diameter (LAD) and left ventricular ejection fraction (LVEF)%. The values for LAD changed from 43.58 (7.53) mm to 37.08 (6.92) mm (p = .03), and the values for LVEF% decreased from 65.75 (6.12) pg/mL to 60.83 (4.06) pg/mL (p = .03). CONCLUSION: In terms of the two types of radiofrequency ablation methods used in HOCM, it has been observed that PIMSRA demonstrates a more favorable early treatment effect compared to ERSA.

Regulation of depressive-like behaviours by palmitoylation: Role of AKAP150 in the basolateral amygdala.

BACKGROUND AND PURPOSE: Protein palmitoylation is involved in learning and memory, and in emotional disorders. Yet, the underlying mechanisms in these processes remain unclear. Herein, we describe that A-kinase anchoring protein 150 (AKAP150) is essential and sufficient for depressive-like behaviours in mice via a palmitoylation-dependent mechanism. EXPERIMENTAL APPROACH: Depressive-like behaviours in mice were induced by chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS). Palmitoylated proteins in the basolateral amygdala (BLA) were assessed by an acyl-biotin exchange assay. Genetic and pharmacological approaches were used to investigate the role of the DHHC2-mediated AKAP150 palmitoylation signalling pathway in depressive-like behaviours. Electrophysiological recording, western blotting and co-immunoprecipitation were performed to define the mechanistic pathway. KEY RESULTS: Chronic stress successfully induced depressive-like behaviours in mice and enhanced AKAP150 palmitoylation in the BLA, and a palmitoylation inhibitor was enough to reverse these changes. Blocking the AKAP150-PKA interaction with the peptide Ht-31 abolished the CRS-induced AKAP150 palmitoylation signalling pathway. DHHC2 expression and palmitoylation levels were both increased after chronic stress. DHHC2 knockdown prevented CRS-induced depressive-like behaviours, as well as attenuating AKAP150 signalling and synaptic transmission in the BLA in CRS-treated mice. CONCLUSION AND IMPLICATIONS: These results delineate that DHHC2 modulates chronic stress-induced depressive-like behaviours and synaptic transmission in the BLA via the AKAP150 palmitoylation signalling pathway, and this pathway may be considered as a promising novel therapeutic target for major depressive disorder.

A rapid method for identification of Lanxangia tsaoko origin and fruit shape: FT-NIR combined with chemometrics and image recognition.

Lanxangia tsaoko's accurate classifications of different origins and fruit shapes are significant for research in L. tsaoko difference between origin and species as well as for variety breeding, cultivation, and market management. In this work, Fourier transform-near infrared (FT-NIR) spectroscopy was transformed into two-dimensional and three-dimensional correlation spectroscopies to further investigate the spectral characteristics of L. tsaoko. Before building the classification model, the raw FT-NIR spectra were preprocessed using multiplicative scatter correction and second derivative, whereas principal component analysis, successive projections algorithm, and competitive adaptive reweighted sampling were used for spectral feature variable extraction. Then combined with partial least squares-discriminant analysis (PLS-DA), support vector machine (SVM), decision tree, and residual network (ResNet) models for origin and fruit shape discriminated in L. tsaoko. The PLS-DA and SVM models can achieve 100% classification in origin classification, but what is difficult to avoid is the complex process of model optimization. The ResNet image recognition model classifies the origin and shape of L. tsaoko with 100% accuracy, and without the need for complex preprocessing and feature extraction, the model facilitates the realization of fast, accurate, and efficient identification.

Glutamate Provides Cytoprotective Effect for Astrocytes Against Ischemic Insult and Promotes Astrogliosis.

Glutamate-mediated excitotoxicity has been extensively explored as a therapeutic target for the development of potential treatments of neurological disorders including stroke. However, the effect of glutamate on astrocytes under pathological conditions has been less studied. Using primary astrocyte culture, we determined the effect of glutamate on astrocytes against ischemic insult. Glutamate provided a cytoprotective effect and acted as an alternative substrate for ATP production in primary astrocytes against oxygen glucose deprivation reoxygenation insult, which was blocked by glutamate uptake inhibition. The cytoprotective effect of glutamate appears to be astrocyte-specific, as glutamate dose-dependently induces cytotoxic action in murine hippocampal HT-22 cell line. Interestingly, the cytoprotective effect of glutamate against glucose deprivation was short-last, as no protection was observed after 3-day glucose deprivation. We determined the metabolic phenotype of primary astrocyte cultured in glucose or glutamate. Primary astrocytes cultured in glutamate displayed a different metabolic phenotype when compared to those cultured in glucose, evidenced by higher basal and maximal oxygen consumption rate (OCR), higher ATP production and proton leak-coupled OCR, as well as lower glycolysis. Furthermore, glutamate exposure resulted in astrocyte activation, evidenced by an increase in astrocyte size and GFAP expression. Our study demonstrated that glutamate exerts a dual effect on astrocytes under ischemic condition. Glutamate provides an alternative substrate for energy metabolism in the absence of glucose, thereby protecting astrocytes against ischemic insults. On the other hand, glutamate exposure induces astrogliosis. Modulation of glutamate uptake and metabolism in astrocytes may provide novel targets for alleviating ischemic injury and improving function recovery after ischemic stroke.

The anterior chamber of the eye technology and its anatomical, optical, and immunological bases.

The anterior chamber of the eye (ACE) is distinct in its anatomy, optics, and immunology. This guarantees that the eye perceives visual information in the context of physiology even when encountering adverse incidents like inflammation. In addition, this endows the ACE with the special nursery bed iris enriched in vasculatures and nerves. The ACE constitutes a confined space enclosing an oxygen/nutrient-rich, immune-privileged, and less stressful milieu as well as an optically transparent medium. Therefore, aside from visual perception, the ACE unexpectedly serves as an excellent transplantation site for different body parts and a unique platform for noninvasive, longitudinal, and intravital microimaging of different grafts. On the basis of these merits, the ACE technology has evolved from the prototypical through the conventional to the advanced version. Studies using this technology as a versatile biomedical research platform have led to a diverse range of basic knowledge and in-depth understanding of a variety of cells, tissues, and organs as well as artificial biomaterials, pharmaceuticals, and abiotic substances. Remarkably, the technology turns in vivo dynamic imaging of the morphological characteristics, organotypic features, developmental fates, and specific functions of intracameral grafts into reality under physiological and pathological conditions. Here we review the anatomical, optical, and immunological bases as well as technical details of the ACE technology. Moreover, we discuss major achievements obtained and potential prospective avenues for this technology.

Development and Validation of a Prognostic Model for Postoperative Anastomotic Recurrence in Siewert II or III Adenocarcinomas Without Neoadjuvant Therapy in an East Asian Population.

PURPOSE: Anastomotic recurrence leads to poor prognosis in patients with Siewert II or III adenocarcinoma who undergo radical gastrectomy and do not receive neoadjuvant therapy. We aimed to establish a prognostic model to evaluate the risk of postoperative anastomotic recurrence in patients with Siewert II or III adenocarcinoma who did not receive neoadjuvant therapy. METHODS: We included 366 patients with Siewert II or III adenocarcinoma who were treated with radical gastrectomy without neoadjuvant therapy at Fujian Provincial Hospital (FPH) between 2012 and 2018 as the development cohort. Cox regression was used to verify prognostic factors for anastomotic recurrence, and a nomogram was established. The nomogram was externally validated using a combined cohort of two external centers. Patients were classified into high- or low-risk groups according to the diagnostic threshold and nomogram scores, and recurrence-related survival analysis was analyzed. RESULTS: The average age was 64.6 years, and 285 patients were male. All surgeries were successfully performed (185 open vs 181 laparoscopic). The 3-year anastomotic recurrence rate was significantly lower in the low-risk group (3.5% vs 18.8%, P < 0.001). The predictive performance was verified in the external validation cohort. This model better stratified patient survival than the American Joint Committee on Cancer (AJCC) TNM staging system. CONCLUSIONS: This novel nomogram with surgical margin, postoperative tumor node metastasis (pTNM) stage, and neural invasion as prognostic factors has a significant predictive performance for the risk of anastomotic recurrence after radical gastrectomy in patients with Siewert II or III adenocarcinoma.

Postnatal treatment and evolution patterns of giant fetal hepatic hemangioma: a case series of 29 patients.

OBJECTIVES: To explore the clinical characteristics, postnatal treatment and prognosis of giant fetal hepatic hemangioma (GFHH). METHOD: Retrospective analysis was performed on children with giant fetal hepatic hemangioma (maximum tumor diameter > 40 mm) diagnosed by prenatal ultrasound and MRI from December 2016 to December 2020. These patients were observed and treated at the Children's Hospital of Fudan University after birth. The clinical data were collected to analyze the clinical characteristics, treatment, and prognosis of GFHH using independent sample t tests or Fisher's exact tests. RESULTS: Twenty-nine patients who were detected by routine ultrasound in the second and third trimester of pregnancy with giant fetal hepatic hemangiomas were included. The first prenatal ultrasound diagnosis of gestational age was 34.0 ± 4.3 weeks, ranging from 22 to 39 weeks. Of the patients, 28 had focal GFHHs and 1 had multifocal GFHHs. Surgery was performed, and the diagnosis was confirmed histopathologically in two patients. There were 8 cases with echocardiography-based evidence of pulmonary hypertension, 11 cases had a cardiothoracic ratio > 0.6, and 4 cases had hepatic arteriovenous fistula (AVF). The median follow-up time was 37 months (range: 14-70 months). During the follow-up, 12 patients received medical treatment with propranolol as the first-line therapy. The treatment group had a higher ratio of cardiothoracic ratio > 0.6 (P = 0.022) and lower albumin levels (P = 0.018). Four (14.8%) lesions showed postnatal growth before involuting. Complete response was observed in 13 (13/29) patients, and partial response was observed in 16 (16/29) patients. CONCLUSIONS: Fetal giant hepatic hemangioma is mainly localized, and its clinical outcome conforms to RICH (rapidly involuting) and PICH (partially involuting), but some fetal giant hepatic hemangiomas will continue to grow after birth and then gradually decrease. For uncomplicated giant fetal hepatic hemangioma, postnatal follow-up is the main concern, while those with complications require aggressive medical treatment. Propranolol may have no effect on the volume change of GFHH.

Characterization of driving factors for the long-term succession of bloom-forming cyanobacterial genera in Lake Erhai, southwest China.

Cyanobacterial blooms pose a global environmental concern, with various genera contributing to their formation. The harmfulness of cyanobacterial blooms varies depending on the specific genus, yet the factors triggering their formation remain incompletely understood. This study conducted qPCR of sediment DNA in Lake Erhai to reconstruct the historical succession of three common bloom-forming cyanobacterial genera (i.e., Microcystis, Dolichospermum, and Aphanizomenon). The driving factors and their corresponding thresholds were identified, and human activities related to driving factors were evaluated. The results revealed two successions in the past century. The first succession transitioned from Aphanizomenon (1902-1978) to Microcystis and Dolichospermum (1978-1999), driven by TN:TP and TP. The second succession shifted from Microcystis and Dolichospermum (1978-1999) to Microcystis (1999-2010), driven by TP, TN:TP, and temperature. The thresholds of TP and TN:TP for the Microcystis bloom were 0.023 mg/L and 17, respectively. TN:TP was significantly influenced by domestic pollution and crop farming in both successions, while TP was significantly impacted by domestic pollution in the first succession and by pollution from crop and dairy farming in the second succession. These results shed light on the underlying mechanism responsible for the blooms of various cyanobacterial genera and could serve as a valuable reference for effectively preventing and controlling nutrient input in the watershed.

Correlation analysis between the in vivo bioavailability and in vitro bioaccessibility of nitro PAHs in soil: Application of simplified FOREhST in vitro methods based on the Chinese pharmacopoeia.

In this study, the relative bioavailability (RBA) of nitrated polycyclic aromatic hydrocarbons (NPAHs) in soil samples (n = 30) was assessed using an in vivo mouse model. Based on the correlation between the bioaccessibility data obtained from the Tenax improved traditional Fed ORganic Estimation human Simulation Test (FOREhST) in vitro method (TITF) and the bioavailability data obtained from in vivo experiments, the TITF method was further optimized and simplified by referring to the "Pharmacopoeia of the People's Republic of China: Volume IV, 2020" to adjust the formulation and parameters of the gastrointestinal fluid (GIF) in order to establish a simpler and lower cost in vitro method for the determination of the bioaccessibilities of NPAHs. The dose-accumulation relationship of the in vivo experiment showed that the linear dose-response was better in adipose tissue (R2 = 0.77-0.93), and the accumulation of NPAHs in adipose tissue was higher than that in kidney or liver tissue. Depending on the mouse adipose model, the NPAHs-RBA ranged from 1.88 % to 73.92 %, and a strongly significant negative relationship (R2 = 0.94, p < 0.05) was found between the NPAHs-RBA and Log Kow. The simplified experiment of the TITF showed that the composition of the GIF medium had a significant effect on the bioaccessibilities of NPAHs. The NPAH bioaccessibilities measured by the Tenax improved simplified FOREhST method (TISF) (9.0-36.5 %) were higher than that of the traditional FOREhST method (6.8-22.8 %) but significantly lower than that of the TITF method (16.8-55.2 %). With an increase in the bile concentration in the GIF (from 6 to 10 g/L), the bioaccessibilities of NPAHs increased from 9.0 to 36.5 % to 12.9-42.4 %. The accuracies of the four in vitro methods for predicting the bioavailabilities of NPAHs was in the following order: Tenax improved simplified FOREhST method with increased bile concentration (TITF-IB) (R2 = 0.54-0.87) ≈ TITF (R2 = 0.55-0.85) > TISF (R2 = 0.41-0.77) > FOREhST (R2 = 0.02-0.68). These results indicated that the simple in vitro method could also effectively predict the bioavailabilities of NPAHs.

Clinical implications of frailty in peritoneal dialysis patients - A prospective observational study.

BACKGROUND: Frailty is an age-related condition that predicts adverse outcomes. The study was aimed to investigate the clinical implications of frailty evolution in patients undergoing peritoneal dialysis (PD). METHOD: In this prospective study, all new-onset (<6 months) and prevalent (≧6 months) PD patients completed frailty assessment at entry and 6 months by a semiautomated frailty index of 80 risk factors (FI80) which also contained the 5 components of Fried frailty phenotype. A score ≧13/80 (FI80 > 0.16) or ≧3/5 (frailty phenotype) was designated to define frailty. RESULT: 337 PD patients were recruited (new-onset 23.4%, prevalent 76.6%). Two hundred (59.3%) and 163 (48.4%) patients were frail by FI80 and frailty phenotype, respectively. Predictors for frailty were old age, dialysis, diabetes mellitus, gout and sleep disorder. New-onset patients aged <55 years displayed the best evolution of frailty over 6 months (stable or improved, n = 29/47, 61.7% by FI80, p = 0.0293), compared with other groups. Survival analysis found that frail patients exhibited the worse outcomes (overall death and hospitalization). Poisson regression showed frailty was associated with increased utilizations of outpatient and ER services; however multivariate Cox models identified only diabetes, gout and low body mass index (<19 kg/m2), but not frailty, predicted overall death and hospitalizations. CONCLUSION: Frailty is a common medical condition in PD patients, and the status of which can be stabilized or improved in new-onset, young patients at least over the short term. Compared with frailty, certain comorbidities (diabetes and gout) and undernutrition appeared to be more robust in the prediction of adverse outcomes.

High SNHG expression may predict a poor lung cancer prognosis based on a meta-analysis.

BACKGROUND: An increasing number of small nucleolar RNA host genes (SNHGs) have been revealed to be dysregulated in lung cancer tissues, and abnormal expression of SNHGs is significantly correlated with the prognosis of lung cancer. The purpose of this study was to conduct a meta-analysis to explore the correlation between the expression level of SNHGs and the prognosis of lung cancer. METHODS: A comprehensive search of six related databases was conducted to obtain relevant literature. Relevant information, such as overall survival (OS), progression-free survival (PFS), TNM stage, lymph node metastasis (LNM), and tumor size, was extracted. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled to evaluate the relationship between SNHG expression and the survival outcome of lung cancers. Sensitivity and publication bias analyses were performed to explore the stability and reliability of the overall results. RESULTS: Forty publications involving 2205 lung cancer patients were included in this meta-analysis. The pooled HR and 95% CI values indicated a significant positive association between high SNHG expression and poor OS (HR: 1.890, 95% CI: 1.595-2.185), disease-free survival (DFS) (HR: 2.31, 95% CI: 1.57-3.39) and progression-free survival (PFS) (HR: 2.01, 95% CI: 0.66-6.07). The pooled odds ratio (OR) and 95% CI values indicated that increased SNHG expression may be correlated with advanced TNM stage (OR: 1.509, 95% CI: 1.267-1.799), increase risk of distant lymph node metastasis (OR: 1.540, 95% CI: 1.298-1.828), and large tumor size (OR: 1.509, 95% CI: 1.245-1.829). Sensitivity analysis and publication bias results showed that each result had strong reliability and robustness, and there was no significant publication bias or other bias. CONCLUSION: Most SNHGs are upregulated in lung cancer tissues, and high expression of SNHGs predicts poor survival outcomes in lung cancer. SNHGs may be potential prognostic markers and promising therapeutic targets.

[Aucubin combined with ADSCs-exos protects TBHP-induced nucleus pulposus cells via TLR4/NF-κB pathway].

This paper aims to investigate the effects and mechanisms of adipose-derived stem cells-exosomes(ADSCs-exos) toge-ther with aucubin in protecting human-derived nucleus pulposus cells(NPCs) from inflammatory injury, senescence, and apoptosis. The tert-butyl hydroperoxide(TBHP)-induced NPCs were assigned into normal, model, aucubin, ADSCs-exos, and aucubin+ADSCs-exos groups. The cell viability was examined by cell counting kit-8(CCK-8), cell proliferation by EdU staining, cell senescence by senescence-associated-ß-galactosidase(SA-ß-Gal), and cell cycle and apoptosis by flow cytometry. Enzyme-linked immunosorbent assay was employed to examine the expression of interleukin-1ß(IL-1ß), IL-10, and tumor necrosis factor-α(TNF-α). Real-time fluorescence quantitative PCR and Western blot were employed to determine the mRNA and protein levels of aggregated proteoglycan(aggrecan), type Ⅱ collagen alpha 1(COL2A1), Toll-like receptor 4(TLR4), and nuclear factor-kappa B(NF-κB). The results showed that compared with the model group, the aucubin or ADSCs-exos group showed enhanced viability and proliferation of NPCs, decreased proportion of G_0/G_1 phase cells, increased proportion of S phase cells, reduced apoptosis and proportion of cells in senescence, lowered IL-1ß and TNF-α levels, elevated IL-10 level, down-regulated mRNA and protein levels of TLR4 and NF-κB, and up-regulated mRNA and protein levels of aggrecan and COL2A1. Compared with the aucubin or ADSCs-exos group, the aucubin+ADSCs-exos combination further increased the viability and proliferation of NPCs, decreased the proportion of G_0/G_1 phase cells, increased the proportion of S phase cells, reduced the apoptosis and proportion of cells in senescence, lowered the IL-1ß and TNF-α levels, elevated the IL-10 level, down-regulated the mRNA and protein levels of TLR4 and NF-κB, and up-regulated the mRNA and protein levels of aggrecan and COL2A1. In summary, both aucubin and ADSCs-exos could exert protective effects by inhibiting inflammatory responses, reducing apoptosis and senescence of NPCs, improving cell viability and proliferation as well as extracellular matrix synthesis, which may be associated with the inhibition of TLR4/NF-κB signaling pathway activation. The combination of both plays a synergistic role in the protective effects.