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Osteopetrosis is an inherited metabolic disease, characterized by increased bone density and narrow marrow cavity. Patients with severe osteopetrosis exhibit abnormal bone brittleness, anemia, and infection complications, which commonly cause death within the first decade of life. Pathologically, osteopetrosis impairs not only the skeletal system, but also the hemopoietic and immune systems during development, while the underlying osteoimmunological mechanisms remain unclear. Osteoclastic mutations are regarded as the major causes of osteopetrosis, while osteoclast non-autonomous theories have been proposed in recent years with unclear underlying mechanisms. Retinoic acid (RA), the metabolite of Vitamin A, is an essential requirement for skeletal and hematopoietic development, through the activation of retinoic acid signaling. RA can relieve osteopetrosis symptoms in some animal models, while its effect on bone health is still controversial and the underlying mechanisms remain unclear. In this study, we constructed an osteoblast-specific inhibitory retinoic acid signaling mouse model and surprisingly found it mimicked the symptoms of osteopetrosis found in clinical cases: dwarfism, increased imperfectly-formed trabecular bone deposition with a reduced marrow cavity, thin cortical bone with a brittle skeleton, and hematopoietic and immune dysfunction. Micro-CT, the three-point bending test, and histological analysis drew a landscape of poor bone quality. Single-cell RNA sequencing (scRNA-seq) of the femur and RNA-seq of osteoblasts uncovered an atlas of pathological skeletal metabolism dysfunction in the mutant mice showing that osteogenesis was impaired in a cell-autonomous manner and osteoclastogenesis was impaired via osteoblast-osteoclast crosstalk. Moreover, scRNA-seq of bone marrow and flow cytometry of peripheral blood, spleen, and bone marrow uncovered pathology in the hematopoietic and immune systems in the mutant mice, mimicking human osteopetrosis. Results showed that hematopoietic progenitors and B lymphocyte differentiation were affected and the osteoblast-dominated cell crosstalk was impaired, which may result from transcriptional impairment of the ligands Pdgfd and Sema4d. In summary, we uncovered previously unreported pathogenesis of osteopetrosis-like disorder in mice with skeletal, hematopoietic, and immune system dysfunction, which was induced by the inhibition of retinoic acid signaling in osteoblasts, and sheds new insights into a potential treatment for osteopetrosis. [ABSTRACT FROM AUTHOR]

A study published in the journal Nephrology Dialysis Transplantation examined the effectiveness of obinutuzumab in treating frequently-relapsing/steroid-dependent minimal change disease (MCD) in adults. The study found that obinutuzumab, a type II anti-CD20 monoclonal antibody, was effective in achieving remission in patients with FR/SD MCD. The study included six patients, and the treatment involved a combination of glucocorticosteroids and obinutuzumab. Further research is needed to determine the long-term efficacy and safety of obinutuzumab for MCD. The article also discusses the use of obinutuzumab in the treatment of focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) in adult patients. The study included six patients with FSGS or MCD who were treated with obinutuzumab. After treatment, all six patients achieved complete remission, and there were no relapses during the follow-up period. The study suggests that obinutuzumab may be an effective and safe treatment option for adult patients with FSGS or MCD. However, the study has limitations, including a small sample size and short follow-up time, and further research is needed to fully understand the long-term outcomes and mechanisms of obinutuzumab treatment. [Extracted from the article]

This study aims to investigate the temporal and spatial attributes of the exit of Taiwanese enterprises from mainland China between 2001 and 2021, by applying enterprise database data. Furthermore, the influence of strategic coupling on Taiwanese enterprises' exit from mainland China was also investigated. The following are the key findings: The spatial distribution pattern of the exit rate of Taiwanese enterprises in mainland China varied at different phases. In contrast, the inland regions of the country's central and western zones, which are characterized by comparatively less developed economies, maintained consistently high exit rates, whereas the eastern coastal region retained a low exit rate. Particularly, the relationship between Taiwanese enterprises and the invested areas changed from Captive coupling to Cooperative coupling and subsequently to Absorptive Coupling. Similarly, the coupling modes significantly influenced the exit of Taiwanese enterprises from mainland China. Moreover, the COVID-19 pandemic has contributed to the backward connection of Taiwanese corporations, which have become more reliant on the mainland China market and local suppliers than earlier. Taiwan-favoring policies and the regional innovation environment have consequently emerged as the primary locational advantages for retaining Taiwanese enterprises in the aftermath of the global financial crisis. Therefore, the aforementioned factors may help to reduce the Taiwanese enterprises' exit from mainland China and possess valuable policy implications for Taiwan investment zones in mainland China. [ABSTRACT FROM AUTHOR]

Alpha‐linolenic acid and antioxidant substances (such as tocopherols and polyphenols) are abundant in chia seed oil, which may prevent certain chronic diseases. This study compared the physicochemical parameters, chemical composition and antioxidant properties of black and white chia seed oil extracted by solvent extraction, pressing and supercritical CO2 extraction. Chia seed oil contained higher levels of polyunsaturated fatty acids, including linoleic acid (18.68%–20.15%) and α‐linolenic acid (60.47%–63.68%). Black and white chia seeds and processing methods had significant effects on minor components (tocopherols, total phenols, phytosterols and squalene), oxidative stability and free radical scavenging ability. Compared with other methods, the contents of tocopherols (512.72–603.04 mg/kg), total phenols (35.21–57.75 mgGAE/kg) and phytosterols (5536.69–5956.65 mg/kg) were higher in the pressing method. In addition, 17 individual polyphenols were identified and quantified, among which genistein and gallic acid had higher contents, which were significantly affected by varieties and processing methods. In general, the pressing process may be the best processing method to improve minor components and antioxidant capacity. This study can provide a valuable reference for producing functional foods supplemented with α‐linolenic acid. [ABSTRACT FROM AUTHOR]

Introduction: High serum phosphorus level has been reported to be a risk factor for disease progression in patients with chronic kidney disease, whereas, its role in IgA nephropathy (IgAN) still remains uncertain. This study aimed to investigate the association between serum phosphorus and progression of IgAN. Methods: A total of 247 patients diagnosed with IgAN from 2016.11 to 2019.12 at the First Affiliated Hospital of Xi'an Jiaotong University were retrospectively enrolled in this study. The association between serum phosphorus and kidney disease progression events, defined as 30% estimated glomerular filtration rate (eGFR) decline or kidney failure, was evaluated using Cox models. Results: Serum phosphorus was an independent risk factor for poor renal outcome after adjusting for age, gender, urine protein, MAP, eGFR, hemoglobin, Oxford S and T scores (HR, 2.586; 95% CI, 1.238–5.400, p = 0.011). The addition of serum phosphorus to the reference model containing clinical and pathological variables significantly improved the risk prediction of IgAN progression (C statistic, 0.836; 95% CI, 0.783–0.889) as compared with the reference model (C statistic, 0.821; 95% CI, 0.756–0.886). The ability of serum phosphorus level to predict progression was much stronger in IgAN patients without use of immunosuppression (HR 5.173; 95% CI, 1.791–14.944; p = 0.002). Conclusion: Higher serum phosphorus levels were independently associated with kidney disease progression in patients with IgAN, especially in those without immunosuppression. The addition of serum phosphorus to clinical and pathological data at the time of biopsy significantly improved risk prediction of IgAN progression. [ABSTRACT FROM AUTHOR]

Transition metal‐embedded heteroatom carbon composites are regarded as an important branch of bifunctional catalysts for rechargeable Zn‐air batteries. The inevitable transition metal particles on the carbon skeleton may affect the availability of the metal‐heteroatom‐carbon catalytic site. Herein, we propose an acid treatment strategy to remove the bare transition metal particles, thus regulating the electrochemical surface area. The OER activities are highly related to the electrochemical surface area for the catalysts with different acid treatment times. In addition, there exists an optimal acid treatment time to achieve the highest ORR and OER activities with the ΔE value of 0.75 V. Given the superior bifunctional activities after acid treatment, we further assemble the rechargeable Zn‐air batteries with the optimal catalyst, which achieves a peak power density of 364 mW cm−2 and long cycling life of 500 h at 10 mA cm−2. This work affords an efficient strategy to enhance the ORR/OER activities and may guide the design of transition metal/heteroatom carbon composites. [ABSTRACT FROM AUTHOR]

Liu starts with a conceptual discussion of migrant networks, maintaining that a migrant's linguistic repertoire determines which network they can enter. While there has been no shortage of studies focusing on migrants and their political incorporation, most of them fixed their attention on the individual migrant or the host country but ignored the unit of the migrant's network. Liu, Amy H. 2021 The Language of Political Incorporation: Chinese Migrants in Europe Philadelphia, Pennsylvania Temple University Press 9781439920121 $ 110.5 (Hardcover) Migration as a global issue has never stopped drawing academic attention. [Extracted from the article]

Purpose: Large-scale, contemporary studies assessing the spectrum of kidney diseases in northwest China are lacking. Therefore, we aimed to assess the profile of 30-year temporal changes in biopsy-proven kidney diseases in northwest China. Methods: This cross-sectional study included all patients with a native kidney biopsy specimen in the First Affiliated Hospital of Xi'an Jiaotong University between 1989 and 2018. Data on demographic characteristics and pathological diagnosis were extracted from medical records and pathological reports. Changing patterns of kidney diseases over the study period and disease distributions in different gender and age groups were examined. Results: This study included 13,620 patients with a mean age of 38.5 ± 16.5 years and included 58.2% of men. Primary glomerulonephritis (PGN), second glomerulonephritis (SGN), tubulointerstitial disease, and other renal diseases accounted for 79.1, 18.3, 2.4, and 0.2% of all kidney diseases, respectively. In PGN, IgA nephropathy (IgAN) (25.1%) was the most common type, followed by non-IgA mesangial proliferative glomerulonephritis (MsPGN) (24.9%) and membranous nephropathy (MN) (17.4%). The frequency of MN dramatically increased (p < 0.001) over the course of the study. Lupus nephritis (6.2%) and Henoch-Schönlein purpura nephritis (HSPN) (4.9%) were leading SGN diagnosis. The frequencies of IgAN, non-IgA MsPGN, and HSPN declined, while those of ANCA/pauci-immune glomerulonephritis and diabetic nephropathy significantly increased. Conclusion: PGN continues to be the predominant kidney disease in northwest China, and IgAN is the most common type. The frequencies of MN and diabetic nephropathy significantly increased. These findings might be explained by behavioral and environmental exposures and provide implications on future hypothesis-driven research. [ABSTRACT FROM AUTHOR]

Objective: By analyzing the pathological characteristics and clinical data of renal biopsy in our hospital in the past 20 years, to further understand the epidemic characteristics and pathological changes of primary glomerular disease, and to provide regional data for the big data of kidney disease in my country. Methods: A retrospective analysis of 9448 patients with primary glomerular disease who were hospitalized in our hospital from January 1, 2000 to December 31, 2019, aged 18 years or older, and undergoing renal biopsy. Divided every 5 years into a group, a total of 4 groups (first group 2000.1.1–2004.12.31, second groups 2005.1.1–2009.12.31; third groups 2010.1.1–2014.12.31, fourth groups 2015.1.1–2019.12.31). Results: ① There were more males than females, and male: female vs 1.53:1. The proportion of men in the past five years has increased compared with the previous 15 years. ② Mostly middle-aged, with a median age of 41.39 years old. The age is increasing over time. There are differences between the four groups, P <0.001; ③ The most common clinical manifestations are nephrotic syndrome, followed by chronic glomerulonephritis. Occult glomerulonephritis, the proportion of patients with nephrotic syndrome increases over time, first to fourth group (40.08%< 42.64% < 47.08%< 53.69%); ④ The most common pathology type from 2000 to 2009 was mesangial proliferative glomerulonephritis. IgA nephropathy was the most common type from 2010 to 2014, but the proportion of membranous nephropathy increased year by year, and it became the most common pathological type from 2015 to 2019; ⑤ The clinical and pathological manifestations of different genders are different, but there is no statistical difference. Conclusion: In the past 20 years, the primary glomerular disease is mainly middle-aged. There are more men than women. The most common type of clinical manifestation is nephrotic syndrome. The pathological type is mesangial proliferative glomerulonephritis. Over time, the average age is increasing, and the proportion of patients with renal syndrome is increasing. IgA nephropathy is the most common pathological type from 2010 to 2014, and membranous nephropathy has become the main pathological type in the past 5 years. [ABSTRACT FROM AUTHOR]

Objective: In patients with acute ischemic stroke (AIS), hemorrhagic transformation (HT) is a major complication after mechanical thrombectomy (MT). This study aimed to investigate the relationship between serum magnesium levels and HT after MT. Methods: We collected 199 cases of consecutive AIS that received MT due to acute anterior circulation occlusions in our institution between January 2017 and January 2020. Baseline serum magnesium was obtained from all patients on admission before MT. The patients were divided into two groups based on the occurrence of HT. Univariate and multivariate analyses were performed to investigate whether magnesium was an independent predictor of HT. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were determined. Results: Of the 199 enrolled patients, 40 (20.1%) presented with HT, and 12 (6%) developed symptomatic intracranial hemorrhage (sICH). Patients with HT had lower serum magnesium levels compared to those without HT (0.76 [0.69–0.80] vs. 0.84 [0.80–0.90], p < 0.001). The multivariate logistic analysis showed that the serum magnesium level (odds ratio, [OR]: 0.000, 95% confidence interval [CI]: 0.000–0.001, p < 0.001) was significantly associated with the occurrence of HT. The ROC curve analysis revealed that the serum magnesium level could predict HT with an AUC of.820 (95% CI: 0.750–0.891 p < 0.001). Serum magnesium ≤ 0.80 mmol/L could predict HT with a sensitivity of 79.2% and a specificity of 70.0%. Of interest, the serum magnesium level was not associated with HT when the baseline of serum magnesium was higher than the cut-off value (0.80 mmol/L) in the subgroup analysis. Conclusions: Lower baseline serum magnesium levels (<0.80 mmol/L) on admission are associated with increased risk of HT in AIS patients receiving MT. [ABSTRACT FROM AUTHOR]

Purpose: Emerging evidence has revealed that gut microbiota plays a pivotal role in the pathogenesis of type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD). However, few studies have used metagenomic sequencing to analyze the alterations of gut microbiota community in patients with early-stage DKD. Methods: We carried out metagenomic sequencing in fecal samples of 10 DKD patients (DKD group) and 10 T2DM patients who appeared to be less prone to DKD (non-DKD group), aiming to compare the composition and function of gut microbiota between the DKD and non-DKD groups. Results: The gut microbial community of the DKD group was significantly different from that of the non-DKD group, characterized by a marked increase in phylum Proteobacteria, genus Selenomonadales, Neosynechococcus, Shigella, Bilophila, Acidaminococcus, species, Escherichia coli, Bacteroides plebeius, Megasphaera elsdenii, Acidaminococcus unclassified, and Bilophila wadsworthia. The amounts of species Citrobacter farmeri and Syntrophaceticus schinkii were significantly and positively correlated with the urinary albumin creatinine ratio in the DKD group. Furthermore, functional analysis based on dbCAN and KEGG databases showed aberrant lipopolysaccharide (LPS) biosynthesis and carbohydrate metabolism in the gut microbiome of the DKD group. Conclusion: Our findings provided evidence for alterations in the composition and function of gut microbiota in patients with DKD versus the non-DKD group. These data may contribute to a more comprehensive understanding of the pathological mechanisms of DKD. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic kidney disease (CKD) are at a high risk of fatal arrhythmias. The extended corrected QT (QTc) interval is a hallmark of ventricular arrhythmias and sudden cardiac death. Previous studies have shown that QT interval and QTc are prolonged with the decline in renal function. However, there were no available results for patients with peritoneal dialysis (PD). In this study, we examined changes in QT interval and QTc in patients with end-stage renal disease (ESRD) who underwent peritoneal dialysis.Methods: A total of 66 ESRD patients who received PD, including 50 males and 16 females, with an average age of 43.56 ± 15.15 years, were enrolled. The follow-up lasted 1 year. The demographics and the etiology of patients were recorded. QTc and clinical/biochemical indexes before dialysis and at 6 and 12 months were determined and analyzed. Dialysis adequacy and peritoneal transport function were assessed in each patient. Analysis of variance (ANOVA), least significant difference (LSD) or Tamhane's T2, Paired T-test, Chi-square test, multiple linear regression analysis, and Pearson correlation coefficient were used to analyze the data. P < 0.05 was considered as statistically significant.Results: With reference to etiology, 37 patients (56.06%) had chronic nephritis, and 11 (16.67%) had diabetic nephropathy. Most of the peritoneal transport functions were low average transport (25, 37.88%), while the least were high transport (2, 3.03%).During the follow-up period, all patients had adequate peritoneal dialysis. Compared with a baseline before dialysis, anemia, low albumin, blood pressure, blood urea nitrogen, creatinine, uric acid, potassium, calcium, phosphorus, and parathyroid hormone improved after 6 and 12 months, while the residual renal function gradually decreased during the follow-up. The mean QTc of all patients was stable during the follow-up period. According to gender, the QTc in males and female patients were similar. Before PD, diastolic blood pressure, calcium concentration, and hemoglobin level were negatively correlated with QTc in end-stage renal disease patients; After PD, the observed clinical indexes were no longer relevant to QTc.Conclusion: Unlike hemodialysis-induced QTc prolongation, PD did not increase the patient's QT interval and QTc interval, which suggested that myocardial electrical activity might be more stable in patients with adequate peritoneal dialysis. [ABSTRACT FROM AUTHOR]

Group 2 innate lymphoid cells (ILC2s) play crucial roles in mediating allergic inflammation. Recent studies also indicate their involvement in regulating tumor immunity. The tumor suppressor liver kinase B1 (LKB1) inactivating mutations are associated with a variety of human cancers; however, the role of LKB1 in ILC2 function and ILC2-mediated tumor immunity remains unknown. Here, we show that ablation of LKB1 in ILC2s results in an exhausted-like phenotype, which promotes the development of lung melanoma metastasis. Mechanistically, LKB1 deficiency leads to a marked increase in the expression of programmed cell death protein-1 (PD-1) in ILC2s through the activation of the nuclear factor of activated T cell pathway. Blockade of PD-1 can restore the effector functions of LKB1-deficient ILC2s, leading to enhanced antitumor immune responses in vivo. Together, our results reveal that LKB1 acts to restrain the exhausted state of ILC2 to maintain immune homeostasis and antitumor immunity. [Display omitted] • LKB1 is essential for ILC2 compartment homeostasis • LKB1 prevents lung ILC2 exhaustion by inhibiting PD-1 expression • LKB1 in ILC2s promotes the control of tumor metastasis in lung Niu et al. demonstrate that LKB1 prevents ILC2 exhaustion by inhibiting PD-1 expression in a cell-intrinsic manner. Therefore, LKB1 is essential to sustain ILC2 effector function in allergic inflammation and lung tumor metastasis. [ABSTRACT FROM AUTHOR]

Purpose. Hyperdense lesions are frequently revealed on flat panel CT (FP-CT) immediately after endovascular thrombectomy in patients with acute ischemic stroke. This study is aimed at discriminating hyperdense lesions caused by extravasation plus hemorrhage from those caused by contrast extravasation alone. Methods. We retrospectively analyzed clinical and radiological data of patients who underwent an immediate postprocedure FP-CT scan and a follow-up noncontrast CT 24 hours after thrombectomy. We especially focused on the Maximum Hounsfield Units (HUmax) of each hyperdense lesion. A hyperdense lesion was judged to be hemorrhagic when it persisted on noncontrast CT and/or developed a mass effect. Results. Of 81 patients included in this study, 32 (39.5%) patients presented 41 hyperdense lesions on FP-CT. The chance of hemorrhagic transformation is higher in patients with hyperdense lesions on FP-CT than that in patients without hyperdense lesions (23/32 vs. 1/49, p < 0.001). The HUmax of hyperdensity on FP-CT can predict hemorrhagic transformation with an area under the curve of 0.805 (95% CI: 0.67-0.94, p = 0.02). The sensitivity, specificity, positive, and negative predictive values of hyperdensity on FP-CT for hemorrhagic transformation were 96%, 84%, 72%, and 98%, respectively. A HUmax of >600 predicted hemorrhagic transformation with a sensitivity of 50% and a specificity of 100%. Conclusions. The presence of hyperdensity on FP-CT can predict hemorrhagic transformation with a high sensitivity and negative predictive value. The measurement of HUmax of hyperdense lesion on FP-CT can be applied to the management of patients undergoing endovascular recanalization. [ABSTRACT FROM AUTHOR]

Blood blister-like aneurysm (BBA) of the internal carotid artery (ICA) is highly challenging to treat owing to its variable morphology and tendency for rupture and regrowth. In this study, we attempted to discuss the key techniques for overlapping low-profile visualized intraluminal support (LVIS) stent-assisted coil embolization, which is used for treating BBAs in our center. Clinical characteristics, endovascular treatment details, outcomes, and follow-up results of 13 patients with BBA treated at our center were retrospectively evaluated in this study. Overlapping LVIS stent-assisted coil embolization was successfully performed in all 13 patients of ruptured BBAs located in the ICAs. Recurrence of aneurysm was observed in 4 cases (30.8%) during the angiographic follow-up; in 2 of these cases, spontaneous healing was observed after discontinuation of antiplatelet therapy. Further, 2 patients with recurrence underwent endovascular treatment with complete obliteration of the aneurysm in one and occlusion of the parent artery after Onyx embolization and stent placement in the other. The overall obliteration rate of the BBAs was 92.3% (12/13). One patient (7.7%) developed intraoperative rupture of the aneurysm with coils protruding outside; however, no severe hemorrhage or neurological dysfunction occurred owing to timely embolization. Overlapping LVIS stent-assisted coil embolization is effective for management of BBA of the ICA. Appropriate adjustment in antiplatelet therapy may improve healing in recurrent cases. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN), a common cardiovascular disease, has been a global health threat. MicroRNAs (miRNAs) have been proposed to frequently participate in the occurrence and development of DN, however, the role of miR‐325‐3p in DN remains uncharacterized. Our research aimed to explore the function and mechanism of miR‐325‐3p in DN. Bioinformatics analysis (Targetscan, http://www.targetscan.org) and a wide range of experiments including RT‐qPCR, CCK‐8 assay, western blot, luciferase reporter assay, RNA immunoprecipitation (RIP) assays, urine protein and blood glucose assays, histology analysis and morphometric analysis were used to explore the function and mechanism of miR‐325‐3p and C‐C motif chemokine ligand 19 (CCL19). CCL19 could facilitate the progression of DN by inhibiting cell viability and promoting inflammation and fibrosis in HK‐2 and HMC cells. In addition, CCL19 was confirmed to be targeted and negatively regulated by miR‐325‐3p. Rescue assays validated that the impacts of miR‐325‐3p mimics on the viability, inflammation and fibrosis of HK‐2 and HMC cells were recovered by CCL19 overexpression. To sum up, miR‐325‐3p inhibits renal inflammation and fibrosis by targeting CCL19 in a DN cell model and mice model, implying miR‐325‐3p as a possible therapeutic target for DN treatment. [ABSTRACT FROM AUTHOR]

Clear cell renal cell carcinoma (ccRCC) is the prominent histological subtype of renal cell carcinoma (RCC) with high incidence of local recurrence and distant metastasis. It has been documented that circular ribonucleic acids (circRNAs) play crucial roles in the development of cancers; however, study on exploring the role of circRNAs in ccRCC still remains limited. In the present study, we aimed to evaluate the biological function of a novel circRNA UBAP2 (circUBAP2) in ccRCC and the underlying mechanism. Our results showed that circUBAP2 expression was significantly down-regulated in ccRCC tissues and cell lines. Overexpression of circUBAP2 significantly inhibited the proliferation, migration, and invasion of ccRCC cells. MiR-148a-3p was a target miRNA of circUBAP2 in ccRCC cells, and its expression levels in ccRCC tissues and cell lines were negatively correlated with circUBAP2 levels. Moreover, miR-148a-3p reversed the inhibitory effects of circUBAP2 on cell proliferation, migration, and invasion in ccRCC cells. Additionally, forkhead box K2 (FOXK2) was found to be a target gene of miR-148a-3p and regulated by miR-148a-3p in ccRCC cells. Furthermore, knockdown of FOXK2 reversed the inhibitory effects of miR-148a-3p inhibitor on ccRCC cells. In conclusion, these findings indicated that circUBAP2 functioned as a novel tumor suppressor in ccRCC through regulating the miR-148a-3p/FOXK2 axis. Therefore, circUBAP2 might serve as a potential therapeutic target for the treatment of ccRCC. [ABSTRACT FROM AUTHOR]

B-cell novel protein 1 (BCNP1) has recently been identified as a new B-cell receptor (BCR) signaling molecule but its physiological function remains unknown. Here, we demonstrate that mice deficient in BCNP1 exhibit impaired B-cell maturation and a reduction of B-1a cells. BCNP1-deficient spleen B cells show enhanced survival, proliferation and Ca2+ influx in response to BCR cross-linking as compared with wild-type spleen B cells. Consistently, mutant B cells show elevated phosphorylation of SYK, B-cell linker protein (BLNK) and PLCγ2 upon BCR cross-linking. In vivo , BCNP1-deficient mice exhibit enhanced humoral immune responses to T-independent and T-dependent antigens. Moreover, aged mutant mice contain elevated levels of serum IgM and IgG3 antibodies and exhibit polyclonal and monoclonal B-cell expansion in lymphoid organs. These results reveal distinct roles for BCNP1 in B-cell development, activation and homeostasis. [ABSTRACT FROM AUTHOR]

The B‐cell receptor (BCR) transmits a tonic survival signal in the absence of antigen stimulation and an antigen‐triggered survival signal. Mature B cells express two types of BCR, IgM and IgD, but it remains unclear how B‐cell survival is differentially regulated by these two receptors. We found that, whereas cross‐linking IgM on spleen B cells greatly enhanced their survival, cross‐linking IgD did not enhance, but rather decreased, their survival. Consistently, cross‐linking both IgM and IgD only moderately enhanced B‐cell survival, suggesting that IgM and IgD play opposing roles in B‐cell survival induced by BCR stimulation. Based on these and additional experimental results, we present a mathematical model integrating IgM‐ and IgD‐mediated survival signals. Our model shows that IgD can transmit a tonic survival signal in the absence of antigen stimulation but cross‐linking IgD not only does not generate a survival signal but also disrupts its tonic signal, resulting in inhibition of B‐cell survival. These results suggest that IgD attenuates BCR‐induced survival in mature B cells, presumably to restrain B‐cell response to weak and/or self‐antigens and prevent nonspecific B‐cell activation and autoimmunity. Cross‐linking IgM on B cells enhances B‐cell survival. In contrast, cross‐linking IgD inhibits B‐cell survival. Based on these and additional experimental results, the authors establish a mathematical model for BCR‐induced B‐cell survival. [ABSTRACT FROM AUTHOR]

Abstract: BMSCs are important in replacement therapy of diabetic nephropathy (DN). MiR‐124a exerts effect on the differentiation capability of pancreatic progenitor cells. The objective of this study was to explore the molecular mechanisms, the functions of miR‐124a and bone marrow mesenchymal stem cells (BMSCs) in the treatment of DN. Characterizations of BMSCs were identified using the inverted microscope and flow cytometer. The differentiations of BMSCs were analysed by immunofluorescence assay and DTZ staining. The expression levels of islet cell‐specific transcription factors, apoptosis‐related genes, podocytes‐related genes and Notch signalling components were detected using quantitative real‐time reverse transcription PCR (qRT‐PCR) and Western blot assays. The production of insulin secretion was detected by adopting radioimmunoassay. Cell proliferation and apoptosis abilities were detected by CCK‐8, flow cytometry and TUNEL assays. We found that BMSCs was induced into islet‐like cells and that miR‐124a could promote the BMSCs to differentiate into islet‐like cells. BMSCs in combination with miR‐124a regulated islet cell‐specific transcription factors, apoptosis‐related genes, podocytes‐related genes as well as the activity of Notch signalling pathway. However, BMSCs in combination with miR‐124a relieved renal lesion caused by DN and decreased podocyte apoptosis caused by HG. The protective effect of BMSCs in combination with miR‐124a was closely related to the inactivation of Notch signalling pathway. MSCs in combination with miR‐124a protected kidney tissue from impairment and inhibited nephrocyte apoptosis in DN. [ABSTRACT FROM AUTHOR]

The current study mainly aims to evaluate the expression pattern and underlying mechanism of upstream stimulating factor 1 (USF1) in the muscle tissues of knee osteoarthritis (KOA) patients. In accordance with previous findings, our data showed that muscle strength was significantly decreased in KOA patients compared with controls. Furthermore, several inflammatory factors, including tumor necrosis factor α (TNFα), IL-8, IL-6 and MCP-1, were associated with reduced muscle strength in KOA patients. Not surprisingly, NF-κB signaling was significantly activated in the muscle tissues of KOA patients compared with control individuals. Furthermore, we showed that USF1 was increased in the muscles of KOA patients compared with controls. More importantly, overexpression of USF1 in primary human skeletal muscle cells significantly increased the activation of NF-κB signaling as well as the levels of pro-inflammatory factors. In summary, we showed novel data that the upregulation of USF1 promoted NF-κB activation-induced inflammatory responses in muscle tissues of KOA patients. [ABSTRACT FROM AUTHOR]

Severe injury of renal tubular epithelial cells may cause acute renal failure, the progression of which results in renal fibrosis, and obstructive nephropathy. Transforming growth factor β 1 and bone morphogenic protein 7 (BMP7) play contradicting roles in and coordinate the process of epithelial-to-mesenchymal transition of renal tubular epithelial cells, but the molecular regulation of BMP7 remains ill-defined. Here, we addressed this question. We found that after induction of unilateral ureteral obstruction (UUO) in mice, the increases in BMP7 mRNA were much more pronounced than BMP7 protein in kidney, suggesting the presence of post-transcriptional control of BMP7. Moreover, significant increases in a BMP7-targeting microRNA, miR-384-5p, were detected in the mouse kidney post UUO. Overexpression of miR-384-5p significantly decreased BMP7 protein, while depletion of miR-384-5p significantly increased BMP7 protein in renal epithelial cells. Bioinformatics study showed that miR-384-5p appeared to suppress BMP7 protein translation, through its direct binding to the 3′-UTR of BMP7 mRNA. Furthermore, suppression of miR-384-5p in vivo attenuated severity of renal injury by UUO. Together, our study sheds light on miR-384-5p as a crucial factor that regulates the fibrosis-related pathogenesis after renal injury, and points to miR-384-5p as a promising innovative therapeutic target for prevention of renal fibrosis. [ABSTRACT FROM AUTHOR]

Context: Nanostructured lipid carriers (NLC) are potentially good colloidal drug carriers for gene delivery. They are advised to be the second lifetime of lipid nanocarriers. Objective: The aim of this study is to develop novel modified NLC as nanomedicine for delivery of plasmid-containing enhanced green fluorescence protein (pEGFP). This system could target the lung cancer cells through receptor-mediated pathways to increase the nuclear uptake of genetic materials. Methods: In the present study, pEGFP-loaded NLC (NLC/pEGFP) were prepared. Transferrin (Tf) containing ligands were used for the surface coating of the vectors.In vitrotransfection efficiency of the modified vectors was evaluated in human alveolar adenocarcinoma cell line (A549 cells) andin vivotransfection efficiency of the modified vectors was evaluated on mice bearing A549 cells model. Results: Tf-modified NLC/pEGFP (Tf-NLC/pEGFP) has a particle size of 157 nm, and ∼82% of gene loading quantity. Tf-NLC/pEGFP displayed remarkably higher transfection efficiency than non-modified NLC/pEGFP bothin vitroandin vivo. Conclusion: The results demonstrate that the novel NLC gene delivery system offers an effective strategy for lung cancer gene therapy. [ABSTRACT FROM PUBLISHER]

Aim Previous genome-wide association studies have identified multiple susceptibility loci for IgA nephropathy (IgAN); however, validation of these findings is still needed. Methods We performed a case-control study among 347 Chinese Han IgAN patients and 310 ethnicity-matched controls. Twenty-two single nucleotide polymorphisms (SNPs) were genotyped and association analysis was performed. Results We found three alleles for IgAN in patients: the allele 'C' of rs2188404 in the CCDC132 gene by recessive model (odds ratio (OR), 1.65; 95% confidence interval (CI), 1.10-2.48; P = 0.014) and additive model (OR, 1.29; 95% CI, 1.03-1.61; P = 0.024) analysis, respectively, the allele 'A' of rs10488764 in FDX1 gene by additive model (OR, 1.27; 95% CI, 1.00-1.61; P = 0.048) analysis, the allele 'A' of rs3803800 in TNFSF13 gene by recessive model (OR, 2.05; 95% CI, 1.16-3.62; P = 0.010) and additive model (OR, 1.35; 95% CI, 1.06-1.72; P = 0.013) analysis, respectively. However, the associations between these SNPs and the risk of IgAN were not significant when adjusted for age and sex. Additionally, we found polymorphisms of rs2188404, rs10488764 and rs3803800 were correlated with urine protein (UPRO), human serum albumin (HSA), total cholesterol (TC) and Lee's pathological grades. Conclusion We did not find any positive association between these SNPs and the risk of IgAN after adjustment by age and sex, but did find a significant and strong correlation with relevant clinical pathological parameters. Our study may provide a new perspective to understanding the aetiology of IgAN. [ABSTRACT FROM AUTHOR]

Tracking-by-detection methods have been widely studied and some promising results have been obtained. These methods use discriminative appearance models to train and update online classifiers. They also use a sliding window to detect samples which will then be classified. Then, the location of the sample with the maximum classifier response will be selected as the new location. Compressive tracking was recently proposed with an appearance model based on features extracted in the compressed domain. However, CT uses a fixed-size tracking box to detect samples, and this is unsuitable for practice applications. CT detects samples around the selected region of the previous frame within a fixed radius. Here, the classifier may become inaccurate if the selected region drifts. The fixed radius is also not suitable for tracking targets that experience abrupt acceleration changes. Furthermore, CT updates the classifier parameters with constant learning rate. If the target is fully occluded for an extended period, the classifier will instead learn the features of the cover object and the target will ultimately be lost. In this paper, we present a multi-scale compressive tracker. This tracker integrates an improved appearance model based on normalized rectangle features extracted in the adaptive compressive domain into the bootstrap filter. This type of feature extraction is efficient, and the computation complexity does not increase as the tracking regions become larger. The classifier response is utilized to generate particle importance weight and a re-sample procedure preserves samples according to weight. A 2-order transition model considers the target velocity to estimate the current position and scale status. In this way, the sampling is not limited to a fixed range. Here, feedback strategies are adopted to adjust learning rate for occlusion. Experimental results on various benchmark challenging sequences have demonstrated the superior performance of our tracker when compared with several state-of-the-art tracking algorithms. [ABSTRACT FROM AUTHOR]

Considering personal privacy and difficulty of obtaining training material for many seldom used English words and (often non-English) names, language-independent (LI) with lightweight speaker-dependent (SD) automatic speech recognition (ASR) is a promising option to solve the problem. The dynamic time warping (DTW) algorithm is the state-of-the-art algorithm for small foot-print SD ASR applications with limited storage space and small vocabulary, such as voice dialing on mobile devices, menu-driven recognition, and voice control on vehicles and robotics. Even though we have successfully developed two fast and accurate DTW variations for clean speech data, speech recognition for adverse conditions is still a big challenge. In order to improve recognition accuracy in noisy environment and bad recording conditions such as too high or low volume, we introduce a novel one-against-all weighted DTW (OAWDTW). This method defines a one-against-all index (OAI) for each time frame of training data and applies the OAIs to the core DTW process. Given two speech signals, OAWDTW tunes their final alignment score by using OAI in the DTW process. Our method achieves better accuracies than DTW and merge-weighted DTW (MWDTW), as 6.97% relative reduction of error rate (RRER) compared with DTW and 15.91% RRER compared with MWDTW are observed in our extensive experiments on one representative SD dataset of four speakers' recordings. To the best of our knowledge, OAWDTW approach is the first weighted DTW specially designed for speech data in adverse conditions. [ABSTRACT FROM AUTHOR]

Bone marrow mesenchymal stem cells (BMSCs) have the ability of self-renewal and multi-directional differentiation. Recent reports showed that BMSCs could differentiate into endocrine cells of pancreas. However, the differentiation is not efficient enough to produce insulin-producing cells for the future therapeutic use. Pdx-1 is a crucial regulator for pancreatic development. Therefore we constructed a eukaryotic expression vector containing Pdx-1 to determine the effect of Pdx-1 expression on differentiation of BMSCs in vitro. The results showed that BMSCs could self-assemble to form functional pancreatic islet-like structures after differentiation in vitro. The proportion of insulin-producing cells differentiated from Pdx-1+BMSCs was 28.23%±2.56%, higher than that from BMSCs transfected with vacant vector and Pdx-1 − BMSCs (7.23%±1.56% and 4.08%±2.69% respectively) by flow cytometry. Immunocytochemical examination also testified the expression of multiple β-cells-specific genes such as insulin, glucagons, somatostatin in differentiated BMSCs. The results also revealed that the expressions of genes mentioned above in Pdx-1+BMSCs were higher than that in Pdx-1−BMSCs, which was confirmed by Western blotting analysis and RT-PCR. Glucose-induced insulin secretion from Pdx-1+BMSCs in 5mmol/L and 25mmol/L glocuse was (56.61±4.82) µU/mL and (115.29±2.56) µU/mL respectively, which were much higher than those from Pdx-1−BMSCs((25.53±6.49) µU/mL and (53.26±7.56) µU/mL respectively). Grafted animals were able to maintain their body weight and survive for relatively longer periods of time than hyperglycemic sham-grafted controls, which demonstrated an overall beneficial effect of the grafted cells on the health of the animals. These findings thus suggested that exogenous expression of Pdx-1 should provide a promising approach for efficiently producing islet-like cells from BMSCs for the future therapeutic use in diabetic patients. [ABSTRACT FROM AUTHOR]

Modeling phonological units of speech is a critical issue in speech recognition. In this paper, our recent development of an overlapping-feature-based phonological model that represents long-span contextual dependency in speech acoustics is reported. In this model, high-level linguistic constraints are incorporated in automatic construction of the patterns of feature-overlapping and of the hidden Markov model (HMM) states induced by such patterns. The main linguistic information explored includes word and phrase boundaries, morpheme, syllable, syllable constituent categories, and word stress. A consistent computational framework developed for the construction of the feature-based model and the major components of the model are described. Experimental results on the use of the overlapping-feature model in an HMM-based system for speech recognition show improvements over the conventional triphone-based phonological model. © 2001 Acoustical Society of America. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide exists widely in mammalian tissues and plays a vital role in physiological and pathophysiological processes. However, striking differences with orders of magnitude were observed for the detected hydrogen sulfide concentrations in biological matrices among different measurements in literature, which lead to the uncertainty for examination the biological relevance of hydrogen sulfide. Here, we developed and validated a liquid chromatography- mass spectrometry (LC-MS/MS) method for the determination of hydrogen sulfide in various biological matrices by determination of a derivative of hydrogen sulfide and monobromobimane named sulfide dibimane (SDB). 36S-labeled SDB was synthesized and validated for using as an internal standard. This method has been successfully used to measure hydrogen sulfide levels in a broad range of biological matrices, such as blood, plasma, tissues, cells, and enzymes, across different species. Moreover, a novel mode that hydrogen sulfide could loosely and non-covalently bind to human serum protein (HSA) and hemoglobin (HB) was revealed by using the developed method. [ABSTRACT FROM AUTHOR]