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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]

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]

Adipose tissue group 2 innate lymphoid cells (ILC2s) help maintain metabolic homeostasis by sustaining type 2 immunity and promoting adipose beiging. Although impairment of the ILC2 compartment contributes to obesity-associated insulin resistance, the underlying mechanisms have not been elucidated. Here, we found that ILC2s in obese mice and humans exhibited impaired liver kinase B1 (LKB1) activation. Genetic ablation of LKB1 disrupted ILC2 mitochondrial metabolism and suppressed ILC2 responses, resulting in exacerbated insulin resistance. Mechanistically, LKB1 deficiency induced aberrant PD-1 expression through activation of NFAT, which in turn enhanced mitophagy by suppressing Bcl-xL expression. Blockade of PD-1 restored the normal functions of ILC2s and reversed obesity-induced insulin resistance in mice. Collectively, these data present the LKB1-PD-1 axis as a promising therapeutic target for the treatment of metabolic disease. [Display omitted] • LKB1 signaling is impaired in adipose tissue ILC2s from both mice and humans • LKB1 deficiency impairs ILC2 function and promotes obesity-associated insulin resistance • LKB1 sustains ILC2 mitochondrial and effector functions by inhibiting PD-1 expression • Targeting the LKB1-PD-1 axis may be a promising approach to metabolic disease therapy Obesity induces ILC2 dysfunction in adipose tissue and insulin resistance by undetermined mechanisms. Here, Sun et al. show that liver kinase B1 (LKB1) signaling protects ILC2s from mitophagy by suppressing PD-1 expression. Moreover, PD-1 blockade restores ILC2 function and reverses obesity-associated insulin resistance. [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]

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]