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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]

Introduction: Group 3 innate lymphoid cells (ILC3s) are enriched in the intestinal mucosa and play important roles in host defense against infection and inflammatory diseases. Sirtuin 6 (SIRT6) is a nicotinamide adenine dinucleotide (NAD+)- dependent deacetylase and has been shown to control intestinal epithelial cell differentiation and survival. However, the role of SIRT6 in ILC3s remains unknown., Methods: To investigate the role of SIRT6 in gut ILC3s, we generated SIRT6 conditional knockout mice by crossing Rorccre and Sirt6flox/flox mice. Cell number and cytokine production was examined using flow cytometry. Citrobacter rodentium infection and dextran sodium sulfate-induced colitis models were used to determine the role of SIRT6 in gut defense. RT-qPCR, flow cytometry and immunohistochemistry were used to assess the intestinal inflammatory responses., Results: Here we show that SIRT6 inhibits IL-22 expression in intestinal ILC3s in a cell-intrinsic manner. Deletion of SIRT6 in ILC3s does not affect the cell numbers of total ILC3s and subsets, but results in increased IL-22 production. Furthermore, ablation of SIRT6 in ILC3s protects mice against Citrobacter rodentium infection and dextran sodium sulfate-induced colitis. Our results suggest that SIRT6 may play a role in ILC3 function by regulating gut immune responses against bacterial infection and inflammation., Discussion: Our finding provided insight into the relation of epigenetic regulators with IL-22 production and supplied a new perspective for a potential strategy against inflammatory bowel disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Su, Zhao, Zhang, Wang, Sun and Shen.)

Humoral immunity depends on the germinal center (GC) reaction where B cells are tightly controlled for class-switch recombination and somatic hypermutation and finally generated into plasma and memory B cells. However, how protein SUMOylation regulates the process of the GC reaction remains largely unknown. Here, we show that the expression of SUMO-specific protease 1 (SENP1) is up-regulated in GC B cells. Selective ablation of SENP1 in GC B cells results in impaired GC dark and light zone organization and reduced IgG1-switched GC B cells, leading to diminished production of class-switched antibodies with high-affinity in response to a TD antigen challenge. Mechanistically, SENP1 directly binds to Paired box protein 5 (PAX5) to mediate PAX5 deSUMOylation, sustaining PAX5 protein stability to promote the transcription of activation-induced cytidine deaminase. In summary, our study uncovers SUMOylation as an important posttranslational mechanism regulating GC B cell response., Competing Interests: Competing interests statement:The authors declare no competing interest.

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., Competing Interests: Declaration of interests H.N., J.S., and L.S. are co-inventors on a patent application filed by Shanghai Institute of Immunology related to this work., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Electrochemical CO 2 reduction reaction (CO 2 RR) powered by renewable energy provides a promising route to CO 2 conversion and utilization. However, the widely used neutral/alkaline electrolyte consumes a large amount of CO 2 to produce (bi)carbonate byproducts, leading to significant challenges at the device level, thereby impeding the further deployment of this reaction. Conducting CO 2 RR in acidic electrolytes offers a promising solution to address the "carbonate issue"; however, it presents inherent difficulties due to the competitive hydrogen evolution reaction, necessitating concerted efforts toward advanced catalyst and electrode designs to achieve high selectivity and activity. This review encompasses recent developments of acidic CO 2 RR, from mechanism elucidation to catalyst design and device engineering. This review begins by discussing the mechanistic understanding of the reaction pathway, laying the foundation for catalyst design in acidic CO 2 RR. Subsequently, an in-depth analysis of recent advancements in acidic CO 2 RR catalysts is provided, highlighting heterogeneous catalysts, surface immobilized molecular catalysts, and catalyst surface enhancement. Furthermore, the progress made in device-level applications is summarized, aiming to develop high-performance acidic CO 2 RR systems. Finally, the existing challenges and future directions in the design of acidic CO 2 RR catalysts are outlined, emphasizing the need for improved selectivity, activity, stability, and scalability., (© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH.)

The electrochemical CO 2 reduction reaction (CO 2 RR) triggered by renewable electricity provides a promising route to produce chemical feedstocks and fuels with low-carbon footprints. The intrinsic challenge for the current CO 2 RR electrolyzer is the carbonate issue arising from the reaction between hydroxide and CO 2 . Acid CO 2 RR electrolyzers, in principle, can effectively solve the carbonate formation, but it remains inevitable practically. In this work, we thoroughly investigated the electrode processes of the CO 2 RR on the benchmark Ag catalyst in mild acid. The root of the carbonate issue arises from the imbalanced supply-consumption rate of protons-the electron transfer vs. mass transport. Regulating the hydrodynamics substantially reduces the proton diffusion length by 80%, increasing the single-pass carbon utilization efficiency of CO 2 -to-CO to 44% at -100 mA cm -2 . The fundamental difference between mass transport and electron transfer on the spatial and temporal scale still leads to unavoidable carbonate formation. Future work to design intrinsically active catalysts in strong acid or metal-cation-free media is critical to solving the carbonate issue., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

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., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

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., (© 2023 Wiley-VCH GmbH.)

Group 3 innate lymphoid cells (ILC3s) play important roles in maintaining intestinal homeostasis by protecting the host from pathogen infections and tissue inflammation. The transcription factor PLZF (promyelocytic leukemia zinc finger), encoded by zinc finger BTB domain containing 16 (Zbtb16), is highly and transiently expressed in ILC precursors (ILCPs). However, the role of PLZF in regulating ILC3 development and function remains unknown. Here, we show that PLZF was specifically expressed in mature intestinal ILC3s compared with other ILC subsets. PLZF was dispensable for ILC3 development. However, PLZF deficiency in ILC3s resulted in increased innate interleukin-22 (IL-22) secretion and protection against gut infection and inflammation. Mechanistically, PLZF negatively regulated IL-22 expression by ILC3s in a cell-intrinsic manner by binding to the IL-22 promoter region for transcriptional repression. Together, our data suggest that PLZF restricts intestinal ILC3 function to regulate gut immune homeostasis., (© 2023. The Author(s), under exclusive licence to CSI and USTC.)

The Ni-rich layered cathode material LiNi 0.8 Co 0.1 Mn 0.1 O 2 (NCM811) with high specific capacity and acceptable rate performance is one of the key cathode materials for high-energy-density lithium-ion batteries. Coprecipitation, the widely utilized method in the precursor synthesis of NCM811 materials, however, suffers long synthetic processes and challenges in uniform element distribution. The spray pyrolysis method is able to prepare oxide precursors in seconds where all transition-metal elements are well distributed, but the difficulty of lithium distribution will also arise when the lithium salts are added in the subsequent sintering process. Herein, a fresh one-step spray pyrolysis approach is proposed for preparing high-performance NCM811 cathode materials by synthesizing lithium-contained precursors in which all elements are well distributed at a molecular level. The precursors with folded morphology and exceptional uniformity are successfully obtained at a low pyrolysis temperature of 300 °C by an acetate system. Furthermore, the final products commendably inherit the folded morphology of the precursors and exhibit excellent cyclic retentions of 94.6% and 88.8% after 100 and 200 cycles at 1 C (1 C = 200 mA g -1 ), respectively.

Vγ9Vδ2 T cells play an important role in the development and progression of psoriasis vulgaris (PV), but how they promote skin inflammation and the molecular mechanisms underlying Vγ9Vδ2 T cell dysfunction are poorly understood. Here, we show that circulating Vγ9Vδ2 T cells are decreased and exhibit enhanced proliferation and increased production of IFN-γ and TNF-α in PV patients. Monocytes from PV patients express higher levels of the phosphoantigen sensor butyrophilin 3A1 (BTN3A1) than monocytes from healthy controls. Blockade of BTN3A1 suppresses Vγ9Vδ2 T cell activation and abolishes the difference in Vγ9Vδ2 T cell activation between PV patients and healthy controls. The CD14 + cells in PV skin lesions highly express BTN3A1 and juxtapose to Vδ2 T cells. In addition, IFN-γ induces the up-regulation of BTN3A1 on monocytes. Collectively, our results demonstrate a crucial role of BTN3A1 on monocytes in regulating Vγ9Vδ2 T cell activation and highlight BTN3A1 as a potential therapeutic target for psoriasis.

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., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Qua-Quine Starch (QQS), an orphan gene exclusively found in Arabidopsis thaliana, interacts with Nuclear Factor Y subunit C4 (NF-YC4) and regulates carbon and nitrogen allocation in different plant species. Several studies uncovered its potential in increasing total protein and resistance against pathogens/pests in Arabidopsis and soybean. However, it is still unclear if these attributes QQS offers are universal in all flowering plants. Here we studied AtQQS and Nicotiana tabacum NF-YC4's (NtNF-YC4) influence on starch/protein content and pest resistance in tobacco. Our results showed both AtQQS and NtNF-YC4 had a positive impact on the plant's total protein accumulation. Simultaneously, we have also observed reduced starch biosynthesis and increased resistance against common pests like whiteflies (Bemisia tabaci) and aphids (Myzus persicae) in tobacco plants expressing AtQQS or overexpressing NtNF-YC4. Real-time PCR also revealed increased NF-YC4 expression after aphid infestation in tobacco varieties with higher pest resistance but decreased/unchanged NF-YC4 expression in varieties susceptible to pests. Further analysis revealed that QQS expression and overexpression of NtNF-YC4 strongly repressed expression of genes such as sugar transporter SWEET10 and Flowering Locus T (FT), suggesting involvement of SWEET10 and FT in the QQS and NF-YC4 mediated carbon and nitrogen allocation in tobacco. Our data suggested that the activity of species-specific orphan genes may not be limited to the original species or its close relatives. Sequence alignment revealed the conserved sequence of the NF-YC4s in different plant species that may be responsible for the resulting shift in metabolism, pest resistance. Cis-acting DNA element analysis of NtNF-YC4 promoter region may outline potential mechanisms for these phenotypic changes., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

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., (© 2022. The Author(s).)

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.

Systemic lupus erythematosus (SLE), a complex polygenic autoimmune disease, is associated with increased complement activation. Complement factor H related protein 5 (CFHR5) may contribute to dysfunctional complement activation, thus predisposing to SLE. The expression levels of anti-dsDNA, C3 and CFHR5 in blood samples from 50 SLE patients and 50 healthy individuals were evaluated, and also their expression levels were measured in an MRL/lpr mouse model and control MRL/MPJ mice. The results showed that CFHR5 expression increased in SLE patients together with the increase of anti-dsDNA in comparison with the healthy control. Furthermore, CFHR5 expression was inversely correlated with C3, down-regulation of which was associated with worse SLE. Previous studies indicated that long noncoding RNA (lncRNA) regulates mRNA synthesis via microRNA (miRNA) inhibition. The present bioinformatics analysis revealed that the target miRNA (miR-222) was combined with both lncRNA MIAT and mRNA CFHR5. H&E staining of the kidney tissues of the MRL/lpr mice revealed that lncRNA MIAT, as a competitive inhibitor of miR-222, enhanced SLE by upregulating CFHR5 expression through the degradation of miR-222 in vivo. Thus, our study revealed for the first time the role of lncRNA MIAT in regulating CFHR5 expression in SLE in vivo and provided new insights into the role of lncRNA in regulation and complement function of SLE pathogenesis., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Termedia.)

Protein tyrosine phosphatase, nonreceptor type 13 (PTPN13), has emerged as a critical cancer-related gene that is implicated in a wide range of cancer types. However, the role of PTPN13 in clear cell renal cell carcinoma (ccRCC) is poorly understood. In the present study, we aimed to evaluate whether PTPN13 participates in the progression of ccRCC. Decreased expression of PTPN13 was found in ccRCC tissues, which predicted a shorter survival rate in ccRCC patients. PTPN13 expression was also lower in ccRCC cell lines, and the upregulation of PTPN13 repressed the proliferation, colony formation and invasion, but enhanced the apoptosis of ccRCC cells. In contrast, the silencing of PTPN13 produced the opposite effects. Further data showed that PTPN13 overexpression decreased the phosphorylation of Akt, while PTPN13 silencing increased the phosphorylation of Akt. Treatment with Akt inhibitor markedly abrogated the PTPN13 silencing-evoked oncogenic effect in ccRCC cells. Xenograft tumor experiments revealed that overexpression of PTPN13 remarkably restricted the tumor formation and growth of ccRCC cells in vivo associated with inactivation of Akt. In conclusion, our data demonstrated that overexpression of PTPN13 restricts the proliferation and invasion of ccRCC cells through inactivation of Akt. Our study suggests a tumor suppressive function of PTPN13 in ccRCC and highlights the potential role of PTPN13 in the progression of ccRCC., (Copyright © 2020 Elsevier Inc. All rights reserved.)

IgA is the most abundantly produced antibody in the body and plays a crucial role in gut homeostasis and mucosal immunity. IgA forms a dimer that covalently associates with the joining (J) chain, which is essential for IgA transport into the mucosa. Here, we demonstrate that the marginal zone B and B-1 cell-specific protein (MZB1) interacts with IgA through the α-heavy-chain tailpiece dependent on the penultimate cysteine residue and prevents the intracellular degradation of α-light-chain complexes. Moreover, MZB1 promotes J-chain binding to IgA and the secretion of dimeric IgA. MZB1-deficient mice are impaired in secreting large amounts of IgA into the gut in response to acute inflammation and develop severe colitis. Oral administration of a monoclonal IgA significantly ameliorated the colitis, accompanied by normalization of the gut microbiota composition. The present study identifies a molecular chaperone that promotes J-chain binding to IgA and reveals an important mechanism that controls the quantity, quality, and function of IgA., Competing Interests: The authors declare no conflict of interest.

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.

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, and its pathogenesis is influenced by both genetic and environmental factors. In this study, we evaluated 23 tag single-nucleotide polymorphisms (tSNPs) in 21 IgAN-associated genes, in 200 subjects with IgAN and 310 healthy gender- and age-matched unrelated control subjects with no history of renal disease or hypertension. Using the co-dominant model, we found that two genotypes of rs3803800 in TNFSF13 were associated with an increased risk of IgAN: "GA" (OR = 1.03, 95% CI = 0.71-1.51, p = 0.018) and "AA" (OR = 2.45, 95% CI = 1.29-4.65, p = 0.018). The "AA" genotype was also associated with an increased risk of IgAN in the recessive model (OR = 2.41, 95% CI = 1.30-4.46, p = 0.018), as was the genotype "AA" rs10488764 in FDX1 (OR = 1.88, 95% CI = 1.01-3.53, p = 0.048). Interestingly, we found that the allele "A" of rs3803800 in TNFSF13 is associated with a decreased risk of IgAN in females (OR = 0.43, 95% CI = 0.20-0.95, p = 0.009), but with an increased risk in males (OR = 1.78, 95% CI = 0.86-3.66, p = 0.009). Our findings, combined with previously reported results, suggest that TNFSF13 and FDX1 have potential roles in IgAN in the Han Chinese population. This information may be useful in the development of early prognostics for IgAN., (Copyright © 2015. Published by Elsevier Inc.)

Intracranial mycotic aneurysm (MA), also known as intracranial infectious aneurysm, is a rare type of intracranial aneurysm. However, it carries a high mortality rate of 80% when ruptured and 30% even when unruptured. Here we report a 22-year-old male patient who consecutively developed two ruptured intracranial MAs related to infective endocarditis. The time interval between the two attacks was approximately seven months. The second aneurysm formed and ruptured regardless of long-term antibiotic therapy and cardiac surgery to replace the dysfunctional aortic valve. This case indicates that intracranial MAs may develop even after successful treatment of the underlying cardiac disorders, and hence close angiographic follow-ups may be warranted following the cardiac surgery.

Background: Nanostructured lipid carriers (NLC), composed of solid and liquid lipids, and surfactants are potentially good colloidal drug carriers. The aim of this study was to develop surface-modified NLC as multifunctional nanomedicine for codelivery of enhanced green fluorescence protein plasmid (pEGFP) and doxorubicin (DOX)., Methods: TWO DIFFERENT NANOCARRIERS: pEGFP- and DOX-loaded NLC, and solid lipid nanoparticles (SLN) were prepared. Transferrin-containing ligands were used for the surface coating of the vectors. Their average size, zeta potential, and drug encapsulation capacity were evaluated. In vitro transfection efficiency of the modified vectors was evaluated in human alveolar adenocarcinoma cell line (A549 cells), and in vivo transfection efficiency of the modified vectors was evaluated in a mouse bearing A549 cells model., Results: Transferrin-modified DOX and pEGFP coencapsulated NLC (T-NLC) has a particle size of 198 nm and a +19 mV surface charge. The in vitro cell viabilities of the T-NLC formulations were over 80% compared with the control. T-NLC displayed remarkably greater gene transfection efficiency and enhanced antitumor activity than DOX- and pEGFP-coencapsulated SLN in vivo., Conclusion: The results demonstrate that T-NLC noticeably enhanced antitumor activity through the combination of gene therapy with chemotherapy. Also coating of active transferrin improved the lung cancer cell-targeting of the carriers. In summary, the novel gene and drug delivery system offers a promising strategy for the treatment of lung cancer.

Objective: To obtain a global view of lymphocyte subset changes in the peripheral blood and cytokine profile in patients with class IV lupus nephritis (LN)., Methods: A total of 30 patients with biopsy proven active class IV LN, 30 patients with biopsy proven active class V LN, and 30 healthy controls were enrolled. Serum concentration of Th1 cytokines (IFN-γ, IL-1, IL-2, and TNF-α) and Th2 cytokines (IL-4, IL-5, IL-6, IL-10, IL-13) were simultaneously analyzed by Fast Quant Human Th1/Th2 protein array. The expression of lymphocyte subsets was measured by flow cytometer. Clinical parameters such as urine protein of 24 h, autoantibodies and complement were detected. Pearson analysis was used to examine the relation between lymphocyte subsets and clinical parameters, cytokine and clinical parameters., Results: The patients with class IV LN had evident anemia (P<0.001), hypocomplementemia, and hypoalbuminemia (P<0.05). There were no significant difference both in the ratio and number of CD4+ lymphocytes between the controls and the patients. In the patients with class IV LN, the ratio and number of CD4+ lymphocytes were both lower than those of the controls (P<0.01). The ratio and number of CD20+ lymphocytes were both higher than those of the controls (P<0.05), and a significant decrease in CD4+CD25+Foxp3+ regulatory T cells (Tregs) was observed in the patients compared with healthy age-matched controls (P<0.001). The abnormality of lymphocytes in class IV patients was obviously notable, especially in CD4+CD25+Foxp3+ regulatory T cells. In class IV patients, most of the detected cytokines levels were markedly elevated as compared with the controls, including Th2 cytokines INF-γ (P<0.05), IL-2 (P<0.05) and TNF-α (P<0.01), and Th2 cytokines IL-4 (P<0.05), IL-6 (P<0.05), IL-10 (P<0.01) and IL-13 (P<0.01). Only 4 out of 9 cytokines significantly increased in class V patients. In addition to IL-2, all of them belonged to Th2 (IL-4, IL-10 and IL-13) cytokines. There was negative correlation between CD4+CD25+Foxp3+ regulatory cells and urine protein, anti-dsDNA titer or SLEDAI (r=-0.781, -0.746 and -0.646, respectively; P<0.05). There was positive correlation between IL-5 and anti-dsDNA titer (r=0.708, P<0.05), between IL-5 and creatinine (r=0.681, P<0.05), and between IL-10 and SLEDAI (r=0.877, P<0.01). There was also negative correlation between IL-10 and urine protein of 24 h (r=-0.659, P<0.05), between IL-10 and hemoglobin concentration (r=-0.856, P<0.01), and between IL-13 and urine protein of 24 h (r=-0.769, P<0.05). There was little correlation between cytokines and clinical parameters in patients with class V LN., Conclusion: There is extensive abnormality in lymphocyte subsets and cytokine profile in patients with class IV LN, which may be the mechanism of immunosuppressive agents to treat patients with class IV LN.