Degradation kinetics of vitamins in different enteral feeding formulas during storage at different temperatures.

Vitamin degradation may be affected differently by various food matrices. In this study, the kinetics of vitamin A, B1, and C degradation were directly compared in two types of enteral feeding formulas (EFFs) with different energy densities over a nine-month storage period at 4, 25, and 30 °C. The content of vitamins A, B1, and C was measured in the initial and stored formulas. The results justified the finding that the content of these vitamins was gradually decreased with storage time or temperature increases during the period. At each temperature during storage, the degradation of vitamins A, B1, and C followed first-order kinetics, and the rate constants calculated indicated the degradation of vitamins was temperature-dependent. The EFF-B exhibited a higher activation energy for vitamin degradation than that in the EFF-A, and the activation energy indicated an inverse relationship with the fat content of EFFs. The outcomes might provide a reference for the development and application of EEFs.

Leaf Senescence Database v5.0: A Comprehensive Repository for Facilitating Plant Senescence Research.

Through an extensive literature survey, we have upgraded the Leaf Senescence Database (LSD v5.0; https://ngdc.cncb.ac.cn/lsd/), a curated repository of comprehensive senescence-associated genes (SAGs) and their corresponding mutants. Since its inception in 2010, LSD undergoes frequent updates to encompass the latest advances in leaf senescence research and its current version comprises a high-quality collection of 31,740 SAGs and 1,209 mutants from 148 species, which were manually searched based on robust experimental evidence and further categorized according to their functions in leaf senescence. Furthermore, LSD was greatly enriched with comprehensive annotations for the SAGs through meticulous curation using both manual and computational methods. In addition, it was equipped with user-friendly web interfaces that facilitate text queries, BLAST searches, and convenient download of SAG sequences for localized analysis. Users can effortlessly navigate the database to access a plethora of information, including literature references, mutants, phenotypes, multi-omics data, miRNA interactions, homologs in other plants, and cross-links to various databases. Taken together, the upgraded version of LSD stands as the most comprehensive and informative plant senescence-related database to date, incorporating the largest collection of SAGs and thus bearing great utility for a wide range of studies related to plant senescence.

RPGR is a guanine nucleotide exchange factor for the small GTPase RAB37 required for retinal function via autophagy regulation.

Although the small GTPase RAB37 acts as an organizer of autophagosome biogenesis, the upstream regulatory mechanism of autophagy via guanosine diphosphate (GDP)-guanosine triphosphate (GTP) exchange in maintaining retinal function has not been determined. We found that retinitis pigmentosa GTPase regulator (RPGR) is a guanine nucleotide exchange factor that activates RAB37 by accelerating GDP-to-GTP exchange. RPGR directly interacts with RAB37 via the RPGR-RCC1-like domain to promote autophagy through stimulating exchange. Rpgr knockout (KO) in mice leads to photoreceptor degeneration owing to autophagy impairment in the retina. Notably, the retinopathy phenotypes of Rpgr KO retinas are rescued by the adeno-associated virus-mediated transfer of pre-trans-splicing molecules, which produce normal Rpgr mRNAs via trans-splicing in the Rpgr KO retinas. This rescue upregulates autophagy through the re-expression of RPGR in KO retinas to accelerate GDP-to-GTP exchange; thus, retinal homeostasis reverts to normal. Taken together, these findings provide an important missing link for coordinating RAB37 GDP-GTP exchange via the RPGR and retinal homeostasis by autophagy regulation.

The miR6445-NAC029 module regulates drought tolerance by regulating the expression of glutathione S-transferase U23 and reactive oxygen species scavenging in Populus.

MicroRNAs are essential in plant development and stress resistance, but their specific roles in drought stress require further investigation. Here, we have uncovered that a Populus-specific microRNAs (miRNA), miR6445, targeting NAC (NAM, ATAF, and CUC) family genes, is involved in regulating drought tolerance of poplar. The expression level of miR6445 was significantly upregulated under drought stress; concomitantly, seven targeted NAC genes showed significant downregulation. Silencing the expression of miR6445 by short tandem target mimic technology significantly decreased the drought tolerance in poplar. Furthermore, 5' RACE experiments confirmed that miR6445 directly targeted NAC029. The overexpression lines of PtrNAC029 (OE-NAC029) showed increased sensitivity to drought compared with knockout lines (Crispr-NAC029), consistent with the drought-sensitive phenotype observed in miR6445-silenced strains. PtrNAC029 was further verified to directly bind to the promoters of glutathione S-transferase U23 (GSTU23) and inhibit its expression. Both Crispr-NAC029 and PtrGSTU23 overexpressing plants showed higher levels of PtrGSTU23 transcript and GST activity while accumulating less reactive oxygen species (ROS). Moreover, poplars overexpressing GSTU23 demonstrated enhanced drought tolerance. Taken together, our research reveals the crucial role of the miR6445-NAC029-GSTU23 module in enhancing poplar drought tolerance by regulating ROS homeostasis. This finding provides new molecular targets for improving the drought resistance of trees.

PTI-ETI synergistic signal mechanisms in plant immunity.

Plants face a relentless onslaught from a diverse array of pathogens in their natural environment, to which they have evolved a myriad of strategies that unfold across various temporal scales. Cell surface pattern recognition receptors (PRRs) detect conserved elicitors from pathogens or endogenous molecules released during pathogen invasion, initiating the first line of defence in plants, known as pattern-triggered immunity (PTI), which imparts a baseline level of disease resistance. Inside host cells, pathogen effectors are sensed by the nucleotide-binding/leucine-rich repeat (NLR) receptors, which then activate the second line of defence: effector-triggered immunity (ETI), offering a more potent and enduring defence mechanism. Moreover, PTI and ETI collaborate synergistically to bolster disease resistance and collectively trigger a cascade of downstream defence responses. This article provides a comprehensive review of plant defence responses, offering an overview of the stepwise activation of plant immunity and the interactions between PTI-ETI synergistic signal transduction.

Novel Finding of Micropenis Caused by Mutation of the ADGRG2 Gene: A Case Report and Literature Review.

BACKGROUND: This study reported a case of micropenis caused by a novel hemizygous mutation in the ADGRG2 gene, which aimed to expand the understanding of sexual dysplasia caused by ADGRG2 gene mutation. CASE PRESENTATION: We present the clinical data and genetic test results of a patient with micropenis admitted in September, 2022, to the Tongji Hospital. The patient was a 9-year-10- month-old male whose chief complaint was the presence of a short penis over a period of three years. In April 2016, the patient underwent corrective surgery for a clubbed penis. Upon admission to the study hospital, his height and weight were 145.0 cm (75-90th percentile) and 37.8 kg (50-75th percentile), respectively, and his BA was 12 years old. His physical characteristics included a normal face, bilateral testicle size of 2 ml, and penile length of about 3 cm. A gonadotrophin-releasing hormone-stimulating test revealed normal hypothalamic-pituitary-gonadal axis function. An HCG stimulation test indicated normal sperm production in the testis. Key abnormalities from auxiliary examinations included low testosterone and high ACTH, dehydroepiandrosterone sulfate, androstenedione, and 17-OH-P levels. Genetic testing revealed a new hemizygous mutation, a splicing mutation in intron 4 of the ADGRG2 gene (ChrX: 19040187 (NM_001079858.3): c.154 + 2T > A, inherited from the mother. CONCLUSION: This study reported a case of micropenis caused by a new hemizygous mutation in the ADGRG2 gene. This indicates the importance of genetic testing and gene-guided treatments to improve prognosis.

The effect of GnRHa treatment on BMI in central precocious puberty: A systematic review and meta-analysis.

BACKGROUND: Recently, numerous studies have addressed the long-term effects of treatment with gonadotropin-releasing hormone analogue (GnRHa) in patients with central precocious puberty (CPP). However, the effects of GnRHa treatment on body mass index (BMI) in patients with CPP remain controversial. OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the association between GnRHa treatment and BMI in patients with CPP. METHOD: A systematic search of databases, PubMed, EMBASE and Web of Science published before August 2021 identified relevant studies. The overall effect analysis was performed using STATA version statistical software 15.0. RESULTS: The study included a total of 28 studies. At the end of GnRHa treatment, the BMI-standard deviation score (BMI-SDS) was greater than baseline BMI-SDS (weighted mean difference (WMD) = 0.14, 95% CI, 0.04-0.23; P = .004), especially in girls with CPP (WMD = 0.15, 95% CI, 0.05-0.25; P = 0.005) and in patients with normal weight (WMD = 0.34, 95% CI, 0.19-0.48, P < 0.001). After reaching adult height, BMI-SDS returned to baseline, suggesting that the effect of GnRHa treatment on BMI would disappear as the child grew (WMD = -0.03, 95% CI, -0.39 to 0.32; P = 0.815). CONCLUSION: For patients with CPP, while treatment with GnRHa may increase the BMI in the short term after treatment, the BMI is likely to return to normal when the patients reach adult height.

Characterization of newly diagnosed type 1 diabetes in children and adolescents from 2017 to 2022 in China: a single-center analysis.

OBJECTIVE: This study investigated the characteristics of newly diagnosed type 1 diabetes mellitus (T1DM) related to autoimmunity and the frequency of diabetic ketoacidosis (DKA) in children and adolescents from 2017-2022 in China. RESEARCH DESIGN AND METHODS: Single-center regional data from the Department of Pediatric Endocrinology, Tongji Hospital, were used to compare 88 children and adolescents newly diagnosed with T1DM from 2020 to 2022 (i.e. during the COVID-19 pandemic in China) and 76 children and adolescents diagnosed with T1DM from 2017 to 2019. Auto-antibodies, including glutamic acid decarboxylase-65 and insulin auto-antibodies, were detected by enzyme-linked immunoassays. DKA was defined as a pH < 7.3 and/or a bicarbonate level < 15 mmol/L. RESULTS: The median age of the 164 children and adolescents newly diagnosed with T1DM from 2017 to 2022 was 7.0 years (interquartile range [IQR]: 3.8-10.0 years; 51.83% male). The mean annual incidence of T1DM was 2.98 per 1,000,000 child years. The estimated frequency of auto-antibody positivity was 51.22% (n = 84), and there was no difference between the 2020-2022 group and 2017-2019 group (55.68% [n = 49] vs. 46.5% [n = 35]; p = 0.219). The frequency of DKA among the entire cohort was 57.93% (n = 95), and peaked in 2020 at 78.9% (15/19 patients). The frequency of DKA was not significantly higher in the 2020-2022 group compared with the 2017-2019 group (60.23% [n = 53] vs. 55.26% [n = 42]; p = 0.521). We found no significant difference in the frequency of DKA between patients who were negative vs. positive for auto-antibodies in the 2020-2022 group (64.10% [n = 25] vs. 57.14% [n = 28], p > 0.05). The C-peptide level and HbA1c (%) were positively correlated with onset age (R1 = 0.389, p < 0.01; R2 = 0.371, p < 0.01), and the estimated mean C-peptide level was 0.26 ng/ml (IQR: 0.2-0.4 ng/ml) in patients with DKA and 0.370 ng/ml (IQR: 0.2-0.6 ng/ml) in patients without DKA (p = 0.044). CONCLUSIONS: This study showed the annual incidence of T1DM was 2.98 per 1,000,000 child years, gradually increased over the study period, and there was no significant increase in T1DM with auto-antibody positivity in children and adolescents newly diagnosed from 2020-2022 in China compared with the previous 3 years. Furthermore, the frequency of DKA was peaked in 2020, and were not significantly different between patients who were negative vs. positive for auto-antibodies.

Induction of human ESC-derived and adult primary multipotent limbal stem cells into retinal pigment epithelial cells and corneal stromal stem cells.

Human embryonic stem cell (hESC)- and human induced pluripotent stem cell (hiPSC)-derived retinal pigment epithelium (RPE) therapies are promising alternatives for the treatment of retinal degenerative diseases caused by RPE degeneration. The generation of autologous RPE cells from human adult donors, which has the advantage of avoiding immune rejection and teratoma formation, is an alternative cell resource to gain mechanistic insight into and test potential therapies for RPE degenerative diseases. Here, we found that limbal stem cells (LSCs) from hESCs and adult primary human limbus have the potential to produce RPE cells and corneal stromal stem cells (CSSCs). We showed that hESC-LSC-derived RPE cells (LSC-RPE) expressed RPE markers, had a phagocytic function, and synthesized tropical factors. Furthermore, during differentiation from LSCs to RPE cells, cells became pigmented, accompanied by a decrease in the level of LSC marker KRT15 and an increase in the level of RPE marker MITF. The Wnt signaling pathway plays a role in LSC-RPE fate transition, promotes MITF expression in the nucleus, and encourages RPE fate transition. In addition, we also showed that primary LSCs (pLSCs) from adult human limbus similar to hESC-LSC could generate RPE cells, which was supported by the co-expression of LSC and RPE cell markers (KRT15/OTX2, KRT15/MITF), suggesting the transition from pLSC to RPE cells, and typical polygonal morphology, melanization, RPE cell marker genes expression (TYR, RPE65), tight junction formation by ZO-1 expression, and the most crucial phagocytotic function. On the other hand, both hESC-LSCs and pLSCs also differentiated into CSSCs (LSC-CSSCs) that expressed stem cell markers (PAX6, NESTIN), presented MSC features, including surface marker expression and trilineage differentiation capability, like those in human CSSCs. Furthermore, the capability of pLSC-CSSC to differentiate into cells expressing keratocyte marker genes (ALDH3A1, PTGDS, PDK4) indicated the potential to induce keratocytes. These results suggest that the adult pLSC is an alternative cell resource, and its application provides a novel potential therapeutic avenue for preventing RPE dysfunction-related retinal degenerative diseases and corneal scarring.

Molecular and functional characterization of Schistosoma japonicum annexin A13.

Schistosomiasis is a neglected tropical disease that affects humans and animals in tropical and subtropical regions worldwide. Schistosome eggs are responsible for the pathogenesis and transmission of schistosomiasis, thus reducing egg production is vital for prevention and control of schistosomiasis. However, the mechanisms underlying schistosome reproduction remain unclear. Annexin proteins (ANXs) are involved in the physiological and pathological functions of schistosomes, but the specific regulatory mechanisms and roles of ANX A13 in the development of Schistosoma japonicum and host-parasite interactions remain poorly understood. Therefore, in this study, the expression profiles of SjANX A13 at different life cycle stages of S. japonicum were assessed using quantitative PCR. In addition, the expression profiles of the homolog in S. mansoni were analyzed in reference to public datasets. The results of RNA interference showed that knockdown of SjANX A13 significantly affected the development and egg production of female worms in vivo. The results of an immune protection assay showed that recombinant SjANX A13 increased production of immunoglobulin G-specific antibodies. Finally, co-culture of S. japonicum exosomes with LX-2 cells using a transwell system demonstrated that SjANX A13 is involved in host-parasite interactions via exosomes. Collectively, these results will help to clarify the roles of SjANX A13 in the development of S. japonicum and host-parasite interactions as a potential vaccine candidate.

Adoptive transfer of immature dendritic cells with high HO-1 expression delays the onset of T1DM in NOD mice.

AIMS: To investigate the potential of imDCs with high expression of HO-1 in preventing or delaying the onset of Type 1 diabetes mellitus (T1DM) in non-obese diabetic (NOD) mice. MATERIALS AND METHODS: The phenotypic features of DCs in each group were assessed using flow cytometry. Western blot analysis was used to confirm the high expression of HO-1 in imDCs induced with CoPP. Additionally, flow cytometry was used to evaluate the suppressive capacity of CoPP-induced imDCs on splenic lymphocyte proliferation. Finally, the preventive effect of CoPP-induced imDCs was tested in NOD mice. KEY FINDINGS: Compared to imDCs, CoPP-induced imDCs exhibited a reduced mean fluorescence intensity (MFI) of the co-stimulatory molecule CD80 on their surface (P < 0.05) and significantly increased HO-1 protein expression (P < 0.05). Following LPS stimulation, the MFI of co-stimulatory molecules CD80 and CD86 on the surface of CoPP-induced imDCs remained at a lower level (P < 0.05). Furthermore, there was a reduced proliferation rate of lymphocytes stimulated with anti-CD3/28 antibodies. The adoptive transfer of CoPP-imDCs significantly reduced the incidence of T1DM (16.66 % vs. control group: 66.67 %, P = 0.004). Furthermore, at 15 weeks of age, the insulitis score was also decreased in the CoPP-induced imDC treatment group (P < 0.05). There were no significant differences in serum insulin levels among all groups. SIGNIFICANCE: ImDCs induced with CoPP and exhibiting high expression of HO-1 demonstrate a robust ability to inhibit immune responses and effectively reduce the onset of diabetes in NOD mice. This finding suggests that CoPP-induced imDCs could potentially serve as a promising treatment strategy for T1DM.

Identification of WUSCHEL-related homeobox gene and truncated small peptides in transformation efficiency improvement in Eucalyptus.

BACKGROUND: The WUSCHEL-related Homeobox (WOX) genes, which encode plant-specific homeobox (HB) transcription factors, play crucial roles in regulating plant growth and development. However, the functions of WOX genes are little known in Eucalyptus, one of the fastest-growing tree resources with considerable widespread cultivation worldwide. RESULTS: A total of nine WOX genes named EgWOX1-EgWOX9 were retrieved and designated from Eucalyptus grandis. From the three divided clades marked as Modern/WUS, Intermediate and Ancient, the largest group Modern/WUS (6 EgWOXs) contains a specific domain with 8 amino acids: TLQLFPLR. The collinearity, cis-regulatory elements, protein-protein interaction network and gene expression analysis reveal that the WUS proteins in E. grandis involve in regulating meristems development and regeneration. Furthermore, by externally adding of truncated peptides isolated from WUS specific domain, the transformation efficiency in E. urophylla × E. grandis DH32-29 was significant enhanced. The transcriptomics data further reveals that the use of small peptides activates metabolism pathways such as starch and sucrose metabolism, phenylpropanoid biosynthesis and flavonoid biosynthesis. CONCLUSIONS: Peptides isolated from WUS protein can be utilized to enhance the transformation efficiency in Eucalyptus, thereby contributing to the high-efficiency breeding of Eucalyptus.

A single-center study of clinical features of pediatric Sjögren's syndrome.

OBJECTIVE: Sjögren's syndrome (SS) is a rare disease with unclear diagnostic criteria among the children and adolescents. The purpose of this study is to describe the clinical features of pediatric Sjögren's syndrome and validate with Japanese diagnostic guidelines criteria of 2018. METHODS: We conducted a retrospective analysis of the clinical data of a cohort of 54 patients with pediatric Sjögren's syndrome admitted to our hospital over a total of 10 years from September 2013 to September 2022. RESULTS: The ratio of females to males was 49:5 among the 54 children (34 cases of primary SS and 20 cases of secondary SS), the average age of onset of symptoms for the first time was 9.9 years, and the average age at diagnosis was 10.2 years. In terms of subjective symptoms, 7 cases (13.0%) presented with dry mouth and 5 cases (9.3%) reported dry eyes. The positive rates were 9.3% for Schirmer I test, 70.4% for salivary gland function test, and 55.6% for salivary gland ultrasonography. The positive rates were 94.4% for Anti-Ro/SSA antibodies, 66.7% for Anti-La/SSB antibodies, 88.9% for ANA, 59.3% for RF, and the elevation rate of IgG was 63.0%. Among the EULAR Sjögren's syndrome disease activity index (ESSDAI) domains, the biological, constitutional, glandular, cutaneous, and lymphadenopathy domains were most involved. Treatment consisted of glucocorticoids in 88.9% of the patients in our study and hydroxychloroquine in 92.6%. As per the Japanese version of the clinical practice guidance for Sjögren's Syndrome in pediatric patients (2018), 5 cases were identified as Definite SS, 35 cases as Probable SS, and 14 cases as Possible SS. With respect to primary and secondary SS, there was essentially no significant difference between the groups in any of the above aspects. CONCLUSIONS: Patients with pediatric SS presented with a wide spectrum of clinical features, a low prevalence of reported symptoms of dry mouth and dry eyes, and various clinical manifestations with multi-system involvement. These are similar to other pediatric study cohorts in terms of epidemiology, auxiliary investigation results, disease activity scores, and treatment. The coincidence between our study and the Japanese version of the clinical practice guidance for Sjögren's Syndrome in pediatric patients (2018) is good for the diagnosis of pediatric SS.

Baicalin Attenuates Panton-Valentine Leukocidin (PVL)-Induced Cytoskeleton Rearrangement via Regulating the RhoA/ROCK/LIMK and PI3K/AKT/GSK-3ß Pathways in Bovine Mammary Epithelial Cells.

Pore-forming toxins (PFTs) exert physiological effects by rearrangement of the host cell cytoskeleton. Staphylococcus aureus-secreted PFTs play an important role in bovine mastitis. In the study, we examined the effects of recombinant Panton-Valentine leukocidin (rPVL) on cytoskeleton rearrangement, and identified the signaling pathways involved in regulating the process in bovine mammary epithelial cells (BMECs) in vitro. Meanwhile, the underlying regulatory mechanism of baicalin for this process was investigated. The results showed that S. aureus induced cytoskeleton rearrangement in BMECs mainly through PVL. S. aureus and rPVL caused alterations in the cell morphology and layer integrity due to microfilament and microtubule rearrangement and focal contact inability. rPVL strongly induced the phosphorylation of cofilin at Ser3 mediating by the activation of the RhoA/ROCK/LIMK pathway, and resulted in the activation of loss of actin stress fibers, or the hyperphosphorylation of Tau at Ser396 inducing by the inhibition of the PI3K/AKT/GSK-3ß pathways, and decreased the microtubule assembly. Baicalin significantly attenuated rPVL-stimulated cytoskeleton rearrangement in BMECs. Baicalin inhibited cofilin phosphorylation or Tau hyperphosphorylation via regulating the activation of RhoA/ROCK/LIMK and PI3K/AKT/GSK-3ß signaling pathways. These findings provide new insights into the pathogenesis and potential treatment in S. aureus causing bovine mastitis.

Comparison of micronutrients in adult enteral formulas widely used in clinical practice.

In recent decades, great progress in the area of enteral nutrition has provided a large variety and commercial availability of enteral formulas, usually produced by the nutrition divisions of several pharmaceutical or dairy manufacturers, with specific compositions for each type of disease or patient condition. Despite the widespread use of enteral formulas, both in hospitals and at home, studies performed on the micronutrient compositions of adult enteral formulas are few in China. The content of micronutrients in 31 commercially available adult enteral formulas in the Chinese market was compared with the Chinese dietary reference intakes (DRIs), the tolerable upper limits (UL), the limit requirements in Food Safety National Standards General Rules of Foods for Special Medical Purposes (GB 29922-2013), and the European Society for Clinical Nutrition and Metabolism (ESPEN) micronutrient guideline (2022). The micronutrient content was calculated by multiplying the value provided on the nutrition label for each product by the daily energy dose of 1500 and 1800 Kcal/day. The research results showed that most adult enteral formulas were generally suitable for patients on long-term total enteral nutrition support in the Chinese market, and foods for special medical purpose (FSMP) formulas were more suitable than enteral nutrition preparation (ENP) formulas. However, the vitamin D, vitamin K, and iron content in these formulas should be appropriately increased to the limit recommended by the ESPEN micronutrient guideline. The results could provide a basis for manufacturers to research and develop more suitable enteral formulas and help clinical dietitians administer more effective enteral nutrition support for patients on long-term total enteral nutrition in clinical practice, especially individualized treatment.

Neuropilin 1 promotes unilateral ureteral obstruction-induced renal fibrosis via RACK1 in renal tubular epithelial cells.

Neuropilin 1 (NRP1) is a single-channel transmembrane glycoprotein whose role and mechanism in renal fibrosis remain incompletely elucidated. Therefore, we investigated the effect of NRP1 on renal fibrosis and its potential mechanism. NRP1 expression in the renal sections from patients with chronic kidney disease (CKD) and a unilateral ureteral obstruction (UUO) mouse model was detected. Nrp1 overexpression or knockdown plasmid was transfected into mice, TKPTS mouse kidney proximal tubular epithelial cells (TECs), and rat kidney fibroblasts, after which pathological injury evaluation and fibrosis marker detection were conducted. The direct interaction of the receptor of activated protein C kinase 1 (RACK1) with NRP1 was validated by immunoprecipitation and Western blot analysis. We found that the upregulated renal NRP1 expression in patients with CKD was located in proximal TECs, consistent with the degree of interstitial fibrosis. In the UUO mouse model, NRP1 expression was upregulated in the kidney, and overexpression of Nrp1 increased the mRNA and protein expression of fibronectin (Fn) and α-smooth muscle actin (α-SMA), whereas Nrp1 knockdown significantly reduced Fn and α-SMA expression and downregulated the inflammatory response. NRP1 promoted transforming growth factor ß1 (TGF-ß1)-induced profibrotic responses in the TKPTS cells and fibroblasts, and Nrp1 knockdown partially reversed these responses. Immunoprecipitation combined with liquid chromatography-tandem mass spectrometry verified that NRP1 can directly bind to RACK1, and Rack1 knockdown reversed the NRP1-induced fibrotic response. In summary, NRP1 may enhance the TGF-ß1 pathway by binding to RACK1, thus promoting renal fibrosis.NEW & NOTEWORTHY Although a few studies have confirmed the correlation between neuropilin 1 (NRP1) and renal diseases, the mechanism of NRP1 in renal fibrosis remains unclear. Here, we investigated the effects of NRP1 on renal fibrosis through in vitro and in vivo experiments and explored the possible downstream mechanisms. We found that NRP1 can stimulate the TGF-ß1 signaling pathway, possibly by binding to RACK1, thereby promoting renal fibrosis.

Predictive Value of COPD History on In-Stent Restenosis in Coronary Arteries Following Percutaneous Coronary Intervention.

Objective: Chronic obstructive pulmonary disease (COPD) is a prevalent chronic respiratory disease that poses a significant health risk to individuals. Patients with COPD are predisposed to a higher incidence of coronary artery disease (CAD) than the general population. This study aims to investigate the correlation between COPD and the incidence of in-stent restenosis (ISR) after percutaneous coronary intervention (PCI). Methods: This study retrospectively analyzed the clinical data and laboratory test results of patients who underwent PCI at our hospital between January 2018 and December 2021 to investigate the relationship between COPD and drug-Eluting Stents (DES) postoperative ISR. We employed the best subset method to select the most suitable combination of predictive factors, utilizing the data, and verified the precision of the model by means of internal validation. We ultimately assessed the performance of the prediction model using an ROC curve. Results: The research indicates that COPD is an independent risk factor for ISR after PCI (OR=2.437, 95% CI [1.336, 4.495], P=0.004). The analysis revealed an area under the receiver operating characteristic (ROC) curve of 0.783 for the training group and 0.705 for the testing group, indicating a model fitting for both groups (both > 0.5). Conclusion: COPD history is a dependable predictor of stent restenosis post percutaneous coronary intervention.

Spliceosomal protein U2B″ delays leaf senescence by enhancing splicing variant JAZ9ß expression to attenuate jasmonate signaling in Arabidopsis.

The regulatory framework of leaf senescence is gradually becoming clearer; however, the fine regulation of this process remains largely unknown. Here, genetic analysis revealed that U2 small nuclear ribonucleoprotein B (U2B″), a component of the spliceosome, is a negative regulator of leaf senescence. Mutation of U2B″ led to precocious leaf senescence, whereas overexpression of U2B″ extended leaf longevity. Transcriptome analysis revealed that the jasmonic acid (JA) signaling pathway was activated in the u2b″ mutant. U2B″ enhances the generation of splicing variant JASMONATE ZIM-DOMAIN 9ß (JAZ9ß) with an intron retention in the Jas motif, which compromises its interaction with CORONATINE INSENSITIVE1 and thus enhances the stability of JAZ9ß protein. Moreover, JAZ9ß could interact with MYC2 and obstruct its activity, thereby attenuating JA signaling. Correspondingly, overexpression of JAZ9ß rescued the early senescence phenotype of the u2b″ mutant. Furthermore, JA treatment promoted expression of U2B″ that was found to be a direct target of MYC2. Overexpression of MYC2 in the u2b″ mutant resulted in a more pronounced premature senescence than that in wild-type plants. Collectively, our findings reveal that the spliceosomal protein U2B″ fine-tunes leaf senescence by enhancing the expression of JAZ9ß and thereby attenuating JA signaling.

Disrupting Hedgehog signaling in melanocytes by SUFU knockout leads to ocular melanocytosis and anterior segment malformation.

Hedgehog (Hh) signaling is well known for its crucial role during development, but its specific role in individual cell lineages is less well characterized. Here, we disrupted Hh signaling specifically in melanocytes by using Cre-mediated cell-type-specific knockout of the Hh regulator suppressor of fused (Sufu). Interestingly, corresponding mice were fully pigmented and showed no developmental alterations in melanocyte numbers or distribution in skin and hair follicles. However, there were ectopic melanoblasts visible in the anterior chamber of the eye that eventually displayed severe malformation. Choroidal melanocytes remained unaltered. Surprisingly, the abnormal accumulation of anterior uveal melanoblasts was not the result of increased cell proliferation but of increased migration to ectopic locations such as the cornea. In melanoblasts in vitro, Sufu knockdown replicated the increase in cell migration without affecting proliferation and was mediated by an increased level of phosphorylated-ERK brought about by a reduction in the levels of the repressor form of GLI3. These results highlight the developmental divergence of distinct melanocyte subpopulations and may shed light on the pathogenesis of human ocular melanocytosis.