Acute kidney injury in critical care: complications of hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is an immune dysfunction characterized by an exaggerated and pathological inflammatory response, potentially leading to systemic inflammatory reactions and multiple-organ failure, including renal involvement. HLH can be classified as primary or secondary, with primary HLH associated with genetic mutations affecting cell degranulation capacity, and secondary HLH often linked to infections, tumors, and autoimmune diseases. The pathogenesis of HLH is not fully understood, but primary HLH is typically driven by genetic defects, whereas secondary HLH involves the activation of CD8+ T cells and macrophages, leading to the release of inflammatory cytokines and systemic inflammatory response syndrome (SIRS). The clinical presentation of HLH includes non-specific manifestations, making it challenging to differentiate from severe sepsis, particularly secondary HLH due to infections. Shared features include prolonged fever, hepatosplenomegaly, hematopenia, hepatic dysfunction, hypertriglyceridemia, and hypofibrinogenemia, along with histiocytosis and hemophagocytosis. However, distinctive markers like dual hemocytopenia, hypertriglyceridemia, hypofibrinogenemia, and elevated sCD25 levels may aid in differentiating HLH from sepsis. Indeed, no singular biomarker effectively distinguishes between hemophagocytic lymphohistiocytosis and infection. However, research on combined biomarkers provides insights into the differential diagnosis. Renal impairment is frequently encountered in both HLH and sepsis. It can result from a systemic inflammatory response triggered by an influx of inflammatory mediators, from direct damage caused by these factors, or as a consequence of the primary disease process. For instance, macrophage infiltration of the kidney can lead to structural damage affecting various renal components, precipitating disease. Presently, tubular necrosis remains the predominant form of renal involvement in HLH-associated acute kidney injury (HLH-AKI). However, histopathological changes may also encompass interstitial inflammation, glomerular abnormalities, microscopic lesions, and thrombotic microangiopathy. Treatment approaches for HLH and sepsis diverge significantly. HLH is primarily managed with repeated chemotherapy to eliminate immune-activating stimuli and suppress hypercellularity. The treatment approach for sepsis primarily focuses on anti-infective therapy and intensive symptomatic supportive care. Renal function significantly influences clinical decision-making, particularly regarding the selection of chemotherapy and antibiotic dosages, which can profoundly impact patient prognosis. Conversely, renal function recovery is a complex process influenced by factors such as disease severity, timely diagnosis, and the intensity of treatment. A crucial aspect in managing HLH-AKI is the timely diagnosis, which plays a pivotal role in reversing renal impairment and creating a therapeutic window for intervention, may have opportunity to improve patient prognosis. Understanding the clinical characteristics, underlying causes, biomarkers, immunopathogenesis, and treatment options for hemophagocytic lymphohistiocytosis associated with acute kidney injury (HLH-AKI) is crucial for improving patient prognosis.

Overexpressed Poldip2 incurs retinal fibrosis via the TGFß1/SMAD3 signaling pathway in diabetic retinopathy.

Retinal fibrosis is one of the major features of Diabetic retinopathy. Our recent research has shown that Poldip2 can affect early DR through oxidative stress, but whether or not Poldip2 would regulate retinal fibrosis during DR development is still enigmatic. Here, Diabetic Sprague-Dawley (SD) rats were induced with STZ and treated with AAV9-Poldip2shRNA, while human retinal pigment epithelial cells (ARPE-19) were treated with high glucose (HG) or Poldip2 siRNA. We identified that in STZ-induced DR rats and ARPE-19 treated with high glucose, the expression of Poldip2, TGFß1, P-SMAD3/SMAD3, MMP9, COL-1, FN, and CTGF increased while the expression of Cadherin decreased. However, deleting Poldip2 inhibited the TGF-ß1/SMAD3 signaling pathway and attenuated the above protein expression in vivo and in vitro. Mechanistically, we found that Poldip2 promotes the activation of SMAD3, and facilitates its nuclear translocation through interacting with it, and significantly enhances the expression of fibrosis makers. Collectively, it was identified that Poldip2 is a novel regulator of DR fibrosis and it is expected to become a therapeutic target for PDR.

Comparative Metabolome and Transcriptome Analyses Reveal Differential Enrichment of Metabolites with Age in Panax notoginseng Roots.

Panax notoginseng is a perennial plant well known for its versatile medicinal properties, including hepatoprotective, antioxidant, anti-inflammatory, anti-tumor, estrogen-like, and antidepressant characteristics. It has been reported that plant age affects the quality of P. notoginseng. This study aimed to explore the differential metabolome and transcriptome of 2-year (PN2) and 3-year-old (PN3) P. notoginseng plant root samples. Principal component analysis of metabolome and transcriptome data revealed major differences between the two groups (PN2 vs. PN3). A total of 1813 metabolites and 28,587 genes were detected in this study, of which 255 metabolites and 3141 genes were found to be differential (p < 0.05) between PN2 vs. PN3, respectively. Among differential metabolites and genes, 155 metabolites and 1217 genes were up-regulated, while 100 metabolites and 1924 genes were down-regulated. The KEGG pathway analysis revealed differentially enriched metabolites belonging to class lipids ("13S-hydroperoxy-9Z, 11E-octadecadionic acid", "9S-hydroxy-10E, 12Z-octadecadionic acid", "9S-oxo-10E, 12Z-octadecadionic acid", and "9,10,13-trihydroxy-11-octadecadionic acid"), nucleotides and derivatives (guanine and cytidine), and phenolic acids (chlorogenic acid) were found to be enriched (p < 0.05) in PN3 compared to PN2. Further, these differentially enriched metabolites were found to be significantly (p < 0.05) regulated via linoleic acid metabolism, nucleotide metabolism, plant hormone signal transduction, and arachidonic acid metabolism pathways. Furthermore, the transcriptome analysis showed the up-regulation of key genes MAT, DMAS, SDH, gallate 1-beta-glucosyltransferase, and beta-D-glucosidase in various plants' secondary metabolic pathways and SAUR, GID1, PP2C, ETR, CTR1, EBF1/2, and ERF1/2 genes observed in phytohormone signal transduction pathway that is involved in plant growth and development, and protection against the various stressors. This study concluded that the roots of a 3-year-old P. notoginseng plant have better metabolome and transcriptome profiles compared to a 2-year-old plant with importantly enriched metabolites and genes in pathways related to metabolism, plant hormone signal transduction, and various biological processes. These findings provide insights into the plant's dynamic biochemical and molecular changes during its growth that have several implications regarding its therapeutic use.

PhiHER2: phenotype-informed weakly supervised model for HER2 status prediction from pathological images.

MOTIVATION: Human epidermal growth factor receptor 2 (HER2) status identification enables physicians to assess the prognosis risk and determine the treatment schedule for patients. In clinical practice, pathological slides serve as the gold standard, offering morphological information on cellular structure and tumoral regions. Computational analysis of pathological images has the potential to discover morphological patterns associated with HER2 molecular targets and achieve precise status prediction. However, pathological images are typically equipped with high-resolution attributes, and HER2 expression in breast cancer (BC) images often manifests the intratumoral heterogeneity. RESULTS: We present a phenotype-informed weakly supervised multiple instance learning architecture (PhiHER2) for the prediction of the HER2 status from pathological images of BC. Specifically, a hierarchical prototype clustering module is designed to identify representative phenotypes across whole slide images. These phenotype embeddings are then integrated into a cross-attention module, enhancing feature interaction and aggregation on instances. This yields a phenotype-based feature space that leverages the intratumoral morphological heterogeneity for HER2 status prediction. Extensive results demonstrate that PhiHER2 captures a better WSI-level representation by the typical phenotype guidance and significantly outperforms existing methods on real-world datasets. Additionally, interpretability analyses of both phenotypes and WSIs provide explicit insights into the heterogeneity of morphological patterns associated with molecular HER2 status. AVAILABILITY AND IMPLEMENTATION: Our model is available at https://github.com/lyotvincent/PhiHER2.

Trichoderma spp. promotes ginseng biomass by influencing the soil microbial community.

Introduction: Ginseng (Panax ginseng C.A. Meyer) has multiple effects on human health; however, soil degradation seriously affects its yield. Trichoderma spp. play an important role in improving plant biomass by influencing the soil environment. Therefore, it is necessary to screen efficient Trichoderma strains that can increase ginseng biomass and determine their mechanisms. Methods: Herein, we selected six Trichoderma species (T. brevicompactum, T. velutinum, T. viridescens, T. atroviride, T. koningiopsis, and T. saturnisporum) isolated from ginseng rhizosphere soil, and evaluated their growth promoting effects on ginseng and their influence on the microbiome and chemical attributes of the ginseng rhizosphere soil. Results: Except for T. saturnisporum (F), compared with the control, the other five species increased ginseng biomass. In terms of chemical properties, the pH value, available potassium content, and available phosphorus content in the ginseng rhizosphere soil increased by 1.16-5.85%, 0.16-14.03%, and 3.92-38.64%, respectively, after root irrigation with spores of Trichoderma species. For the soil microbiome, fungal Chao1 and Ace richness indices decreased. Application of Trichoderma enhanced the relative level of Proteobacteria, but reduced the relative level of Ascomycota. At the genus level, application of Trichoderma enhanced the relative levels of Sphingomonas, Blastomonas, and Trichoderma, but reduced the relative level of Fusarium. Available K and available P were the most important elements that affected the structure of the bacterial community, while total K was the most influential element for the structure of the fungal community structure. Conclusion: The results indicated that the application of Trichoderma spp. could increase soil nutrients and regulate the structure and composition of the soil microbial community, thereby enhancing the biomass of ginseng. The results will provide guidance for soil improvement in ginseng cultivation.

First Report of Calonectria montana Causing Leaf Spot on Ligularia fischeri in China.

Ligularia fischeri (Ledeb.) is a perennial herbal plant of Compositae that is cultivated commercially in China as a medicinal, ornamental, and edible plant. Leaf spots were observed in 2-year-old L. fischeri in Benxi County of northeast China, in August 2021. Irregular reddish brown spots ranging from 3 to 11 mm were observed on infected leaves, and each leaf had dozens of spots (Fig. 1). As the disease progressed, the diseased spots withered and the centers fell out, and multiple lesions merge into large diseased spots, causing leaf wilting. The roots and stem bases were not infected during the reproductive stage. More than 37% of the plants in a 18 ha field were infected in 2021. The ten diseased leaves were collected and cut into small (3-5 mm) pieces, which were surface-disinfested by immersing into 1% NaOCl for 2 min and rinsing with sterile distilled water three times. The leaf pieces were then placed on acidified potato dextrose agar (PDA) in petri plates and incubated in the dark at 25°C. Twenty isolates with the same morphological characteristics were obtained. Isolates were further purified by starting a new colony for each isolate from a single spore collected from water agar. Isolate TYTW7 was randomly selected for identification and pathogenicity testing. It grew rapidly and produced profuse aerial mycelia with a carmine red underside. The conidiophores had many fertile branches and formed an elongated stipe with a sphaeropedunculate vesicle at the tip. The one-septate conidia were cylindrical and almost straight with parallel walls and rounded ends. Their sizes ranged from 30.35 to 51.76 × 2.93 to 5.01 µm (n = 100) and the pathogens were initially identified as Calonectria sp. (Crous 2002; Crous et al. 2004; Lombard et al. 2015, 2016). Further confirmation of the identification was determined according to published method (Liu and Chen 2017; Shao and Li 2021). The partial gene regions including the translation elongation factor 1-alpha (GenBank accession no. OP290551), histone H3 (OP290552), calmodulin (OP290553) and ß-tubulin (OP290554) were obtained, and BLAST searches showed 99-100% homology with the ex-type culture CERC 8952 (MF527049, MF527065, MF527081 and MF527107) and phylogenetic analysis combining all loci revealed that the isolate TYTW7 and the type strain of Ca. montana clustered in one group (Fig. 2). Based on morphological characteristics and phylogenetic analysis, isolate TYTW7 was identified as Ca. Montana. Healthy 2-year-old plants were used for the pathogenicity test. A spore suspension (1×105 spores/mL water) was used to inoculate three host plants; sterile water was sprayed on the same number plants serving as a control. The experiment was repeated three times. All plants were incubated at 27±2°C (12h photoperiod) and were evaluated after seven days. The inoculated plants showed lesions on the leaf surface, similar to those in the field, and the control remained symptomless. The pathogens were successfully reisolated and identified by sequencing, and no pathogens were isolated from symptomless control plants. To our knowledge, this is the first report of Ca. montana causing L. fischeri leaf spot. The disease poses a threat to the production and more control strategies are needed on management options to minimize losses.

Anthracnose of Macleaya cordata Caused by Colletotrichum aenigma in China.

Macleaya cordata (Willd.) R. Br. is a perennial herbaceous medicinal plant (Papaveraceae) commercially cultivated in China which has been studied for detumescence, detoxification, and insecticidal effect (Lin et al. 2018). In August 2021, anthracnose was observed in 2-year-old M. cordata plants in Benxi county, northeast China (41°45'48″N, 123°69'15″E). Dozens of irregular reddish-brown spots (3-11 mm) were observed on each diseased leaf. The lesions were covered with a layer of gray-white mycelia. As the disease progressed, the spots became necrosis and perforation or they would merged into large lesions, ultimately resulting in wilted leaves (Fig. 1). More than 33% of the plants in a 16-ha field were infected in 2021. The diseased leaves were collected and cut into 3-8 mm pieces, surface-disinfested by immersing them into 1% NaOCl for 2 min, and rinsed three times with sterile distilled water. They were then dried with sterilized absorbent paper, placed on PDA medium amended with chloramphenicol (40 mg/L), and incubated in darkness at 25°C with a 12-h photoperiod. Twenty isolates (BLH1 to 20) were obtained and purified using a single-spore method. Isolate BLH12 was identified and used for the pathogenicity test. Colonies were sparsely fluffy with smooth edges, and gradually became gray to pale orange from the initial white. The underside of the colonies was pale orange towards the center. Conidia were single-celled, cylindrical, and transparent with broadly blunt ends, measuring (15.13 ± 1.14) × (5.80 ± 0.60) µm (n=50). Appressoria were single-celled, brown-to-dark brown, usually elliptical or irregular, and sometimes lobed. Setae were not observed. The isolate was initially identified as Colletotrichum gloeosporioides complex (Prihastuti et al. 2009). The identification was confirmed as described previously (Weir et al. 2012). The rDNA internal transcribed spacer region (OP415560), the glyceraldehyde-3-phosphate dehydrogenase (OP433642), chitin synthase (OP433643), calmodulin (OP433644), actin (OP433645), glutamine synthetase (OP433646), ß-tubulin (OP433647), and superoxide dismutase (OP433648) gene sequences were obtained (Carbone & Kohn 1999; Weir et al. 2012), and BLAST searches revealed 99-100% homology with the type culture ICMP 18608 (JX010244, JX010044, JX009683, JX009443, JX009744, JX010078, JX010389, and JX010311). A phylogenetic analysis of combining all loci indicated BLH12 and the type strain of C. aenigma were clustered in one group (Fig. 2). Based on the basis of morphological characteristics and phylogenetic relationships, BLH12 was identified as C. aenigma. For the pathogenicity test, healthy 2-year-old plants were sprayed with a BLH12 spore suspension (1 × 105/mL). Control plants were sprayed with sterile water.There were three replicates (five plants each) per treatment. All plants were incubated at 25°C (12-h photoperiod and 86% relative humidity) and examined after 7 days. The experiment was repeated twice. The inoculated plants showed lesions on the leaf surface, similar to those in the field, whereas the control plants were asymptomatic. The pathogen was successfully reisolated and identified as the methods mentioned above. This fungus reportedly infects the leaves of many woody plants in China (Wang et al. 2020; Zhang et al. 2021). This is the first report of C. aenigma causing anthracnose on M. cordata, which will provide an guideline for developing effective field control practices for the disease.

Superior Electromechanical Compatibility in Lead-Free Piezoceramics with Mobile Transition-Metal Defects.

Donor and acceptor ions serving as extrinsic defects in piezoelectrics are mostly used to improve the performance merits to satisfy the industrial application. However, the conventional doping strategy is unable to overcome the inherent trade-off between the piezoelectric coefficient (d33) and mechanical quality factor (Qm). Herein, inspired by the valence state variation observed in manganese oxides during sintering, this study focuses on manipulating intrinsic oxygen vacancies and extrinsic manganese defects in potassium sodium niobate (KNN) ceramics via heat treatment. The annealing process results in a simultaneous improvement in both d33 (20%) and Qm (80%), leading to comparable performance with commercial PZT-5A ceramics and enabling their application in atomizer components. Moreover, the mechanism of manganese occupation and diffusion is proposed by an extended X-ray absorption fine structure and density functional theory analysis. The improved electromechanical performance in the annealed KNN ceramic is associated with the optimized redistribution of acceptor and donor manganese defects, which is facilitated by the recombination of oxygen vacancies. This work breaks longstanding obstacles in comprehending the existing forms of manganese in KNN and offers potential in popularizing KNN-based piezoceramics to replace traditional PZT lead-based counterparts in the industrial market.

Anthracnose of Brachybotrys paridiformis Caused by Colletotrichum siamense in Northeast China.

Brachybotrys paridiformis Maxim. ex Oliv. (Boraginaceae) is a perennial medicinal plant and vegetable that is cultivated commercially in China. Anthracnose is a devastating disease of B. paridiformis, with annual production losses exceeding 33% based on our survey. In July 2021, anthracnose of B. paridiformis was observed on 2-year-old plants in Shenyang city, Northeast China, which is the most important region for B. paridiformis cultivation. Round or irregular-shaped black spots were exhibited on leaves, with the leaf edges most commonly infected. As the necrosis expanded, the leaves withered and dropped; young leaves were generally not infected (Fig. 1). More than 40% of the plants in a 21-ha sampling field were infected in 2021. Symptomatic leaves (n = 20) were collected and the diseased tissue was cut into small pieces, immersed in 1% NaOCl for 2 min, rinsed three times with sterile water, and placed on acidified potato dextrose agar (PDA) in Petri dishes. After a 3-day incubation in darkness at 25 °C, 18 suspected single-pure morphologically identical Colletotrichum isolates were obtained and sequenced. Isolate SQZ9 was randomly selected and identified. Colonies on PDA were initially white, but gradually became pale brownish with a reverse side that was pale yellowish to pinkish. Aerial mycelia were grayish-white, dense, and cottony, with microsclerotia detected on some aging mycelia. The detected single-celled conidia (11.65-17.25 × 4.25-6.15 µm; n = 50) were fusiform to cylindrical with obtuse to slightly rounded ends. Appressoria were ovoid to clavate and medium brown. Setae were not observed. The morphological characteristics were similar to those of Colletotrichum spp. (Prihastuti et al. 2009; Weir et al. 2012). Initial BLAST searches of the GenBank database revealed the SQZ9 rDNA internal transcribed spacer region (OP389109, 566 bp), glyceraldehyde-3-phosphate dehydrogenase (OP407730, 260 bp), chitin synthase (OP407731, 301 bp), calmodulin (OP407732, 712 bp), actin (OP407733, 282 bp), glutamine synthetase (OP407734, 909 bp), ß-tublin (OP407735, 498 bp), and superoxide dismutase (OP407736, 396 bp) sequences were respectively 99%-100% similar to the C. siamense type strain JX010278, JX010019, JX009709, GQ856775, GQ856730, JX010100, JX010410, and JX010332 sequences (Carbone & Kohn 1999; Moriwaki & Tsukiboshi 2009; Stephenson et al. 1997). The SQZ9 identity was confirmed by constructing a phylogenetic tree combining all loci, which grouped the isolate and the C. siamense type strain in the same clade (Fig. 2). For pathogenicity tests, 15 healthy 2-year-old plants (3 plants per pot) were spray-inoculated with SQZ9 conidial suspension (1 × 105 conidia/mL) at 2 mL per plant. Same number of plants sprayed with water were used as control. This experiment was repeated twice. All plants were covered with clear plastic bags for 72 h to maintain high humidity and then placed in a greenhouse (29 °C, natural light, and 85% relative humidity). After six days, the inoculated leaves exhibited symptoms that were similar to those observed in the field, but the controls were symptomless. The same fungus was recovered from inoculated symptomatic leaves, and its identity was confirmed by sequencing and a phylogenetic analysis. This is the first report of C. siamense causing anthracnose on B. paridiformis in China. Future studies should assess the effectiveness of chemical and biological control measures for managing this disease.

Nirmatrelvir/ritonavir use in patients with COVID-19 on hemodialysis: a case series.

Patients undergoing hemodialysis (HD) are particularly vulnerable to coronavirus disease 2019 (COVID-19) and are at increased risk of developing severe infection. However, given the exclusion of such patients from clinical trials, there are limited data regarding the effectiveness of the antiviral drug nirmatrelvir/ritonavir (N/R) in patients on HD. We prescribed N/R to 4 patients on HD with COVID-19 after obtaining informed consent. Their clinical symptoms were improved at approximately 3 days after N/R administration. The viral load was reduced after approximately 10 days. The main adverse effects were nausea and vomiting. Rational dosage adjustment obtained good tolerance but did not influence the efficacy. These results suggest that N/R may be a promising agent for patients on HD with COVID-19.

Cytohesin-4 Upregulation in Glioma-Associated M2 Macrophages Is Correlated with Pyroptosis and Poor Prognosis.

Cytohesin-4 (CYTH4) is a member of the PSCD family. Members of this family appear to mediate the regulation of protein sorting and membrane trafficking. In previous studies, CYTH4 has been linked with multiple brain diseases, but not glioma, the most common type of brain tumor. We utilized multiple glioma single-cell RNA sequencing datasets and bulk data from the TCGA and CGGA and conducted GSEA and KEGG and GO analyses. Biomarker potential was tested via ROC curve analysis. Radar plots were used to study TMB and MSI correlations. Immune cell studies were conducted using CIBERSORT. All statistical analyses were performed in R software and GraphPad Prism 9. CYTH4 was overexpressed in the glioma macrophage population in several single-cell RNA sequencing datasets and was most correlated with M2 macrophages. CYTH4 expression was higher in tumor tissues and was correlated with survival and WHO grade. ROC curves suggested CYTH4 overexpression to be a potential glioma biomarker. GSEA results indicated a relationship between CYTH4 and apoptosis, and PPI analysis supported a pyroptosis correlation. KEGG and GO analysis results linked CYTH4 with antigen processing and presentation and neutrophil activities. In summary, the study identified a CYTH4/pyroptosis/M2 macrophage axis. CYTH4 was upregulated in M2 macrophages in glioma and affected pyroptosis. CYTH4 overexpression is a potential biomarker predicting a poor prognosis.

Pan-Cancer Analysis and Validation Reveals that D-Dimer-Related Genes are Prognostic and Downregulate CD8+ T Cells via TGF-Beta Signaling in Gastric Cancer.

Background: Cancer is considered one of the most lethal diseases worldwide. Venous thromboembolism (VTE) is the second leading cause of death in cancer patients. As one of the most reproducible predictors of thromboembolism, the D-dimer level is commonly considered by oncologists. Previous studies have demonstrated that the most correlated genes at the D-dimer level are F3, F5 and FGA. Methods: Using data from TCGA and multiple webtools, including GEPIA2, UALCAN, TIMER2.0, Kaplan-Meier Plotter and CIBERSORTx, we analyzed the tumor mutation burden (TMB), microsatellite instability (MSI) and functions of D-dimer-related genes in cancer. Validation was conducted via quantitative real-time polymerase chain reaction (qRT-PCR) and independent GEO + GTEx cohort. All statistical analyses were performed in R software and GraphPad Prism 9. Results: F3, F5 and FGA were expressed differently in multiple cancer types. TMB, MSI and anti-PD1/PDL1 therapy responses were correlated with D-dimer-related gene expression. D-Dimer-related genes expression affect the survival of cancer patients. F3 and F5 functioned in TGF-beta signaling. F3 and F5 were related to immunity and affected the fraction of CD8+ T cells by upregulating the TGF-beta signaling pathway, forming an F3, F5/TGF-beta signaling/CD8+ T cell axis. Conclusion: F3, F5 and FGA serve as satisfactory GC multibiomarkers and potentially influence the immune microenvironment and survival of cancer patients by influencing TGF-beta signaling.

Role of Canonical Wnt/ß-Catenin Pathway in Regulating Chondrocytic Hypertrophy in Mesenchymal Stem Cell-Based Cartilage Tissue Engineering.

In the past 3 decades, the cartilage repair potential of mesenchymal stromal cells, or mesenchymal stem cells (MSCs), has been widely examined in animal studies. Unfortunately, the phenotype and physical properties of MSC-derived cartilage tissue are not comparable to native hyaline cartilage. In particular, chondrocytic hypertrophy, a phenotype that is not observed in healthy hyaline cartilage, is concomitant with MSC chondrogenesis. Given that hypertrophic chondrocytes potentially undergo apoptosis or convert into osteoblasts, this undesired phenotype needs to be prevented or minimized before MSCs can be used to repair cartilage injuries in the clinic. In this review, we first provide an overview of chondrocytic hypertrophy and briefly summarize current methods for suppressing hypertrophy in MSC-derived cartilage. We then highlight recent progress on modulating the canonical Wnt/ß-catenin pathway for inhibiting hypertrophy. Specially, we discuss the potential crosstalk between Wnt/ß-catenin with other pathways in regulating hypertrophy. Lastly, we explore future perspectives to further understand the role of Wnt/ß-catenin in chondrocytic hypertrophy.

Bioactive peptide apelin rescues acute kidney injury by protecting the function of renal tubular mitochondria.

Mitochondrial dysfunction in proximal tubular epithelial cells is a key event in acute kidney injury (AKI), which is a risk factor for the development of chronic kidney disease (CKD). Apelin is a bioactive peptide that protects against AKI by alleviating inflammation, inhibiting apoptosis, and preventing lipid oxidation, but its role in protecting against mitochondrial damage remains unknown. Herein, we examined the protective effects of apelin on mitochondria in cisplatin-stimulated human renal proximal tubular epithelial cells and evaluated its therapeutic efficacy in cisplatin-induced AKI mice. In vitro, apelin inhibited the cisplatin-induced mitochondrial fission factor (MFF) upregulation and the fusion-promoting protein optic atrophy 1 (OPA1) downregulation. Apelin co-treatment reversed the decreased levels of the deacetylase, Sirt3, and the increased levels of protein acetylation in mitochondria of cisplatin-stimulated cells. Overall, apelin improved the mitochondrial morphology and membrane potential in vitro. In the AKI model, apelin administration significantly attenuated mitochondrial damage, as evidenced by longer mitochondrial profiles and increased ATP levels in the renal cortex. Suppression of MFF expression, and maintenance of Sirt3 and OPA1 expression in apelin-treated AKI mice was also observed. Finally, exogenous administration of apelin normalized the serum level of creatinine and urea nitrogen and the urine levels of NGAL and Kim-1. We also confirmed a regulatory pathway that drives mitochondrial homeostasis including PGC-1α, ERRα and Sirt3. In conclusion, we demonstrated that apelin ameliorates renal functions by protecting tubular mitochondria through Sirt3 upregulation, which is a novel protective mechanism of apelin in AKI. These results suggest that apelin has potential renoprotective effects and may be an effective agent for AKI treatment to significantly retard CKD progression.

Overexpression of PLXDC2 in Stromal Cell-Associated M2 Macrophages Is Related to EMT and the Progression of Gastric Cancer.

The tumor microenvironment (TME) comprises distinct cell types, including stromal types such as fibroblast cells and macrophage cells, which have recently become a critical factor in tumor development and progression. Here, we identified the TME-related gene, plexin domain containing 2 (PLXDC2), in a high-stromal-score population. And we revealed that this gene was related to poor survival and advanced (tumor-node-metastasis) stage in gastric cancer (GC) patients from The Cancer Genome Atlas database. An integrated gene profile and functional analysis of the proportions of tumor-infiltrating immune cells revealed that the expression of the M2 macrophages cell marker CD163 was positively correlated with PLXDC2 expression. In addition, the M2 macrophages gene signature and high PLXDC2 expression were associated with the inflammatory signaling pathway and the epithelial-to-mesenchymal transition (EMT)-related gene signature. Single-cell study of GC identified PLXDC2 was enriched specifically in fibroblasts and monocytes/macrophages populations, which supported its important role in the stroma. Furthermore, according to a tissue microarray immunohistochemistry analysis, the expression of PLXDC2 elevated in human GC stromal specimens compared to tumor tissue specimens. Moreover, PLXDC2 overexpression in the stromal compartment was associated with CD163-positive regulatory M2 macrophages, and its functions were related to the pathogenesis of GC. Multiplexed immunohistochemistry verified PLXDC2's correlation with EMT markers. Our data suggested that PLXDC2 was expressed in stromal cells and that its crosstalk with tumor-associated macrophages could contribute to cancer biology by inducing the EMT process.

Author Correction: Whole-genome and time-course dual RNA-Seq analyses reveal chronic pathogenicity-related gene dynamics in the ginseng rusty root rot pathogen Ilyonectria robusta.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Acute Kidney Injury in Oncology Patients.

With rapid progress in cancer diagnosis and treatment in the last two decades, outcomes in oncological patients have improved significantly. However, the incidence of acute kidney injury (AKI) in this population has also increased significantly. AKI complicates many aspects of patients' care and adversely affects their prognoses; thus, accurately diagnosing the risk factors for AKI ensures appropriate management. AKI may be caused by pre-renal, intrinsic renal, and post-renal reasons, as well as for combined reasons. This review summarizes the potential etiologies of AKI according to the three classifications. For each underlying cause of AKI, the cancer itself and/or cancer treatment may contribute to a patient developing AKI. Therefore, we present disease- and treatment-related factors for each cause category, with special focus on immune checkpoint inhibitors, which are being used increasingly more often. It is important for nephrology services to be knowledgeable to provide the best level of care.

Whole-genome and time-course dual RNA-Seq analyses reveal chronic pathogenicity-related gene dynamics in the ginseng rusty root rot pathogen Ilyonectria robusta.

Ilyonectria robusta causes rusty root rot, the most devastating chronic disease of ginseng. Here, we for the first time report the high-quality genome of the I. robusta strain CD-56. Time-course (36 h, 72 h, and 144 h) dual RNA-Seq analysis of the infection process was performed, and many genes, including candidate effectors, were found to be associated with the progression and success of infection. The gene expression profile of CD-56 showed a trend of initial inhibition and then gradually returned to a profile similar to that of the control. Analyses of the gene expression patterns and functions of pathogenicity-related genes, especially candidate effector genes, indicated that the stress response changed to an adaptive response during the infection process. For ginseng, gene expression patterns were highly related to physiological conditions. Specifically, the results showed that ginseng defenses were activated by CD-56 infection and persisted for at least 144 h thereafter but that the mechanisms invoked were not effective in preventing CD-56 growth. Moreover, CD-56 did not appear to fully suppress plant defenses, even in late stages after infection. Our results provide new insight into the chronic pathogenesis of CD-56 and the comprehensive and complex inducible defense responses of ginseng root to I. robusta infection.

[Effect of light intensity on growth and quality of Asarum heterotropoides var. mandshuricum].

To study the infection rate of leaf spot disease, the drying rate of root and volatile oil content of Asarum heterotropoides var. mandshuricum at the unwrapping stage, blooming stage, the initial fruit stage, fructescence and wither stage during the growth period under the different sunlight intensity of 100% (I), 50% (II), 28% (III), 12% (IV). The volatile oil content was measured according to the method of Chinese Pharmacopoeia and the oil composition was determined by GC-MS. The unwrapping stage, blooming stage and the early fruit stage postponed about 2 days with decrease of the sunlight intensity. The infection rate of leaf was 88.46%, 70.00%, 0.23%, 0.07% under light intensity of I, II, III and IV, respectively, the drying rate was 25.14%, 28.27%, 30.23%, 31.57% under light intensity of I, II, III and IV, respectively, and the volatile oil content was 18.1, 17.6, 16.3, 15.3 mL x kg(-1) under light intensity of I, II, III and IV, respectively. The composition of the oil determined by GC-MS was different between the groups, but the content did not changed significantly with the decrease of the light intensity.