Immune Regulation and Immune Therapy in Melanoma: Review with Emphasis on CD155 Signalling.

Melanoma is commonly diagnosed in a younger population than most other solid malignancies and, in Australia and most of the world, is the leading cause of skin-cancer-related death. Melanoma is a cancer type with high immunogenicity; thus, immunotherapies are used as first-line treatment for advanced melanoma patients. Although immunotherapies are working well, not all the patients are benefitting from them. A lack of a comprehensive understanding of immune regulation in the melanoma tumour microenvironment is a major challenge of patient stratification. Overexpression of CD155 has been reported as a key factor in melanoma immune regulation for the development of therapy resistance. A more thorough understanding of the actions of current immunotherapy strategies, their effects on immune cell subsets, and the roles that CD155 plays are essential for a rational design of novel targets of anti-cancer immunotherapies. In this review, we comprehensively discuss current anti-melanoma immunotherapy strategies and the immune response contribution of different cell lineages, including tumour endothelial cells, myeloid-derived suppressor cells, cytotoxic T cells, cancer-associated fibroblast, and nature killer cells. Finally, we explore the impact of CD155 and its receptors DNAM-1, TIGIT, and CD96 on immune cells, especially in the context of the melanoma tumour microenvironment and anti-cancer immunotherapies.

Tomo-seq identifies NINJ1 as a potential target for anti-inflammatory strategy in thoracic aortic dissection.

BACKGROUND: Thoracic aortic dissection (TAD) is a life-threatening disease caused by an intimal tear in the aorta. The histological characteristics differ significantly between the tear area (TA) and the distant area. Previous studies have emphasized that certain specific genes tend to cluster at the TA. Obtaining a thorough understanding of the precise molecular signatures near the TA will assist in discovering therapeutic strategies for TAD. METHODS: We performed a paired comparison of the pathological patterns in the TA with that in the remote area (RA). We used Tomo-seq, genome-wide transcriptional profiling with spatial resolution, to obtain gene expression signatures spanning from the TA to the RA. Samples from multiple sporadic TAD patients and animal models were used to validate our findings. RESULTS: Pathological examination revealed that the TA of TAD exhibited more pronounced intimal hyperplasia, media degeneration, and inflammatory infiltration compared to the RA. The TA also had more apoptotic cells and CD31+α-SMA+ cells. Tomo-seq revealed four distinct gene expression patterns from the TA to the RA, which were inflammation, collagen catabolism, extracellular matrix remodeling, and cell stress, respectively. The spatial distribution of genes allowed us to identify genes that were potentially relevant with TAD. NINJ1 encoded the protein-mediated cytoplasmic membrane rupture, regulated tissue remodeling, showed high expression levels in the tear area, and co-expressed within the inflammatory pattern. The use of short hairpin RNA to reduce NINJ1 expression in the beta-aminopropionitrile-induced TAD model led to a significant decrease in TAD formation. Additionally, it resulted in reduced infiltration of inflammatory cells and a decrease in the number of CD31+α-SMA+ cells. The NINJ1-neutralizing antibody also demonstrated comparable therapeutic effects and can effectively impede the formation of TAD. CONCLUSIONS: Our study showed that Tomo-seq had the advantage of obtaining spatial expression information of TAD across the TA and the RA. We pointed out that NINJ1 may be involved in inflammation and tissue remodeling, which played an important role in the formation of TAD. NINJ1 may serve as a potential therapeutic target for TAD.

Deciphering mechanisms of cardiomyocytes and non-cardiomyocyte transformation in myocardial remodeling of permanent atrial fibrillation.

INTRODUCTION: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, and it significantly increases the risk of cardiovascular complications and morbidity, even with appropriate treatment. Tissue remodeling has been a significant topic, while its systematic transcriptional signature remains unclear in AF. OBJECTIVES: Our study aims to systematically investigate the molecular characteristics of AF at the cellular-level. METHODS: We conducted single-nuclei RNA-sequencig (snRNA-seq) analysis using nuclei isolated from the left atrial appendage (LAA) of AF patients and sinus rhythm. Pathological staining was performed to validate the key findings of snRNA-seq. RESULTS: A total of 30 cell subtypes were identified among 80, 592 nuclei. Within the LAA of AF, we observed a specific subtype of dedifferentiated cardiomyocytes (CMs) characterized by reduced expression of cardiac contractile proteins (TTN and TRDN) and heightened expression of extracellular-matrix related genes (COL1A2 and FBN1). Transcription factor prediction analysis revealed that gene expression patterns in dedifferentiated CMs were primarily regulated by CEBPG and GISLI. Additionally, we identified a distinct subtype of endothelial progenitor cells (EPCs) demonstrating elevated expression of PROM1 and KDR, a population decreased within the LAA of AF. Epicardial adipocytes disclosed a reduced release of the anti-inflammatory and anti-fibrotic factor PRG4, and an augmented secretion of VEGF signals targeting CMs. Additionally, we noted accumulation of M2-like macrophages and CD8+ T cells with high pro-inflammatory score in LAA of AF. Furthermore, the analysis of intercellular communication revealed specific pathways related to AF, such as inflammation, extracellular matrix, and vascular remodeling signals. CONCLUSIONS: This study has discovered the presence of dedifferentiated CMs, a decrease in endothelial progenitor cells, a shift in the secretion profile of adipocytes, and an amplified inflammatory response in AF. These findings could offer crucial insights for future research on AF and serve as valuable references for investigating novel therapeutic approaches for AF.

Type I Mirizzi syndrome treated by electrohydraulic lithotripsy under the direct view of SpyGlass: A case report.

BACKGROUND: Mirizzi syndrome is an uncommon clinical complication for which the available treatment options mainly include open surgery, laparoscopic surgery, endoscopic retrograde cholangiopancreatography (ERCP), electrohydraulic lithotripsy, and laser lithotripsy. Here, a patient diagnosed with type I Mirizzi syndrome was treated with electrohydraulic lithotripsy under SpyGlass direct visualization, which may provide a reference to explore new treatments for Mirizzi syndrome. CASE SUMMARY: This paper describes a middle-aged female patient with suspected choledocholithiasis who complained for over 1 mo of intermittent abdominal pain, dark yellow urine, jaundice, and was proposed to undergo ERCP lithotomy. Mirizzi syndrome was found during the operation and confirmed by SpyGlass. Electrohydraulic lithotripsy was performed under the direct vision of SpyGlass. After the lithotripsy, the stones were extracted using the stone extraction basket and balloon. After the operation, the patient developed transient hyperamylasemia. Through a series of symptomatic treatments (such as fasting, fluids and anti-inflammation medications), the symptoms of the patient improved. Finally, laparoscopic cholecystectomy or open cholecystectomy was performed after a half-year post-operatively. CONCLUSION: Direct visualization-guided laser or electrohydraulic lithotripsy with SpyGlass is feasible and minimally invasive for type I Mirizzi syndrome without apparent unsafe outcomes.

PILRA is associated with immune cells infiltration in atrial fibrillation based on bioinformatics and experiment validation.

Background and aims: inflammation plays an important role in atrial fibrillation (AF). In this study, we investigated the significance of immune cell infiltration in AF and identified the potential Hub genes involved in the regulation of immune cell infiltration in AF. Methods: we obtained AF datasets from the GEO database and analyzed them for obtaining differentially expressed genes (DEGs) by R software. Then, we performed GO, KEGG, and GSEA enrichment analyses of DEGs. The Hub genes of AF were determined by least absolute shrinkage selection operator (LASSO) regression analysis and weighted gene co-expression network analysis (WGCNA). Their validation was verified by using quantitative polymerase chain reaction (qPCR) in the AF rat model. Finally, we used a single sample GSEA (ssGSEA) to analyze immune cell infiltration and its relationship with hub genes. Results: We obtained 298 DGEs from the heatmap and found that DGEs were closely related to inflammation, immunity, and cytokine interactions by enrichment analyses. We obtained 10 co-expression modules by WGCNA. Among them, the module including CLEC4A, COTL1, EVI2B, FCER1G, GAPT, HCST, NCF2, PILRA, TLR8, and TYROBP had the highest correlation with AF. Four Hub genes (PILRA, NCF2, EVI2B, GAPT) were obtained further by LASSO analysis. The results suggested that the expression level of PILRA was significantly elevated in the rats with AF by qPCR, compared to the rats without AF. The results revealed that the infiltration of neutrophils, macrophages, monocytes, mast cells, immature B cells, myeloid-derived suppressor cell (MDSC), dendritic cell, and T cells and their partial subpopulations were closely related to AF by ssGSEA analysis, and PILRA was positively correlated with immature B cell, monocyte, macrophage, mast cell, dendritic cell, and T cells and their partial subpopulations by Spearman correlation analysis. Conclusions: PILRA was closely related to multiple types of immune cell infiltration, which may be associated with AF. PILRA may be a novel target of intervention for AF.

Determination of vitamin K in infant formulas by liquid chromatography-online electrochemical reduction based on porous Pt/Ti electrode-fluorescence detection.

A highly sensitive and selective HPLC method for the determination of vitamin K vitamers including phylloquinone (PK) and menaquinones (MK-4) in infant formulas is described. The K vitamers were quantified with a fluorescence detector after online post-column electrochemical reduction occurring in a laboratory-made electrochemical reactor (ECR) equipped with platinum plated porous titanium (Pt/Ti) electrodes. The morphology of the electrode showed that the grain size of Pt was homogeneous and well plated on the porous Ti substrate, resulting in largely improved electrochemical reduction efficiency due to the large specific surface area. In addition, the operation parameters such as mobile phase/supporting electrolyte and working potential were optimized. The detection limits of PK and MK-4 were 0.81 and 0.78 ng g-1. Infant formula varying in stages were detected, showing PK ranged from 26.4 to 71.2 µg/100 g, while MK-4 was not detected.

Hydrothermal synthesis and formation mechanism of controllable magnesium silicate nanotubes derived from coal fly ash.

A novel controllable magnesium silicate nanotube (MSN) material derived from coal fly ash was successfully synthesized via a hydrothermal process for the first time, and the reaction conditions and mechanism of synthesizing MSN materials from magnesium oxide and sodium silicate extracted from the fly ash were studied. The optimal preparation conditions are temperature = 220 °C, pH = 13.5, and Mg: Si molar ratio = 3:2, and the tubular structure gradually appeared and showed controllable and regular growth with the increase of synthesis time. The mechanism revealed that with the gradual dissolution of brucite into the sodium silicate solution, the reaction product begins to crystallize and transform from an initial sheet-like structure to a tubular structure, and finally becomes a uniformly arranged nanotube. The formation process of MSN follows Pauling's fourth rule, Si-O tetrahedral coordination and Mg-OH octahedral coordination is further condensed to form a two-layer structure by the action of active oxygen, then the sheet is rolled into a tube under its structural stress. The growth of both outer tubular diameter and inner tubular diameter has good linear law and controllable, and the growth rate are 0.289 nm h-1and 0.071 nm h-1, respectively.

Positive Predictive Value of ICD-10-CM Codes for Myocarditis in Claims Data: A Multi-Institutional Study in Taiwan.

Purpose: The validity of the diagnosis codes to identify myocarditis cases in healthcare databases research remains unclear, and this study aimed to determine the coding accuracy of myocarditis in Taiwan. Methods: We conducted a cross-sectional study based on Taiwan's largest multi-institutional healthcare system to identify inpatients newly diagnosed with ICD-10-CM myocarditis codes at discharge between January 1st, 2017 and March 31st, 2022. We ascertained the myocarditis diagnosis by a gold standard biopsy or by review of electronic medical records, and the positive predictive values (PPV) with 95% confidence intervals (CI) of the ICD-10-CM codes for myocarditis were determined. Results: We included a total of 498 inpatients (mean age: 33.8 years old; female: 38.8%) with new myocarditis diagnosis at discharge. Codes I409 (30.1%) and I514 (45.4%) constituted the majority of myocarditis diagnostic codes in any coding position, and the overall PPV of the myocarditis codes was 73.5% (95% CI: 69.6-77.4%). However, the highest PPV (96.6%) for myocarditis diagnosis was noted with code I409 as the primary diagnosis. We found 132 inpatients (26.5%) who were false-positive myocarditis cases, identified by the ICD-10-CM codes, and potential reasons for misclassification included other inflammation diseases (n=35, 26.5%), pre-existing heart failure (n= 25, 18.9%) and acute myocardial infarction (n=16, 12.1%). Conclusion: The PPV of ICD-10-CM codes for myocarditis in Taiwan was acceptable, but some other inflammation diseases and pre-existing heart diseases may be falsely coded as myocarditis. Our results may serve future secondary database studies as a fundamental reference on the validity of myocarditis diagnosis codes.

Differentiation of umbilical cord mesenchymal stem cells into hepatocytes with CYP450 metabolic enzyme activity induced by a liver injury microenvironment.

The aim of this study was to observe the effect of a simulated liver tissue injury microenvironment on the directed differentiation of umbilical cord mesenchymal stem cells into hepatocytes with CYP450 metabolic activity in vitro, and to explore the mechanisms underlying this directed differentiation. Normal and damaged liver tissue homogenate supernatants (LHS and CCl4-LHS, respectively) were used as induction fluids. After induction for different durations, Western blot and RT-PCR were used to measure the protein and gene expression of the hepatocellular proteins AFP, CK18, ALB, and the CYP450 family. Simultaneously, the metabolic activity of CYP450 in hepatocytes was determined. Compared with the LHS and CCl4-LHS controls, the LHS and CCl4-LHS induction groups showed a significantly elevated protein and gene expression of AFP, CK18, ALB, CYP1A1/2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 (P < 0.05). The metabolic activity of CYP450 in hepatocytes was increased (P < 0.05). In addition, compared with the LHS group, the CCl4-LHS group induced cell differentiation more rapidly and with a higher efficiency. The results suggested that a liver injury microenvironment is conducive for the directed differentiation of umbilical cord mesenchymal stem cells into hepatocytes with metabolic enzyme activity.

An epithelial-to-mesenchymal transition induced extracellular vesicle prognostic signature in non-small cell lung cancer.

Despite significant therapeutic advances, lung cancer remains the leading cause of cancer-related death worldwide1. Non-small cell lung cancer (NSCLC) patients have a very poor overall five-year survival rate of only 10-20%. Currently, TNM staging is the gold standard for predicting overall survival and selecting optimal initial treatment options for NSCLC patients, including those with curable stages of disease. However, many patients with locoregionally-confined NSCLC relapse and die despite curative-intent interventions, indicating a need for intensified, individualised therapies. Epithelial-to-mesenchymal transition (EMT), the phenotypic depolarisation of epithelial cells to elongated, mesenchymal cells, is associated with metastatic and treatment-refractive cancer. We demonstrate here that EMT-induced protein changes in small extracellular vesicles are detectable in NSCLC patients and have prognostic significance. Overall, this work describes a novel prognostic biomarker signature that identifies potentially-curable NSCLC patients at risk of developing metastatic NSCLC, thereby enabling implementation of personalised treatment decisions.

Autophagy Is Essential for Neural Stem Cell Proliferation Promoted by Hypoxia.

Hypoxia as a microenvironment or niche stimulates proliferation of neural stem cells (NSCs). However, the underlying mechanisms remain elusive. Autophagy is a protective mechanism by which recycled cellular components and energy are rapidly supplied to the cell under stress. Whether autophagy mediates the proliferation of NSCs under hypoxia and how hypoxia induces autophagy remain unclear. Here, we report that hypoxia facilitates embryonic NSC proliferation through HIF-1/mTORC1 signaling pathway-mediated autophagy. Initially, we found that hypoxia greatly induced autophagy in NSCs, while inhibition of autophagy severely impeded the proliferation of NSCs in hypoxia conditions. Next, we demonstrated that the hypoxia core regulator HIF-1 was necessary and sufficient for autophagy induction in NSCs. Considering that mTORC1 is a key switch that suppresses autophagy, we subsequently analyzed the effect of HIF-1 on mTORC1 activity. Our results showed that the mTORC1 activity was negatively regulated by HIF-1. Finally, we provided evidence that HIF-1 regulated mTORC1 activity via its downstream target gene BNIP3. The increased expression of BNIP3 under hypoxia enhanced autophagy activity and proliferation of NSCs, which was mediated by repressing the activity of mTORC1. We further illustrated that BNIP3 can interact with Rheb, a canonical activator of mTORC1. Thus, we suppose that the interaction of BNIP3 with Rheb reduces the regulation of Rheb toward mTORC1 activity, which relieves the suppression of mTORC1 on autophagy, thereby promoting the rapid proliferation of NSCs. Altogether, this study identified a new HIF-1/BNIP3-Rheb/mTORC1 signaling axis, which regulates the NSC proliferation under hypoxia through induction of autophagy.

The protective pattern of chitosan-based active coating on texture stabilization of refrigerated carp fillets from the perspective of proteolysis.

Herein, the protective pattern of chitosan coating enriched with green tea extract on texture stabilization of refrigerated grass carp fillets was explored. In general, higher shear force and lower endogenous enzyme activities were observed in coated fillets, with the max. level of cathepsins and calpain decreasing by 30.2 âˆ¼ 39.6 % when compared to the control during storage. Meanwhile, the coating reduced protein composition changes and accumulation of protein degradation products. According to label-free proteomic analysis, the proteome closer to fresh sample was observed in coated fillets than that of the control, as supported by PCA and hierarchical cluster analysis. Meanwhile, 33 differential proteins involved in tissue structure, protein phosphorylation and protein turnover were further screened out, and most DAPs showed up-regulation in coated fillets compared to the control on day 12. Presumably, the coating modulated endogenous enzyme-induced myofibrillar protein degradation and protein phosphorylation level, thereby stabilizing the texture properties of refrigerated fillets.

Status quo of Extracellular Vesicle isolation and detection methods for clinical utility.

Extracellular vesicles (EVs) are nano-sized particles that hold tremendous potential in the clinical space, as their biomolecular profiles hold a key to non-invasive liquid biopsy for cancer diagnosis and prognosis. EVs are present in most bodily fluids, hence are easily obtainable from patients, advantageous to that of traditional, invasive tissue biopsies and imaging techniques. However, there are certain constraints that hinder clinical use of EVs. The translation of EV biomarkers from "bench-to-bedside" is encumbered by the methods of EV isolation and subsequent biomarker detection currently implemented in laboratories. Although current isolation and detection methods are effective, they lack practicality, with their requirement for high bodily fluid volumes, low equipment availability, slow turnaround times and high costs. The high demand for techniques that overcome these limitations has resulted in significant advancements in nanotechnological devices. These devices are designed to integrate EV isolation and biomarker detection into a one-step method of direct EV detection from bodily fluids. This provides promise for the acceleration of EVs into current clinical standards. This review highlights the importance of EVs as cancer biomarkers, the methodological obstacles currently faced in clinical studies and how novel nanodevices could advance clinical translation.

Spatial transcriptomic analysis of the mouse brain following chronic social defeat stress.

Depression is a highly prevalent and disabling mental disorder, involving numerous genetic changes that are associated with abnormal functions in multiple regions of the brain. However, there is little transcriptomic-wide characterization of chronic social defeat stress (CSDS) to comprehensively compare the transcriptional changes in multiple brain regions. Spatial transcriptomics (ST) was used to reveal the spatial difference of gene expression in the control, resilient (RES) and susceptible (SUS) mouse brains, and annotated eight anatomical brain regions and six cell types. The gene expression profiles uncovered that CSDS leads to gene synchrony changes in different brain regions. Then it was identified that inhibitory neurons and synaptic functions in multiple regions were primarily affected by CSDS. The brain regions Hippocampus (HIP), Isocortex, and Amygdala (AMY) present more pronounced transcriptional changes in genes associated with depressive psychiatric disorders than other regions. Signalling communication between these three brain regions may play a critical role in susceptibility to CSDS. Taken together, this study provides important new insights into CSDS susceptibility at the ST level, which offers a new approach for understanding and treating depression.

BNIP3 phosphorylation by JNK1/2 promotes mitophagy via enhancing its stability under hypoxia.

Mitophagy is an important metabolic mechanism that modulates mitochondrial quality and quantity by selectively removing damaged or unwanted mitochondria. BNIP3 (BCL2/adenovirus e1B 19 kDa protein interacting protein 3), a mitochondrial outer membrane protein, is a mitophagy receptor that mediates mitophagy under various stresses, particularly hypoxia, since BNIP3 is a hypoxia-responsive protein. However, the underlying mechanisms that regulate BNIP3 and thus mediate mitophagy under hypoxic conditions remain elusive. Here, we demonstrate that in hypoxia JNK1/2 (c-Jun N-terminal kinase 1/2) phosphorylates BNIP3 at Ser 60/Thr 66, which hampers proteasomal degradation of BNIP3 and drives mitophagy by facilitating the direct binding of BNIP3 to LC3 (microtubule-associated protein 1 light chain 3), while PP1/2A (protein phosphatase 1/2A) represses mitophagy by dephosphorylating BNIP3 and triggering its proteasomal degradation. These findings reveal the intrinsic mechanisms cells use to regulate mitophagy via the JNK1/2-BNIP3 pathway in response to hypoxia. Thus, the JNK1/2-BNIP3 signaling pathway strongly links mitophagy to hypoxia and may be a promising therapeutic target for hypoxia-related diseases.

Benefits of an online multimodal nursing program among patients with peripherally inserted central catheter-related thrombosis.

Background: Asymptomatic peripherally inserted central catheter-related thrombosis (PICC-RT) is one of the most common and dangerous complications caused by peripherally inserted central catheter (PICC) insertion. A variety of factors might lead to huge psychological pressures on patients and markedly affect their quality of life. The aim of this study was to evaluate the benefits of an online multimodal nursing program on the quality of life and psychological resilience of asymptomatic PICC-RT patients with ovarian cancer. Methods: This was a prospective cohort study on patients with asymptomatic PICC-RT. Patients in the control group received routine nursing care, while patients in the intervention group obtained extra assistance through an online multimodal nursing program. Individual guidance, psychological support, and real-time consultation were provided to patients in the intervention group. All participants were followed for 3 months. The health-related quality of life and psychological resilience of patients were evaluated by using the 36-item Short Form Health Survey (SF-36) and Connor-Davidson Resilience Scale (CD-RISC), respectively. Results: Compared to baseline, most of the items in the SF-36 scores were significantly increased in both intervention and control groups after 3 months (all p < 0.05), except for the role emotional domain (p = 0.085 in control group). However, the SF-36 scores of the intervention group were significantly higher than those of the control group in All health domains, including physical functioning (p = 0.001), role physical (p = 0.004), bodily pain (p = 0.003), general health (p < 0.001), vitality (p < 0.001), social functioning (p < 0.001), role emotional (p = 0.002), mental health (p < 0.001) and health transition (p < 0.001). For CD-RISC scores, the mean value of the control group was 42.03 ± 4.42 at baseline and increased to 50.36 ± 4.70 after 3 months (p < 0.001), while the intervention group was 40.00 ± 6.61 at baseline and increased to 65.12 ± 5.21 after 3 months (p < 0.001). Moreover, the CD-RISC score in the intervention group was significantly higher than that in the control group after 3 months (p < 0.001). Conclusion: The application of an online multimodal nursing program could significantly improve the health-related quality of life and psychological resilience of asymptomatic PICC-RT patients. These findings provide evidence to support the necessity of an online multimodal nursing program in routine long-term follow-up, especially in the era of COVID-19.

Hybrid aluminum nitride and silicon devices for integrated photonics.

Aluminum nitride has advantages ranging from a large transparency window to its high thermal and chemical resistance, piezoelectric effect, electro-optic property, and compatibility with the complementary metal-oxide-semiconductor fabrication process. We propose a hybrid aluminum nitride and silicon platform for integrated photonics. Hybrid aluminum nitride-silicon basic photonic devices, including the multimode interferometer, Mach-Zehnder interferometer, and micro-ring resonator, are designed and fabricated. The measured extinction ratio is > 22 dB and the insertion loss is < 1 dB in a wavelength range of 40 nm for the Mach-Zehnder interferometer. The extinction ratio and intrinsic quality factor of the fabricated micro-ring resonator are > 16 dB and 43,300, respectively. The demonstrated hybrid integrated photonic platform is promising for realizing ultralow-power optical switching and electro-optic modulation based on the piezoelectric and electro-optic effects of aluminum nitride thin films.

Two new cryptic species within Periphyllus koelreuteriae (Hemiptera: Aphididae) feeding on Koelreuteria (Sapindaceae) in China.

Based on integrative taxonomic practices by incorporating morphological, genetic, and ecological data, two new aphid species, Periphyllus blackmani Li Huang sp. nov. and Periphyllus guangxuei Li Huang sp. nov., are proposed from the known species P. koelreuteriae. Apterous and alate viviparous females of the new species are described and differences with their most similar species P. koelreuteriae are presented. These aphids of P. koelreuteriae species complex feed exclusively on Koelreuteria (Sapindaceae), a native tree group and commonly cultivated as ornamental plants in China. A key to the Chinese species of P. koelreuteriae species complex is provided.

Autophagy regulated by the HIF/REDD1/mTORC1 signaling is progressively increased during erythroid differentiation under hypoxia.

For hematopoietic stem and progenitor cells (HSPCs), hypoxia is a specific microenvironment known as the hypoxic niche. How hypoxia regulates erythroid differentiation of HSPCs remains unclear. In this study, we show that hypoxia evidently accelerates erythroid differentiation, and autophagy plays a pivotal role in this process. We further determine that mTORC1 signaling is suppressed by hypoxia to relieve its inhibition of autophagy, and with the process of erythroid differentiation, mTORC1 activity gradually decreases and autophagy activity increases accordingly. Moreover, we provide evidence that the HIF-1 target gene REDD1 is upregulated to suppress mTORC1 signaling and enhance autophagy, thereby promoting erythroid differentiation under hypoxia. Together, our study identifies that the enhanced autophagy by hypoxia favors erythroid maturation and elucidates a new regulatory pattern whereby autophagy is progressively increased during erythroid differentiation, which is driven by the HIF-1/REDD1/mTORC1 signaling in a hypoxic niche.

Comparative analysis of tangential flow filtration and ultracentrifugation, both combined with subsequent size exclusion chromatography, for the isolation of small extracellular vesicles.

Small extracellular vesicles (sEVs) provide major promise for advances in cancer diagnostics, prognostics, and therapeutics, ascribed to their distinctive cargo reflective of pathophysiological status, active involvement in intercellular communication, as well as their ubiquity and stability in bodily fluids. As a result, the field of sEV research has expanded exponentially. Nevertheless, there is a lack of standardisation in methods for sEV isolation from cells grown in serum-containing media. The majority of researchers use serum-containing media for sEV harvest and employ ultracentrifugation as the primary isolation method. Ultracentrifugation is inefficient as it is devoid of the capacity to isolate high sEV yields without contamination of non-sEV materials or disruption of sEV integrity. We comprehensively evaluated a protocol using tangential flow filtration and size exclusion chromatography to isolate sEVs from a variety of human and murine cancer cell lines, including HeLa, MDA-MB-231, EO771 and B16F10. We directly compared the performance of traditional ultracentrifugation and tangential flow filtration methods, that had undergone further purification by size exclusion chromatography, in their capacity to separate sEVs, and rigorously characterised sEV properties using multiple quantification devices, protein analyses and both image and nano-flow cytometry. Ultracentrifugation and tangential flow filtration both enrich consistent sEV populations, with similar size distributions of particles ranging up to 200 nm. However, tangential flow filtration exceeds ultracentrifugation in isolating significantly higher yields of sEVs, making it more suitable for large-scale research applications. Our results demonstrate that tangential flow filtration is a reliable and robust sEV isolation approach that surpasses ultracentrifugation in yield, reproducibility, time, costs and scalability. These advantages allow for implementation in comprehensive research applications and downstream investigations.