Composition-dependent ordering transformations in Pt-Fe nanoalloys.

SignificanceDynamically understanding the microscopic processes governing ordering transformations has rarely been attained. The situation becomes even more challenging for nanoscale alloys, where the significantly increased surface-area-to-volume ratio not only opens up a variety of additional freedoms to initiate an ordering transformation but also allows for kinetic interplay between the surface and bulk due to their close proximity. We provide direct evidence of the microscopic processes controlling the ordering transformation through the surface-bulk interplay in Pt-Fe nanoalloys and new features rendered by variations in alloy composition and chemical stimuli. These results provide a mechanistic detail of ordering transformation phenomena which are widely relevant to nanoalloys as chemical ordering occurs in most multicomponent materials under suitable environmental bias.

Different metazoan parasites, different transcriptomic responses, with new insights on parasitic castration by digenetic trematodes in the schistosome vector snail Biomphalaria glabrata.

BACKGROUND: Gastropods of the genus Biomphalaria (Family Planorbidae) are exploited as vectors by Schistosoma mansoni, the most common causative agent of human intestinal schistosomiasis. Using improved genomic resources, overviews of how Biomphalaria responds to S. mansoni and other metazoan parasites can provide unique insights into the reproductive, immune, and other systems of invertebrate hosts, and their responses to parasite challenges. RESULTS: Using Illumina-based RNA-Seq, we compared the responses of iM line B. glabrata at 2, 8, and 40 days post-infection (dpi) to single infections with S. mansoni, Echinostoma paraensei (both digenetic trematodes) or Daubaylia potomaca (a nematode parasite of planorbid snails). Responses were compared to unexposed time-matched control snails. We observed: (1) each parasite provoked a distinctive response with a predominance of down-regulated snail genes at all time points following exposure to either trematode, and of up-regulated genes at 8 and especially 40dpi following nematode exposure; (2) At 2 and 8dpi with either trematode, several snail genes associated with gametogenesis (particularly spermatogenesis) were down-regulated. Regarding the phenomenon of trematode-mediated parasitic castration in molluscs, we define for the first time a complement of host genes that are targeted, as early as 2dpi when trematode larvae are still small; (3) Differential gene expression of snails with trematode infection at 40dpi, when snails were shedding cercariae, was unexpectedly modest and revealed down-regulation of genes involved in the production of egg mass proteins and peptide processing; and (4) surprisingly, D. potomaca provoked up-regulation at 40dpi of many of the reproduction-related snail genes noted to be down-regulated at 2 and 8dpi following trematode infection. Happening at a time when B. glabrata began to succumb to D. potomaca, we hypothesize this response represents an unexpected form of fecundity compensation. We also document expression patterns for other Biomphalaria gene families, including fibrinogen domain-containing proteins (FReDs), C-type lectins, G-protein coupled receptors, biomphalysins, and protease and protease inhibitors. CONCLUSIONS: Our study is relevant in identifying several genes involved in reproduction that are targeted by parasites in the vector snail B. glabrata and that might be amenable to manipulation to minimize their ability to serve as vectors of schistosomes.

Deficiency of Kif15 gene inhibits tumor growth due to host CD8+T lymphocytes increase.

Kif15, also name kinesin-12, is a microtubule (MT) associate protein, which functions as a regulator of MT-dependent transport or spindle organization. Previous studies reported Kif15 increases in many tumors, however the effect of host Kif15 gene lack on tumor growth is not investigated. In this study, CRISPR/Cas9 mediated Kif15 gene knockout (Kif15-/-) mice were established and HE (Hematoxylin-Eosin) assay revealed no significant differences of morphology in most adult tissues (heart, liver, lung, kidney, and brain) except a retarded development of spleen in adult Kif15-/- mice. RNA sequence analysis of adult spleen tissues of Kif15-/- and Kif15+/+ mice was performed, and the results revealed that a total of 438 mRNAs were significantly differentially expressed in Kif15 knockout spleen, showing the top biological process was immune system process. FCM (Flow Cytometry) assay showed the percentage of CD8+ T lymphocytes notably increased in spleens of 9 w and 12 w old Kif15-/- mice. The CD8+ T lymphocytes are cytotoxic effector cells fighting against tumor. We thus detected the tumor growth in Kif15-/- mice using the melanoma cells inoculated subcutaneously. The tumor size significantly reduced in Kif15-/- mice. We finally detected whether Kif15 dysfunction affects the phagocytic function of macrophages on tumor cells, and the result showed Kif15 inhibitor treated macrophages significantly promoted the phagocytosis in vitro. In summary, this study revealed that the tumor-bearing mice of Kif15 gene deficiency notably inhibited tumor growth due to innate immune activation, which was the first report of the relation of Kif15 on the immunoreactivity.

Oxidative Stress-Involved Mitophagy of Retinal Pigment Epithelium and Retinal Degenerative Diseases.

The retinal pigment epithelium (RPE) is a highly specialized and polarized epithelial cell layer that plays an important role in sustaining the structural and functional integrity of photoreceptors. However, the death of RPE is a common pathological feature in various retinal diseases, especially in age-related macular degeneration (AMD) and diabetic retinopathy (DR). Mitophagy, as a programmed self-degradation of dysfunctional mitochondria, is crucial for maintaining cellular homeostasis and cell survival under stress. RPE contains a high density of mitochondria necessary for it to meet energy demands, so severe stimuli can cause mitochondrial dysfunction and the excess generation of intracellular reactive oxygen species (ROS), which can further trigger oxidative stress-involved mitophagy. In this review, we summarize the classical pathways of oxidative stress-involved mitophagy in RPE and investigate its role in the progression of retinal diseases, aiming to provide a new therapeutic strategy for treating retinal degenerative diseases. The role of mitophagy in AMD and DR. In AMD, excessive ROS production promotes mitophagy in the RPE by activating the Nrf2/p62 pathway, while in DR, ROS may suppress mitophagy by the FOXO3-PINK1/parkin signaling pathway or the TXNIP-mitochondria-lysosome-mediated mitophagy.

Kif15 deficiency contributes to depression-like behavior in mice.

Neuropsychiatric disorders have a high incidence worldwide. Kinesins, a family of microtubule-based molecular motor proteins, play essential roles in intracellular and axonal transport. Variants of kinesins have been found to be related to many diseases, including neurodevelopmental/neurodegenerative disorders. Kinesin-12 (also known as Kif15) was previously found to affect the frequency of both directional microtubule transports. However, whether Kif15 deficiency impacts mood in mice is yet to be investigated. In this study, we used the CRISPR/Cas9 method to obtain Kif15-/- mice. In behavioral tests, Kif15-/- female mice exhibited prominent depressive characteristics. Further studies showed that the expression of BDNF was significantly decreased in the frontal cortex, corpus callosum, and hippocampus of Kif15-/- mice, along with the upregulation of Interleukin-6 and Interleukin-1ß in the corpus callosum. In addition, the expression patterns of AnkG were notably changed in the developing brain of Kif15-/- mice. Based on our previous studies, we suggested that this appearance of altered AnkG was due to the maladjustment of the microtubule patterns induced by Kif15 deficiency. The distribution of PSD95 in neurites notably decreased after cultured neurons treated with the Kif15 inhibitor, but total PSD95 protein level was not impacted, which revealed that Kif15 may contribute to PSD95 transportation. This study suggested that Kif15 may serve as a potential target for future depression studies.

Microglia Modulate Neurodevelopment in Autism Spectrum Disorder and Schizophrenia.

Neurodevelopmental disorders (NDDs) include various neurological disorders with high genetic heterogeneity, characterized by delayed or impaired cognition, communication, adaptive behavior, and psychomotor skills. These disorders result in significant morbidity for children, thus burdening families and healthcare/educational systems. However, there is a lack of early diagnosis and effective therapies. Therefore, a more connected approach is required to explore these disorders. Microglia, the primary phagocytic cells within the central nervous system, are crucial in regulating neuronal viability, influencing synaptic dynamics, and determining neurodevelopmental outcomes. Although the neurobiological basis of autism spectrum disorder (ASD) and schizophrenia (SZ) has attracted attention in recent decades, the role of microglia in ASD and SZ remains unclear and requires further discussion. In this review, the important and frequently multifaceted roles that microglia play during neurodevelopment are meticulously emphasized and potential microglial mechanisms that might be involved in conditions such as ASD and SZ are postulated. It is of utmost importance to acquire a comprehensive understanding of the complexities of the interplay between microglia and neurons to design effective, targeted therapeutic strategies to mitigate the effects of NDDs.

Interleukin 35: protective role and mechanism in type 1 diabetes.

Interleukin 35 (IL-35), a cytokine secreted by regulatory T (Treg) cells from the differentiation of conventional CD4+ T cells, is a member of the IL-12 family. The IL-12 family of cytokines exhibits an anti-inflammatory property. IL-35 has recently been shown to influence the immune modulation in various diseases, including inflammatory bowel disease, Graves' disease, rheumatoid arthritis, colitis, psoriasis, and type 1 diabetes (T1D). T1D is an immune-related disease caused by destruction of pancreatic ß cells, characterized by an absolute lack of insulin. Recently, studies have suggested that protective effects of IL-35 work by improving blood glucose levels and preventing an attack of inflammatory factors on the islets. The protective mechanism may be closely related to the anti-inflammatory properties of IL-35, which include regulating macrophage phenotype, suppressing T cell proliferation, decreasing the differentiation of Th17 cells, increasing the Treg cell population, and inducing IL-35-producing regulatory T cells (iTr35). Here, we review the protective effects and mechanisms of action of IL-35 in T1D.

Prognostic significance of prognostic nutritional index and systemic immune-inflammation index in patients after curative breast cancer resection: a retrospective cohort study.

BACKGROUND: Nutritional status and inflammation are closely associated with poor outcome in malignant tumors. However, the prognostic impact of postoperative in these variables on breast cancer (BC) remains inconclusive. We aimed to determine whether prognostic nutritional index (PNI), systemic immune-inflammation index (SII), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) affect two long-term outcomes among patients after curative resection of BC. METHODS: We retrospectively reviewed 508 patients with BC treated with curative surgery between February 5, 2013 and May 26, 2020. All patients were divided into 3 groups based on tertiles (T1-T3) of PNI, SII, NLR, and PLR. The effects of four indexes on disease-free survival (DFS) and overall survival (OS) have been evaluated using Cox proportional hazards models and Kaplan-Meier method. RESULTS: Compared with PNI-lowest cases, patients with highest PNI showed significantly longer DFS (multivariate adjusted hazard ratio [HR] = 0.37, 95% confident interval [CI] 0.19-0.70, P for trend = 0.002), whereas higher PLR seemed to be marginally associated with poorer DFS (P for trend = 0.086 and 0.074, respectively). Subgroup analyses indicate the potential modification effects of family history of BC and radiotherapy on the prognosis value of PNI to DFS in BC patients (P for interaction = 0.004 and 0.025, respectively). In addition, the levels of three inflammatory indices, namely SII, NLR, and PLR might be positively related with increased age at diagnosis (all P for trend < 0.001). CONCLUSIONS: A high PNI was associated with better DFS, supporting its roles as prognostic parameters for patients with BC. The nutritional status and systemic immune may exert great effects on patient prognosis. Further studies are warrant to explore the prognosis value of PLR.

Involvement of the fatty acid-binding protein in the growth of Schistosoma japonicum schistosomula.

This study aimed to explore the effect and mechanism underlying the role of the Schistosoma japonicum antigen of fatty acid-binding protein (SjFABP) on the growth of the schistosomula. SjFABP levels were evaluated by quantitative real-time polymerase chain reaction of samples of mice infected with S. japonicum; SjFABP was expressed and its levels gradually increased during all stages of S. japonicum schistosomula, including on 3, 10, 14, and 21 days of the growth process. Immunohistochemistry results demonstrated that SjFABP was distributed in the parenchyma, especially in the digestive tract of the S. japonicum schistosomula. RNA interference resulted in more than 60% knockdown of SjFABP leading to a reduction in length, volume, width, and area of the schistosomula as compared to control samples, as determined by light microscopy. Terminal deoxynucleotidyl transferase dUTP nick-end labeling detection further suggested that SjFABP knockdown resulted in increased apoptosis of schistosomes. Taken together, these results suggest that SjFABP may be related to the growth and survival of S. japonicum schistosomula, thereby representing a potential target for the treatment of schistosomiasis.

Umbilical cord-derived mesenchymal stromal/stem cells expressing IL-24 induce apoptosis in gliomas.

Although much progress has been made in the treatment of gliomas, the prognosis for patients with gliomas is still very poor. Stem cell-based therapies may be promising options for glioma treatment. Recently, many studies have reported that umbilical cord-derived mesenchymal stromal/stem cells (UC-MSCs) are ideal gene vehicles for tumor gene therapy. Interleukin 24 (IL-24) is a pleiotropic immunoregulatory cytokine that has an apoptotic effect on many kinds of tumor cells and can inhibit the growth of tumors specifically without damaging normal cells. In this study, we investigated UC-MSCs as a vehicle for the targeted delivery of IL-24 to tumor sites. UC-MSCs were transduced with lentiviral vectors carrying green fluorescent protein (GFP) or IL-24 complementary DNA. The results indicated that UC-MSCs could selectively migrate to glioma cells in vitro and in vivo. Injection of IL-24-UC-MSCs significantly suppressed tumor growth of glioma xenografts. The restrictive efficacy of IL-24-UC-MSCs was associated with the inhibition of proliferation as well as the induction of apoptosis in tumor cells. These findings indicate that UC-MSC-based IL-24 gene therapy may be able to suppress the growth of glioma xenografts, thereby suggesting possible future therapeutic use in the treatment of gliomas.

Genome-wide discovery, and computational and transcriptional characterization of an AIG gene family in the freshwater snail Biomphalaria glabrata, a vector for Schistosoma mansoni.

BACKGROUND: The AIG (avrRpt2-induced gene) family of GTPases, characterized by the presence of a distinctive AIG1 domain, is mysterious in having a peculiar phylogenetic distribution, a predilection for undergoing expansion and loss, and an uncertain functional role, especially in invertebrates. AIGs are frequently represented as GIMAPs (GTPase of the immunity associated protein family), characterized by presence of the AIG1 domain along with coiled-coil domains. Here we provide an overview of the remarkably expanded AIG repertoire of the freshwater gastropod Biomphalaria glabrata, compare it with AIGs in other organisms, and detail patterns of expression in B. glabrata susceptible or resistant to infection with Schistosoma mansoni, responsible for the neglected tropical disease of intestinal schistosomiasis. RESULTS: We define the 7 conserved motifs that comprise the AIG1 domain in B. glabrata and detail its association with at least 7 other domains, indicative of functional versatility of B. glabrata AIGs. AIG genes were usually found in tandem arrays in the B. glabrata genome, suggestive of an origin by segmental gene duplication. We found 91 genes with complete AIG1 domains, including 64 GIMAPs and 27 AIG genes without coiled-coils, more than known for any other organism except Danio (with > 100). We defined expression patterns of AIG genes in 12 different B. glabrata organs and characterized whole-body AIG responses to microbial PAMPs, and of schistosome-resistant or -susceptible strains of B. glabrata to S. mansoni exposure. Biomphalaria glabrata AIG genes clustered with expansions of AIG genes from other heterobranch gastropods yet showed unique lineage-specific subclusters. Other gastropods and bivalves had separate but also diverse expansions of AIG genes, whereas cephalopods seem to lack AIG genes. CONCLUSIONS: The AIG genes of B. glabrata exhibit expansion in both numbers and potential functions, differ markedly in expression between strains varying in susceptibility to schistosomes, and are responsive to immune challenge. These features provide strong impetus to further explore the functional role of AIG genes in the defense responses of B. glabrata, including to suppress or support the development of medically relevant S. mansoni parasites.

mTOR may interact with PARP-1 to regulate visible light-induced parthanatos in photoreceptors.

BACKGROUND: Excessive light exposure is a detrimental environmental factor that plays a critical role in the pathogenesis of retinal degeneration. However, the mechanism of light-induced death of retina/photoreceptor cells remains unclear. The mammalian/mechanistic target of rapamycin (mTOR) and Poly (ADP-ribose) polymerase-1 (PARP-1) have become the primary targets for treating many neurodegenerative disorders. The aim of this study was to elucidate the mechanisms underlying light-induced photoreceptor cell death and whether the neuroprotective effects of mTOR and PARP-1 inhibition against death are mediated through apoptosis-inducing factor (AIF). METHODS: Propidium iodide (PI)/Hoechst staining, lentiviral-mediated short hairpin RNA (shRNA), Western blot analysis, cellular fraction separation, plasmid transient transfection, laser confocal microscopy, a mice model, electroretinography (ERG), and hematoxylin-eosin (H & E) staining were employed to explore the mechanisms by which rapamycin/3-Aminobenzamide (3AB) exert neuroprotective effects of mTOR/PARP-1 inhibition in light-injured retinas. RESULTS: A parthanatos-like death mechanism was evaluated in light-injured 661 W cells that are an immortalized photoreceptor-like cell line that exhibit cellular and biochemical feature characteristics of cone photoreceptor cells. The death process featured over-activation of PARP-1 and AIF nuclear translocation. Either PARP-1 or AIF knockdown played a significantly protective role for light-damaged photoreceptors. More importantly, crosstalk was observed between mTOR and PARP-1 signaling and mTOR could have regulated parthanatos via the intermediate factor sirtuin 1 (SIRT1). The parthanatos-like injury was also verified in vivo, wherein either PARP-1 or mTOR inhibition provided significant neuroprotection against light-induced injury, which is evinced by both structural and functional retinal analysis. Overall, these results elucidate the mTOR-regulated parthanatos death mechanism in light-injured photoreceptors/retinas and may facilitate the development of novel neuroprotective therapies for retinal degeneration diseases. CONCLUSIONS: Our results demonstrate that inhibition of the mTOR/PARP-1 axis exerts protective effects on photoreceptors against visible-light-induced parthanatos. These protective effects are conducted by regulating the downstream factors of AIF, while mTOR possibly interacts with PARP-1 via SIRT1 to regulate parthanatos. Video Abstract Schematic diagram of mTOR interacting with PARP-1 to regulate visible light-induced parthanatos. Increased ROS caused by light exposure penetrates the nuclear membrane and causes nuclear DNA strand breaks. PARP-1 detects DNA breaks and synthesizes PAR polymers to initiate the DNA repair system that consumes a large amount of cellular NAD+. Over-production of PAR polymers prompts the release of AIF from the mitochondria and translocation to the nucleus, which leads to parthanatos. Activated mTOR may interact with PARP-1 via SIRT1 to regulate visible light-induced parthanatos.

Differential gene expression profile in monocytic myeloid-derived suppressor cells at maternal-fetal interface in a mouse model of spontaneous abortion.

ABSTRACTBACKGROUND: Monocytic myeloid-derived suppressor cells (MO-MDSCs) play an important role in maintaining normal pregnancy. However, it is still not clear what kind of changes in MO-MDSCs may lead to miscarriage, and which gene expression changes take place when MO-MDSCs migrate to the uterus as bone marrow-derived cells. METHODS: We used flow sorting technology to obtain MO-MDSCs from the maternal-fetal interface and bone marrow, respectively. Affymetrix 3'IVT expression profiling chip technology was used to detect the differential gene expression profiles in MO-MDSCs at the maternal-fetal interface in a mouse model of spontaneous abortion compared with the normal fertility control mice. We also compared the differential gene expression of MO-MDSCs at the maternal-fetal interface compared with bone marrow in the normal fertility control mice. RESULTS: We found that 3,409 genes in MO-MDSCs were upregulated and 1,539 genes were downregulated at the maternal-fetal interface in the spontaneous abortion mice compared with the normal fertility mice. These genes are enriched in cellular components, biological processes, molecular functions, and protein binding, tumor signaling pathway, the PI3K-Akt signaling pathway, intratumoral proteoglycans, and extracellular matrix receptor interactions. Furthermore, we found that 270 genes in MO-MDSCs were upregulated and 383 genes were downregulated at the maternal-fetal interface in the normal fertility mice compared with those in the bone marrow. These genes are enriched in cellular components, biological processes, molecular functions, cell cycle, tumor transcriptional disorder, and cell adhesion molecules. CONCLUSION: Differential gene expression in MO-MDSCs likely contributes to a successful pregnancy in fetal-maternal immunotolerance.

Exosomal and extracellular HMGB1 have opposite effects on SASH1 expression in rat astrocytes and glioma C6 cells.

Exosomes are a type of extracellular vesicles derived from cells and mediators of intercellular communication. Different cell types have their own unique exosomes for exchanging information. We previously found that SASH1, a tumor suppressor, was lowly expressed or absent in glioma tissues and glioma C6 cells, but the structure and function of the corresponding exosomes had been unclear. Hence, we aimed to investigate whether exosomes generated from normal glial cells and glioma cells form different protein patterns and whether those derived from normal glial cells affect SASH1 expression in glioma cells. We collected exosomes from astrocytes and C6 cells and identified their exosomal proteins through mass spectrometry. We also performed gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses, whose results showed that both the total and unique exosomal proteins from each cell type were similar. Moreover, the KEGG analysis revealed different clusters of unique exosomal proteins in glial cells and glioma cells. In the normal glial cells, the top clusters were mainly involved in processes with RNA transcripts and proteins, whereas in glioma cells the clusters were attributed to PI3K-Akt signaling, cell adhesion, and cancer-related pathways. Western blot analysis showed that HMGB1 exists in exosomes derived from cultured astrocytes, although its expression was higher in glioma C6 cells. Furthermore, we found that exosomes extracted from astrocytes could increase SASH1 expression in C6 cells (P = 0.040), whereas those derived from HMGB1-depleted astrocytes could not (P = 0.6133). The expression levels of SASH1 decreased after the addition of extracellular recombinant HMGB1 protein, whereas that of TLR4 increased. Our study is the first to demonstrate that HMGB1 plays different roles depending on its form: as an extracellular protein, HMGB1 decreases SASH1 expression, but as an exosomal protein, HMGB1 increases SASH1 expression. Nevertheless, the mechanism, which partly depends on the TLR4 pathway, behind these opposing effects requires further study. Our novel findings on the structure-dependent roles of the cytokine HMGB1 in promoting or inhibiting cancer provide a fresh insight into the interactions of cancer cells with the microenvironment.

The YY1-HOTAIR-MMP2 Signaling Axis Controls Trophoblast Invasion at the Maternal-Fetal Interface.

We aimed to determine the effect of YY1 expression on the expression profile of long noncoding RNAs (lncRNAs) in trophoblasts, and we studied the involvement of certain lncRNAs and YY1 in the pathogenesis of recurrent miscarriage (RM). RT2 lncRNA PCR arrays revealed that YY1 overexpression in trophoblasts significantly promoted the expression of the HOX transcript antisense RNA HOTAIR and demonstrated that HOTAIR expression was significantly lower in the RM trophoblasts than in control trophoblasts. Ectopic HOTAIR overexpression and knockdown experiments revealed that it was a novel target of YY1. Bioinformatics analysis identified two YY1-binding sites in the HOTAIR promoter region, and chromatin immunoprecipitation (ChIP) analysis verified that YY1 binds directly to its promoter region. Interestingly, HOTAIR overexpression enhanced trophoblast invasion in an ex vivo explant culture model, while its knockdown repressed these effects. Furthermore, liquid chromatography-tandem mass spectrometry (LC-MS/MS) label-free quantitative proteomics screening revealed that HOTAIR overexpression activated phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) signaling in trophoblasts. In an ex vivo explant culture model, HOTAIR overexpression effectively elevated matrix metalloproteinase 2 (MMP2) expression via the PI3K-AKT signaling pathway, enhancing trophoblast migration and invasion. These findings reveal a new regulatory pathway in which YY1 activates PI3K-AKT signaling via HOTAIR, promoting MMP2 expression, suggesting that HOTAIR is a potential therapeutic target for RM.

The role of KIR genes and their cognate HLA class I ligands in childhood acute lymphoblastic leukemia.

Killer cell immunoglobulin-like receptors (KIRs), via interaction with their cognate HLA class I ligands, play a crucial role in the development and activity of natural killer cells. Following recent reports of KIR gene associations in childhood acute lymphoblastic leukemia (ALL), we present a more in-depth investigation of KIR genes and their cognate HLA ligands on childhood ALL risk. Genotyping of 16 KIR genes, along with HLA class I groups C1/C2 and Bw4 supertype ligands, was carried out in 212 childhood ALL cases and 231 healthy controls. Frequencies of KIR genes, KIR haplotypes, and combinations of KIR-HLA ligands were tested for disease association using logistic regression analyses. KIR A/A genotype frequency was significantly increased in cases (33.5%) compared with controls (24.2%) (odds ratio [OR] = 1.57; 95% confidence interval [CI], 1.04-2.39). Stratifying analysis by ethnicity, a significant difference in KIR genotype frequency was demonstrated in Hispanic cases (34.2%) compared with controls (21.9%) (OR = 1.86; 95% CI, 1.05-3.31). Homozygosity for the HLA-Bw4 allele was strongly associated with increased ALL risk exclusively in non-Hispanic white children (OR = 3.93; 95% CI, 1.44-12.64). Our findings suggest a role for KIR genes and their HLA ligands in childhood ALL etiology that may vary among ethnic groups.

Thin-layer chromatographic identification of Chinese propolis using chemometric fingerprinting.

INTRODUCTION: Poplar tree gum has a similar chemical composition and appearance to Chinese propolis (bee glue) and has been widely used as a counterfeit propolis because Chinese propolis is typically the poplar-type propolis, the chemical composition of which is determined mainly by the resin of poplar trees. The discrimination of Chinese propolis from poplar tree gum is a challenging task. OBJECTIVE: To develop a rapid thin-layer chromatographic (TLC) identification method using chemometric fingerprinting to discriminate Chinese propolis from poplar tree gum. METHODS: A new TLC method using a combination of ammonia and hydrogen peroxide vapours as the visualisation reagent was developed to characterise the chemical profile of Chinese propolis. Three separate people performed TLC on eight Chinese propolis samples and three poplar tree gum samples of varying origins. Five chemometric methods, including similarity analysis, hierarchical clustering, k-means clustering, neural network and support vector machine, were compared for use in classifying the samples based on their densitograms obtained from the TLC chromatograms via image analysis. RESULTS: Hierarchical clustering, neural network and support vector machine analyses achieved a correct classification rate of 100% in classifying the samples. A strategy for TLC identification of Chinese propolis using chemometric fingerprinting was proposed and it provided accurate sample classification. CONCLUSION: The study has shown that the TLC identification method using chemometric fingerprinting is a rapid, low-cost method for the discrimination of Chinese propolis from poplar tree gum and may be used for the quality control of Chinese propolis.

GLIPR2: a potential biomarker and therapeutic target unveiled - Insights from extensive pan-cancer analyses, with a spotlight on lung adenocarcinoma.

Background: Glioma pathogenesis related-2 (GLIPR2), an emerging Golgi membrane protein implicated in autophagy, has received limited attention in current scholarly discourse. Methods: Leveraging extensive datasets, including The Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx), Human Protein Atlas (HPA), and Clinical Proteomic Tumor Analysis Consortium (CPTAC), we conducted a comprehensive investigation into GLIPR2 expression across diverse human malignancies. Utilizing UALCAN, OncoDB, MEXPRESS and cBioPortal databases, we scrutinized GLIPR2 mutation patterns and methylation landscapes. The integration of bulk and single-cell RNA sequencing facilitated elucidation of relationships among cellular heterogeneity, immune infiltration, and GLIPR2 levels in pan-cancer. Employing ROC and KM analyses, we unveiled the diagnostic and prognostic potential of GLIPR2 across diverse cancers. Immunohistochemistry provided insights into GLIPR2 expression patterns in a multicenter cohort spanning various cancer types. In vitro functional experiments, including transwell assays, wound healing analyses, and drug sensitivity testing, were employed to delineate the tumor suppressive role of GLIPR2. Results: GLIPR2 expression was significantly reduced in neoplastic tissues compared to its prevalence in healthy tissues. Copy number variations (CNV) and alterations in methylation patterns exhibited discernible correlations with GLIPR2 expression within tumor tissues. Moreover, GLIPR2 demonstrated diagnostic and prognostic implications, showing pronounced associations with the expression profiles of numerous immune checkpoint genes and the relative abundance of immune cells in the neoplastic microenvironment. This multifaceted influence was evident across various cancer types, with lung adenocarcinoma (LUAD) being particularly prominent. Notably, patients with LUAD exhibited a significant decrease in GLIPR2 expression within practical clinical settings. Elevated GLIPR2 expression correlated with improved prognostic outcomes specifically in LUAD. Following radiotherapy, LUAD cases displayed an increased presence of GLIPR2+ infiltrating cellular constituents, indicating a notable correlation with heightened sensitivity to radiation-induced therapeutic modalities. A battery of experiments validated the functional role of GLIPR2 in suppressing the malignant phenotype and enhancing treatment sensitivity. Conclusion: In pan-cancer, particularly in LUAD, GLIPR2 emerges as a promising novel biomarker and tumor suppressor. Its involvement in immune cell infiltration suggests potential as an immunotherapeutic target.

Developing a prognosis and chemotherapy evaluating model for colon adenocarcinoma based on mitotic catastrophe-related genes.

Mitotic catastrophe (MC) is a novel form of cell death that plays an important role in the treatment and drug resistance of colon adenocarcinoma (COAD). However, MC related genes in COAD treatment and prognosis evaluation are rarely studied. In this study, the transcriptome data, somatic mutation and copy number variation data were obtained from The Cancer Genome Atlas (TCGA) database. The mitotic catastrophe related genes (MCRGs) were obtained from GENCARDS website. Differential gene analysis was conducted with LIMMA package. Univariate Cox regression analysis was used to identify prognostic related genes. Mutation analysis was performed and displayed by maftools package. RCircos package was used for localizing the position of genes on chromosomes. "Glmnet" R package was applied for constructing a risk model via the LASSO regression method. Consensus clustering analyses was implemented for clustering different subtypes. Functional enrichment analysis through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) methods, immune infiltration analysis via single sample gene set enrichment analysis (ssGSEA), tumor mutation burden and drug sensitivity analysis by pRRophetic R package were also carried out for risk model or molecular subtype's assessment. Additionally, the connections between the expression of hub genes and overall survival (OS) were obtained from online Human Protein Atlas (HPA) website. Real-Time Quantitative Polymerase Chain Reaction (RT­qPCR) further validated the expression of hub genes. A total of 207 differentially expressed MCRGs were selected in the TCGA cohort, 23 of which were significantly associated with OS in COAD patients. Subsequently, we constructed risk score prognostic models with 5 hub MCRGs, including SYCE2, SERPINE1, TRIP6, LIMK1, and EEPD1. The high-risk patients suffered from poorer prognosis. Furthermore, we developed a nomogram that gathered age, sex, staging, and risk score to accurately forecast the clinical survival outcomes in 1, 3, and 5 years. The results of functional enrichment suggested a significant correlation between MCRGs characteristics and cancer progression, with important implications for the immune microenvironment. Moreover, patients who displayed high TMB and high risk score showed worse prognosis, and risk characteristics were associated with different chemotherapeutic agents. Finally, RT­qPCR verified the increased expression of the five MCRGs in clinical samples. The five MCRGs in the prognostic signature were associated with prognosis, and could be treated as reliable prognostic biomarkers and therapeutic targets for COAD patients with distinct clinicopathological characteristics, thereby providing a foundation for the precise application of pertinent drugs in COAD patients.