Severe Infection Mimicking AML due to Bone Marrow Suppression: a Diagnostic Challenge.

BACKGROUND: Infection may lead to agranulocytosis due to bone marrow suppression. However, a rare case with infection presented with morphological features of acute myeloid leukemia (AML). METHODS: We report a case of extreme agranulocytosis due to severe infection mimicking acute myeloid leukemia. The case was definitively diagnosed by subsequent morphology, flow cytometry, and bone marrow biopsy, and subsequent successful anti-infective treatment confirmed the diagnosis. CONCLUSIONS: To date, no case of a patient diagnosed with severe infection mimicking AML has been reported. The case emphasizes the importance of an integrated diagnostic work-up, especially careful clinical observation and differential diagnosis.

RSVdb: a comprehensive database of transcriptome RNA structure.

RNA fulfills a crucial regulatory role in cells by folding into a complex RNA structure. To date, a chemical compound, dimethyl sulfate (DMS), has been developed to probe the RNA structure at the transcriptome level effectively. We proposed a database, RSVdb (https://taolab.nwafu.edu.cn/rsvdb/), for the browsing and visualization of transcriptome RNA structures. RSVdb, including 626 225 RNAs with validated DMS reactivity from 178 samples in eight species, supports four main functions: information retrieval, research overview, structure prediction and resource download. Users can search for species, studies, transcripts and genes of interest; browse the quality control of sequencing data and statistical charts of RNA structure information; preview and perform online prediction of RNA structures in silico and under DMS restraint of different experimental treatments and download RNA structure data for species and studies. Together, RSVdb provides a reference for RNA structure and will support future research on the function of RNA structure at the transcriptome level.

miR-HCC2 suppresses hepatitis B virus replication by inhibiting the activity of the enhancer I/X promoter.

miR-HCC2 has been reported to markedly promote the growth, metastasis, and stemness of hepatocellular carcinoma (HCC) cells in vitro and in vivo. Deep sequencing showed that miR-HCC2 was significantly upregulated in hepatitis B virus (HBV)-positive (HBV+) HCC tissue samples compared with HBV-negative (HBV-) HCC tissue samples. miR-HCC2 expression was further evaluated in HCC tissues and cells, and the expression of miR-HCC2 was found to be significantly higher in HBV+ HCC tissues and cells than in HBV- HCC tissues and cells, suggesting that high miR-HCC2 expression could be induced by HBV infection. To explore the relationship between miR-HCC2 and HBV, we investigated the effect of miR-HCC2 on HBV antigen expression, transcription, and replication. We found that miR-HCC2 was involved in the negative feedback regulation of HBV replication. Further mechanistic studies revealed that miR-HCC2 suppressed HBV replication by inhibiting the activity of the enhancer I/X promoter. Our study demonstrates the effect of the inhibition of miR-HCC2 on HBV gene expression and replication, which can help to illustrate the complex regulatory network involving host miRNAs and HBV.

A laminin 511 matrix is regulated by TAZ and functions as the ligand for the α6Bß1 integrin to sustain breast cancer stem cells.

Understanding how the extracellular matrix impacts the function of cancer stem cells (CSCs) is a significant but poorly understood problem. We report that breast CSCs produce a laminin (LM) 511 matrix that promotes self-renewal and tumor initiation by engaging the α6Bß1 integrin and activating the Hippo transducer TAZ. Although TAZ is important for the function of breast CSCs, the mechanism is unknown. We observed that TAZ regulates the transcription of the α5 subunit of LM511 and the formation of a LM511 matrix. These data establish a positive feedback loop involving TAZ and LM511 that contributes to stemness in breast cancer.

Elaiophylin Elicits Robust Anti-Tumor Responses via Apoptosis Induction and Attenuation of Proliferation, Migration, Invasion, and Angiogenesis in Pancreatic Cancer Cells.

Pancreatic cancer remains a formidable challenge in oncology due to its aggressive nature and limited treatment options. In this study, we investigate the potential therapeutic efficacy of elaiophylin, a novel compound, in targeting BxPC-3 and PANC-1 pancreatic cancer cells. We comprehensively explore elaiophylin's impact on apoptosis induction, proliferation inhibition, migration suppression, invasion attenuation, and angiogenesis inhibition, key processes contributing to cancer progression and metastasis. The results demonstrate that elaiophylin exerts potent pro-apoptotic effects, inducing a substantial increase in apoptotic cells. Additionally, elaiophylin significantly inhibits proliferation, migration, and invasion of BxPC-3 and PANC-1 cells. Furthermore, elaiophylin exhibits remarkable anti-angiogenic activity, effectively disrupting tube formation in HUVECs. Moreover, elaiophylin significantly inhibits the Wnt/ß-Catenin signaling pathway. Our findings collectively demonstrate the multifaceted potential of elaiophylin as a promising therapeutic agent against pancreatic cancer via inhibition of the Wnt/ß-Catenin signaling pathway. By targeting diverse cellular processes crucial for cancer progression, elaiophylin emerges as a prospective candidate for future targeted therapies. Further investigation of the in vivo efficacy of elaiophylin is warranted, potentially paving the way for novel and effective treatment approaches in pancreatic cancer management.

The relationship between integrin avß6 and HBV infection in patients with liver cirrhosis and hepatocellular carcinoma: a preliminary report.

OBJECTIVE: the aim of this study was to investigate the expression of integrin αvß6 in normal, hepatitis B, HBV-associated cirrhosis and HBV-associated HCC liver tissues. METHODS: immunohistochemistry and real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) were used to study the expression of integrin αvß6 in HBV-associated cirrhosis (n = 88), chronic hepatitis B ( n= 11), HBV-associated HCC (n = 84) and normal (n = 10) human liver tissues. RESULTS: the expression of integrin αvß6 was significantly upregulated in HBV-associated liver cirrhosis and the expression increased with an increase in severity of cirrhosis. Furthermore, it was moderately or weakly expressed in chronic hepatitis B and HBV-associated HCC liver tissues when compared to normal liver tissue. CONCLUSION: integrin αvß6 could be a predictive marker for the progression of liver cirrhosis associated with HBV infection. Further studies are needed to determine the association between the expression of integrin αvß6 in hepatitis B and HBV-associated HCC liver tissues.

miR-377-3p drives malignancy characteristics via upregulating GSK-3ß expression and activating NF-κB pathway in hCRC cells.

MicroRNA (miRNA) dysregulation has been associated with carcinogenesis in many cancers, including human colorectal cancer (hCRC). However, the effect and mechanism of miR-377-3p on CRC remains elusive. Herein, we first found that miR-377-3p was upregulated in CRC tissues and promoted tumorigenic activity by accelerating the G1 -S phase transition, promoting cell proliferation and epithelial-mesenchymal transition (EMT) while repressing apoptosis in CRC cells. Glycogen synthase kinase-3ß (GSK-3ß) was a direct target of miR-377-3p, and upregulated by miR-377-3p. Knockdown of GSK-3ß partly rescued miR-377-3p-mediated malignancy characteristics. Most importantly, we showed that miR-377-3p promoted carcinogenesis by activating NF-κB pathway. Taken together, our results first reported that miR-377-3p functions as an oncogene and promotes carcinogenesis via upregulating GSK-3ß expression and activating NF-κB pathway in hCRC cells.

Effects of GSTP1 and GPX1 Polymorphisms on the Risk of Preeclampsia in Chinese Han Women.

BACKGROUND/AIMS: Increasing evidence shows that oxidative stress plays an important part in the pathophysiological mechanisms of preeclampsia (PE). Polymorphic variants of oxidative stress-related candidate genes GST1 and GPX1 can affect the antioxidant activities of their encoded enzymes. Therefore, this study aimed to explore the associational analysis between GSTP1 and GPX1 single nucleotide polymorphisms (SNPs) and susceptibility to PE in Chinese Han women. METHODS: DNA from 1130 PE patients and 1226 healthy individuals was genotyped for SNPs rs1695 in GSTP1 and rs1050450 in GPX1 using a predesigned TaqMan SNP genotyping assay. The χ2 test compared differences in genetic distributions between the two groups in a case-control study. RESULTS: No significant differences in allelic or genotypic frequencies of GSTP1 rs1695 or GPX1 rs1050450 were detected between cases and controls (GSTP1 rs1695: χ2=1.122, p=0.571 by genotype, χ2=0.138, p=0.710, odds ratio=1.027, 95% confidence interval 0.892-1.183 by allele; GPX1 rs1050450: χ2=0.036, p=0.982 by genotype, χ2=0.002, p=0.960, odds ratio=1.005, 95% confidence interval 0.822-1.229 by allele). Moreover, no significant differences in genetic distribution were found between early/late-onset PE or mild/severe PE and control subgroups. CONCLUSION: Our results suggest that GSTP1 rs1695 and GPX1 rs1050450 SNPs have no effects on the risk of PE in the Chinese Han population. However, these results should be confirmed by replication in different populations.

Integrin ß6 acts as an unfavorable prognostic indicator and promotes cellular malignant behaviors via ERK-ETS1 pathway in pancreatic ductal adenocarcinoma (PDAC).

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most deadly cancers and is expected to become the second leading cause of cancer death by 2030. Despite extensive efforts to improve surgical treatment, limited progress has been made. Increasing evidence indicates that integrin ß6 plays a crucial role in carcinoma invasion and metastasis. However, the expression and role of ß6 in PDAC remain largely unknown. In the present study, we investigated the expression of ß6 in PDAC and its potential value as a prognostic factor and therapeutic target. ß6 upregulation was identified as an independent unfavorable prognostic indicator. Integrin ß6 markedly promoted the proliferation and invasion of pancreatic carcinoma cells and induced ETS1 phosphorylation in an ERK-dependent manner, leading to the upregulation of matrix metalloprotease-9, which is essential for ß6-mediated invasiveness of pancreatic carcinoma cells. Accordingly, small interfering RNA-mediated silencing of integrin ß6 markedly suppressed xenograft tumor growth in vivo. Taken together, our results suggest that integrin ß6 plays important roles in the progression of pancreatic carcinoma and contributes to reduced survival times, and may serve as a novel therapeutic target for the treatment of PDAC.

PA-X is a virulence factor in avian H9N2 influenza virus.

H9N2 influenza viruses have been circulating worldwide in multiple avian species, and regularly infect pigs and humans. Recently, a novel protein, PA-X, produced from the PA gene by ribosomal frameshifting, was demonstrated to be an antivirulence factor in pandemic 2009 H1N1, highly pathogenic avian H5N1 and 1918 H1N1 viruses. However, a similar role of PA-X in the prevalent H9N2 avian influenza viruses has not been established. In this study, we compared the virulence and cytopathogenicity of H9N2 WT virus and H9N2 PA-X-deficient virus. Loss of PA-X in H9N2 virus reduced apoptosis and had a marginal effect on progeny virus output in human pulmonary adenocarcinoma (A549) cells. Without PA-X, PA was less able to suppress co-expressed GFP in human embryonic kidney 293T cells. Furthermore, absence of PA-X in H9N2 virus attenuated viral pathogenicity in mice, which showed no mortality, reduced progeny virus production, mild-to-normal lung histopathology, and dampened proinflammatory cytokine and chemokine response. Therefore, unlike previously reported H1N1 and H5N1 viruses, we show that PA-X protein in H9N2 virus is a pro-virulence factor in facilitating viral pathogenicity and that the pro- or antivirulence role of PA-X in influenza viruses is virus strain-dependent.

Twenty amino acids at the C-terminus of PA-X are associated with increased influenza A virus replication and pathogenicity.

The PA-X protein, arising from ribosomal frameshift during PA translation, was recently discovered in influenza A virus (IAV). The C-terminal domain 'X' of PA-X proteins in IAVs can be classified as full-length (61 aa) or truncated (41 aa). In the main, avian influenza viruses express full-length PA-X proteins, whilst 2009 pandemic H1N1 (pH1N1) influenza viruses harbour truncated PA proteins. The truncated form lacks aa 232-252 of the full-length PA-X protein. The significance of PA-X length in virus function remains unclear. To address this issue, we constructed a set of contemporary influenza viruses (pH1N1, avian H5N1 and H9N2) with full and truncated PA-X by reverse genetics to compare their replication and host pathogenicity. All full-length PA-X viruses in human A549 cells conferred 10- to 100-fold increase in viral replication and 5-8% increase in apoptosis relative to corresponding truncated PA-X viruses. Full-length PA-X viruses were more virulent and caused more severe inflammatory responses in mice. Furthermore, aa 233-252 at the C terminus of PA-X strongly suppressed co-transfected gene expression by ∼ 50%, suggesting that these terminal 20 aa could play a role in enhancing viral replication and contribute to virulence.

Research Progress on Extracellular Matrix Involved in the Development of Preeclampsia.

Preeclampsia (PE) is a serious pregnancy complication, and its primary clinical manifestations are gestational hypertension and proteinuria. Trophoblasts are responsible for the basic functions of the placenta during placental development; recent studies have revealed that placental "shallow implantation" caused by the decreased invasiveness of placental trophoblasts plays a crucial role in PE pathogenesis. The interaction between the cells and the extracellular matrix (ECM) plays a crucial role in trophoblast proliferation, differentiation, and invasion. Abnormal ECM function can result in insufficient migration and invasion of placental trophoblasts, thus participating in PE. This article summarizes the recent studies on the involvement of ECM components, including small leucine-rich proteoglycans, syndecans, glypicans, laminins, fibronectin, collagen, and hyaluronic acid, in the development of PE. ECM plays various roles in PE development, most notably by controlling the activities of trophoblasts. The ECM is structurally stable and can serve as a biological diagnostic marker and therapeutic target for PE.

Integrin αvß6 mediates the immune escape through regulation of PD-L1 and serves as a novel marker for immunotherapy of colon carcinoma.

The immune escape of colon cancer and its role in the response to immunotherapies such as PD-1/PD-L1 checkpoint inhibitors have long been of great interest. The positive outcomes of immunotherapy are limited by the immunosuppressive nature of the tumor microenvironment. Integrin αvß6, which can regulate the progression of colon cancer, was recently reported to be involved in the immune suppression of colon cancer. In the present study, we explored the correlation between αvß6 and PD-L1 expression by immunohistochemistry of colon cancer tissues. Then, the regulation of PD-L1 signaling by αvß6 in colon cancer cells was demonstrated. We constructed an in vivo model and performed immunophenotyping experiments to analyze further the regulation of the immune response by αvß6. The role of αvß6 in the response to anti-PD-1 therapy in colon cancer was also verified. αvß6-positive tissues exhibited increased PD-L1 expression. Inhibition of αvß6 not only downregulated constitutive PD-L1 expression but also decreased IFN-γ-induced PD-L1 expression. In addition, αvß6-induced PD-L1 expression was suppressed by the ERK inhibitor PD98059, and knockdown of the ß6-ERK2 binding site had the equivalent effect. αvß6 decreased CD8+ T cell infiltration and granzyme B expression in CD8+ T cells in colon cancer patients. Furthermore, mice engrafted with αvß6-expressing colon cancer cells exhibited an unsatisfactory response to anti-PD-1 therapy, and anti-PD-1-induced increases in CD4+ and CD8+ T cell infiltration could be inhibited by αvß6. These results indicate that αvß6 mediates immune escape in colon cancer by upregulating PD-L1 through the ERK/MAPK pathway. Moreover, αvß6 could serve as a marker for the efficacy of anti-PD-1 therapy in colon cancer.

A flexible ultra-highly sensitive capacitive pressure sensor for basketball motion monitoring.

Recently, flexible sensors with high sensitivity have been applied in wearable sports sensing field. Here, we reported a flexible and sensitive capacitive pressure sensor based on nylon textile and polyvinylidene fluoride (PVDF) dielectric film. From the experimental results, the sensor has an extremely high sensitivity of 33.5 kPa-1, a low detection limit of 0.84 Pa, a quick response time of 27 ms. Moreover, the pressure sensor shows excellent reliability under over 100,000 working cycles. With their superior overall performance, capacitive sensors have effectively proved their enormous potential for basketball motion monitoring. This research will promote the development of wearable sports sensors.

The regulatory effect of the YY1/miR­HCC2/BAMBI axis on the stemness of liver cancer cells.

Cancer stem cells serve key roles in liver cancer recurrence and metastasis. Therefore, the present study evaluated novel regulators of stem cell factor expression to identify novel therapeutic strategies that could target liver cancer stem cells. Deep sequencing was performed to identify novel microRNAs (miRNAs) that were specifically altered in liver cancer tissues. The expression levels of stem cell markers were investigated by reverse transcription­quantitative PCR and western blotting. Sphere formation assays and flow cytometry were used to assess tumor sphere­forming ability and evaluate the population of cluster of differentiation 90+ cells. Tumor xenograft analyses were used to evaluate tumorigenicity, metastasis and stemness in vivo. Bioinformatics analyses and enhanced green fluorescent protein reporter assays or luciferase reporter assays were performed to identify the direct targets of miR­HCC2 and its upstream transcription factors. MiR­HCC2 strongly promoted the cancer stem cell­like properties of liver cancer cells in vitro; it also contributed to tumorigenicity, metastasis and stemness in vivo. Bone morphogenic protein and activin membrane­bound inhibitor homolog, a direct target of miR­HCC2, activated the Wnt/ß­catenin signaling pathway to promote stemness in liver cancer cells. The transcription factor YY1 bound to the promoter of miR­HCC2 and activated its transcription. The present study demonstrated the importance of miR­HCC2 in the induction of stemness in liver cancer, providing new insights into liver cancer metastasis and recurrence.

The Novel SLRP Family Member Lumican Suppresses Pancreatic Cancer Cell Growth.

OBJECTIVES: The past studies clearly indicated that lumican was important in the context of pancreatic cancer (PC) onset and progression, but failed to clarify the underlying mechanistic basis for such activity. As such, we evaluated the functional importance of lumican in the context of pancreatic ductal adenocarcinoma (PDAC) to understand its mechanistic role in PC. METHODS: Lumican levels were evaluated in PDAC patient tissues via quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry approaches. The role of lumican was additionally assessed via transfecting PDAC cell lines (BxPC-3, PANC-1) with lumican knockdown or overexpression constructs and treating PDAC cell lines with exogenous recombinant human lumican. RESULTS: Lumican expression levels were significantly higher in pancreatic tumor tissues relative to healthy paracancerous tissues. Lumican knockdown in BxPC-3 and PANC-1 enhanced their proliferation and migration, but reduced cellular apoptosis. Alternatively, lumican overexpression and exogenous lumican exposure failed to alter the proliferative activity of these cells. Further, lumican knockdown in BxPC-3 and PANC-1 cells results in marked P53 and P21 dysregulation. CONCLUSIONS: Lumican may suppress PDAC tumor growth by regulating P53 and P21, and the function of lumican sugar chains in the context of PC is worth studying in future studies.

Effects of superficial gas velocity on the performance of an air-lift internal circulation partial nitrification-anammox granular sludge reactor.

The airlift internal circulation reactor for partial nitrification-anammox (PNA-ALR) has the advantages of a small footprint, high mass transfer efficiency, and the ease of formation of granular sludge, thus making it an effective biological treatment for ammonia-containing wastewater. Although superficial gas velocity (SGV) is an essential parameter for PNA-ALR, it is unclear how the magnitude of SGV impacts nitrogen removal performance. In this study, the nitrogen removal efficiencies of five PNA-ALRs with different SGV were measured during feeding with synthetic municipal wastewater. At an optimal SGV of 2.35 cm s-1, the PNA-ALR consistently maintained the total inorganic nitrogen (TIN) removal efficiency at 76.31% and the effluent TIN concentration was less than 10 mg L-1. By increasing or decreasing the SGV, the nitrogen removal efficiency decreased to a range between 30% and 50%. At lower SGV, the dead space in the PNA-ALR was increased by 21.15%, and the feast/famine ratio of sludge increased to greater than 0.5, which caused a disruption in the structure, and a large loss of, granular sludge. Computational fluid dynamics (CFD) simulations showed operation at a higher SGV, resulting in excessive shear stress of 3.25 N m-2 being generated from bubble rupture in the degassing section. Fluorescent staining determined a decrease of 26.5% in viable bacteria. These results have improved our understanding of the effects of SGV on a PNA-ALR during mainstream wastewater treatment.

Aloe-Emodin Suppresses Oxidative Stress and Inflammation via a PI3K-Dependent Mechanism in a Murine Model of Sepsis.

Background: This study was designed to assess the impact of aloe-emodin (AE) on oxidative stress and inflammation in a murine model of LPS-induced sepsis. In addition, the mechanistic basis for anti-inflammatory and antioxidant activity was assessed. Methods: Male ICR mice received an intraperitoneal injection of LPS (10 mg/kg), and the preventive properties of AE (80 or 150 mg/kg) on these mice were assessed by monitoring spleen index, and levels of inflammatory and oxidative stress-related factors. Peripheral blood TNF-α and IL-6 levels were assessed via ELISA kits, while changes in hepatic SOD and GSH-Px levels were assessed using appropriate biochemical kits. Splenic PI3K, AKT, and mTOR levels were assessed via qPCR and western blotting. Results: Relative to animals in the LPS model group, those in the AE treatment groups exhibited reduced spleen index, decreased inflammatory cytokine levels, and improved SOD and GSH-Px activity in liver tissues. Splenic PI3K, Akt, and mTOR levels were also reduced in response to AE treatment. Conclusions: These findings indicated that AE can alleviate sepsis-related tissue damage, inflammation, and oxidative stress, at least in part by suppressing the PI3K/Akt/mTOR signaling pathway. These results offer a clinical basis for the use of AE to treat sepsis and associated diseases.

Plasma Exosomal hsa_circ_0015286 as a Potential Diagnostic and Prognostic Biomarker for Gastric Cancer.

Circular RNA (circRNA) is stable and abundant in exosomes as a potential biomarker for the diagnosis and prognosis of tumor. In this study, cancer specific exosomal circRNAs were identified through circRNA microarray, and 58 circRNAs were significantly upregulated in cancer cells derived exosomes. Then 60 patients with newly diagnosed gastric cancer (GC), 30 chronic gastritis patients and 30 healthy subjects were enrolled for further clinical validation. We detected that hsa_circ_0015286 was remarkably highly expressed in GC tissue, plasma and cancer cells compared with normal controls. Results of ROC curve analysis showed that the area under curve (AUC) of hsa_circ_0015286, CEA and CA 19-9 was 0.778, 0.673, and 0.665, respectively. The combined detection of three indicators had the highest AUC (0.843). Exosomal hsa_circ_0015286 expression was closely associated with tumor size, TNM stage and lymph node metastasis. The expression level of exosomal hsa_circ_0015286 in GC patients decreased significantly after surgery. Overall survival of patients with low hsa_circ_0015286 expression was longer than those with high expression. Our data demonstrated that exosomal hsa_circ_0015286 might be a promising noninvasive biomarker for the diagnosis and prognosis evaluation of GC.

Research on the Mechanism and Prevention Methods of the Drying Shrinkage Effect of Earthen Sites.

In view of the fact that it is easy for the ancient city soil site of Cai Kingdom to expand and crack when encountering water, this paper explores the methods to improve the expansion and shrinkage deformation, dry shrinkage cracks and easy water absorption characteristics of the expanded site soil based on a lime and silicone hydrophobic agent. In this paper, the expansive clay in the old city site of Cai Kingdom in Zhumadian was taken as the research object, and the dry-shrinkage fissure test of saturated expansive soil was carried out, to study the influencing factors of the dry-shrinkage cracking of expansive soil in this area. The site soil was modified with lime and glue powder, and the fissure image was quantitatively analyzed by MATLAB. The test shows that the smaller the particle size, the faster the evaporation of water and the smaller the surface fissure rate; the thicker the thickness of the soil sample, the greater the surface fissure rate and the greater the crack width; and with the increase in the number of drying and wetting cycles, the surface fissure rate of the soil sample increases. In this paper, lime and waterproof materials are used to improve the expansive soil. This not only reduces the dry shrinkage crack rate, but also improves the waterproof performance and durability of expansive soil.