The role of exosomes in cancer-related programmed cell death.

Cancer arises from the growth and division of uncontrolled erroneous cells. Programmed cell death (PCD), or regulated cell death (RCD), includes natural processes that eliminate damaged or abnormal cells. Dysregulation of PCD is a hallmark of cancer, as cancer cells often evade cell death and continue to proliferate. Exosomes nanoscale extracellular vesicles secreted by different types of cells carrying a variety of molecules, including nucleic acids, proteins, and lipids, to have indispensable role in the communication between cells, and can influence various cellular processes, including PCD. Exosomes have been shown to modulate PCD in cancer cells by transferring pro- or antideath molecules to neighboring cells. Additionally, exosomes can facilitate the spread of PCD to surrounding cancer cells, making them promising in the treatment of various cancers. The exosomes' diagnostic potential in cancer is also an active area of research. Exosomes can be isolated from a wide range of bodily fluids and tissues, such as blood and urine, and can provide a noninvasive way to monitor cancer progression and treatment response. Furthermore, exosomes have also been employed as a delivery system for therapeutic agents. By engineering exosomes to carry drugs or other therapeutic molecules, they can be targeted specifically to cancer cells, reducing toxicity to healthy tissues. Here, we discussed exosomes in the diagnosis and prevention of cancers, tumor immunotherapy, and drug delivery, as well as in different types of PCD.

Microarray-Based CD38 Peptide Probe Screening for Multiple Myeloma Imaging.

Assessing CD38 expression in vivo has become a significant element in multiple myeloma (MM) therapy, as it can be used to detect lesions and forecast the effectiveness of treatment. Accurate diagnosis requires a multifunctional, high-throughput probe screening platform to develop molecular probes for tumor-targeted multimodal imaging and treatment. Here, we investigated a microarray chip-based strategy for high-throughput screening of peptide probes for CD38. We obtained two new target peptides, CA-1 and CA-2, from a 105 peptide library with a dissociation constant (KD) of 10-7 M. The specificity and affinity of the target peptides were confirmed at the molecular and cellular levels. Peptide probes were labeled with indocyanine green (ICG) dye and 68Ga-DOTA, which were injected into a CD38-positive Ramos tumor-bearing mouse via its tail vein, and small animal fluorescence and positron emission tomography (PET) imaging showed that the peptide probes could show specific enrichment in the tumor tissue. Our study shows that a microchip-based screening of peptide probes can be used as a promising imaging tool for MM diagnosis.

Mucous cell histopathology and label-free quantitative proteomic analysis of skin mucus in fat greenling (Hexagrammos otakii) infected with Vibrio harveyi.

Hexagrammos otakii is favored by consumers and aquaculture practitioners because of its strong adaptability and fast growth. However, recently, frequent outbreaks of diseases in the breeding of H. otakii have led to significant economic losses, especially due to bacterial diseases, which limit the healthy breeding of H. otakii. As a luminescent Gram-negative bacterium, Vibrio harveyi is the main pathogenic bacteria of H. otakii. In this study, the histopathology and label-free quantitative proteomics analysis were performed to reveal the changes of skin mucus proteins in H. otakii after infection with V. harveyi. The histopathological changes in the skin of H. otakii showed that when the bacteria were injected into the epithelial cells, it caused an increase in the number of mucous cells and a certain degree of damage and deformation in skin. Moreover, the quantitative proteomics analysis revealed a total of 364 differentially expressed proteins (DEPs), and these DEPs were found to be involved in environmental information processing, metabolism, infectious diseases: bacteria, replication and repair. More importantly, the enrichment analysis of the DEPs revealed that these different proteins were mainly targeted immune-related pathways. After infection of bacteria, the host's immune ability will be weakened, causing V. harveyi to enter the organism more easily, resulting in increased mucus in H. otakii, which will eventually lead to a decline in its physical function. These results provided an insight into a series of physiological changes after the bacterial infection of fish at the proteomic level and basic data for further exploration of the potential mechanism of skin mucus. Taken together, the results indicated more opportunities for the future designs and discoveries of effective antibacterial vaccines and antibacterial drugs for H. otakii.

Improved visual outcomes of central retinal artery occlusion with local intra-arterial fibrinolysis beyond the conventional time window.

Local intra-arterial fibrinolysis (LIF) is a promising therapeutic option for CRAO. However, the narrow time window of 6 h has greatly limited the application of LIF. In this study, we explored the efficacy of LIF beyond the conventional time windows and compared the result with conservative therapy. This prospective study included 179 CRAO patients with baseline visual acuity (VA) ≤ 20/400 treated at Renmin Hospital of Wuhan University. The mean time from vision loss to presentation was 5.5 days. 58 patients received conventional standard therapy (CST) alone.121 patients underwent LIF. Main outcome was VA improvement ≥ 0.3 logMAR. Secondary outcome was a favorable VA outcome of 20/200 or better. Logistic regressions were performed to identify predictors of visual improvement. 43% patients in the LIF group experienced VA improvement versus 19% with CST (P = 0.002). LIF was associated with 4.0-fold higher likelihood of visual improvement compared to CST (P = 0.001). Poor baseline VA (light perception or no light perception) and shortened prothrombin time (PT) were associated with greater chance of visual improvement with LIF. However, LIF showed no significant advantage over CST for favorable VA outcomes. No major complications occurred. LIF beyond the therapeutic time window improved vision in functionally blind CRAO patients and showed better efficacy when compared with CST. PT may be a potential predictor of visual outcome after LIF. Our findings could complement existing time-based treatment guidelines and potentially allow for personalized decisions on the use of LIF beyond time windows.

Severe coagulopathy and inflammation occurred after resection of giant right ventricular intimal sarcoma with cardiopulmonary bypass: a case report.

BACKGROUND: Primary malignant cardiac tumors are rare in clinic, and surgical resection under cardiopulmonary bypass (CPB) remains the main treatment. The non-physiological perfusion process of CPB leads to contact activation, and the resulting coagulopathy and systemic inflammatory response syndrome (SIRS) are common complications. However, it is difficult to predict the impact of foreign tumor fragments on this pathophysiological process once they enter the bloodstream, making this phenomenon more complex and challenging. CASE PRESENTATION: We report a case of cardiac intimal sarcoma who developed severe coagulopathy and widespread inflammation after excision of massive right ventricular tumor and replacement of tricuspid valve by median sternotomy under CPB. Although the procedure was expected to cause tumor cell necrosis and precautions were taken, uncontrolled massive postoperative bleeding, persistent fever, abnormally elevated inflammatory markers, and recurrent malignant arrhythmias occurred after surgery. In addition to common factors, the most possible underlying mechanism is contact activation triggered following surgical procedure for intimal sarcoma with CPB. CONCLUSION: Patients with intracardiac malignant tumors are at a high risk for serious contact activation during CPB. Preventive application of comprehensive anti-inflammatory measures such as drugs and adsorptive CPB technology, as well as point-of-care (POC) monitoring of coagulation status will be helpful for individualized guidance and optimization of CPB management, and improvement of patient prognosis.

Severe tricuspid regurgitation with chordae tendinae rupture in CABG surgery.

A 58-year-old male patient was admitted with chest pain and was diagnosed with coronary heart disease. He was scheduled for coronary artery bypass grafting (CABG) under cardiopulmonary bypass (CPB). Intraoperative real-time transesophageal echocardiography (TEE) showed that the tricuspid valves were well-aligned and subtle regurgitation. Real-time TEE after separation from CPB showed severe tricuspid regurgitation and prolapsed chordae tendineae. The tricuspid chordae tendineae rupture due to a right atrial venous return cannula. The use of negative pressure to improve venous drainage during CPB may result in the tricuspid valve being adsorbed to the cannula, increasing the likelihood of injury to the tricuspid valve.

A case of tricuspid valve stenosis after pacemaker implantation with infective endocarditis.

A 68-year-old male patient was admitted for extremities edema and diagnosed with infective endocarditis (IEIE). The patient underwent mitral and aortic valve mechanical valve replacement due to rheumatic heart valve disease 26 years ago. He underwent mechanical aortic valve and bioprosthetic tricuspid valve replacement due to mechanical aortic valve dysfunction and severe tricuspid valve regurgitation 1 year ago. Two months ago, the patient underwent emergency permanent pacemaker implantation due to syncope caused by a third-degree atrioventricular block. The patient was admitted to the emergency with fever and worsening dyspnea 1 h ago. Transthoracic echocardiography revealed prosthetic aortic valve severe paravalvular leak and tricuspid valve stenosis with vegetation. The patient was scheduled to undergo mechanical aortic valve and bioprosthetic tricuspid valve replacement under median thoracotomy. The intraoperative transesophageal echocardiography (TEE) view showed severe paravalvular aortic valve leakage and tricuspid valve vegetation. The coronary sinus was significantly enlarged with thrombus formation, vegetation can be seen in the bioprosthetic tricuspid valve leaflets. This is a rare case of infective endocarditis with tricuspid stenosis and coronary sinus thrombosis after the placement of implanted pacemakers.

Sonic hedgehog (shh) gene from Pseudopleuronectes yokohamae (Teleostei: Pleuronectidae): Molecular cloning, characterization, and expression profile during early embryonic, juvenile, and adult stages.

The hedgehog signaling pathway plays an important role in early development and growth of most vertebrates. Sonic hedgehog (shh) gene is a critical regulator of embryonic development in many species, including humans. However, it is not clear what roles shh can play in the development of fish. In this paper, shh gene was cloned from Pseudopleuronectes yokohamae. The full-length complementary DNA (cDNA) of P. yokohamae sonic hedgehog gene (Pyshh) comprises 3194 bp, with a 1317-bp open reading frame (ORF) that encodes a polypeptide of 438 amino acids with a typical HH-signal domain and Hint-N domain. The conserved sequences of the protein among species were predicted by using multiple sequence comparison. The phylogenetic tree construction showed that PySHH is clustered in a branch of Pleuronectidae. To explore the expression of Pyshh gene in various tissues of P. yokohamae, we used real-time fluorescence quantitative PCR technology to detect it. The results showed that Pyshh gene is widely distributed in various tissues of P. yokohamae juveniles, different tissues of adult males and females, and is particularly expressed in immune organs. The Pyshh gene expression was higher in the muscle and brain of juvenile fish, and higher in bone, gill, and skin of male fish than that of female fish, suggesting that Pyshh might be involved in the formation of immune organs of P. yokohamae. The expression of Pyshh gene significantly upregulated from the gastrula stage to the hatching stage. Western blotting of the expression levels of PySHH during different embryonic development stages revealed that PySHH levels increased gradually during development stages from oosperm stage to hatching stage. These results indicate that Pyshh is highly conserved among species and plays a critical role in the complex process of embryonic development. Its precise regulation is essential for the proper formation of many organs and tissues in the body, and disruptions in its function may have serious consequences for the formation of immune organs in fish.

The coming future: The role of the oral-microbiota-brain axis in aroma release and perception.

The field of aroma release and perception during the oral process has been well studied. However, the traditional approaches have not fully explored the integration of oral biology, microbiology, and neurology to further understand aroma release and perception mechanisms. Herein, to address the existing challenges in this field, we introduce the oral-microbiota-brain axis (OMBA), an innovative framework that encapsulates the interactive relationships among saliva and the oral mucosa, the oral microbiota, and the brain in aroma release and perception. This review introduces the OMBA and highlights its role as a key interface facilitating the sensory experience of aroma. Based on a comprehensive literature survey, the specific roles of the oral mucosa, oral microbiota, saliva, and brain in the OMBA are discussed. This integrated approach reveals the importance of each component and the interconnected relationships within this axis in the overall process of aroma release and perception. Saliva and the oral mucosa play fundamental roles in aroma release and perception; the oral microbiota regulates aroma release and impacts olfactory perception; and the brain's intricate neural circuitry is central to the decoding and interpretation of aroma signals. The components of this axis are interdependent, and imbalances can disrupt aroma perception. The OMBA framework not only enhances our comprehension of aroma release and perception but also paves the way for innovative applications that could heighten sensory experiences.

Efficacy relevance of PD-L1 expression on circulating tumor cells in metastatic breast cancer patients treated with anti-PD-1 immunotherapy.

PURPOSE: Breast cancer has become the leading cause of cancer mortality in women. Although immune checkpoint inhibitors targeting programmed death-1 (PD-1) are promising, it remains unclear whether PD-L1 expression on circulating tumor cells (CTCs) has predictive and prognostic values in predicting and stratifying metastatic breast cancer (MBC) patients who can benefit from anti-PD-1 immunotherapy. METHODS: Twenty six MBC patients that received anti-PD-1 immunotherapy were enrolled in this study. The peptide-based Pep@MNPs method was used to isolate and enumerate CTCs from 2.0 ml of peripheral venous blood. The expression of PD-L1 on CTCs was evaluated by an established immunoscoring system categorizing into four classes (negative, low, medium, and high). RESULTS: Our data showed that 92.3% (24/26) of patients had CTCs, 83.3% (20/26) of patients had PD-L1-positive CTCs, and 65.4% (17/26) of patients had PD-L1-high CTCs. We revealed that the clinical benefit rate (CBR) of patients with a cut-off value of ≥ 35% PD-L1-high CTCs (66.6%) was higher than the others (29.4%). We indicated that PD-L1 expression on CTCs from MBC patients treated with anti-PD-1 monotherapy was dynamic. We demonstrated that MBC patients with a cut-off value of ≥ 35% PD-L1-high CTCs had longer PFS (P = 0.033) and OS (P = 0.00058) compared with patients with a cut-off value of < 35% PD-L1-high CTCs. CONCLUSION: Our findings suggested that PD-L1 expression on CTCs could predict the therapeutic response and clinical outcomes, providing a valuable predictive and prognostic biomarker for patients treated with anti-PD-1 immunotherapy.

Interferometry-Integrated Noise-Immune Quantum Memory.

A quantum memory with the performances of low noise, high efficiency, and high bandwidth is of crucial importance for developing practical quantum information technologies. However, the excess noises generated during the highly efficient processing of quantum information inevitably destroy quantum state. Here, we present a quantum memory with built-in excess-noise eraser by integrating a photon-correlated quantum interferometry in quantum memory, where the memory efficiency can be enhanced and the excess noises can be suppressed to the vacuum level via destructive interference. This quantum memory is demonstrated in a rubidium vapor cell with a 10-ns-long photonics signal. We observe ∼80% noise suppression, the write-in efficiency enhancement from 87% to 96.2% without and with interferometry, and the corresponding memory efficiency excluding the noises from 70% to 77%. The fidelity is 93.7% at the single-photon level, significantly exceeding the no-cloning limit. Such interferometry-integrated quantum memory, the first expansion of quantum interference techniques to quantum information processing, simultaneously enables low noise, high bandwidth, high efficiency, and easy operation.

Hollow CdS-ZnS-ZIF-8 Polyhedron for Visible Light-Induced Cr(VI) Reduction.

By loading a small amount of cadmium acetate dihydrate on the zeolitic imidazolate framework-8 (ZIF-8), a hollow CdS-ZnS-ZIF-8 composite was facilely synthesized by rapid solid-phase grinding with thioacetamide. The evolution of the structure, composition, and photoelectrochemical properties was studied by a series of methods. When it was used as a photocatalyst, the hollow CdS-ZnS-ZIF-8 composite demonstrated a highly visible light response as well as a robust ability and reusability for Cr(VI) reduction, which could be ascribed to the hollow structure and ultrasmall CdS nanoparticles. Notably, the presence of ZIF-8-S (ZIF-8 ground with thioacetamide) could also obviously enhance the stability of CdS by promoting the separation of the photogenerated charge during light irradiation.

Effects of remote ischemic preconditioning on coronary blood flow and microcirculation.

This study aimed to determine the effect of short-term remote ischemic preconditioning (RIPC) on coronary blood flow and microcirculation function using the quantitative flow ratio (QFR) and index of microcirculatory resistance (IMR). We randomly divided 129 patients undergoing coronary angiography (CAG) into RIPC and control groups. Following the first CAG, we randomly divided the patients further into the unilateral upper limb and lower limb groups for four cycles of ischemia/reperfusion circulation; subsequently, we performed the second CAG. During each CAG, contrast-flow QFR (cQFR), fixed-flow QFR (fQFR), and IMR (in patients with cardiac syndrome X) were calculated and compared. We measured 253 coronary arteries in 129 patients. Compared to the control group, the average cQFR of the RIPC group increased significantly after RIPC. Additionally, 23 patients with cardiac syndrome X (IMR > 30) were included in this study. Compared to the control group, IMR and the difference between cQFR and fQFR (cQFR-fQFR) both decreased significantly after receiving RIPC. The application of RIPC can increase coronary blood flow and improve coronary microcirculation function.

Atrial septal hematogenous cyst with calcification mimicking myxoma: A rare case.

A 61-year-old female presented with right atrial mass during physical examination. Contrast-enhanced left heart echocardiography revealed a mass with the size of 32*23 mm in the right atrium, attached to the atrial septum; there was a certain degree of activity and deformation. MRI showed a mass of about 35*22 mm in the right atrium adjacent to the atrial septum, which was diagnosed with right atrial myxoma. Intraoperative TEE showed that the mass was located in the atrial septum close to the inferior vena cava and spontaneous echo contrast with hyperechoic images within the mass. The lesion was resected under cardiopulmonary bypass. Pathological examination revealed that the filling defect was an atrial septal hematogenous cyst with calcification.

The diagnostic utility of nanopore targeted sequencing in suspected endophthalmitis.

PURPOSE: This paper aimed to assess the diagnostic utility of a newly developed gene-based technology-nanopore targeted sequencing (NTS) in suspected endophthalmitis patients. METHODS: This retrospective study included 43 patients (44 eyes) with suspected endophthalmitis. NTS was applied along with microbiological culture to detect unknown pathogens in intraocular fluid samples. The diagnostic utility of NTS was mainly evaluated from three aspects, including the positivity rate of bacterial/fungal presence, diagnostic turnaround time and the frequency of change in treatment based on etiology test results. Non-parametric, two-sided Wilcoxon rank sum test, the McNemar's test and the kappa statistic were used for statistical comparisons. RESULTS: NTS showed significant advantages over traditional culture in positivity rates and diagnostic time (P < 0.001, kappa = 0.082; Z = -5.805, P < 0. 001). As regards antibiotic strategy, 17 patients (39.53%) and 5 patients (11.63%) underwent medication change following NTS and culture results respectively (P < 0.001, kappa = 0.335). With reasonable use of antibiotic and surgical intervention, most patients responded favorably, judged by significantly improved visual acuity (Z = -4.249, P < 0.001). The mean duration of hospitalization was 8.49 ± 2.45 days (range, 1-16 days). CONCLUSION: The high efficiency feature of NTS in pathogen detection renders it a valuable supplementary to traditional culture. Additionally, it has facilitated patients' management for the early and precise diagnosis of endophthalmitis.

Bioinformatic Analysis Identifying PSMB 1/2/3/4/6/8/9/10 as Prognostic Indicators in Clear Cell Renal Cell Carcinoma.

Renal cancer incidence has been increasing across the world, clear cell renal cell carcinoma (ccRCC) represents the major subtype of renal cancer. The proteasome is involved in onset, metabolism and survival of tumor and has been recognized as a therapeutic target for various malignancies, while the role of ß subunits of proteasome, PSMB gene family, in ccRCC has not been fully unveiled. Herein we investigated the expression and the prognostic role of PSMBs in ccRCC by analyzing a series of databases, including ONCOMINE, UALCAN, cBioPortal, STRING, GEPIA, GO and KEGG. Over-expressions of PSMB1/2/4/7/8/9/10 mRNA were found in ccRCC tissues compared to normal tissues, transcriptional levels of PSMB2/3/4/6/8/9/10 were significantly positively associated with patients' individual cancer stages and grades. Similar or higher levels of proteins encoded by PSMB1/2/3/7/8/9/10 were observed in tumor tissues compared to normal renal tissues. Further, high mRNA levels of PSMB1/2/3/4/6/10 were correlated with shorter overall survival in univariate analysis. Taken together, the results of our analysis implied that overexpression of PSMB1/2/3/4/6/8/9/10 were indicative of worse prognosis of ccRCC. However, further researches were required to validate our findings.

Echocardiographic characteristics of PRKAG2 syndrome: a research using three-dimensional speckle tracking echocardiography compared with sarcomeric hypertrophic cardiomyopathy.

BACKGROUND: PRKAG2 syndrome is a rare disease characterized as left ventricular hypertrophy (LVH), ventricular preexcitation syndrome, and sudden cardiac death. Its natural course, treatment, and prognosis were significantly different from sarcomeric hypertrophic cardiomyopathy (HCM). However, it is often clinically misdiagnosed as sarcomeric HCM. PRKAG2 patients tend to experience delayed treatment. The delay may lead to adverse outcomes. This study aimed to identify the echocardiographic parameters which can differentiate PRKAG2 syndrome from sarcomeric HCM. METHODS: Nine PRKAG2 patients with LVH, 41 HCM patients with sarcomere gene mutations, and 202 healthy volunteers were enrolled. Clinical characteristics, conventional echocardiography, and three-dimensional images were recorded, and reviewed by an attending cardiologist. We evaluated the parameters of left ventricular strains from three-dimensional speckle tracking echocardiography (3D STE) by TomTec software. Receiver operating characteristic (ROC) curves analysis was used to assess clinical and echocardiographic parameters' differential diagnosis potential. RESULTS: The heart rate (HR) of the PRKAG2 group was significantly lower than both the healthy group (53.11 ± 10.14 vs. 69.22 ± 10.48 bpm, P < 0.001) and the sarcomeric HCM group (53.11 ± 10.14 vs. 67.23 ± 10.32 bpm, P = 0.001). The PRKAG2 group had similar interventricular septal thickness (IVS), posterior wall thickness (PWT), and maximum wall thickness (MWT) to the HCM group (P > 0.05). The absolute value of GLS in the PRKAG2 group was significantly higher than HCM patients (-18.92 ± 4.98 vs. -13.43 ± 4.30%, P = 0.004). SV calculated from EDV and ESV in PRKAG2 syndrome showed a higher value than sarcomeric HCM (61.83 ± 13.52 vs. 44.96 ± 17.53%, P = 0.020). The area under the ROC curve (AUC) for HR + GLS was 0.911 (0.803 -1). For HR + GLS, the sensitivity and specificity of the best cut-off value (0.114) were 69.0% and 100%, respectively. CONCLUSIONS: PRKAG2 patients present deteriorated LV diastolic function and preserved LV systolic function. Bradycardia and preserved GLS are useful to identify PRKAG2 syndrome from sarcomeric HCM, which may be beneficial for clinical decision-making.

Successful treatment of pulmonary injury due to nitrogen oxide exposure with extracorporeal membrane oxygenation: a report of two cases and literature review.

Background: Severe nitrogen oxide poisoning can lead to life-threatening pulmonary injury.Methods: we report two cases of severe nitrogen-oxide-induced hypoxia treated with veno-venous extracorporeal membrane oxygenation (ECMO). After exposure, the conditions of both patients continued to deteriorate despite maximal mechanical ventilation with a fraction of inspired oxygen of 100%; therefore, we started veno-venous ECMO. The times from presentation to the initiation of ECMO in the two patients were 1 and 2 days. The hypoxemia and respiratory failure improved quickly after ECMO support.Results: The patients were discharged without complications. The durations of ECMO for the two patients were 5 and 6 days. Conclusion: This report describes how early ECMO support was used to treat potentially fatal pulmonary injury after exposure to nitrogen oxide. The duration of the ECMO run is a critical determinant of patient survival.

Profiling of chromatin accessibility identifies transcription factor binding sites across the genome of Aspergillus species.

BACKGROUND: The identification of open chromatin regions and transcription factor binding sites (TFBs) is an important step in understanding the regulation of gene expression in diverse species. ATAC-seq is a technique used for such purpose by providing high-resolution measurements of chromatin accessibility revealed through integration of Tn5 transposase. However, the existence of cell walls in filamentous fungi and associated difficulty in purifying nuclei have precluded the routine application of this technique, leading to a lack of experimentally determined and computationally inferred data on the identity of genome-wide cis-regulatory elements (CREs) and TFBs. In this study, we constructed an ATAC-seq platform suitable for filamentous fungi and generated ATAC-seq libraries of Aspergillus niger and Aspergillus oryzae grown under a variety of conditions. RESULTS: We applied the ATAC-seq assay for filamentous fungi to delineate the syntenic orthologue and differentially changed chromatin accessibility regions among different Aspergillus species, during different culture conditions, and among specific TF-deleted strains. The syntenic orthologues of accessible regions were responsible for the conservative functions across Aspergillus species, while regions differentially changed between culture conditions and TFs mutants drove differential gene expression programs. Importantly, we suggest criteria to determine TFBs through the analysis of unbalanced cleavage of distinct TF-bound DNA strands by Tn5 transposase. Based on this criterion, we constructed data libraries of the in vivo genomic footprint of A. niger under distinct conditions, and generated a database of novel transcription factor binding motifs through comparison of footprints in TF-deleted strains. Furthermore, we validated the novel TFBs in vivo through an artificial synthetic minimal promoter system. CONCLUSIONS: We characterized the chromatin accessibility regions of filamentous fungi species, and identified a complete TFBs map by ATAC-seq, which provides valuable data for future analyses of transcriptional regulation in filamentous fungi.

Exploring the five different genes associated with PKCα in bladder cancer based on gene expression microarray.

Much progress has been made in understanding the mechanism of bladder cancer (BC) progression. Protein kinase C-α (PKCα) is overexpressed in many kinds of cancers. Additionally, PKCα is considered an oncogene that regulates proliferation, invasion, migration, apoptosis and cell cycle in multiple cancers. However, the mechanism underlying how these cellular processes are regulated by PKCα remains unknown. In the present study, we used PKCα siRNA to knock down PKCα gene expression and found that down-regulation of PKCα could significantly inhibit cell proliferation, migration and invasion and induce apoptosis and G1/S cell cycle arrest in vitro. Overexpression of PKCα promotes tumour growth in vivo. We applied cDNA microarray technology to detect the differential gene expression in J82 cells with PKCα knockdown and found that five key genes (BIRC2, BIRC3, CDK4, TRAF1 and BMP4) were involved in proliferation and apoptosis according to GO analysis and pathway analyses. Correlation analysis revealed a moderate positive correlation between PKCα expression and the expression of five downstream genes. BIRC2 and BIRC3 inhibit apoptosis, whereas CDK4, TRAF1 and BMP4 promote proliferation. Essentially, all five of these target genes participated in proliferation, and apoptosis was regulated by PKCα via the NF-kB signalling pathway.