PPM1G-mediated TBL1X mRNA splicing promotes cell migration in hepatocellular carcinoma.

The progression of hepatocellular carcinoma (HCC) is coincident with aberrant splicing of numerous tumor-related genes. Identification of the tumor-specific splice variants that facilitate HCC metastasis may provide a more comprehensive insight into the mechanisms of HCC metastasis. Through RNA sequencing and bioinformatic analyses, PPM1G was identified as a biomarker associated with HCC metastasis. Our data mapped a transcriptome-wide landscape of alternative splicing events modulated by PPM1G in HCC. Notably, we characterized the exon six-skipping transcript of TBL1X as an onco-splice variant regulated by PPM1G. Experimental validation revealed the enrichment of TBL1X-S in response to PPM1G overexpression. Moreover, mRNA stability analyses revealed that PPM1G prolonged the half-life of the TBL1X-S transcript. Both PPM1G and TBL1X-S exhibited metastasis-promoting phenotypes, with PPM1G-driven metastasis in HCC being partially dependent on TBL1X-S. Mechanistically, different TBL1X splice variants showed varying affinities for ZEB1, with TBL1X-S significantly enhancing ZEB1 activation and repressing CDH1 transcription, potentially accelerating the epithelial-mesenchymal transition (EMT) process. In conclusion, our study highlights the biological role of PPM1G and TBL1X-S in tumor metastasis. The PPM1G/TBL1X-S signaling axis presents a new view for investigating liver cancer metastasis mechanisms.

Interfacial Dipole Engineering for Energy Level Alignment in NiOx-Based Quantum Dot Light-Emitting Diodes.

The solution-derived non-stoichiometric nickel oxide (NiOx) is a promising hole-injecting material for stable quantum dot light-emitting diodes (QLEDs). However, the carrier imbalance due to the misalignment of energy levels between the NiOx and polymeric hole-transporting layers (HTLs) curtails the device efficiency. In this study, the modification of the NiOx surface is investigated using either 3-cyanobenzoic acid (3-CN-BA) or 4-cyanobenzoic acid (4-CN-BA) in the QLED fabrication. Morphological and electrical analyses revealed that both 4-CN-BA and 3-CN-BA can enhance the work function of NiOx, reduce the oxygen vacancies on the NiOx surface, and facilitate a uniform morphology for subsequent HTL layers. Moreover, it is found that the binding configurations of dipole molecules as a function of the substitution position of the tail group significantly impact the work function of underlying layers. When integrated in QLEDs, the modification layers resulted in a significant improvement in the electroluminescent efficiency due to the enhancement of energy level alignment and charge balance within the devices. Specifically, QLEDs incorporating 4-CN-BA achieved a champion external quantum efficiency (EQE) of 20.34%, which is a 1.8X improvement in comparison with that of the devices utilizing unmodified NiOx (7.28%). Moreover, QLEDs with 4-CN-BA and 3-CN-BA modifications exhibited prolonged operational lifetimes, indicating potential for practical applications.

Blue valorization of lignin-derived monomers via reprogramming marine bacterium Roseovarius nubinhibens.

Biological valorization of lignin, the second most abundant biopolymer on Earth, is an indispensable sector to build a circular economy and net-zero future. However, lignin is recalcitrant to bioupcycling, demanding innovative solutions. We report here the biological valorization of lignin-derived aromatic carbon to value-added chemicals without requesting extra organic carbon and freshwater via reprogramming the marine Roseobacter clade bacterium Roseovarius nubinhibens. We discovered the unusual advantages of this strain for the oxidation of lignin monomers and implemented a CRISPR interference (CRISPRi) system with the lacI-Ptrc inducible module, nuclease-deactivated Cas9, and programmable gRNAs. This is the first CRISPR-based regulatory system in R. nubinhibens, enabling precise and efficient repression of genes of interest. By deploying the customized CRISPRi, we reprogrammed the carbon flux from a lignin monomer, 4-hydroxybenzoate, to achieve the maximum production of protocatechuate, a pharmaceutical compound with antibacterial, antioxidant, and anticancer properties, with minimal carbon to maintain cell growth and drive biocatalysis. As a result, we achieved a 4.89-fold increase in protocatechuate yield with a dual-targeting CRISPRi system, and the system was demonstrated with real seawater. Our work underscores the power of CRISPRi in exploiting novel microbial chassis and will accelerate the development of marine synthetic biology. Meanwhile, the introduction of a new-to-the-field lineage of marine bacteria unveils the potential of blue biotechnology leveraging resources from the ocean.IMPORTANCEOne often overlooked sector in carbon-conservative biotechnology is the water resource that sustains these enabling technologies. Similar to the "food-versus-fuel" debate, the competition of freshwater between human demands and bioproduction is another controversial issue, especially under global water scarcity. Here, we bring a new-to-the-field lineage of marine bacteria with unusual advantages to the stage of engineering biology for simultaneous carbon and water conservation. We report the valorization of lignin monomers to pharmaceutical compounds without requesting extra organic substrate (e.g., glucose) or freshwater by reprogramming the marine bacterium Roseovarius nubinhibens with a multiplex CRISPR interference system. Beyond the blue lignin valorization, we present a proof-of-principle of leveraging marine bacteria and engineering biology for a sustainable future.

A nomogram model for predicting intramyocardial hemorrhage post-PCI based on SYNTAX score and clinical features.

OBJECTIVE: The aim of this study is to develop a nomogram model for predicting the occurrence of intramyocardial hemorrhage (IMH) in patients with Acute Myocardial Infarction (AMI) following Percutaneous Coronary Intervention (PCI). The model is constructed utilizing clinical data and the SYNTAX Score (SS), and its predictive value is thoroughly evaluated. METHODS: A retrospective study was conducted, including 216 patients with AMI who underwent Cardiac Magnetic Resonance (CMR) within a week post-PCI. Clinical data were collected for all patients, and their SS were calculated based on coronary angiography results. Based on the presence or absence of IMH as indicated by CMR, patients were categorized into two groups: the IMH group (109 patients) and the non-IMH group (107 patients). The patients were randomly divided in a 7:3 ratio into a training set (151 patients) and a validation set (65 patients). A nomogram model was constructed using univariate and multivariate logistic regression analyses. The predictive capability of the model was assessed using Receiver Operating Characteristic (ROC) curve analysis, comparing the predictive value based on the area under the ROC curve (AUC). RESULTS: In the training set, IMH post-PCI was observed in 78 AMI patients on CMR, while 73 did not show IMH. Variables with a significance level of P < 0.05 were screened using univariate logistic regression analysis. Twelve indicators were selected for multivariate logistic regression analysis: heart rate, diastolic blood pressure, ST segment elevation on electrocardiogram, culprit vessel, symptom onset to reperfusion time, C-reactive protein, aspartate aminotransferase, lactate dehydrogenase, creatine kinase, creatine kinase-MB, high-sensitivity troponin T (HS-TnT), and SYNTAX Score. Based on multivariate logistic regression results, two independent predictive factors were identified: HS-TnT (Odds Ratio [OR] = 1.61, 95% Confidence Interval [CI]: 1.21-2.25, P = 0.003) and SS (OR = 2.54, 95% CI: 1.42-4.90, P = 0.003). Consequently, a nomogram model was constructed based on these findings. The AUC of the nomogram model in the training set was 0.893 (95% CI: 0.840-0.946), and in the validation set, it was 0.910 (95% CI: 0.823-0.970). Good consistency and accuracy of the model were demonstrated by calibration and decision curve analysis. CONCLUSION: The nomogram model, constructed utilizing HS-TnT and SS, demonstrates accurate predictive capability for the risk of IMH post-PCI in patients with AMI. This model offers significant guidance and theoretical support for the clinical diagnosis and treatment of these patients.

Discovery of Dehydroabietylamine Derivatives as Antibacterial and Antifungal Agents.

A diverse array of biologically active derivatives was derived by modifying the chemically active sites of dehydroabietylamine. Herein, we describe the synthesis of a new series of C-19-arylated dehydroabietylamine derivatives using a palladium-catalyzed C(sp3)-H activation reaction. Five analogues (3b, 3d, 3h, 3n, and 4a) exhibited antibacterial activity against Escherichia coli. Compound 4a exhibited strong inhibitory activity against DNA Topo II and Topo IV. Molecular docking modeling indicated that it can bind effectively to the target through interactions with amino acid residues. The synthesized compounds were tested in vitro for their antifungal activity against six common phytopathogenic fungi. The mechanism of action of compound 4c against Rhizoctorzia solani was investigated, revealing that it disrupts the morphology of the mycelium and enhances cell membrane permeability.

How accurate is predicted root movement achieved in four first-premolar extraction cases with Invisalign?

OBJECTIVES: This study aims to compare the achieved and predicted root movements in adults after four first-premolar extractions and Invisalign treatment. MATERIALS AND METHODS: Thirty-three consecutive adults (22 Class I, 9 Cusp-to-cusp Class II and 2 Cusp-to-cusp Class III) from a single clinical division who completed the first series of aligners after premolar extractions were included in this retrospective study. A pretreatment cone-beam computed tomography model was registered onto the pretreatment surface-scanned dental model (SSDM) to locate the pretreatment root apices of the whole dentition. These were copied and transferred to the predicted and achieved post-treatment SSDMs to acquire the locations of the predicted and achieved post-treatment root apices. The differences between predicted and achieved root movements (DPARMs) were tested using the paired t-test or Wilcoxon signed rank test. RESULTS: In the anteroposterior direction, posterior root movements of maxillary and mandibular anterior teeth were poorly achieved (3.24-5.74 mm DPARMs, p < .05). In the vertical direction, roots of maxillary anterior teeth achieved greater intrusion (0.70-0.93 mm DPARMs, p < .05), while those of mandibular incisors achieved less intrusion (0.57-0.65 mm DPARMs, p < .05) than predicted. In the mediolateral direction, lateral incisor roots did not move distally (-0.65 to -0.96 mm DPARMs, p < .05), while those of canines did not move buccally, compared with the prediction (-0.75 mm DPARMs, p < .05). CONCLUSIONS: In the four first-premolar extraction treatments with Invisalign, root movements were not achieved as predicted, particularly for anterior teeth in the anteroposterior direction.

Analysis of the phytochemical components of Prunella vulgaris using high-performance liquid chromatography quadrupole time-of-flight mass spectrometry combined with molecular networking and assessment of their antioxidant and anti-α-glucosidase activities.

Prunella vulgaris has long been used in traditional medicine and is consumed as a tea in China. Here, the total phenolic and flavonoid concentrations of plants from different geographical regions were measured. It was found that the total phenolic acid concentration ranged from 4.15 to 8.82 g of gallic acid equivalent per 100 g of dry weight (DW), and the total flavonoid concentration was 4.67-7.33 g of rutin equivalent per 100 g DW. Antioxidant activities were measured using 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt, and the results ranged from 73.47% to 94.43% and 74.54% to 93.39%, respectively, whereas α-glucosidase inhibition was between 75.31% and 95.49%. Correlation analysis showed that the total flavonoids in P. vulgaris had superior antioxidant and anti-α-glucosidase activities compared to the total phenolic compounds. The active components of P. vulgaris were analyzed using high-performance liquid chromatography quadrupole time-of-flight mass spectrometry combined with both classical molecular networking and feature-based molecular networking on the Global Natural Products Social platform, identifying 32 compounds, namely 14 flavonoids, 12 phenolic compounds, and 6 other chemical components. These results could provide useful information on the use of P. vulgaris as a functional tea.

Cuproptosis-Associated lncRNA Gene Signature Establishes New Prognostic Profile and Predicts Immunotherapy Response in Endometrial Carcinoma.

Uterine corpus endometrial carcinoma (UCEC), a prevalent kind of cancerous tumor in female reproductive system that has a dismal prognosis in women worldwide. Given the very limited studies of cuproptosis-related lncRNAs (CRLs) in UCEC. Our purpose was to construct a prognostic profile based on CRLs and explore its assess prognostic value in UCEC victims and its correlation with the immunological microenvironment. METHODS: 554 UCEC tumor samples and 23 normal samples' RNA-seq statistics and clinical details were compiled from data in the TCGA database. CRLs were obtained using Pearson correlation analysis. Using LASSO Cox regression, multivariate Cox regression, and univariate Cox regression analysis, six CRLs are confirmed to develop a risk prediction model at last.We identified two main molecular subtypes and observed that multilayer CRLs modifications were related to patient clinicopathological features, prognosis, and tumor microenvironment (TME) cell infiltration characteristics, and then we verified the prognostic hallmark of UCEC and examined its immunological landscape.Finally, using qRT-PCR, model hub genes' expression patterns were confirmed. RESULTS: A unique CRL signature was established by the combination of six differently expressed CRLs that were highly linked with the prognosis of UCEC patients. According to their CRLs signatures, the patients were divided into two groups: the low-risk and the high-risk groups. Compared to individuals at high risk, patients at low risk had higher survival rates (p < 0.001). Additionally, Cox regression reveals that the profiles of lncRNAs linked to cuproptosis may independently predict prognosis in UCEC patients. The 1-, 3-, and 5-year risks' respective receiver operating characteristics (ROC) exhibited AUC values of 0.778, 0.810, and 0.854. Likewise, the signature could predict survival in different groups based on factors like stage, age, and grade, among others. Further investigation revealed differences between the different risk score groups in terms of drug sensitivity,immune cell infiltration,tumor mutation burden (TMB) score and microsatellite instability (MSI) score. Compared to the group of high risk, the low-risk group had greater rates of TMB and MSI. Results from qRT-PCR revealed that in UCEC vs normal tissues, AC026202.2, NRAV, AC079466.2, and AC090617.5 were upregulated,while LINC01545 and AL450384.1 were downregulated. CONCLUSIONS: Our research clarified the relationship between CRLs signature and the immunological profile and prognosis of UCEC.This signature will establish the framework for future investigations into the endometrial cancer CRLs mechanism as well as the exploitation of new diagnostic tools and new therapeutic.

Flexible Substrate-Compatible and Efficiency-Improved Quantum-Dot Light-Emitting Diodes with Reduced Annealing Temperature of NiOx Hole-Injecting Layer.

The growing demand for wearable and attachable displays has sparked significant interest in flexible quantum-dot light-emitting diodes (QLEDs). However, the challenges of fabricating and operating QLEDs on flexible substrates persist due to the lack of stable and low-temperature processable charge-injection/-transporting layers with aligned energy levels. In this study, we utilized NiOx nanoparticles that are compatible with flexible substrates as a hole-injection layer (HIL). To enhance the work function of the NiOx HIL, we introduced a self-assembled dipole modifier called 4-(trifluoromethyl)benzoic acid (4-CF3-BA) onto the surface of the NiOx nanoparticles. The incorporation of the dipole molecules through adsorption treatment has significantly changed the wettability and electronic characteristics of NiOx nanoparticles, resulting in the formation of NiO(OH) at the interface and a shift in vacuum level. The alteration of surface electronic states of the NiOx nanoparticles not only improves the carrier balance by reducing the hole injection barrier but also prevents exciton quenching by passivating defects in the film. Consequently, the NiOx-based red QLEDs with interfacial modification demonstrate a maximum current efficiency of 16.1 cd/A and a peak external quantum efficiency of 10.3%. This represents a nearly twofold efficiency enhancement compared to control devices. The mild fabrication requirements and low annealing temperatures suggest potential applications of dipole molecule-modified NiOx nanoparticles in flexible optoelectronic devices.

[Research Progress in Complement Receptor of the Immunoglobulin Superfamily in Regulating Liver Immunity].

Kupffer cells (KC),an important subset of immune cells in the liver,are essential for maintaining tissue homeostasis and responding quickly to liver damage.The complement receptor of the immunoglobulin superfamily (CRIg) is a receptor protein on the KC membrane.CRIg can not only capture pathogens in the blood flowing through the liver by complement binding but also mediate immune responses by regulating immune cells in the liver.Recent studies have confirmed the role of CRIg in regulating liver immunity.This article reviews the main modes of action of CRIg and the research progress of CRIg in regulating liver immunity.

Real-World Effectiveness of Primary Series and Booster Doses of Inactivated Coronavirus Disease 2019 Vaccine Against Omicron BA.2 Variant Infection in China: A Retrospective Cohort Study.

BACKGROUND: China has been using inactivated coronavirus disease 2019 (COVID-19) vaccines as primary series and booster doses to protect the population from severe to fatal COVID-19. We evaluated primary and booster vaccine effectiveness (VE) against Omicron BA.2 infection outcomes. METHODS: This was a 13-province retrospective cohort study of quarantined close contacts of BA.2-infected individuals. Outcomes were BA.2 infection, COVID-19 pneumonia or worse, and severe/critical COVID-19. Absolute VE was estimated by comparison with an unvaccinated group. RESULTS: There were 289 427 close contacts ≥3 years old exposed to Omicron BA.2 cases; 31 831 turned nucleic acid amplification test-positive during quarantine, 97.2% with mild or asymptomatic infection, 2.6% with COVID-19 pneumonia, and 0.15% with severe/critical COVID-19. None died. Adjusted VE (aVE) against any infection was 17% for primary series and 22% when boosted. Primary series aVE in adults >18 years was 66% against COVID-19 pneumonia or worse and 91% against severe/critical COVID-19. Booster dose aVE was 74% against pneumonia or worse, and 93% against severe/critical COVID-19. CONCLUSIONS: Inactivated COVID-19 vaccines provided modest protection from infection, very good protection against pneumonia, and excellent protection against severe/critical COVID-19. Booster doses are necessary to provide strongest protection.

Base editing for reprogramming cyanobacterium Synechococcus elongatus.

Cyanobacteria can directly convert carbon dioxide (CO2) at the atmospheric level to biofuels, value-added chemicals and food products, making them ideal candidates to alleviate global climate change. Despite decades-long pioneering successes, the development of genome-editing tools, especially the CRISPR-Cas-based approaches, seems to lag behind other microbial chassis, slowing down the innovations of cyanobacteria. Here, we adapted and tailored base editing for cyanobacteria based on the CRISPR-Cas system and deamination. We achieved precise and efficient genome editing at a single-nucleotide resolution and demonstrated multiplex base editing in the model cyanobacterium Synechococcus elongatus. By using the base-editing tool, we successfully manipulated the glycogen metabolic pathway via the introduction of premature STOP codons in the relevant genes, building engineered strains with elevated potentials to produce chemicals and food from CO2. We present here the first report of base editing in the phylum of cyanobacteria, and a paradigm for applying CRISPR-Cas systems in bacteria. We believe that our work will accelerate the metabolic engineering and synthetic biology of cyanobacteria and drive more innovations to alleviate global climate change.

Degradation of Antibiotic Resistance Genes by VADER with CRISPR-Cas Immunity.

The evolution and dissemination of antibiotic resistance genes (ARGs) are prompting severe health and environmental issues. While environmental processes, e.g., biological wastewater treatment, are key barriers to prevent the spread of ARGs, they are often sources of ARGs at the same time, requiring upgraded biotechnology. Here, we present VADER, a synthetic biology system for the degradation of ARGs based on CRISPR-Cas immunity, an archaeal and bacterial immune system for eliminating invading foreign DNAs, to be implemented for wastewater treatment processes. Navigated by programmable guide RNAs, VADER targets and degrades ARGs depending on their DNA sequences, and by employing an artificial conjugation machinery, IncP, it can be delivered via conjugation. The system was evaluated by degrading plasmid-borne ARGs in Escherichia coli and further demonstrated via the elimination of ARGs on the environmentally relevant RP4 plasmid in Pseudomonas aeruginosa. Next, a prototype conjugation reactor at a 10-mL scale was devised, and 100% of the target ARG was eliminated in the transconjugants receiving VADER, giving a proof of principle for the implementation of VADER in bioprocesses. By generating a nexus of synthetic biology and environmental biotechnology, we believe that our work is not only an enterprise for tackling ARG problems but also a potential solution for managing undesired genetic materials in general in the future. IMPORTANCE Antibiotic resistance has been causing severe health problems and has led to millions of deaths in recent years. Environmental processes, especially those of the wastewater treatment sector, are an important barrier to the spread of antibiotic resistance from the pharmaceutical industry, hospitals, or civil sewage. However, they have been identified as a nonnegligible source of antibiotic resistance at the same time, as antibiotic resistance with its main cause, antibiotic resistance genes (ARGs), may accumulate in biological treatment units. Here, we transplanted the CRISPR-Cas system, an immune system via programmable DNA cleavage, to tackle the antibiotic resistance problem raised in wastewater treatment processes, and we propose a new sector specialized in ARG removal with a conjugation reactor to implement the CRISPR-Cas system. Our study provides a new angle for resolving public health issues via the implementation of synthetic biology in environmental contexts at the process level.

No-touch endoscopic full-thickness resection technique for gastric gastrointestinal stromal tumors.

BACKGROUND : There remain concerns regarding the technical feasibility of endoscopic resection for large gastrointestinal stromal tumors (GISTs), mainly relating to the risk of tumor rupture and the adequacy of the resection margins. This study aimed to evaluate the feasibility and therapeutic outcomes of the newly developed no-touch endoscopic full-thickness resection (NT-EFTR) technique for GISTs. METHODS : In this retrospective study, 92 patients with gastric GISTs undergoing NT-EFTR were included. Clinicopathological, endoscopic, and follow-up data were collected and analyzed. RESULTS : The median tumor size was 2.5 cm and en bloc resection was achieved in all patients with negative surgical margins. The median time of the NT-EFTR procedure was 59.5 minutes. Large tumors (> 3.0 cm), extraluminal tumor growth pattern, and large gastric defects were significant contributors to long operative times. Patients were discharged within 4 days postoperatively. During follow-up, all patients were free from local recurrence and distant metastasis. CONCLUSIONS : NT-EFTR was a feasible method for the resection of gastric GISTs and can be expected to achieve complete radical resection. Large tumors with extraluminal growth and large gastric defects impact procedural difficulty.

Effectiveness and safety of REBACIN as a non-invasive intervention for persistent high-risk human papillomavirus infection: A real-world prospective multicenter cohort study.

BACKGROUND: We previously reported that REBACIN effectively eliminates persistent high-risk human papillomavirus (hrHPV) infection. Here, we conducted a prospective multicenter cohort study to evaluate the safety and effectiveness of REBACIN, taking into account factors such as specific hrHPV subtype and patient's age. METHODS: According to inclusion/exclusion criteria and participant willingness, 3252 patients were divided into REBACIN group while 249 patients into control group. Patients in REBACIN group received one course treatment of intravaginal administration of REBACIN while no treatment in control group. After drug withdrawal, participants in both groups were followed up. RESULTS: The clearance rate of persistent hrHPV infection in REBACIN group was 60.64%, compared to 20.08% in control group. Specifically, the clearance rates for single-type infection of HPV16 or HPV18 were 70.62% and 69.23%, respectively, which was higher than that of HPV52 (59.04%) or HPV58 (62.64%). In addition, the single, double, and triple/triple+ infections had a clearance rate of 65.70%, 53.31%, and 38.30%, respectively. Moreover, 1635 patients under 40 years old had a clearance rate of 65.14%, while it was 55.08% for 1447 patients over 40 years old. No serious adverse effects were found. CONCLUSION: This study confirmed that REBACIN can effectively and safely eliminate persistent hrHPV infection, which the clearance rate of HPV16/18 is higher than that of HPV52/58, the clearance rate of single-type infection is higher than that of multiple-type infections, and the clearance rate in young patients is higher than that in elder patients, providing a guidance for REBACIN application in clearing hrHPV persistent infection in real-world settings. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry Registration Number: ChiCTR1800015617 http://www.chictr.org.cn/showproj.aspx?proj=26529 Date of Registration: 2018-04-11.

Clinical, biological, and outcome features of P2RY8-CRLF2 and CRLF2 over-expression in pediatric B-cell precursor acute lymphoblastic leukemia according to the CCLG-ALL 2008 and 2018 protocol.

OBJECTIVES: CRLF2 alterations are associated with B-cell precursor acute lymphoblastic leukemia (BCP-ALL). This study aimed to explore the clinical, biological, and outcome features of pediatric BCP-ALL with CRLF2 abnormalities. METHODS: This study enrolled 630 childhood BCP-ALLs treated on CCLG-ALL 2008 or 2018 protocol. P2RY8-CRLF2 was determined by Sanger sequencing and CRLF2 expression was evaluated by qRT-PCR. The correlation between clinical, biological features and outcomes with P2RY8-CRLF2 or CRLF2 over-expression were analyzed. RESULTS: P2RY8-CRLF2 and CRLF2 over-expression were found in 3.33% and 5.71% respectively. P2RY8-CRLF2 was associated with male, higher frequency of CD7 expression, high WBC and MRD before consolidation. CRLF2 over-expression showed ETV6-RUNX1- , higher frequency of CD22, CD34, CD66c, CD86 expression, hyperdiploidy and high MRD at early treatment. The lower overall survival (OS) was found in patients with P2RY8-CRLF2 and confined only in IR group. Furthermore, adverse event-free survival and OS of P2RY8-CRLF2 were discovered comparing to those without known fusions or treated on CCLG-ALL 2008 protocol. However, P2RY8-CRLF2 was not confirmed as independent prognostic factors and no prognostic impact of CRLF2 over-expression was found. CONCLUSIONS: These findings indicate P2RY8-CRLF2 identifies a subset of patients with specific features and adverse outcomes that could be improved by risk-directed treatment.

Purinergic ATP triggers moxibustion-induced local anti-nociceptive effect on inflammatory pain model.

Purinergic signalling adenosine and its A1 receptors have been demonstrated to get involved in the mechanism of acupuncture (needling therapy) analgesia. However, whether purinergic signalling would be responsible for the local analgesic effect of moxibustion therapy, the predominant member in acupuncture family procedures also could trigger analgesic effect on pain diseases, it still remains unclear. In this study, we applied moxibustion to generate analgesic effect on complete Freund's adjuvant (CFA)-induced inflammatory pain rats and detected the purine released from moxibustioned-acupoint by high-performance liquid chromatography (HPLC) approach. Intramuscular injection of ARL67156 into the acupoint Zusanli (ST36) to inhibit the breakdown of ATP showed the analgesic effect of moxibustion was increased while intramuscular injection of ATPase to speed up ATP hydrolysis caused a reduced moxibustion-induced analgesia. These data implied that purinergic ATP at the location of ST36 acupoint is a potentially beneficial factor for moxibustion-induced analgesia.

MicroRNA: Crucial modulator in purinergic signalling involved diseases.

Both microRNAs (miRNAs) and purinergic signalling are widely and respectively expressed in various tissues of different organisms and play vital roles in a variety of physiological and pathological processes. Here, we reviewed the current publications contributed to the relationship of miRNAs and purinergic signalling in cardiovascular diseases, gastrointestinal diseases, neurological diseases, and ophthalmic diseases. We tried to decode the miRNAs-purinergic signalling network of purinergic signalling involved diseases. The evidence indicated that more than 30 miRNAs (miR-22, miR-30, miR-146, miR-150, miR-155, miR-187, etc.) directly or indirectly modulate P1 receptors (A1, A2A, A2B, A3), P2 receptors (P2X1, P2X3, P2X4, P2X7, P2Y2, P2Y6, P2Y12), and ecto-enzymes (CD39, CD73, ADA2); P2X7 and CD73 could be modulated by multiple miRNAs (P2X7: miR-21, miR-22, miR-30, miR-135a, miR-150, miR-186, miR-187, miR-216b; CD73: miR-141, miR-101, miR-193b, miR-340, miR-187, miR-30, miR-422a); miR-187 would be the common miRNA to modulate P2X7 and CD73.

Hotair promotes the migration and proliferation in ovarian cancer by miR-222-3p/CDK19 axis.

Previous studies in our laboratory have reported that miR-222-3p was a tumor-suppressive miRNA in OC. This study aims to further understand the regulatory role of miR-222-3p in OC and provide a new mechanism for its prevention and treatment. We first found that miR-222-3p inhibited the migration and proliferation of OC cells. Then, we observed CDK19 was highly expressed in OC and inversely correlated with miR-222-3p. Besides, we observed that miR-222-3p directly binds to the 3'-UTR of CDK19 and inhibits CDK19 translation, thus inhibiting OC cell migration and proliferation in vitro and repressed tumor growth in vivo. We also observed the inhibitory effect of Hotair on miR-222-3p in OC. In addition, Hotair could promote the proliferation and migration of OC cells in vitro and facilitate the growth and metastasis of tumors in vivo. Moreover, Hotair was positively correlated with CDK19 expression. These results suggest Hotair indirectly up-regulates CDK19 through sponging miR-222-3p, which enhances the malignant behavior of OC. This provides a further understanding of the mechanism of the occurrence and development of OC.

Comprehensive analysis of the PTPN13 expression and its clinical implication in breast cancer.

Protein tyrosine phosphatases non-receptor 13 (PTPN13) could be a potential biomarker in breast cancer (BRCA), but its genetic variation and biological significance in BRCA remain undefined. Hereon, we comprehensively investigated the clinical implication of PTPN13 expression/gene mutation in BRCA. In our study, a total of 14 cases of triple-negative breast cancers (TNBC) treated with neoadjuvant therapy were enrolled, and post-operation TNBC tissues were collected for next-generation sequencing (NGS) analysis (422 genes including PTPN13). According to the disease-free survival (DFS) time, 14 TNBC patients were divided into Group A (long-DFS) and Group B (short-DFS). The NGS data displayed that the overall mutation rate of PTPN13 was 28.57% as the third highest mutated gene, and PTPN13 mutations appeared only in Group B with short-DFS. In addition, The Cancer Genome Atlas (TCGA) database demonstrated that PTPN13 was lower expressed in BRCA than in normal breast tissues. However, PTPN13 high expression was identified to be related to a favorable prognosis in BRCA using data from the Kaplan-Meier plotter. Moreover, Gene Set Enrichment Analysis (GSEA) revealed that PTPN13 is potentially involved in interferon signaling, JAK/STAT signaling, Wnt/ß-catenin signaling, PTEN pathway, and MAPK6/MAPK4 signaling in BRCA. This study provided evidence that PTPN13 might be a tumor suppressor gene and a potential molecular target for BRCA, and genetic mutation and/or low expression of PTPN13 predicted an unfavorable prognosis in BRCA. The anticancer effect and molecular mechanism of PTPN13 in BRCA may be associated with some tumor-related signaling pathways.