The PPP2R1B gene, which encodes the beta isoform of the A subunit of the serine/threonine protein phosphatase 2A (PP2A), was identified as a putative human tumor suppressor gene. Sequencing of the PPP2R1B gene, located on human chromosome 11q22-24, revealed somatic alterations in 15% (5 out of 33) of primary lung tumors, 6% (4 out of 70) of lung tumor-derived cell lines, and 15% (2 out of 13) of primary colon tumors. One deletion mutation generated a truncated PP2A-Abeta protein that was unable to bind to the catalytic subunit of the PP2A holoenzyme. The PP2R1B gene product may suppress tumor development through its role in cell cycle regulation and cellular growth control.

Reactive gliosis and glial scar formation have been evidenced in the animal model of ischemic stroke, but not in human ischemic brain. Here, we have found that GFAP, ED1 and chondroitin sulphate proteoglycans (CSPG) expression were significantly increased in the cortical peri-infarct regions after ischemic stroke, compared with adjacent normal tissues and control subjects. Double immunolabeling showed that GFAP-positive reactive astrocytes in the peri-infarct region expressed CSPG, but showed no overlap with ED1-positive activated microglia. Our findings suggest that reactive gliosis and glial scar formation as seen in animal models of stroke are reflective of what occurs in the human brain after an ischemic injury.

The mortality rate of hemorrhagic African swine fever (ASF), which targets domestic pigs and wild boars is caused by African swine fever virus (ASFV), can reach 100%. Since the first confirmed ASF outbreak in China on 3 August 2018, 156 ASF outbreaks were detected in 32 provinces. About 1,170,000 pigs were culled in order to halt further spread. There is no effective treatment or vaccine for it and the present molecular diagnosis technologies have trade-offs in sensitivity, specificity, cost and speed, and none of them cater perfectly to ASF control. Thus, a technology that overcomes the need for laboratory facilities, is relatively low cost, and rapidly and sensitively detects ASFV would be highly valuable. Here, we describe an RAA-Cas12a-based system that combines recombinase aided amplification (RAA) and CRISPR/Cas12a for ASFV detection. The fluorescence intensity readout of this system detected ASFV p72 gene levels as low as 10 aM. For on-site ASFV detection, lateral-flow strip readout was introduced for the first time in the RAA-Cas12a based system (named CORDS, Cas12abased On-site and Rapid Detection System). We used CORDS to detect target DNA highly specifically using the lateral-flow strip readout and the assay displayed no crossreactivity to other 13 swine viruses including classical swine fever (CSF). CORDS could identify the ASFV DNA target at femtomolar sensitivity in an hour at 37 • C, and only requires an incubator. For ease of use, the reagents of CORDS were lyophilized to three tubes and remained the same sensitivity when stored at 4 • C for at least 7 days. Thus, CORDS provide a rapid, sensitive and easily operable method for ASFV on-site detection. Lyophilized CORDS can withstand long-term transportation and storage, and is ready for field-based applications.

Chronic cerebral hypoperfusion (CCH) increases the risk of Alzheimer disease (AD) through several biologically plausible pathways, but the relationship between CCH and the development of AD remains uncertain. To investigate expression of APP, BACE1 and A beta in the hippocampus of BCCAO rats and study pathophysiological mechanism of AD from CCH. CCH rat model was established by chronic bilateral common carotid artery occlusion (BCCAO). Behavior was evaluated after BCCAO with Morris water maze and open-field task. Expression of A beta was measured by enzyme linked immunosorbent assay (ELISA). beta-Amyloid precursor protein cleavage enzyme 1 (BACE1) and beta-amyloid precursor protein (APP) were tested by ELISA, Western blotting and RT-PCR. Cognitive impairment occurred with CCH by Morris water maze test and open-field task. The BACE1 and A beta level in BCCAO rats was more increased than sham-operation control rats (P < 0.01) but APP had no difference(P > 0.05). The expression of BACE1 and A beta has no inter-group difference in BCCAO rats (P > 0.05). The level of BACE1 and A beta had positive correlation with cognitive impairment (P < 0.01) while no correlation was observed between APP and cognitive impairment. Chronic cerebral ischemia contributes to cognitive impairment and vascular pathogenesis of Alzheimer's disease that chronic cerebral hypoperfusion increases BACE1 and A beta level in brain.

To compare the efficacy and toxicities of irinotecan/ platinum (IP) with etoposide/platinum (EP) in patients with previously untreated extensive-stage small cell lung cancer (E-SCLC). Methods: The PubMed database, the Cochrane Library, conference proceedings, databases of ongoing trials, and references of published trials and review articles were searched. Two reviewers independently assessed the quality of the trials and extracted data. The relative risk for overall response to treatment, hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios for the different types of toxicity were pooled by STATA package. Results: Six trials involving 1476 patients with previously untreated E-SCLC were ultimately analyzed. The intention-totreatment analysis indicated that IP regimens could acquire more overall response than EP regimens (relative risk ϭ 1.10, 95% confidence interval ͓CI͔: 1.00 -1.21, p ϭ 0.043). The pooled HR showed that IP could prolong OS (HR ϭ 0.81, 95% CI: 0.66 -0.99, p ϭ 0.044). Nevertheless, the pooled HR failed to show a favorable PFS in IP regimens (HR ϭ 0.82, 95% CI: 0.64 -1.06, p ϭ 0.139). IP regimens led to less grade 3 to 4 anemia, neutropenia, and thrombocytopenia but more grade 3 to 4 vomiting and diarrhea than EP regimens. Treatment-related deaths were comparable between the two groups. Conclusion: Although the PFS was similar from this meta-analysis, our results suggest that IP might have an advantage in overall response and OS compared with EP with less hematological toxicities. The IP regimens may be an alternative of EP regimens in the first-line treatment of E-SCLC.

Objective Nitric oxide (NO) was speculated to play an important role in the pathophysiology of cerebral ischemia. Minocycline, a tetracycline derivative, reduced inflammation and protected against cerebral ischemia. To study the neuroprotection mechanism of minocycline for vascular dementia, the influences of minocycline on expressions of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) were observed in the brains of Wistar rats. Methods The vascular dementia rat model was established by permanent bilateral common carotid arteries occlusion (BCCAO). Wistar rats were divideded into 3 groups randomly: sham-operation group (S group), vascular dementia model group (M group), and minocycline treatment group (MT group). The behaviour was tested with Morris water maze and open-field task. Expressions of iNOS and eNOS were measured by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). The optical density value was measured by imaging analysis. Percentage of positive cells with iNOS and eNOS expression was analyzed with optical microscope. Results Minocycline attenuated cognitive impairment. Inducible NOS was significantly down-regulated in MT group, compared with that in M group (P < 0.01), while eNOS was significantly up-regulated, compared with that in M group (P < 0.01). The expressions of iNOS and eNOS in M and MT groups were higher than those in S group (P < 0.01). Conclusion Minocycline can down-regulate the expression of iNOS and up-regulate the expression of eNOS in vascular dementia, which restrains apoptosis and oxidative stress to protect neural function.

Integrated single-cell RNA sequencing technologies reveal a high-resolution immune landscape of colorectal primary tumors and liver metastasis, identifying major immune cell types and distinct cell functional states of T and B cells as well as predictions of complex cell-cell interactions.

In the present study, we synthesized a novel cationic copolymer composed of polyethylene glycol 5000 (PEG5K), vitamin E (VE), and diethylenetriamine (DET) at 1:4:20 molar ratio. The resulting PEG5K-VE4-DET20 copolymer formed nanoassemblies when mixed with the neutral PEG5K-VE4 copolymer at 1:8 weight ratio, which were investigated as the nanocarriers for combined delivery of paclitaxel and let-7b mimic. We found that the PEG5K-VE4-DET20 nanoassemblies could entrap paclitaxel for an extended period and burst release the drug in the presence of cathepsin B, demonstrating the biodegradability of the copolymers. At N/P ratio of 12:1, the PEG5K-VE4-DET20 nanoassemblies formed stable polyplexes with let-7b mimic, which were efficiently taken up by tumor cells and underwent endosomal escape. In non-small cell lung cancer A549 cells that harbor mutant KRAS, paclitaxel and let-7b mimic-loaded nanoassemblies (N-PTX/let-7b) markedly potentiated the cytotoxicity of paclitaxel, induced apoptosis, and diminished the invasiveness of tumor cells. In mice bearing subcutaneous A549 xenografts, intravenous administration of N-PTX/let-7b retarded tumor growth more efficaciously than Taxol. Our study demonstrates the promise of the PEG5K-VE4-DET20 nanoassemblies for concurrent delivery of hydrophobic drugs and miRNA mimics.