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Abstract Acute lung injury (ALI) is a common critical respiratory disease in clinical practice, especially in the ICU, with a high mortality rate. The pathogenesis of ALI is relatively complex, mainly involving inflammatory response imbalance, oxidative stress, cell apoptosis, and other aspects. However, currently, the treatment measures taken based on the above mechanisms have not had significant effects. Recent research shows that mitochondrial dysfunction and pyroptosis play an important role in ALI, but there is not much analysis on the relationship between mitochondrial dysfunction and pyroptosis at present. This article reviews the situation of mitochondrial dysfunction in ALI, pyroptosis in ALI, whether mitochondrial dysfunction is related to pyroptosis in ALI, and how to do so, and further analyzes the relationship between them in ALI. This review describes how to alleviate mitochondrial dysfunction, and then suppress the associated immunological pyroptosis, providing new ideas for the clinical treatment of ALI.

Abstract Circular RNA (circRNA) is thought to mediate the occurrence and development of human cancer and usually acts as a tiny RNA (miRNA) sponge to regulate downstream gene expression. However, it is not clear whether and how circACVR2A (hsa_circ_0001073) is involved in the progression of HCC. The purpose of this study is to clarify the potential role and molecular mechanism of circACVR2A in regulating the progression of hepatocellular carcinoma cells (HCC). The abundance of related proteins in circACVR2A, microRNA (miR511-5p) and PI3K-Akt signaling pathway was determined by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) or Western blotting. Cell viability, invasion and apoptosis were analyzed by CCK-8, Transwell analysis and Tunel staining, respectively. The interaction between circACVR2A and microRNA was evaluated by double luciferase reporter gene assay. The results showed that circACVR2A was highly expressed in hepatocellular carcinoma cell lines. Our in vivo and in vitro data showed that circACVR2A promoted the proliferation, migration and invasion of HCC. In terms of mechanism, we found that circACVR2A can directly interact with miR511-5p and act as a miRNA sponge to regulate the expression of related proteins in PI3K-Akt signaling pathway. In HCC, circACVR2A can mediate miR-511-5p/mRNA network to activate PI3K signal pathway. This shows that the molecular regulatory network with circACVR2A as the core is a new potential target for diagnosis and treatment of hepatocellular carcinoma.

ABSTRACT African swine fever (ASF) is a highly fatal viral disease that poses a significant threat to domestic pigs and wild boars globally. In our study, we aimed to explore the potential of a multiplexed CRISPR-Cas system in suppressing ASFV replication and infection. By engineering CRISPR-Cas systems to target nine specific loci within the ASFV genome, we observed a substantial reduction in viral replication in vitro. This reduction was achieved through the concerted action of both Type II and Type III RNA polymerase-guided gRNA expression. To further evaluate its anti-viral function in vivo, we developed a pig strain expressing the multiplexable CRISPR-Cas-gRNA via germline genome editing. These transgenic pigs exhibited normal health with continuous expression of the CRISPR-Cas-gRNA system, and a subset displayed latent viral replication and delayed infection. However, the CRISPR-Cas9-engineered pigs did not exhibit a survival advantage upon exposure to ASFV. To our knowledge, this study represents the first instance of a living organism engineered via germline editing to assess resistance to ASFV infection using a CRISPR-Cas system. Our findings contribute valuable insights to guide the future design of enhanced viral immunity strategies.IMPORTANCEASFV is currently a devastating disease with no effective vaccine or treatment available. Our study introduces a multiplexed CRISPR-Cas system targeting nine specific loci in the ASFV genome. This innovative approach successfully inhibits ASFV replication in vitro, and we have successfully engineered pig strains to express this anti-ASFV CRISPR-Cas system constitutively. Despite not observing survival advantages in these transgenic pigs upon ASFV challenges, we did note a delay in infection in some cases. To the best of our knowledge, this study constitutes the first example of a germline-edited animal with an anti-virus CRISPR-Cas system. These findings contribute to the advancement of future anti-viral strategies and the optimization of viral immunity technologies.

UAV swarm passive positioning technology only requires the reception of electromagnetic signals to achieve the positioning and tracking of radiation sources. It avoids the active positioning strategy that requires active emission of signals and has the advantages of good concealment, long acting distance, and strong anti-interference ability, which has received more and more attention. In this paper, we propose a new UAV swarm formation flight method based on pure azimuth passive positioning. Specifically, we propose a two-circle positioning model, which describes the positional deviation of the receiving UAV using trigonometric functions relative to the target in polar coordinates. Furthermore, we design a two-step adjustment strategy that enables the receiving UAV to reach the target position efficiently. Based on the above design, we constructed an optimized UAV swarm formation scheme. In experiments with UAV numbers of 8 and 20, compared to the representative comparison strategy, the proposed UAV formation scheme reduces the total length of the UAV formation by 34.76% and 55.34%, respectively. It demonstrates the effectiveness of the proposed method in the application of assigning target positions to UAV swarms.

Etomidate is a general anesthetic that has shown good hemodynamic stability without significant cardiovascular or respiratory depression. Despite several kinds of dosage forms having been reported for this drug, formulation types are very limited in clinical practice, and brain-targeted formulations for this central nervous system (CNS) drug have been rarely reported. Moreover, studies on the biocompatibility, toxicity, and anesthetic effects of the etomidate preparations in vivo were inadequate. The present study was to develop lactoferrin-modified liposomal etomidate (Eto-lip-LF) for enhanced drug distribution in the brain and improved anesthetic effects. Eto-lip-LF had good stability for storage and hemocompatibility for intravenous injection. Compared with the non-lactoferrin-containing liposomes, the lactoferrin-modified liposomes had notably enhanced brain-targeting ability in vivo, which was probably realized by the binding of transferrin with the transferrin and lactoferrin receptors highly distributed in the brain. Eto-lip-LF had a therapeutic index of about 25.3, higher than that of many other general anesthetics. Moreover, compared with the commercial etomidate emulsion, Eto-lip-LF could better achieve rapid onset of general anesthesia and rapid recovery from anesthesia, probably due to the enhanced drug delivery to the brain. The above results demonstrated the potential of this lactoferrin-modified liposomal etomidate to become an alternative preparation for clinical general anesthesia.

The endocrine disrupting activity of bisphenol compounds is well documented, but less is known regarding their impact on cell division and early embryo formation. Here, we tested the effects of acute in vitro exposure to bisphenol A (BPA) and its common substitute, bisphenol F (BPF), during critical stages of mouse pre-implantation embryo development, including the first mitotic division, cell polarization, as well as morula and blastocyst formation. Timing of initial cleavage was determined by live-cell imaging, while subsequent divisions, cytoskeletal organization and lineage marker labeling were assessed by high-resolution fluorescence microscopy. Our analysis reveals that brief culture with BPA or BPF impeded cell division and disrupted embryo development at all stages tested. Surprisingly, BPF was more detrimental to the early embryo than BPA. Notably, poor embryo development was associated with cytoskeletal disruptions of the actomyosin network, apical domain formation during cell polarization, actin ring zippering for embryo sealing and altered cell lineage marker profiles. These results underscore that bisphenols can disrupt cytoskeletal integrity and remodeling that is vital for early embryo development and raise concerns regarding the use of BPF as a ‘safe’ BPA substitute.

It is challenging to obtain wafer-scaled aligned films for completely exploiting the promising properties of semiconducting single-walled carbon nanotubes (s-SWCNTs). Aligned s-SWCNTs with a large area can be obtained by combining water evaporation and slow withdrawal-induced self-assembly in a dip-coating process. Moreover, the tunability of deposition morphology parameters such as stripe width and spacing is examined. The polarized Raman results show that s-SWCNTs can be aligned in ±8.6°. The derived two terminal photodetector shows both a high negative responsivity of 41 A/W at 520 nm and high polarization sensitivity. Our results indicate that aligned films with a large area may be useful to electronics- and optoelectronics-related applications.

Precision genome engineering using homology donors and the endogenous DNA break repair machinery and recently CRISPR-Cas9 targeted APOBECs have been demonstrated. Here the authors design zinc-finger and TALE chimeric deaminases and investigate editing efficiency and off-target effects.

Human umbilical cord mesenchymal stem cells (hUCMSCs) are superior to other sources of mesenchymal stem/stromal cells (MSCs), and they are used as a novel tool for cell-based cancer therapy. However, the mechanism underlying hUCMSC-induced cancer cell death is not clear. In the present study, we aimed to evaluate the effect of secreted factors of hUCMSCs on the breast cancer cell line MCF7 by exposing them to the conditioned medium (CM) of hUCMSCs. We evaluated the morphological changes, cell viability, cell cycle, apoptosis, DNA fragmentation, and interleukin-1β (IL-1β) secretion of CM-exposed MCF7 cells. The results showed that the secreted factors of hUCMSCs could cause MCF7 cell death by inducing pyroptosis. We also sequenced the total RNA, and the differentially expressed genes (DEGs) were subjected to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. A total of 2597 (1822 upregulated and 775 downregulated) genes were identified and 14 pathways were significantly enriched. The results showed that the expression of the pyroptosis-related genes NLRP1 and CASP4 and the inflammation-related pathways changed significantly in MCF7 cells exposed to the CM. To the best of our knowledge, this study is the first to report that the secreted factors of hUCMSCs can cause MCF7 cell pyroptosis. Furthermore, it is the first to examine the global gene expression in MCF7 cells exposed to CM. These results will provide valuable information for further studies on the mechanism of MCF7 cell pyroptosis induced by the secreted factors of hUCMSCs. It will also help understand the effect of hUCMSCs on cell-based breast cancer therapy.

Nature Communications 7: Article number: 13330 (2016); Published 2 November 2016; Updated 9 October 2017. The original version of this Article contained an error in the email address of the corresponding author George Church. The correct email is gchurch@genetics.med.harvard.edu. The error has been corrected in the HTML and PDF versions of the Article.

In order to quickly adjust the production process of biochar, keep the consistency of production conditions and reduce the production cost of biochar. In this paper, maize straw and rice husk were used as raw material for biochar preparation under 350–600 o C fully pyrolyzed by fixed bed quartz tube pyrolysis device. The image recognition technology was used to acquire the RGB value of biochar and translated into gray value. The relationship between gray value and pyrolysis temperature, proximate analysis, and calorific value was studied; the result showed that the gray value had a strong linear relationship with carbonization temperature. Moreover, the relationships between gray scale and volatile, fixed carbon met the DoseResp mold; the R2 reached nearly 0.999. However, the correlations between gray value and ash and net calorific value were weak. This study provided theoretical support for the rapid detection of biochar and timely feedback of large-scale production conditions of biochar. [ABSTRACT FROM AUTHOR]

Watershed surface runoff potentially induced serious river water environmental problems. To effectively achieve river water environmental protection, this study conducted vegetation buffer zones to reduce watershed surface runoff based on the VFSMOD model. The Dagu River watershed, Qingdao, China was selected as the case study area. Results showed that tall arbors, shrubs, and herbaceous plants constitute the chief vegetation buffer zones in the Dagu River watershed. These vegetation strips cover a myriad of watershed earth surface, which effectively intercepts sediment and greatly reduce surface runoff by increasing watershed surface roughness. The sediment interception rate and the runoff reduction efficiency highly depend on the vegetation types and large spacing. The sediment interception rate increased with the increasing width and length of the vegetation buffer zone but decrease with the vegetation spacing, slope, and roughness. This study provides an effective method for catchment soil loss reduction in the Dagu River and can be implied in similar river catchments worldwide. [ABSTRACT FROM AUTHOR]

Germline editing, the process by which the genome of an individual is edited in such a way that the change is heritable, has been applied to a wide variety of animals [D. A. Sorrell, A. F. Kolb, Biotechnol. Adv. 23, 431-469 (2005); D. Baltimore et al., Science 348, 36-38 (2015)]. Because of its relevancy in agricultural and biomedical research, the pig genome has been extensively modified using a multitude of technologies [K. Lee, K. Farrell, K. Uh, Reprod. Fertil. Dev. 32, 40-49 (2019); C. Proudfoot, S. Lillico, C. Tait-Burkard, Anim. Front. 9, 6-12 (2019)]. In this perspective, we will focus on using pigs as the model system to review the current methodologies, applications, and challenges of mammalian germline genome editing. We will also discuss the broad implications of animal germline editing and its clinical potential. [ABSTRACT FROM AUTHOR]

Accurate chromosome segregation relies on correct chromosome-microtubule interactions within a stable bipolar spindle apparatus. Thus, exposure to spindle disrupting compounds can impair meiotic division and genomic stability in oocytes. The endocrine disrupting activity of bisphenols such as bisphenol A (BPA) is well recognized, yet their damaging effects on spindle microtubules (MTs) is poorly understood. Here, we tested the effect(s) of acute exposure to BPA and bisphenol F (BPF) on assembled spindle stability in ovulated oocytes. Brief (4 h) exposure to increasing concentrations (5, 25, and 50 µg/mL) of BPA or BPF disrupted spindle organization in a dose-dependent manner, resulting in significantly shorter spindles with highly unfocused poles and fragmented pericentrin. The chromosomes remained congressed in an abnormally elongated metaphase-like configuration, yet normal end-on chromosome-MT attachments were reduced in BPF-treated oocytes. Live-cell imaging revealed a rapid onset of bisphenol-mediated spindle MT disruption that was reversed upon compound removal. Moreover, MT stability and regrowth were impaired in BPAexposed oocytes, with few cold-stable MTs and formation of multipolar spindles upon MT regrowth. MT-associated kinesin-14 motor protein (HSET/KIFC1) labeling along the spindle was also lower in BPA-treated oocytes. Conversely, cold stable MTs and HSET labeling persisted after BPF exposure. Notably, inhibition of Aurora Kinase A limited bisphenol-mediated spindle pole widening, revealing a potential interaction. These results demonstrate rapid MT disrupting activity by bisphenols, which is highly detrimental to meiotic spindle stability and organization. Moreover, we identify an important link between these defects and altered distribution of key spindle associated factors as well as Aurora Kinase A activity. [ABSTRACT FROM AUTHOR]

Mouse oocytes lack canonical centrosomes and instead contain unique acentriolar microtubule-organizing centers (aMTOCs). To test the function of these distinct aMTOCs in meiotic spindle formation, pericentrin (Pcnt), an essential centrosome/MTOC protein, was knocked down exclusively in oocytes by using a transgenic RNAi approach. Here, we provide evidence that disruption of aMTOC function in oocytes promotes spindle instability and severe meiotic errors that lead to pronounced female subfertility. Pcnt-depleted oocytes from transgenic (Tg) mice were ovulated at the metaphase-II stage, but show significant chromosome misalignment, aneuploidy and premature sister chromatid separation. These defects were associated with loss of key Pcnt-interacting proteins (γ-tubulin, Nedd1 and Cep215) from meiotic spindle poles, altered spindle structure and chromosome–microtubule attachment errors. Live-cell imaging revealed disruptions in the dynamics of spindle assembly and organization, together with chromosome attachment and congression defects. Notably, spindle formation was dependent on Ran GTPase activity in Pcnt-deficient oocytes. Our findings establish that meiotic division is highly error-prone in the absence of Pcnt and disrupted aMTOCs, similar to what reportedly occurs in human oocytes. Moreover, these data underscore crucial differences between MTOC-dependent and -independent meiotic spindle assembly. [ABSTRACT FROM AUTHOR]

The shortage of organs for transplantation is a major barrier to the treatment of organ failure. Although porcine organs are considered promising, their use has been checked by concerns about the transmission of porcine endogenous retroviruses (PERVs) to humans. Here we describe the eradication of all PERVs in a porcine kidney epithelial cell line (PK15). We first determined the PK15 PERVcopy number to be 62. Using CRISPR-Cas9, we disrupted all copies of the PERV pol gene and demonstrated a >1000-fold reduction in PERV transmission to human cells, using our engineered cells. Our study shows that CRISPR-Cas9 multiplexability can be as high as 62 and demonstrates the possibility that PERVs can be inactivated for clinical application of porcine-to-human xenotransplantation. [ABSTRACT FROM AUTHOR]