Sub-okra leaf shape conferred via chromosomal introgression from Gossypium barbadense L. improves photosynthetic productivity in short-season cotton (Gossypium hirsutum L.).

Leaf shape is a vital agronomic trait that affects plant and canopy architecture, yield, and other production attributes of upland cotton. Compared with normal leaves, lobed leaves have potential advantages in improving canopy structure and increasing cotton yield. A chromosomal introgression segment from Gossypium barbadense L. conferring sub-okra leaf shape to Gossypium hirsutum L. was identified on chromosome D01. To determine the effects of this transferred sub-okra leaf shape on the leaf anatomical characteristics, photosynthesis-related traits, and yield of short-season cotton, we performed a field experiment with three sets of near-isogenic lines carrying okra, sub-okra, and normal leaf shape in Lu54 (L54) and Shizao 2 (SZ2) backgrounds. Compared with normal leaves, sub-okra leaves exhibited reduced leaf thickness and smaller leaf mass per area; moreover, the deeper lobes of sub-okra leaves improved the plant canopy structure by decreasing leaf area index by 11.24%-22.84%. Similarly, the intercepted PAR rate of lines with sub-okra leaf shape was also reduced. The chlorophyll content of sub-okra leaves was lower than that of okra and normal leaf shapes; however, the net photosynthetic rate of sub-okra leaves was 8.17%-29.81% higher than that of other leaf shapes at most growth stages. Although the biomass of lines with sub-okra leaf shape was less than that of lines with normal leaves, the average first harvest yield and total yield of lines with the sub-okra leaf shape increased by 6.36% and 5.72%, respectively, compared with those with normal leaves. Thus, improvements in the canopy structure and photosynthetic and physiological characteristics contributed to optimizing the light environment, thereby increasing the yield of lines with sub-okra leaf shape. Our results suggest that the sub-okra leaf trait from G. barbadense L. may have practical applications for cultivating short-season varieties with high photosynthetic efficiency, and improving yield, which will be advantageous for short-season varieties.

Establishment of a nomogram model for predicting distant metastasis in pancreatic ductal adenocarcinoma: a comparative analysis of different lymph node staging systems based on the SEER database.

The purpose of this study was to compare the predictive value of different lymph node staging systems and to develop an optimal prognostic nomogram for predicting distant metastasis in pancreatic ductal adenocarcinoma (PDAC). Our study involved 6364 patients selected from the Surveillance, Epidemiology, and End Results (SEER) database and 126 patients from China. Independent risk factors for distant metastasis were screened by univariate and multivariate logistic regression analyses, and a model-based comparison of different lymph node staging systems was conducted. Furthermore, we developed a nomogram for predicting distant metastasis using the optimal performance lymph node staging system. The lymph node ratio (LNR), log odds of positive lymph nodes (LODDS), age, primary site, grade, tumor size, American Joint Committee on Cancer (AJCC) 7th Edition T stage, and radiotherapy recipient status were significant predictors of distant metastasis in PDAC patients. The model with the LODDS was a better fit than the model with the LNR. We developed a nomogram model based on LODDS and six clinical parameters. The area under the curve (AUC) and concordance index (C-index) of 0.753 indicated that this model satisfied the discrimination criteria. Kaplan-Meier curves indicate a significant difference in OS among patients with different metastasis risks. LODDS seems to have a superior ability to predict distant metastasis in PDAC patients compared with the AJCC 8th Edition N stage, PLN and LNR staging systems. Moreover, we developed a nomogram model for predicting distant metastasis. Clinicians can use the model to detect patients at high risk of distant metastasis and to make further clinical decisions.

Effects of olanzapine on hippocampal CA3 and the prefrontal cortex local field potentials.

Olanzapine is an antipsychotic drug applied in psychiatry to treat psychoses, especially schizophrenia and schizoaffective disorders with similar or better improvement than haloperidol and risperidone in the treatment of depressive and negative symptoms. The effect of olanzapine on neural synchrony remains to be explored. We investigated the effects of olanzapine on gamma oscillations in the CA3 region of the hippocampus and frontal association cortex. Olanzapine reduced carbachol (CCh)-induced gamma oscillation power in CA3 slice and gamma oscillation power in the frontal association cortex in vivo. The power of theta oscillations was increased in the presence of olanzapine. The phase amplitude coupling of theta and gamma wave was strengthened by the administration of olanzapine in the frontal association cortex in vivo. Taken together, these results show that olanzapine modulates local field potential and the neuronal activity.

Potential prognostic biomarkers of hepatocellular carcinoma based on 4D label-free quantitative proteomics analysis pilot investigation.

BACKGROUND: Hepatocellular carcinoma carries a poor prognosis and poses a serious threat to global health. Currently, there are few potential prognostic biomarkers available for the prognosis of hepatocellular carcinoma. METHODS: This pilot study used 4D label-free quantitative proteomics to compare the proteomes of hepatocellular carcinoma and adjacent non-tumor tissue. A total of 66,075 peptides, 6363 identified proteins, and 772 differentially expressed proteins were identified in specimens from three hepatocellular carcinoma patients. Through functional enrichment analysis of differentially expressed proteins by Gene Ontology, KEGG pathway, and protein domain, we identified proteins with similar functions. RESULTS: Twelve differentially expressed proteins (RPL17, RPL27, RPL27A, RPS5, RPS16, RSL1D1, DDX18, RRP12, TARS2, YARS2, MARS2, and NARS1) were selected for identification and validation by parallel reaction monitoring. Subsequent Western blotting confirmed overexpression of RPL27, RPS16, and TARS2 in hepatocellular carcinoma compared to non-tumor tissue in 16 pairs of clinical samples. Analysis of The Cancer Genome Atlas datasets associated the increased expression of these proteins with poor prognosis. Tissue microarray revealed a negative association between high expression of RPL27 and TARS2 and the prognosis of hepatocellular carcinoma patients, although RPS16 was not significant. CONCLUSIONS: These data suggest that RPL27 and TARS2 play an important role in hepatocellular carcinoma progression and may be potential prognostic biomarkers of overall survival in hepatocellular carcinoma patients.

Effect of RPL27 knockdown on the proliferation and apoptosis of human liver cancer cells.

RPL27 is linked to the development of various diseases including malignant tumors. RPL27 may play an oncogenic function in hepatocellular carcinoma (HCC), but this is unknown. So, the aim of this study was to investigate how the human liver cancer cell lines SNU449 and HepG2 responded to RPL27 knockdown in terms of proliferation and apoptosis. SNU449 and HepG2 were cultured and infected with shCon and shRPL27 lentiviral particles to induce RPL27 knockdown, and then RPL27 expression was detected using qPCR and Western blot. Cell proliferation was measured using CCK8, cell cloning, cell scraping, and transwell migration and invasion, while apoptosis was measured using flow cytometry (FCM). The qPCR revealed that mRNA expression of RPL27 decreased after knocking down RPL27 in cells. The CCK8 and cell cloning assay confirmed that knocking down RPL27 significantly reduced cell viability. The cell scratch assay and transwell assays showed that the proliferation rate decreased after knocking down RPL27. A substantial increase in apoptotic cells was discovered by FCM. According to WB, RPL27 knockdown increased the expression of Bax and Caspase-3 while decreasing the expression of bcl-2. The findings showed that RPL27 knockdown inhibited cell proliferation in SNU449 and HepG2 via inducing apoptosis, proving that RPL27 is a novel gene linked with HCC and is crucial for both proliferation and apoptosis. These outcomes imply that RPL27 may be a potential target for liver cancer diagnosis and therapy.

Study on Spontaneous Reactivation and Aging of Acetylcholinesterase Inhibited by Paraoxon and Malaoxon in Ten Species.

Organophosphorus insecticides (OPs), acting as serine phosphorylating agents in acetylcholinesterase (AChE), are highly effective neurotoxic insecticides. In our previous research, we found that six herbivorous pests and four ladybirds howed significantly higher AChE LC50 values than seven parasitoids and a predator (Epistrophe balteate), and that there was a significant correlation with the corresponding bimolecular rate constant (Ki) value. The Ki value of pests was much smaller than that of natural enemies and had a higher LC50 value.Then, we speculated that the low sensitivity of the pest AChE to OPs may be associated with its higher recovery and lower aging ability. In this work, the I50 and I90 were calculated, to determine the sensibility of AChE in ten representative species, including Plutella xylostella, Prodenia litura, Musca domestica, and Cavia porcellus, to paraoxon and malaoxon. The enzyme activities were measured at various time points, and kinetic calculations were used to obtain their spontaneous reactivation (Ks) and aging (Ka) constants, which were comprehensively compared. We conclude that the Ka and Ks of the AChE inhibited by OPs showed primarily species-specific correlations, and little correlation with the sensitivity to OPs. The differences in the AChE sensitivity to paraoxon among the ten species were much greater than in the sensitivity to malaoxon. Compared to paraoxon, malaoxon was more selective for Cavia porcellus. Coleoptera insects showed a stronger dephosphorylation ability than other insect groups. The recovery ability of phospho-AChE was stronger in mammals than in insects, which could be related to the low sensitivity of the AChE site of action to OPs. The Ka of the AChE inhibited by malaoxon was larger than that inhibited by paraoxon with the corresponding biomaterials, indicating that the OP type had a substantial relationship with the Ka of the AChE. We further discovered that, when insects were inhibited by OP, the tendency of AChE to undergo aging was greater than that of dephosphorylation. Overall, the study provides valuable information on the action mechanism of various OPs on AChE in several species, which could be used to further research into AChE and the potential dangers that organophosphates pose to animals.

Garlic-derived exosome-like nanovesicles alleviate dextran sulphate sodium-induced mouse colitis via the TLR4/MyD88/NF-κB pathway and gut microbiota modulation.

Plant-derived exosome-like nanovesicles play an important role in transferring their biological cargos to recipient cells. The effect of garlic-derived exosome-like nanovesicles (GENs) against inflammatory bowel disease (IBD) remains unknown. This study aimed to investigate the effect of GENs on dextran sulphate sodium (DSS)-induced colitis in mice. A comprehensive analysis of bioactive components in GENs was performed. Data showed that GENs contained 26 lipids, 61 proteins and 127 known microRNAs (miRNAs). Han-miR3630-5p in GENs could bind to the 3' untranslated region of toll-like receptor 4 (TLR4), which led to the inhibition of TLR4 expression. Besides, GENs significantly up-regulated the expression of barrier-related proteins and inhibited the overproduction of pro-inflammatory cytokines in LPS-induced Caco-2 cells. As a result, pretreatment with GENs at 100 mg kg-1 efficiently ameliorated the inflammatory bowel behavior, intestinal histological pathological damage, and tight junction protein dysfunction induced by DSS in the colon tissue. Intake of GENs significantly down-regulated the expressions of TLR4, myeloid differentiation primary response gene 88 (MyD88), and nuclear factor kappa-B (NF-κB), which suppressed the downstream cascades and led to less secretion of pro-inflammatory cytokines induced by DSS. Furthermore, pretreatment with GENs altered the gut microbiota profile of colitis mice by recovering the relative abundance of Lachnospiraceae and reducing the relative abundance of Helicobacter. Totally, GENs had potential to protect the colon against DSS-induced damage through inhibiting the TLR4/MyD88/NF-κB signaling pathway and regulating gut microbiota. This study clarified the role of miRNAs of GENs in anti-colitis and proved that GENs had a potential application for IBD prevention.

EphA1 aggravates neuropathic pain by activating CXCR4/RhoA/ROCK2 pathway in mice.

Neuropathic pain is a refractory disease with limited treatment options due to its complex mechanisms. Whereas erythropoietin-producing hepatocyte A1 (EphA1) mediates the production of inflammatory factors that are important in the progression of neurological diseases, its role and molecular mechanisms in neuropathic pain remain unclear. In the present study, we established a mouse model of chronic constriction injury (CCI). EphA1 expression was observed to be progressively upregulated at the mRNA and protein levels with the progression of the disease. Subsequently, knockdown of EphA1 expression levels using adenovirus short hairpin RNA (AAV-shEphA1) revealed an increase in mechanical stimulation withdrawal threshold (PWT) and withdrawal latency (PWL) when EphA1 expression was decreased, accompanied by improved dorsal root ganglion injury, increased leukocytosis, decreased microglia, and decreased levels of pro-inflammatory factors. For the underlying mechanism, it was found that EphA1 regulates the activity of the RhoA/ROCK2 pathway by modulating the level of CXCR4. Inhibition of CXCR4 and RhoA/ROCK2 could effectively alleviate the promoting effect of EphA1 upregulation on neuropathic pain. In conclusion, our study suggests that depletion of EphA1 ameliorates neuropathic pain by modulating the CXCR4/RhoA/ROCK2 signaling pathway, and targeting EphA1 may be a potential clinical treatment for neuropathic pain.

Influencing factors of predation on five keystone prey species in Haizhou Bay based on Delta-GAMMs.

Trophic dynamics is one of the major regulators of fishery production in marine ecosystems, which is important for the implementation of ecosystem-based fisheries management. Based on data collected form bottom trawl surveys in Haizhou Bay and adjacent waters during autumn of 2011 and 2018, Delta-GAMMs (Delta-generalized additive mixed models) were constructed to evaluate the effects of biotic and abiotic factors on the predation of five key prey species (including Leptochela gracilis, Alpheus japonicus, Loligo spp., Larimichthys polyactis, and Oratosquilla oratoria) in the Haizhou Bay. Percent frequency of occurrence and predation pressure index were used to identify their major predators. Variance inflation factor and full subsets regression were analyzed to quantify the degree of multicollinearity between these factors. The results showed that the occurrence frequency of keystone prey species in the stomach of predators ranged from 8.5% to 42.2%, and the weight percentage ranged from 4.2% to 40.9%. The average deviance explanation rate of the "binomial" model was 16.1%, and the average deviance explanation rate of the "positive" model was 23.8%. Body length of predator, predator population density, and sea bottom temperature were important factors influencing prey-predator trophic interactions. Predator length was the most important factor, with feeding probability and weight percentage of keystone prey species all increasing with body length of predator. Feeding probability and weight percentage of key prey species decreased with predator population density. The effects of environmental factors such as sea bottom temperature, depth of water, latitude, and sea bottom salinity showed different trends, depending on the prey-predator assemblage. This study showed that the Delta-GAMMs was an effective method to explore the trophic interactions between prey and predators in marine ecosystems, and could provide a theoretical basis for the conservation and sustainable use of fisheries resources.

Experimental Investigation on Spontaneous Imbibition of Surfactant Mixtures in Low Permeability Reservoirs.

Spontaneous imbibition of surfactants could efficiently enhance oil recovery in low permeability sandstone reservoirs. The majority of studies have considered the application of individual surfactants to alter wettability and reduce interfacial tension (IFT). However, a significant synergistic effect has been reported between different types of surfactants and between salts and surfactants. Therefore, this study systematically studied the capability of a binary surfactant mixture (anionic/nonionic) and a ternary surfactant mixture (anionic/nonionic/strong base-weak acid salt) in imbibition enhanced oil recovery (IEOR). The interfacial properties and the cores' wettability were explored by IFT and contact angle measurements, respectively. Subsequently, the imbibition performances of different types of surfactant solutions were discussed. The results suggested that the surfactants' potential to enhance oil recovery followed the order of ternary surfactant mixture > binary surfactant mixture > anionic > nonionic > amphoteric > polymer. The ternary surfactant mixture exhibited strong capacity to reverse the rock surface from oil-wet (125°) to strongly water-wet (3°), which was more significant than both binary surfactant mixtures and individual surfactants. In addition, the ternary surfactant mixture led to an ultralow IFT value of 0.0015 mN/m, achieving the highest imbibition efficiency (45% OOIP). This research puts forward some new ideas on the application of the synergistic effects of surfactants in IEOR from low-permeability sandstone reservoirs.

A glutathione S-transferase GhTT19 determines flower petal pigmentation via regulating anthocyanin accumulation in cotton.

Anthocyanin accumulations in the flowers can improve seed production of hybrid lines, and produce higher commodity value in cotton fibre. However, the genetic mechanism underlying the anthocyanin pigmentation in cotton petals is poorly understood. Here, we showed that the red petal phenotype was introgressed from Gossypium bickii through recombination with the segment containing the R3 bic region in the A07 chromosome of Gossypium hirsutum variety LR compared with the near-isogenic line of LW with white flower petals. The cyanidin-3-O-glucoside (Cy3G) was the major anthocyanin in red petals of cotton. A GhTT19 encoding a TT19-like GST was mapped to the R3 bic site associated with red petals via map-based cloning, but GhTT19 homologue gene from the D genome was not expressed in G. hirsutum. Intriguingly, allelic variations in the promoters between GhTT19LW and GhTT19LR , rather than genic regions, were found as genetic causal of petal colour variations. GhTT19-GFP was found localized in both the endoplasmic reticulum and tonoplast for facilitating anthocyanin transport. An additional MYB binding element found only in the promoter of GhTT19LR , but not in that of GhTT19LW , enhanced its transactivation by the MYB activator GhPAP1. The transgenic analysis confirmed the function of GhTT19 in regulating the red flower phenotype in cotton. The essential light signalling component GhHY5 bonded to and activated the promoter of GhPAP1, and the GhHY5-GhPAP1 module together regulated GhTT19 expression to mediate the light-activation of petal anthocyanin pigmentation in cotton. This study provides new insights into the molecular mechanisms for anthocyanin accumulation and may lay a foundation for faster genetic improvement of cotton.

The potential applications of artificially modified exosomes derived from mesenchymal stem cells in tumor therapy.

Mesenchymal stem cells (MSCs) have tumor-homing ability and play critical roles in tumor treatment, but their dual influences on tumor progression limit their therapeutic applications. Exosomes derived from MSCs (MSC-exosomes) exhibit great potential in targeted tumor treatment due to their advantages of high stability, low immunogenicity, good biocompatibility, long circulation time and homing characteristics. Furthermore, the artificial modification of MSC-exosomes could amplify their advantages and their inhibitory effect on tumors and could overcome the limit of tumor-promoting effect. In this review, we summarize the latest therapeutic strategies involving artificially modified MSC-exosomes in tumor treatment, including employing these exosomes as nanomaterials to carry noncoding RNAs or their inhibitors and anticancer drugs, and genetic engineering modification of MSC-exosomes. We also discuss the feasibility of utilizing artificially modified MSC-exosomes as an emerging cell-free method for tumor treatment and related challenges.

Development of the Gemini Gel-Forming Surfactant with Ultra-High Temperature Resistance to 200 °C.

In order to broaden the application of clean fracturing fluid in ultra-high temperature reservoirs, a surfactant gel for high-temperature-resistant clean fracturing fluid was developed with a gemini cationic surfactant as the main agent in this work. As the fracturing fluid, the rheological property, temperature resistance, gel-breaking property, filtration property, shear recovery performance and core damage property of surfactant gel were systematically studied and evaluated. Results showed the viscosity of the system remained at 25.2 mPa·s for 60 min under a shear rate of 170 s-1 at 200 °C. The observed core permeability damage rate was only 6.23%, indicating low formation damage after fracturing. Due to micelle self-assembly properties in surfactant gel, the fluid has remarkable shear self-repairability. The filtration and core damage experimental results meet the national industry standard for fracturing fluids. The gel system had simple formulation and excellent properties, which was expected to enrich the application of clean fracturing fluid in ultra-high temperature reservoirs.

Characterization of somatic structural variations in 528 Chinese individuals with Esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) demonstrates high genome instability. Here, we analyze 528 whole genomes to investigate structural variations' mechanisms and biological functions. SVs show multi-mode distributions in size, indicating distinct mutational processes. We develop a tool and define five types of complex rearrangements with templated insertions. We highlight a type of fold-back inversion, which is associated with poor outcomes. Distinct rearrangement signatures demonstrate variable genomic metrics such as replicating time, spatial proximity, and chromatin accessibility. Specifically, fold-back inversion tends to occur near the centrosome; TD-c2 (Tandem duplication-cluster2) is significantly enriched in chromatin-accessibility and early-replication region compared to other signatures. Analyses of TD-c2 signature reveal 9 TD hotspots, of which we identify a hotspot consisting of a super-enhancer of PTHLH. We confirm the oncogenic effect of the PTHLH gene and its interaction with enhancers through functional experiments. Finally, extrachromosomal circular DNAs (ecDNAs) are present in 14% of ESCCs and have strong selective advantages to driver genes.

Case report: Ultrasound-guided multi-site electroacupuncture stimulation for a patient with spinal cord injury.

Introduction: Spinal cord injury causes permanent neurological deficits, which have devastating physical, social, and vocational consequences for patients and their families. Traditional Chinese medicine uses acupuncture to treat neuropathic pain and improve nerve conduction velocity. This treatment can also reduce peripheral nerve injury joint contracture and muscle atrophy in affected patients. And it's got a remarkable restoration when electrical stimulation therapy on impaired peripheral nerves in animal models and clinical trials. Case description: A 48-year-old woman was hit by a heavy object that injured her lower back. The patient had a T12-L1 vertebral flexion and stretch fracture with traumatic spinal stenosis. The patient was transferred to the rehabilitation department after posterior T12-L2-segment pedicle screw system distraction and reduction, internal fixation, decompression, and bone graft fusion. Ultrasound-guided electroacupuncture was used to stimulate the sacral nerve, the spinal nerve, and the head of the patient, accompanied by spinal joint loosening training, respiratory training, lumbar comprehensive sports training, paraplegic limbs comprehensive training, and other manipulative treatment. Outcomes: After the intervention, the patient showed significant improvements in sensory and motor scores, resulting in functional recovery according to ASIA and FIM. The patient gradually showed reasonable functional remission. Discussion: The sacral nerve, the spinal cord, and the head were electrically stimulated by ultrasound-guided electroacupuncture in terms of intervention, and various functions of the patient were alleviated to a certain extent. The efficacy of ultrasound-guided electroacupuncture stimulation in treating neurologic symptoms should be validated in future clinical trials.

Role of 5-HT2A Receptor in Modulating Glutamatergic Activity in the Ventrolateral Orbital Cortex: Implication in Trigeminal Neuralgia.

5-HT2A receptors (5-HT2ARs) are widely expressed in the central nervous system, including in the ventrolateral orbital cortex (VLO). The VLO is an important cortical component for pain processing. Brain 5-HT2ARs are implicated in both pro- and anti- nociceptive functions. However, the roles of 5-HT2ARs in the VLO in trigeminal neuralgia and neuronal synaptic function remain to be understood. We used chronic constriction injury of infraorbital nerve (IoN-CCI) model and shRNA mediated gene knockdown in mice to investigate the role of 5-HT2ARs in the VLO in trigeminal neuralgia. We found that knockdown of 5-HT2ARs in the VLO aggravated spontaneous pain and mechanical allodynia in mice after IoN-CCI. At the synaptic level, decreasing 5-HT2AR expression by shRNA or inhibition of 5-HT2AR activity by its antagonist ketanserin decreased the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) of the neurons in the VLO, whereas 5-HT2AR partial agonist 2,5-Dimethoxy-4-iodoamphetamine (DOI) enhanced sEPSCs of the neurons in the VLO. In summary, 5-HT2ARs in the VLO modulate the trigeminal pain by regulating neuronal glutamatergic activity.

Lipid-related FABP5 activation of tumor-associated monocytes fosters immune privilege via PD-L1 expression on Treg cells in hepatocellular carcinoma.

Monocytes/macrophages, a plastic and heterogeneous cell population of the tumor microenvironment (TME), can constitute a major component of most solid tumors. Under the pressure of rapid proliferation of the tumor, monocytes/macrophages can be educated and foster immune tolerance via metabolic reprogramming. Our studies have shown that the activation of FABP5, a lipid-binding protein, decreases the rate of ß-oxidation causing the accumulation of lipid droplets in monocytes. We found that hepatocellular carcinoma cells (HCC) increased IL-10 secretion by monocytes, which depended on the expression of FABP5 and suppressing of the PPARα pathway. Moreover, the elevated level of IL-10 promotes PD-L1 expression on Treg cells via the JNK-STAT3 pathway activation. We also observed that elevation of FABP5 in monocytes was negatively related to HCC patients' overall survival time. Thus, FABP5 promotes monocyte/macrophage lipid accumulation, fosters immune tolerance formation, and might represent itself as a therapeutic target in both tumor-associated monocytes (TAMs) and cancer cells.

Numerical and Experimental Study on the Direct Chill Casting of Large-Scale AA2219 Billets via Annular Coupled Electromagnetic Field.

The internal coupled electromagnetic melt treatment (ICEMT) method is firstly proposed to produce high-quality and large-sized aluminum alloy billets. A three-dimensional model was established to describe the ICEMT process of direct chill casting (DC casting). The effect of ICEMT on the fluid flow patterns and temperature field in the DC casting of ϕ880 mm AA2219 billets is numerically analyzed. Moreover, the mechanisms of the ICEMT process on grain refinement and macrosegregation were discussed. The calculated results indicate that the electromagnetic field appears to be coupled circinate at the cross section of the melt, the fluid flow becomes unstable accompanied by the bias flow, and the temperature profiles are significantly more uniform. An experimental verification was conducted and the results prove that compared with traditional direct chill casting, the microstructures of the AA2219 large-scale billet under the ICEMT process are uniform and fine.

Macrophages and Metabolic Reprograming in the Tumor Microenvironment.

Due to the emergence of traditional drug resistance in tumor treatment, the anti-cancer therapies are facing multiple challenges. Immunotherapy, as a new and universal treatment, has been gradually concerned. The macrophages, as an important part of the immune system, play an important role in it. Many studies have shown that immune state is essential in cancer progression and prognosis, rebuilding the architecture and functional orientation of the tumor region. Most tumors are complex ecosystems that change temporally and spatially under the pressure of proliferation, apoptosis, and extension of every cell in the microenvironment. Here, we review how macrophages states can be dynamically altered in different metabolic states and we also focus on the formation of immune exhaustion. Finally, we look forward to the explorations of clinical treatment for immune metabolism process.

The RNA m6A reader YTHDC1 silences retrotransposons and guards ES cell identity.

The RNA modification N6-methyladenosine (m6A) has critical roles in many biological processes1,2. However, the function of m6A in the early phase of mammalian development remains poorly understood. Here we show that the m6A reader YT521-B homology-domain-containing protein 1 (YTHDC1) is required for the maintenance of mouse embryonic stem (ES) cells in an m6A-dependent manner, and that its deletion initiates cellular reprogramming to a 2C-like state. Mechanistically, YTHDC1 binds to the transcripts of retrotransposons (such as intracisternal A particles, ERVK and LINE1) in mouse ES cells and its depletion results in the reactivation of these silenced retrotransposons, accompanied by a global decrease in SETDB1-mediated trimethylation at lysine 9 of histone H3 (H3K9me3). We further demonstrate that YTHDC1 and its target m6A RNAs act upstream of SETDB1 to repress retrotransposons and Dux, the master inducer of the two-cell stage (2C)-like program. This study reveals an essential role for m6A RNA and YTHDC1 in chromatin modification and retrotransposon repression.