Atomic-level polarization reversal in sliding ferroelectric semiconductors.

Intriguing "slidetronics" has been reported in van der Waals (vdW) layered non-centrosymmetric materials and newly-emerging artificially-tuned twisted moiré superlattices, but correlative experiments that spatially track the interlayer sliding dynamics at atomic-level remain elusive. Here, we address the decisive challenge to in-situ trace the atomic-level interlayer sliding and the induced polarization reversal in vdW-layered yttrium-doped γ-InSe, step by step and atom by atom. We directly observe the real-time interlayer sliding by a 1/3-unit cell along the armchair direction, corresponding to vertical polarization reversal. The sliding driven only by low energetic electron-beam illumination suggests rather low switching barriers. Additionally, we propose a new sliding mechanism that supports the observed reversal pathway, i.e., two bilayer units slide towards each other simultaneously. Our insights into the polarization reversal via the atomic-scale interlayer sliding provide a momentous initial progress for the ongoing and future research on sliding ferroelectrics towards non-volatile storages or ferroelectric field-effect transistors.

Overview and Comparison of Chinese and Western Medical Treatments for Osteoporosis.

Objective: Traditional Chinese medicine (TCM) can achieve similar effects to Western medicine in increasing bone mineral density, improving the destruction of bone micro-structure, inhibiting bone resorption, etc. However, there exist great differences between TCM and Western medicine in terms of theoretical basis and treatment methods. Therefore, to gain insights into their differences in treating osteoporosis (OP), we compared the disease name, etiology, pathogenesis, and clinical effectiveness to explore the potential benefits of combining the two approaches. Methods Overview: The method of literature review is used in the study. We firstly use academic databases such as PubMed and CNKI to search relevant literature on the understanding of OP in TCM and Western medicine in the past 10 years, then exclude the literature that is not relevant to the study topic or does not meet the study purpose, and finally compare and summarize the findings, views and conclusions of the literature. Key Findings or Insights: In the study, we find that the integrated approach of TCM and Western medicine can provide a gentler and more individualized treatment for patients with OP. By combining the conditioning means of Chinese herbs, compound prescription, acupuncture, moxibustion and Tuina can make up for the adverse reactions and side effects of Western medicine. Besides, TCM can make use of the clinical trials and animal experiments of Western medicine to prove the effectiveness of TCM theories and promote the clinical application. Practical Implications: By exploring the differences between TCM and Western medicine and the potential benefits of their combination, this study can provide a theoretical basis for the individualized treatment of OP. Especially for the patients with postmenopausal OP, senile OP, long-term hormone use, hyperthyroidism and other secondary OP, this study can provide a more comprehensive rehabilitation guidance, prevent the recurrence of these diseases, and improve the quality of patients' life. Recommendations or Future Directions: It is suggested that further clinical trials should be conducted to evaluate the effectiveness of the integrated treatment.

The potent analgesia of intrathecal 2R, 6R-HNK via TRPA1 inhibition in LF-PENS-induced chronic primary pain model.

BACKGROUND: Chronic primary pain (CPP) is an intractable pain of unknown cause with significant emotional distress and/or dysfunction that is a leading factor of disability globally. The lack of a suitable animal model that mimic CPP in humans has frustrated efforts to curb disease progression. 2R, 6R-hydroxynorketamine (2R, 6R-HNK) is the major antidepressant metabolite of ketamine and also exerts antinociceptive action. However, the analgesic mechanism and whether it is effective for CPP are still unknown. METHODS: Based on nociplastic pain is evoked by long-term potentiation (LTP)-inducible high- or low-frequency electrical stimulation (HFS/LFS), we wanted to develop a novel CPP mouse model with mood and cognitive comorbidities by noninvasive low-frequency percutaneous electrical nerve stimulation (LF-PENS). Single/repeated 2R, 6R-HNK or other drug was intraperitoneally (i.p.) or intrathecally (i.t.) injected into naïve or CPP mice to investigate their analgesic effect in CPP model. A variety of behavioral tests were used to detect the changes in pain, mood and memory. Immunofluorescent staining, western blot, reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and calcium imaging of in cultured dorsal root ganglia (DRG) neurons by Fluo-8-AM were used to elucidate the role and mechanisms of 2R, 6R-HNK in vivo or in vitro. RESULTS: Intrathecal 2R, 6R-HNK, rather than intraperitoneal 2R, 6R-HNK or intrathecal S-Ketamine, successfully mitigated HFS-induced pain. Importantly, intrathecal 2R, 6R-HNK displayed effective relief of bilateral pain hypersensitivity and depressive and cognitive comorbidities in a dose-dependent manner in LF-PENS-induced CPP model. Mechanically, 2R, 6R-HNK markedly attenuated neuronal hyperexcitability and the upregulation of calcitonin gene-related peptide (CGRP), transient receptor potential ankyrin 1 (TRPA1) or vanilloid-1 (TRPV1), and vesicular glutamate transporter-2 (VGLUT2) in peripheral nociceptive pathway. In addition, 2R, 6R-HNK suppressed calcium responses and CGRP overexpression in cultured DRG neurons elicited by the agonists of TRPA1 or/and TRPV1. Strikingly, the inhibitory effects of 2R, 6R-HNK on these pain-related molecules and mechanical allodynia were substantially occluded by TRPA1 antagonist menthol. CONCLUSIONS: In the newly designed CPP model, our findings highlighted the potential utility of intrathecal 2R, 6R-HNK for preventing and therapeutic modality of CPP. TRPA1-mediated uprgulation of CGRP and neuronal hyperexcitability in nociceptive pathways may undertake both unique characteristics and solving process of CPP.

Novel mechanistic insights underlying fungal allergic inflammation.

The worldwide prevalence of asthma and allergic disorders (allergic rhinitis, atopic dermatitis, food allergy) has been steadily rising in recent decades. It is now estimated that up to 20% of the global population is afflicted by an allergic disease, with increasing incidence rates in both high- and low-income countries. The World Allergy Organization estimates that the total economic burden of asthma and allergic rhinitis alone is approximately $21 billion per year. While allergic stimuli are a complex and heterogenous class of inputs including parasites, pollens, food antigens, drugs, and metals, it has become clear that fungi are major drivers of allergic disease, with estimates that fungal sensitization occurs in 20-30% of atopic individuals and up to 80% of asthma patients. Fungi are eukaryotic microorganisms that can be found throughout the world in high abundance in both indoor and outdoor environments. Understanding how and why fungi act as triggers of allergic type 2 inflammation will be crucial for combating this important health problem. In recent years, there have been significant advances in our understanding of fungi-induced type 2 immunity, however there is still much we don't understand, including why fungi have a tendency to induce allergic reactions in the first place. Here, we will discuss how fungi trigger type 2 immune responses and posit why this response has been evolutionarily selected for induction during fungal encounter.

Effect of ibudilast on thalamic magnetization transfer ratio and volume in progressive multiple sclerosis.

BACKGROUND: Thalamic volume (TV) is a sensitive biomarker of disease burden of injury in multiple sclerosis (MS) and appears to reflect overall lesion loads. Ibudilast showed significant treatment effect on brain atrophy and magnetization transfer ratio (MTR) of normal-appearing brain tissue but not in new/enlarging T2 lesion in the SPRINT-MS randomized clinical trial. OBJECTIVE: To evaluate the effect of ibudilast on thalamic tissue integrity and volume in the SPRINT-MS. METHODS: A total of 255 participants with progressive MS were randomized to oral ibudilast or placebo, and thalamic MTR and normalized TV over 96 weeks were quantified. Mixed-effect modeling assessed treatment effects on the thalamic MTR and TV, separately. Similarly, the measures were compared between the participants with confirmed disability progression (CDP). RESULTS: Ibudilast's treatment effect was observed compared to placebo for thalamic MTR (p = 0.03) but not for TV (p = 0.68) while TV correlated with T2 lesion volume (p < 0.001). CDP associated with thalamic MTR (p = 0.04) but not with TV (p = 0.7). CONCLUSION: Ibudilast showed an effect on thalamic MTR, which was associated with CDP, suggesting a clinically relevant effect on thalamic tissue integrity. However, the treatment effect was not observed in TV, suggesting that thalamic atrophy is more closely associated with global inflammatory activity than local tissue integrity. CLINICALTRIALS.GOV: NCT01982942.

Analysis of Fatty Acid Metabolism in Fetal and Failing Hearts by Single-Cell RNA Sequencing Revealed SLC27A6 as a Critical Gene in Heart Maturation.

Background: Heart failure is associated with shifts in substrate preferences and energy insufficiency. Although cardiac metabolism has been explored at the organ level, the metabolic changes at the individual cell level remain unclear. This study employed single-cell ribonucleic acid (RNA) sequencing to investigate the cell-type-specific characteristics of gene expression related to fatty acid metabolism. Methods: Single-cell RNA sequencing data from fetal hearts were processed to analyze gene expression patterns related to fatty acid metabolism. Immunofluorescence staining and Western blotting techniques were employed to validate the expression of specific proteins. Additionally, calcium recording and contractility measurements were performed to assess the functional implications of fatty acid metabolism in cardiomyocytes. Results: Based on single-cell RNA sequencing data analysis, we found that a decrease in overall energy requirements underlies the downregulation of fatty acid oxidation-related genes in the later period of heart maturation and the compensatory increase of fatty acid metabolism in individual cardiomyocytes during heart failure. Furthermore, we found that solute carrier family 27 member 6 (SLC27A6), a fatty acid transport protein, is involved in cardiac maturation. SLC27A6 knockdown in human induced pluripotent stem cell-derived cardiomyocytes resulted in an immature cardiomyocyte transcriptional profile, abnormal morphology, impaired Ca2+ handling activity, and contractility. Conclusions: Overall, our study offers a novel perspective for exploring cardiac fatty acid metabolism in fetal and failing hearts along with new insights into the cellular mechanism underlying fatty acid metabolic alterations in individual cardiac cells. It thus facilitates further exploration of cardiac physiology and pathology.

Single-cell RNA sequencing to reveal non-parenchymal cell heterogeneity and immune network of acetaminophen-induced liver injury in mice.

The role of non-parenchymal cells (NPCs) in the early phase of acetaminophen (APAP)-induced liver injury (AILI) remains unclear. Therefore, single-cell sequencing (scRNA-seq) was performed to explore the heterogeneity and immune network of NPCs in the livers of mice with AILI. Mice were challenged with saline, 300 mg/kg APAP, or 750 mg/kg APAP (n = 3 for each group). After 3 h, the liver samples were collected, digested, and subjected to scRNA-seq. Immunohistochemistry and immunofluorescence were performed to confirm the expression of Makorin ring finger protein 1 (Mkrn1). We identified 14 distinct cell subtypes among the 120,599 cells. A variety of NPCs were involved, even in the early stages of AILI, indicating highly heterogeneous transcriptome dynamics. Cholangiocyte cluster 3, which had high deleted in malignant brain tumors 1 (Dmbt1) expression, was found to perform drug metabolism and detoxification functions. Liver sinusoidal endothelial cells exhibited fenestrae loss and angiogenesis. Macrophage cluster 1 displayed a M1 polarization phenotype, whereas cluster 3 tended to exhibit M2 polarization. Kupffer cells (KCs) exhibited pro-inflammatory effects due to the high expression of Cxcl2. qRT-PCR and western blotting verified that the LIFR-OSM axis might promote the activation of MAPK signaling pathway in RAW264.7 macrophages. Mkrn1 was highly expressed in the liver macrophages of AILI mice and AILI patients. Interaction patterns between macrophages/KCs and other NPCs were complex and diverse. NPCs were highly heterogeneous and were involved in the immune network during the early phase of AILI. In addition, we propose that Mkrn1 may serve as a potential biomarker of AILI.

Walking out of the light verb jungle: Exploring the translation strategies of light verb constructions in Chinese-English consecutive interpreting.

Cross-linguistic features of light verb constructions (LVCs) profile a major facet of the typological difference between Chinese and English. By adopting a theory-driven, context-based interpreting task, this study explores the effectiveness and variability of translation strategies in dealing with 12 target LVCs extracted from a Chinese-English Consecutive Interpreting test to capture effective translation strategies fit for Chinese English-as-foreign-language (EFL) learners (N = 66). Appropriate rates and entropy values denoting variability of strategy selection are calculated by using 12 LVC segments and nine strategies, respectively. A correlation test is also carried out for vocabulary knowledge and the appropriate rates of LVCs to assess the efficacy of learners' vocabulary knowledge in interpreting performance. Results show the general preferences for strategy selection among Chinese EFL learners as well as typical structural patterns in LVC translation. The degree of lightness of the light verbs exerts a reverse effect on the appropriate rates and consistency of strategy selection, and the positive correlation between vocabulary knowledge and LVCs' appropriate rates suggests the need to incorporate the constructional teaching into the EFL learning curriculum. Thus felicitous conditions of applying the strategies have been proposed.

Adhesion to the Brain Endothelium Selects Breast Cancer Cells with Brain Metastasis Potential.

Tumor cells metastasize from a primary lesion to distant organs mainly through hematogenous dissemination, in which tumor cell re-adhesion to the endothelium is essential before extravasating into the target site. We thus hypothesize that tumor cells with the ability to adhere to the endothelium of a specific organ exhibit enhanced metastatic tropism to this target organ. This study tested this hypothesis and developed an in vitro model to mimic the adhesion between tumor cells and brain endothelium under fluid shear stress, which selected a subpopulation of tumor cells with enhanced adhesion strength. The selected cells up-regulated the genes related to brain metastasis and exhibited an enhanced ability to transmigrate through the blood-brain barrier. In the soft microenvironments that mimicked brain tissue, these cells had elevated adhesion and survival ability. Further, tumor cells selected by brain endothelium adhesion expressed higher levels of MUC1, VCAM1, and VLA-4, which were relevant to breast cancer brain metastasis. In summary, this study provides the first piece of evidence to support that the adhesion of circulating tumor cells to the brain endothelium selects the cells with enhanced brain metastasis potential.

Modeling the spread dynamics of multiple-variant coronavirus disease under public health interventions: A general framework.

The COVID-19 pandemic was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is a single-stranded positive-stranded RNA virus with a high multi-directional mutation rate. Many new variants even have an immune-evading property, which means that some individuals with antibodies against one variant can be reinfected by other variants. As a result, the realistic is still suffering from new waves of COVID-19 by its new variants. How to control the transmission or even eradicate the COVID-19 pandemic remains a critical issue for the whole world. This work presents an epidemiological framework for mimicking the multi-directional mutation process of SARS-CoV-2 and the epidemic spread of COVID-19 under realistic scenarios considering multiple variants. The proposed framework is used to evaluate single and combined public health interventions, which include non-pharmaceutical interventions, pharmaceutical interventions, and vaccine interventions under the existence of multi-directional mutations of SARS-CoV-2. The results suggest that several combined intervention strategies give optimal results and are feasible, requiring only moderate levels of individual interventions. Furthermore, the results indicate that even if the mutation rate of SARS-CoV-2 decreased 100 times, the pandemic would still not be eradicated without appropriate public health interventions.

Low-Dimensional-Materials-Based Flexible Artificial Synapse: Materials, Devices, and Systems.

With the rapid development of artificial intelligence and the Internet of Things, there is an explosion of available data for processing and analysis in any domain. However, signal processing efficiency is limited by the Von Neumann structure for the conventional computing system. Therefore, the design and construction of artificial synapse, which is the basic unit for the hardware-based neural network, by mimicking the structure and working mechanisms of biological synapses, have attracted a great amount of attention to overcome this limitation. In addition, a revolution in healthcare monitoring, neuro-prosthetics, and human-machine interfaces can be further realized with a flexible device integrating sensing, memory, and processing functions by emulating the bionic sensory and perceptual functions of neural systems. Until now, flexible artificial synapses and related neuromorphic systems, which are capable of responding to external environmental stimuli and processing signals efficiently, have been extensively studied from material-selection, structure-design, and system-integration perspectives. Moreover, low-dimensional materials, which show distinct electrical properties and excellent mechanical properties, have been extensively employed in the fabrication of flexible electronics. In this review, recent progress in flexible artificial synapses and neuromorphic systems based on low-dimensional materials is discussed. The potential and the challenges of the devices and systems in the application of neuromorphic computing and sensory systems are also explored.

Chick early amniotic fluid component improves heart function and protects against inflammation after myocardial infarction in mice.

Myocardial infarction (MI) is the major cause of mortality around the world. We recently demonstrated that chick early amniotic fluid (ceAF) can effectively rescue ischemic heart injury, indicating that it has a therapeutic function in MI. However, its functional components and the underlying mechanisms remain to be clarified. Here, we demonstrated that a fraction of ceAF, peak 8 (P8), had a protective effect on acute MI. P8 significantly decreased cardiomyocyte cross-sectional areas and cardiomyocyte apoptosis in MI mice. Using a human embryonic stem cell-derived cardiomyocyte model, which was subjected to hypoxia and reoxygenation, mimicking MI state, we found that P8 treatment reduced apoptosis and reversed myocardial contractility. Mechanistically, P8 improved cardiac function by inhibiting NF-κB signaling and downregulating inflammatory cytokine expression. Using mass spectrometry, we identified that guanosine and deoxynucleoside were the main functional components of P8 that suppressed the inflammatory response in human embryonic stem cell-derived cardiomyocytes. Collectively, our data suggest that specific components from ceAF are promising therapeutic agents for ischemic heart injury and could be a potential supplement to current medications for MI.

ß-hydroxybutyrate inhibits ferroptosis-mediated pancreatic damage in acute liver failure through the increase of H3K9bhb.

Acute pancreatitis and hyperamylasemia are often seen in patients with acute liver failure (ALF). However, the underlying mechanisms remain elusive. This study describes pancreatic tissue damage and exocrine dysfunction in a mouse model of major-liver-resection-induced ALF. The analysis of 1,264 clinical cases of liver failure (LF) showed that the incidence of hyperamylasemia and hyperlipasemia in patients with LF is 5.5% and 20%, respectively. Metabolomic studies indicate that glutathione (GSH)-deficiency-caused ferroptosis contributes to pancreatic damage in mouse ALF. ß-hydroxybutyrate (ß-HB) is the only metabolite downregulated in the liver, serum, and pancreas. Our data suggest that ß-HB protects pancreatic cells and tissues from GSH-deficiency-caused ferroptosis. ß-HB administration in ALF mice restores the expression of ferroptosis-suppressor genes through histone H3 lysine 9 ß-hydroxybutyrylation (H3K9bhb)-mediated chromatin opening. Our findings highlight ß-HB as an endogenous metabolite regulating ferroptosis in the pancreas and extend our understanding of the pathophysiology of ALF-induced pancreatitis.

Activation of Pancreatic Acinar FXR Protects against Pancreatitis via Osgin1-Mediated Restoration of Efficient Autophagy.

Pancreatitis is the leading cause of hospitalization in gastroenterology, and no medications are available for treating this disease in current clinical practice. FXR plays an anti-inflammatory role in diverse inflammatory diseases, while its function in pancreatitis remains unknown. In this study, we initially observed a marked increase of nuclear FXR in pancreatic tissues of human patients with pancreatitis. Deleting the FXR in pancreatic acinar cells (FXRacinarΔ/Δ ) led to more severe pancreatitis in mouse models of caerulein-induced acute and chronic pancreatitis, while the FXR agonist GW4064 significantly attenuated pancreatitis in caerulein or arginine-induced acute pancreatitis and caerulein-induced chronic pancreatitis. FXR deletion impaired the viability and stress responses of pancreatic exocrine organoids (PEOs) in vitro. Utilizing RNA-seq and ChIP-seq of PEOs, we identified Osgin1 as a direct target of FXR in the exocrine pancreas, which was also increasingly expressed in human pancreatitis tissues compared to normal pancreatic tissues. Pancreatic knockdown of Osgin1 by AAV-pan abolished the therapeutic effects of FXR activation on pancreatitis, whereas pancreatic overexpression of Osgin1 effectively alleviated caerulein-induced pancreatitis. Mechanistically, we found that the FXR-OSGIN1 axis stimulated autophagic flux in the pancreatic tissues and cell lines, which was considered as the intrinsic mechanisms through which FXR-OSGIN1 protecting against pancreatitis. Our results highlight the protective role of the FXR-OSGIN1 axis in pancreatitis and provided a new target for the treatment of this disease.

Prognostic analysis of m6A-related lncRNAs as potential biomarkers in intrahepatic cholangiocarcinom.

Intrahepatic cholangiocarcinoma (iCCA) patients had no obvious symptoms at early stage and poor postoperative survival. Therefore, the establishment of an iCCA prognostic prediction model to carry out refined management of iCCA patients is expected to improve the survival of the iCCA patient population. In this paper, we analyzed the expression profiling data of patients from 32 iCCA tissues and eight paracancerous tissues in The Cancer Genome Atlas (TCGA) database. Perl software was used to separate M6A-related genes and lncRNAs from expression matrix files obtained from the TCGA database. The differentially expressed lncRNAs in the iCCA samples and the normal samples were screened out by differential analysis using the R package limma, and the m6A-related lncRNAs were further screened by Pearson correlation analysis. WGCNA clustering analysis constructs a random network to extract the module genes most related to iCCA, and take the intersection of differentially expressed lncRNAs related to m6A. Univariate Cox screening was performed for the intersection lncRNAs that had significant influence on the prognosis of iCCA patients, and further screening was performed by LASSO method and multivariate Cox regression analysis. Risk model was constructed and prognostic ability was evaluated according to risk score. In conclusion, we identified four m6A-related lncRNAs with potential prognostic value in iCCA, and established a novel m6A-related lncRNA-based prognostic model, which can be used as an independent prognostic factor to predict the prognosis of clinical patients.

Cholesterol sulfate alleviates ulcerative colitis by promoting cholesterol biosynthesis in colonic epithelial cells.

Cholesterol sulfate, produced by hydroxysteroid sulfotransferase 2B1 (SULT2B1), is highly abundant in the intestine. Herein, we study the functional role and underlying intestinal epithelial repair mechanisms of cholesterol sulfate in ulcerative colitis. The levels of cholesterol and cholesterol sulfate, as well as the expression of Sult2b1 and genes involved in cholesterol biosynthesis, are significantly higher in inflamed tissues from patients with ulcerative colitis than in intestinal mucosa from healthy controls. Cholesterol sulfate in the gut and circulation is mainly catalyzed by intestinal epithelial SULT2B1. Specific deletion of the Sult2b1 gene in the intestinal epithelial cells aggravates dextran sulfate sodium-induced colitis; however, dietary supplementation with cholesterol sulfate ameliorates this effect in acute and chronic ulcerative colitis in mice. Cholesterol sulfate promotes cholesterol biosynthesis by binding to Niemann-Pick type C2 protein and activating sterol regulatory element binding protein 2 in colonic epithelial cells, thereby alleviates ulcerative colitis. In conclusion, cholesterol sulfate contributes to the healing of the mucosal barrier and exhibits therapeutic efficacy against ulcerative colitis in mice.

GATA3/long noncoding RNA MHC-R regulates the immune activity of dendritic cells in chronic obstructive pulmonary disease induced by air pollution particulate matter.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous illness associated with aberrant inflammatory immune reaction in the lung in response to noxious particles and gases. Our previous epidemiological studies discovered that long-term exposure to air pollution PM was associated with an increase in the incidence of COPD and lung function decline, but the impact of air pollution on the onset of COPD and its pathogenesis remains obscure. In recent years, long noncoding RNAs (lncRNAs) have been documented to have a crucial role in COPD. Our preliminary study found that the expression of lncRNA MHC-R in the lung tissues of rats exposed to air pollution PM was dramatically elevated, and the specific expression was mainly focused on the immune-related MHC I, antigen-presenting, and adaptive immune response. After transcription factor prediction, it was found that GATA3 could be combined with the specific sequence of the lncRNA MHC-R promoter region. Dendritic cells (DCs) are necessary antigen-presenting cells (APCs) with the most potent antigen-presenting function. We proved that GATA3/lncRNA MHC-R might regulate the immune activities of DCs to participate in the pathogenic mechanism of COPD induced by air pollution PM, which opens up a new way for early COPD diagnosis and treatment.

Therapeutic application of chick early amniotic fluid: effective rescue of acute myocardial ischemic injury by intravenous administration.

Myocardial regeneration has been considered a promising option for the treatment of adult myocardial injuries. Previously, a chick early amniotic fluid (ceAF) preparation was shown to contain growth-related factors that promoted embryonic growth and cellular proliferation, though the nature of the components within ceAF were not fully defined. Here we tested whether this ceAF preparation is similarly effective in the promotion of myocardial regeneration, which could provide an alternative therapeutic for intervening myocardial injury. In this study, a myocardial ischemic injury model was established in adult mice and pigs by multiple research entities, and we were able to show that ceAF can efficiently rescue damaged cardiac tissues and markedly improve cardiac function in both experimental models through intravenous administration. ceAF administration increased cell proliferation and improved angiogenesis, likely via down-regulation of Hippo-YAP signaling. Our data suggest that ceAF administration can effectively rescue ischemic heart injury, providing the key functional information for the further development of ceAF for use in attenuating myocardial injury.

Teaching machines to optimizing machining parameters: using independent fuzzy logic controller and image data.

Optimization of machining parameters like cutting speed, feed, and depth of cut is one of the extensively studied fields in the past two decades. While researchers agree optimization of these parameters is essential, there is no conscience as to what the objective of the optimization should be. The studies consider production cost, production time, surface finish, among others, as the objective of parameter optimization, but there are very few studies that consider the manufacturer prescribed tool life as the criteria for parament optimization. Among the methods that do consider tool life as an optimization objective, very few are closed-loop systems and these systems are facing challenges to generalizing when the application changes or the machining material changes or the tool geometry changes. Considering this, a novel image feedback using a convolution neural network-based method combined with principles of fuzzy logic is used to optimize machining parameters. Since the system is based on online feedback from the images of the inserts, it can be used for different materials, and the system is invariant to the different tool geometries and grades as the decisions are based on the wear mechanisms detected. The hybrid system is validated through experimentation for the turning application, but the methodology can be easily adapted for other machining applications.

The pro-tumorigenic activity of p38γ overexpression in nasopharyngeal carcinoma.

It is urgent to identify and validate biomarkers for early diagnosis and efficient treatment of nasopharyngeal carcinoma (NPC). Recent studies have proposed p38 gamma (p38γ) as a cyclin-dependent kinase (CDK)-like kinase that phosphorylates retinoblastoma (Rb) to promote cyclins expression and tumorigenesis. Here the Gene Expression Profiling Interactive Analysis (GEPIA) database and results from the local NPC tissues demonstrate that p38γ is significantly upregulated in NPC tissues, correlating with poor overall survival. Furthermore, p38γ mRNA and protein expression is elevated in established NPC cell lines (CNE-1 HONE-1 and CNE-2) and primary human NPC cells, but low expression detected in human nasal epithelial cells. In established and primary NPC cells, p38γ depletion, using the shRNA strategy or the CRISPR/Cas9 gene-editing method, largely inhibited cell growth, proliferation and migration, and induced significant apoptosis activation. Contrarily, ectopic p38γ overexpression exerted opposite activity and promoted NPC cell proliferation and migration. Retinoblastoma (Rb) phosphorylation and cyclin E1/A expression were decreased in NPC cells with p38γ silencing or knockout, but increased after p38γ overexpression. Moreover, mitochondrial subcellular p38γ localization was detected in NPC cells. Significantly, p38γ depletion disrupted mitochondrial functions, causing mitochondrial depolarization, reactive oxygen species production, oxidative injury and ATP depletion in NPC cells. In vivo, intratumoral injection of adeno-associated virus-packed p38γ shRNA potently inhibited primary human NPC xenograft growth in nude mice. In p38γ shRNA virus-injected NPC xenograft tissues, p38γ expression, Rb phosphorylation, cyclin E1/A expression and ATP levels were dramatically decreased. Taken together, we conclude that p38γ overexpression is required for NPC cell growth, acting as a promising therapeutic target of NPC.