Enhanced performance of GaN-based thin-film flip-chip LEDs with reflective current blocking layers.

To further enhance the performance of GaN-based thin-film flip-chip light-emitting diodes (TFFC-LEDs), we designed and fabricated two sets of high-power blue chips with conventional and reflective current-blocking layers (CBL) The conventional CBL is composed of SiO, whereas the reflective CBL consists of SiO and a distributed Bragg reflector (DBR). We systematically characterized their optoelectronic performance. The results indicate that at an injection current of 350 mA, the light output power (LOP) and external quantum efficiency (EQE) of the TFFC-LEDs with a reflective CBL increased by 4.

Inhibitors of APE1 redox and ATM synergistically sensitize osteosarcoma cells to ionizing radiation by inducing ferroptosis.

The resistance of osteosarcoma (OS) to ionizing radiation (IR) is an obstacle for effective patient treatment. Apurinic/apyrimidinic endonuclease-reduction/oxidation factor 1 (APE1/Ref-1) is a multifunctional protein with DNA repair and reduction/oxidation (redox) activities. We previously revealed the role of APE1 in OS radioresistance; however, whether the redox activity of APE1 is involved in OS radioresistance is unclear.

Pregnancy induced hypertension and umbilical cord blood DNA methylation in newborns: an epigenome-wide DNA methylation study.

Objectivies: Pregnancy induced hypertension (PIH) syndrome is a disease that unique to pregnant women and is associated with elevated risk of offspring cardiovascular diseases (CVDs) and neurodevelopmental disorders in their kids. Previous research on cord blood utilizing the Human Methylation BeadChip or EPIC array revealed that PIH is associated with specific DNA methylation site. Here, we investigate the whole genome DNA methylation landscape of cord blood from newborns of PIH mother.

DNA demethylase Tet2 promotes the terminal maturation of natural killer cells.

The cytotoxicity feature to eliminate malignant cells makes natural killer (NK) cells a candidate for tumor immunotherapy. However, this scenario is currently hampered by inadequate understanding of the regulatory mechanisms of NK cell development. Ten-Eleven-Translocation 2 (Tet2) is a demethylase whose mutation was recently shown to cause phenotypic defects in NK cells.

mTOR Signaling Promotes Rapid m6A mRNA Methylation to Regulate NK-Cell Activation and Effector Functions.

NK cells can be rapidly activated in response to cytokines during host defense against malignant cells or viral infection. However, it remains unclear what mechanisms precisely and rapidly regulate the expression of a large number of genes involved in activating NK cells. In this study, we discovered that NK-cell N6-methyladenosine (m6A) methylation levels were rapidly upregulated upon short-term NK-cell activation and were repressed in the tumor microenvironment (TME).

Radiofrequency radiation reshapes tumor immune microenvironment into antitumor phenotype in pulmonary metastatic melanoma by inducing active transformation of tumor-infiltrating CD8 T and NK cells.

Immunosuppression by the tumor microenvironment is a pivotal factor contributing to tumor progression and immunotherapy resistance. Priming the tumor immune microenvironment (TIME) has emerged as a promising strategy for improving the efficacy of cancer immunotherapy. In this study we investigated the effects of noninvasive radiofrequency radiation (RFR) exposure on tumor progression and TIME phenotype, as well as the antitumor potential of PD-1 blockage in a model of pulmonary metastatic melanoma (PMM).

The ω-3 Polyunsaturated Fatty Acid Docosahexaenoic Acid Enhances NK-Cell Antitumor Effector Functions.

ω-3 polyunsaturated fatty acids (PUFA) are known to directly repress tumor development and progression. In this study, we explored whether docosahexaenoic acid (DHA), a type of ω-3 PUFA, had an immunomodulatory role in inhibiting tumor growth in immunocompetent mice. The number of natural killer (NK) cells but not the number of T or B cells was decreased by DHA supplementation in various tissues under physiologic conditions.

Comprehensive analysis of mA methylomes in idiopathic pulmonary arterial hypertension.

Idiopathic pulmonary arterial hypertension (IPAH) is a serious and fatal disease. Recently, m6A has been reported to play an important role in the lungs of IPAH patients and experimental pulmonary hypertension models. However, the meaning of m6A mRNAs in the peripheral blood of IPAH patients remains largely unexplored.

Advances in mRNA vaccines for viral diseases.

Since the onset of the pandemic caused by severe acute respiratory syndrome coronavirus 2, messenger RNA (mRNA) vaccines have demonstrated outstanding performance. mRNA vaccines offer significant advantages over conventional vaccines in production speed and cost-effectiveness, making them an attractive option against other viral diseases. This article reviewed recent advances in viral mRNA vaccines and their delivery systems to provide references and guidance for developing mRNA vaccines for new viral diseases.

mTORC2 acts as a gatekeeper for mTORC1 deficiency-mediated impairments in ILC3 development.

Group 3 innate lymphoid cells (ILC3s) are mediators of intestinal immunity and barrier function. Recent studies have investigated the role of the mammalian target of rapamycin complex (mTOR) in ILC3s, whereas the mTORC1-related mechanisms and crosstalk between mTORC1 and mTORC2 involved in regulating ILC3 homeostasis remain unknown. In this study, we found that mTORC1 but not mTORC2 was critical in ILC3 development, IL-22 production, and ILC3-mediated intestinal homeostasis.

Revolutionizing viral disease vaccination: the promising clinical advancements of non-replicating mRNA vaccines.

The mRNA vaccine technology was developed rapidly during the global pandemic of COVID-19. The crucial role of the COVID-19 mRNA vaccine in preventing viral infection also have been beneficial to the exploration and application of other viral mRNA vaccines, especially for non-replication structure mRNA vaccines of viral disease with outstanding research results. Therefore, this review pays attention to the existing mRNA vaccines, which are of great value for candidates for clinical applications in viral diseases.

Sex differences exist in adult heart group 2 innate lymphoid cells.

Background: Group 2 innate lymphoid cells (ILC2s) are the most dominant ILCs in heart tissue, and sex-related differences exist in mouse lung ILC2 phenotypes and functions; however, it is still unclear whether there are sex differences in heart ILC2s.

Results: Compared with age-matched wild-type (WT) male mice, 8-week-old but not 3-week-old WT female mice harbored an obviously greater percentage and number of heart ILC2s in homeostasis. However, the percentage of killer-cell lectin-like receptor G1 (Klrg1) ILC2s was higher, but the Klrg1 ILC2s were lower in female mice than in male mice in both heart tissues of 3- and 8-week-old mice.

Docosahexaenoic acid supplementation represses the early immune response against murine cytomegalovirus but enhances NK cell effector function.

Background: Docosahexaenoic acid (DHA) supplementation is beneficial for several chronic diseases; however, its effect on immune regulation is still debated. Given the prevalence of cytomegalovirus (CMV) infection and because natural killer (NK) cells are a component of innate immunity critical for controlling CMV infection, the current study explored the effect of a DHA-enriched diet on susceptibility to murine (M) CMV infection and the NK cell effector response to MCMV infection.

Results: Male C57BL/6 mice fed a control or DHA-enriched diet for 3 weeks were infected with MCMV and sacrificed at the indicated time points postinfection.

Targeting the RNA mA modification for cancer immunotherapy.

N-methyladenosine (mA) is the most abundant epigenetic modification of RNA, and its dysregulation drives aberrant transcription and translation programs that promote cancer occurrence and progression. Although defective gene regulation resulting from mA often affects oncogenic and tumor-suppressing networks, mA can also modulate tumor immunogenicity and immune cells involved in anti-tumor responses. Understanding this counterintuitive concept can aid the design of new drugs that target mA to potentially improve the outcomes of cancer immunotherapies.

Identification of nafamostat mesylate as a selective stimulator of NK cell IFN-γ production via metabolism-related compound library screening.

Natural killer (NK) cells play important roles in controlling virus-infected and malignant cells. The identification of new molecules that can activate NK cells may effectively improve the antiviral and antitumour activities of these cells. In this study, by using a commercially available metabolism-related compound library, we initially screened the capacity of compounds to activate NK cells by determining the ratio of interferon-gamma (IFN-γ) NK cells by flow cytometry after the incubation of peripheral blood mononuclear cells (PBMCs) with IL-12 or IL-15 for 18 h.

Screening for Active Compounds Targeting Human Natural Killer Cell Activation Identifying Daphnetin as an Enhancer for IFN-γ Production and Direct Cytotoxicity.

Natural killer (NK) cells are a potent weapon against tumor and viral infection. Finding active compounds with the capacity of enhancing NK cell effector functions will be effective to develop new anti-cancer drugs. In this study, we initially screened 287 commercially available active compounds by co-culturing with peripheral blood mononuclear cells (PBMCs).

Proteomic analysis identified potential age-associated prognostic biomarkers in pneumonia-derived paediatric sepsis.

Purpose: Our aim was to investigate the age-associated plasma protein profiles in pneumonia-derived sepsis between infants and toddlers and identify potential age-adapted prognostic markers for poor outcome of pneumonia-derived pediatric sepsis.

Experimental Design: A nested case-control study strategy was applied. The plasma proteomes of pneumonia-derived pediatric septic patients with different outcomes between infants and toddlers were respectively analysed compared to their age-matched controls.

Prenatal inflammation exposure-programmed hypertension exhibits multi-generational inheritance via disrupting DNA methylome.

The multi-generation heredity trait of hypertension in human has been reported, but the molecular mechanisms underlying multi-generational inheritance of hypertension remain obscure. Recent evidence shows that prenatal inflammatory exposure (PIE) results in increased incidence of cardiovascular diseases, including hypertension. In this study we investigated whether and how PIE contributed to multi-generational inheritance of hypertension in rats.

Conditional knockout of Tsc1 in RORγt-expressing cells induces brain damage and early death in mice.

Background: Tuberous sclerosis complex 1 (Tsc1) is known to regulate the development and function of various cell types, and RORγt is a critical transcription factor in the immune system. However, whether Tsc1 participates in regulating RORγt-expressing cells remains unknown.

Methods: We generated a mouse model in which Tsc1 was conditionally deleted from RORγt-expressing cells (Tsc1) to study the role of RORγt-expressing cells with Tsc1 deficiency in brain homeostasis.

PLA1A expression as a diagnostic marker of BRAF-mutant metastasis in melanoma cancer.

BRAF and NRAS are the most reported mutations associated to melanomagenesis. The lack of accurate diagnostic markers in response to therapeutic treatment in BRAF/NRAS-driven melanomagenesis is one of the main challenges in melanoma personalized therapy. In order to assess the diagnostic value of phosphatidylserine-specific phospholipase A1-alpha (PLA1A), a potent lysophospholipid mediating the production of lysophosphatidylserine, PLA1A mRNA and serum levels were compared in subjects with malignant melanoma (n = 18), primary melanoma (n = 13), and healthy subjects (n = 10).

Natural Killer Cells: Friend or Foe in Metabolic Diseases?

The worldwide epidemic of metabolic diseases, especially obesity and other diseases caused by it, has shown a dramatic increase in incidence. A great deal of attention has been focused on the underlying mechanisms of these pathological processes and potential strategies to solve these problems. Chronic inflammation initiated by abdominal adipose tissues and immune cell activation in obesity is the major cause of the consequent development of complications.

Identification of a Five-Autophagy-Related-lncRNA Signature as a Novel Prognostic Biomarker for Hepatocellular Carcinoma.

Although great progresses have been made in the diagnosis and treatment of hepatocellular carcinoma (HCC), its prognostic marker remains controversial. In this current study, weighted correlation network analysis and Cox regression analysis showed significant prognostic value of five autophagy-related long non-coding RNAs (AR-lncRNAs) (including TMCC1-AS1, PLBD1-AS1, MKLN1-AS, LINC01063, and CYTOR) for HCC patients from data in The Cancer Genome Atlas. By using them, we constructed a five-AR-lncRNA prognostic signature, which accurately distinguished the high- and low-risk groups of HCC patients.

Landscape of active enhancers developed de novo in cirrhosis and conserved in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) patients always have a background of cirrhosis. Aberrant epigenetic changes in cirrhosis provide a conductive environment for HCC tumorigenesis. Active enhancers (AEs) are essential for epigenetic regulation and play an important role in cell development and the progression of many diseases.