Individuals with Internet gaming disorder (IGD) show deficits in face processing due to long-term Internet-game social activities based on cartoon faces in the popular online game "Strike of Kings." However, the abnormal neurocognitive mechanism of face recognition and processing in individuals with IGD has not been systematically explored. This study used event-related potential (ERP) methods and the reversed deviant-standard oddball paradigm to comprehensively compare four ERP components, namely, P100, N170, P200, and mismatch negativity (MMN), induced in the unconscious and automatic processing of realistic and cartoon faces in individuals with IGD. Results showed that, with respect to cartoon faces, individuals with IGD exhibited not only P100, P200 and MMN enhancements but also the absence of the N170 dominance effect in the left hemisphere. Our results also demonstrated that individuals with IGD had the advantages of early automatic perception of cartoon faces and automatic detection of changes in "cartoon" features. This study enhances our understanding of the mechanism of IGD from the neurocognitive perspective and provides candidate electrophysiological indicators for the clinical diagnosis of IGD.

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy with high mortality that urgently requires new treatments. ROCK1 plays an essential role in regulating growth and survival in AML cells. In this study, we evaluated GSK269962A, a selective ROCK1 inhibitor, in preclinical models of AML. Compared with solid tumors, GSK269962A selectively inhibited cell growth and clonogenicity of AML cells. Furthermore, GSK269962A arrested AML cells in the G2 phase and induced apoptosis by regulating multiple cell cycle- and apoptosis-associated proteins. Strikingly, GSK269962A could eliminate leukemia cells from bone marrow, liver, and spleen in an animal model of AML and significantly prolong mouse survival. Mechanistically, GSK269962A could inhibit the growth of AML by blocking ROCK1/c-Raf/ERK signaling pathway. Notably, a correlation was found between the expression levels of ROCK1 protein and the sensitivity of GSK269962A in AML. These data highlight the potential role of ROCK1 as an attractive target for treating AML, as well as the potential of GSK269962A for use in clinical trials of AML.

Long non-coding ribonucleic acids (lncRNAs) are a class of non-coding RNAs implicated in the development of many malignancies, including gastric cancer (GC). In this study, we investigated the functions and molecular mechanisms of non-coding RNA activated by deoxyribonucleic acid damage (NORAD) in GC.

Oral administration offered a painless way and improved compliance for diabetics. However, the emerging GLP-1 analog peptide drugs for diabetes primarily rely on the injection route, and the development of oral dosage forms was hampered by the low oral bioavailability due to the structural vulnerability to digestive enzymes and molecule impermeability in the gastrointestinal tract.

To evaluate the relationship between the DNA mismatch repair (MMR) status and histone lysine-specific demethylase 6A (KDM6A) on the prognosis of colorectal cancer (CRC).

The chloroplast is a semi-autonomous organelle with its own genome. The expression of chloroplast genes depends on both chloroplasts and the nucleus. Although many nucleus-encoded proteins have been shown to localize in chloroplasts and are essential for chloroplast gene expression, it is not clear whether transcription factors can regulate gene expression in chloroplasts. Here we report that the transcription factor NAC102 localizes in both chloroplasts and nucleus in Arabidopsis. Specifically, NAC102 localizes in chloroplast nucleoids. Yeast two-hybrid assay and co-immunoprecipitation assay suggested that NAC102 interacts with chloroplast RNA polymerases. Furthermore, overexpression of NAC102 in chloroplasts leads to reduced chloroplast gene expression and chlorophyll content, indicating that NAC102 functions as a repressor in chloroplasts. Our study not only revealed that transcription factors are new regulators of chloroplast gene expression, but also discovered that transcription factors can function in chloroplasts in addition to the canonical organelle nucleus.

The fidelity of alternative splicing (AS) patterns is essential for growth development and cell fate determination. However, the scope of the molecular switches that regulate AS remains largely unexplored. Here we show that MEN1 is a previously unknown splicing regulatory factor. MEN1 deletion resulted in reprogramming of AS patterns in mouse lung tissue and human lung cancer cells, suggesting that MEN1 has a general function in regulating alternative precursor mRNA splicing. MEN1 altered exon skipping and the abundance of mRNA splicing isoforms of certain genes with suboptimal splice sites. Chromatin immunoprecipitation and chromosome walking assays revealed that MEN1 favored the accumulation of RNA polymerase II (Pol II) in regions encoding variant exons. Our data suggest that MEN1 regulates AS by slowing the Pol II elongation rate and that defects in these processes trigger R-loop formation, DNA damage accumulation and genome instability. Furthermore, we identified 28 MEN1-regulated exon-skipping events in lung cancer cells that were closely correlated with survival in patients with lung adenocarcinoma, and MEN1 deficiency sensitized lung cancer cells to splicing inhibitors. Collectively, these findings led to the identification of a novel biological role for menin in maintaining AS homeostasis and link this role to the regulation of cancer cell behavior.

The role of vascular endothelial cells in acute and chronic vascular inflammatory response has long been recognized. Therefore, persistent vascular inflammation may lead to endothelial dysfunction, thus resulting in the release of pro-inflammatory cytokines and the expression of adhesion molecules, which in turn promote monocyte/macrophage adhesion. Inflammation serves a key role in the development of vascular diseases, such as atherosclerosis. Tyrosol is a natural polyphenolic compound with diverse biological functions, found in large quantities in olive oil or in Rhodiola rosea. The current study aimed to investigate the regulatory in vitro effects of tyrosol on pro-inflammatory phenotypes using Cell Counting Kit-8, cell adhesion assay, wound healing, ELISA, western blotting, duel-luciferase, reverse transcription-quantitative PCR and flow cytometry. The results showed that tyrosol significantly inhibited the adhesion of THP-1 human umbilical vein endothelial cells, reduced lipopolysaccharide-induced cell migration and decreased the release of pro-inflammatory factors and the expression levels of adhesion-related molecules, such as TNF-α, monocyte chemotactic protein-1, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. Previous studies indicate that NF-κB could serve a pivotal role in initiating the inflammatory responses of endothelial cells and particularly in regulating the expression of adhesion molecules and inflammatory factors. The results of the current study demonstrated that tyrosol was associated with decreased expression of adhesion molecules and monocyte-endothelial cell adhesion, thus suggesting that tyrosol could be a novel pharmacological approach for treating inflammatory vascular diseases.

Aberrant intracellular or intercellular signaling pathways are important mechanisms that contribute to the development and progression of cancer. However, the intercellular communication associated with the development of ccRCC is currently unknown. The purpose of this study was to examine the aberrant tumor cell-to-cell communication signals during the development of ccRCC.

Human immunodeficiency virus type 1 (HIV-1) infection is characterized by progressive depletion of CD4+ T lymphocytes and dysfunction of the immune system. The numbers of CD4+ T lymphocytes in the human body are maintained constantly by homeostatic mechanisms that failed during HIV-1 infection, resulting in progressive loss of CD4+ T cells mainly via apoptosis. Recently, a non-apoptotic form of necrotic programmed cell death, named necroptosis, has been investigated in many biological and pathological processes. We then determine whether HIV-1-infected cells also undergo necroptosis. In this report, we demonstrate that HIV-1 not only induces apoptosis, but also mediates necroptosis in the infected primary CD4+ T lymphocytes and CD4+ T-cell lines. Necroptosis-dependent cytopathic effects are significantly increased in HIV-1-infected Jurkat cells that is lack of Fas-associated protein-containing death domain (FADD), indicating that necroptosis occurs as an alternative cell death mechanism in the absence of apoptosis. Unlike apoptosis, necroptosis mainly occurs in HIV-infected cells and spares bystander damage. Treatment with necrostatin-1(Nec-1), a RIP1 inhibitor that specifically blocks the necroptosis pathway, potently restrains HIV-1-induced cytopathic effect and interestingly, inhibits the formation of HIV-induced syncytia in CD4+ T-cell lines. This suggests that syncytia formation is mediated, at least partially, by necroptosis-related processes. Furthermore, we also found that the HIV-1 infection-augmented tumor necrosis factor-alpha (TNF-α) plays a key role in inducing necroptosis and HIV-1 Envelope and Tat proteins function as its co-factors. Taken together,necroptosis can function as an alternative cell death pathway in lieu of apoptosis during HIV-1 infection, thereby also contributing to HIV-1-induced cytopathic effects. Our results reveal that in addition to apoptosis, necroptosis also plays an important role in HIV-1-induced pathogenesis.

Myeloid-derived suppressor cells (MDSCs) have been known to be a key factor in the regulation of the immune system under numerous conditions such as tumors, infections, autoimmune diseases, and transplantations. In contrast to the proposed deleterious role of MDSCs in tumors and infections, MDSCs with their suppressive function are now proved to have the beneficial potential of suppressing the autoimmune response and promoting tolerance to transplantation. Therefore, the expansion of MDSCs could be a promising therapeutic strategy for many diseases. In this study, we aimed to identify FDA-approved drugs that could aid in the expansion of functional MDSCs. We performed a high-throughput screening (HTS) of FDA-approved drugs based on the in vitro human MDSC-differentiation system and identified finasteride (FIN) to have the best potency to aid the generation of human MDSCs. The FIN-induced MDSCs were quite similar to monocytic MDSCs with regard to their surface phenotype, morphology, immunosuppressive function, and related gene expression. Next, we aimed to determine the mechanism of action of FIN and found that FIN induced the expansion of MDSCs through up-regulation of the COX2/PGE2 pathway by enhancing the activity of COX2 promoter. In addition, the administration of indomethacin (IND), a COX2 inhibitor, abrogated the effect of FIN. Based on these results, we suggested that FIN could find applications in the future in the expansion of MDSCs. Further development of FIN-like compounds could be a novel strategy for generating functional MDSCs for immunosuppressive therapies in various immune disorder conditions.

Curcumenol, an effective ingredient of Wenyujin, has been reported that exerted its antitumor potential in a few cancer types. However, the effect and molecular mechanism of curcumenol in lung cancer are largely unknown. Here, we found that curcumenol induced cell death and suppressed cell proliferation in lung cancer cells. Next, we demonstrated that ferroptosis was the predominant method that contributed to curcumenol-induced cell death of lung cancer in vitro and vivo for the first time. Subsequently, using RNA sequencing, we found that the long non-coding RNA H19 (lncRNA H19) was significantly downregulated in lung cancer cells treated with curcumenol, when compared to untreated controls. Overexpression of lncRNA H19 eliminated the anticancer effect of curcumenol, while lncRNA H19 knockdown promoted ferroptosis induced by curcumenol treatment. Mechanistically, we showed that lncRNA H19 functioned as a competing endogenous RNA to bind to miR-19b-3p, thereby enhanced the transcription activity of its endogenous target, ferritin heavy chain 1 (FTH1), a marker of ferroptosis. In conclusion, our data show that the natural product curcumenol exerted its antitumor effects on lung cancer by triggering ferroptosis, and the lncRNA H19/miR-19b-3p/FTH1 axis plays an essential role in curcumenol-induced ferroptotic cell death. Therefore, our findings will hopefully provide a valuable drug for treating lung cancer patients.

Transcription factors (TFs) play crucial regulatory roles in controlling the expression of the target genes in plants. APETALA2/Ethylene-responsive factors (AP2/ERF) are part of a large superfamily of plant-specific TFs whose members are involved in the control of plant metabolism, development and responses to various biotic and abiotic stresses. However, the AP2/ERF superfamily has not been identified systematically in Masson pine (Pinus massoniana), which is one of the most important conifer in southern China. Therefore, we performed systematic identification of the AP2/ERF superfamily using transcriptome sequencing data from Masson pine. In the current study, we obtained 88 members of the AP2/ERF superfamily. All PmAP2/ERF members could be classified into 3 main families, AP2 (7 members), RAV (7 members), ERF (73 members) families, and a soloist protein. Subcellular localization assays suggested that two members of PmAP2/ERF were nuclear proteins. Based on pine wood nematode (PWN) inoculated transcriptome and qPCR analysis, we found that many members of PmAP2/ERF could respond to PWN inoculation and PWN related treatment conditions in vitro. In general, members of the AP2/ERF superfamily play an important role in the response of Masson pine responds to PWN. Furthermore, the roles of the AP2/ERF superfamily in other physiological activities of Masson pine remain to be further studied.

Diabetic peripheral neuropathy (DPN) is one of the most common microvascular complications of diabetes mellitus, with an incidence ranging from 60% to 90%. With the change in modern dietary structure, the incidence of diabetes is increasing year by year, and DPN is also on the rise. Tuina therapy has been widely used in the treatment of DPN, but there is no systematic review on the treatment of DPN. Therefore, this study aimed to conduct a meta-analysis of Tuina in the treatment of DPN to clarify its efficacy.

Erianin, a natural product derived from Dendrobium chrysotoxum Lindl, has been proved to play antitumor activity in various cancers. However, the effects and molecular mechanisms of erianin in bladder cancer cells remain unexplored. In this study, we found that erianin triggered cell death and cell cycle arrest in bladder cancer cells. Then we demonstrated that erianin could promote the accumulation of lethal lipid-based reactive oxygen species (ROS) and the depletion of glutathione (GSH), suggesting the induction of ferroptosis. In the further study, the ferroptosis inhibitor deferoxamine (DFO), N-Acetylcysteine (NAC) and GSH but not necrostatin-1, CQ or Z-VAD-FMK rescued erianin-caused cell death, showing ferroptosis played a major role in erianin-caused cell death. In vivo, we also showed that erianin suppressed the tumor growth by inducing ferroptosis. Mechanistically, we demonstrated that nuclear factor E2-related factor 2 (NRF2) inactivation was a key determinant of ferroptosis caused by erianin. In bladder cancer cells, the compound tert-butylhydro-quinone (TBHQ), an activator of NRF2, suppressed erianin-induced ferroptosis. Whereas, NRF2 inhibition used shRNA augmented the ferroptosis response induced by erianin treatment. In conclusion, our data provide the first evidence that erianin can initiate ferroptosis-like cell death and lipid peroxidation in bladder cancer, which will hopefully become a promising anticancer compound for the treatment of bladder cancer.

Renal fibrosis is a serious condition that results in the development of chronic kidney diseases. The MEN1 gene is an epigenetic regulator that encodes the menin protein and its role in kidney tissue remains unclear.

We aimed to investigate the composition and functions discrepancy of supragingival plaque associated with active deciduous teeth caries in mixed dentitions.

Alzheimer's disease (AD) is a brain illness that affects learning and memory capacities over time. In recent investigations, acupuncture has been shown to be an effective alternative treatment for AD. We investigated the effect of acupuncture on learning and memory abilities using a water maze in APP/PS1 transgenic mice. The amounts of Aβ and tau protein in mice's hippocampal tissue were determined using Western blot. The levels of IL-1β, IL-10, LPS and TNF-α in mice's serum were measured using ELISA. The variations of gut microbiota in mice's feces were determined using the 16SrDNA technique, and the metabolites were examined using a untargeted metabolomics methodology. The results showed that acupuncture treatment improved mice's learning and memory abilities substantially. Acupuncture therapy regulated the Aβ and tau protein concentration as well as the levels of IL-10 and LPS. Acupuncture treatment influenced the mouse microbiota and metabolites and had been linked to six biochemical pathways. This study adds to our understanding of the effect of acupuncture on AD and opens the door to further research into the alterations of intestinal bacteria in the presence of AD.

Gastric ulcer (GU) is a clinically common disease of the digestive system that adversely affects patients' quality of life and work ability. Although some articles have reported that acupuncture can improve the clinical symptoms of GU, the efficacy of acupuncture has not been scientifically or methodically evaluated. This study aimed to evaluate the effectiveness and safety of acupuncture for the treatment of patients with gastric ulcers.

Drought is a major abiotic stress factor limiting maize production, and elucidating the genetic control of root system architecture and plasticity to water-deficit stress is a crucial problem to improve drought adaptability. In this study, 13 root and shoot traits and genetic plasticity were evaluated in a recombinant inbred line (RIL) population under well-watered (WW) and water stress (WS) conditions. Significant phenotypic variation was observed for all observed traits both under WW and WS conditions. Most of the measured traits showed significant genotype-environment interaction (GEI) in both environments. Strong correlations were observed among traits in the same class. Multi-environment (ME) and multi-trait (MT) QTL analyses were conducted for all observed traits. A total of 48 QTLs were identified by ME, including 15 QTLs associated with 9 traits showing significant QTL-by-Environment interactions (QEI). QTLs associated with crown root angle (CRA2) and crown root length (CRL1) were identified as having antagonistic pleiotropic effects, while 13 other QTLs showed signs of conditional neutrality (CN), including 9 and 4 QTLs detected under WW and WS conditions, respectively. MT analysis identified 14 pleiotropic QTLs for 13 traits, SNP20 (1@79.2 cM) was associated with the length of crown root (CR), primary root (PR), and seminal root (SR) and might contribute to increases in root length under WS condition. Taken together, these findings contribute to our understanding of the phenotypic and genotypic patterns of root plasticity in response to water deficiency, which will be useful to improve drought tolerance in maize.