Identification of differentially expressed genes in the medial prefrontal cortex of rats subjected to chronic unpredictable mild stress and treated with electroacupuncture.

Major depressive disorder is a chronic mental health condition that seriously impacts afflicted individuals. Although electroacupuncture has proven to be an effective therapy for depression, its underlying biological mechanism remains largely unknown. In this study, we aimed to investigate the effects of electroacupuncture on depression-like behavior and to identify potential target genes related to those effects. To achieve this, we subjected rats to chronic unpredictable mild stress (CUMS) and used sucrose preference, forced swimming, and open-field tests to determine their depression-like behavior in the absence or after receipt of electroacupuncture treatment. RNA sequencing technology was then used to reveal the differentially expressed genes associated with depression and electroacupuncture treatment effects in the medial prefrontal cortex (mPFC). Repeated electroacupuncture treatments at the Baihui (GV20) and Taichong (LR3) acupoints significantly alleviated depression-like behavioral defects in the animals. Genomic RNA sequencing revealed several significant changes in the mPFC transcriptome of rats that received treatment. Through differential gene expression analysis, we found that electroacupuncture reversed the CUMS-induced downregulation of 46 genes and upregulation of 13 genes. Among the differentially expressed genes, Casr, Bdkrb2, Gnb3, and Ccl1 were found to be associated with depression and electroacupuncture treatment effects. In conclusion, we verified that electroacupuncture treatment has an effective antidepressant effect, and the underlying mechanism involves multiple systems and targets.

Multiomics analysis of canine myocardium after circumferential pulmonary vein ablation: Effect of neuropeptide Y on long-term reinduction of atrial fibrillation.

Catheter ablation (CA) is an essential method for the interventional treatment of atrial fibrillation (AF), and it is very important to reduce long-term recurrence after CA. The mechanism of recurrence after CA is still unclear. We established a long-term model of beagle canines after circumferential pulmonary vein ablation (CPVA). The transcriptome and proteome were obtained using high-throughput sequencing and TMT-tagged LC-MS/LC analysis, respectively. Differentially expressed genes and proteins were screened and enriched, and the effect of fibrosis was found and verified in tissues. A downregulated protein, neuropeptide Y (NPY), was selected for validation and the results suggest that NPY may play a role in the long-term reinduction of AF after CPVA. Then, the molecular mechanism of NPY was further investigated. The results showed that the atrial effective refractory period (AERP) was shortened and fibrosis was increased after CPVA. Atrial myocyte apoptosis was alleviated by NPY intervention, and Akt activation was inhibited in cardiac fibroblasts. These results suggest that long-term suppression of NPY after CPVA may lead to induction of AF through promoting cardiomyocyte apoptosis and activating the Akt pathway in cardiac fibroblasts, which may make AF more likely to reinduce.

Spatiotemporal transcriptomic atlas of rhizome formation in Oryza longistaminata.

Rhizomes are modified stems that grow underground and produce new individuals genetically identical to the mother plant. Recently, a breakthrough has been made in efforts to convert annual grains into perennial ones by utilizing wild rhizomatous species as donors, yet the developmental biology of this organ is rarely studied. Oryza longistaminata, a wild rice species featuring strong rhizomes, provides a valuable model for exploration of rhizome development. Here, we first assembled a double-haplotype genome of O. longistaminata, which displays a 48-fold improvement in contiguity compared to the previously published assembly. Furthermore, spatiotemporal transcriptomics was performed to obtain the expression profiles of different tissues in O. longistaminata rhizomes and tillers. Two spatially reciprocal cell clusters, the vascular bundle 2 cluster and the parenchyma 2 cluster, were determined to be the primary distinctions between the rhizomes and tillers. We also captured meristem initiation cells in the sunken area of parenchyma located at the base of internodes, which is the starting point for rhizome initiation. Trajectory analysis further indicated that the rhizome is regenerated through de novo generation. Collectively, these analyses revealed a spatiotemporal transcriptional transition underlying the rhizome initiation, providing a valuable resource for future perennial crop breeding.

Microfluidic paper-based chemiluminescence sensing platform based on functionalized CaCO3 for time-resolved multiplex detection of avian influenza virus biomarkers.

Multiplex detection can enhance diagnostic precision and improve diagnostic efficiency, providing important assistance for epidemiological investigation and epidemic prevention. There is a great need for multi-detection sensing platforms to accurately diagnose diseases. Herein, we reported a µPAD-based chemiluminescence (CL) assay for ultrasensitive multiplex detection of AIV biomarkers, based on three DNAzyme/Lum/PEI/CaCO3. Three time-resolved CL signals were sequentially generated with detection limits of 0.32, 0.34, and 0.29 pM for H1N1, H7N9, and H5N1, respectively, and with excellent selectivity against interfering DNA. The recovery test in human serum displayed satisfactory analysis capabilities for complex biological samples. The µPAD-based CL assay achieved multiplex detection within 70 s, with a high time resolution of 20 s. The proposed strategy has the advantages of low cost, high sensitivity, good selectivity, and wide time resolution, the µPAD-based CL assay has shown great potential in the early and accurate diagnosis of diseases.

iTRAQ-based proteomic study on monocyte cell model discovered an association of LAMP2 downregulation with HIV-1 latency.

BACKGROUND: Patients with immunodeficiency virus-1 (HIV-1) infection are challenging to be cured completely due to the existence of HIV-1 latency reservoirs. However, the knowledge of the mechanisms and biomarkers associated with HIV-1 latency is limited. Therefore, identifying proteins related to HIV-1 latency could provide new insights into the underlying mechanisms of HIV-1 latency, and ultimately contribute to the eradication of HIV reservoirs. METHODS: An Isobaric Tags for Relative and Absolute Quantification (iTRAQ)-labeled subcellular proteomic study was performed on an HIV-1 latently infected cell model (U1, a HIV-1-integrated U937 cell line) and its control (U937). Differentially expressed proteins (DEPs) were analyzed using STRING-DB. Selected DEPs were further evaluated by western blotting and multiple reaction monitoring technology in both cell model and patient-derived cluster of differentiation 4 (CD4)+ T cells. Finally, we investigated the relationship between a specific DEP lysosome-associated membrane glycoprotein 2 (LAMP2) and HIV-1 reactivation by panobinostat or lysosome regulation by a lysosomotropic agent hydroxychloroquine in U1 and U937 cells. RESULTS: In total, 110 DEPs were identified in U1 cells comparing to U937 control cells. Bioinformatics analysis suggested associations of the altered proteins with the immune response and endosomal/lysosomal pathway. LAMP2, leukocyte surface antigen CD47, CD55, and ITGA6 were downregulated in HIV-1 latent cells. Downregulated LAMP2 was further confirmed in resting CD4+ T cells from patients with latent HIV-1 infection. Furthermore, both HIV-1 reactivation by panobinostat and stimulation with hydroxychloroquine upregulated LAMP2 expression. CONCLUSIONS: Our results indicated the involvement of the endosomal/lysosomal pathway in HIV-1 latency in macrophage cell model. The down-modulation of LAMP2 was associated with HIV latency, and the restoration of LAMP2 expression accompanied the transition of viral latency to active infection. This study provides new insights into the mechanism of HIV-1 latency and potential strategies for eradicating HIV-1 reservoirs by targeting LAMP2 expression.

Impact of different CEBPA mutations on therapeutic outcome in acute myeloid leukemia.

Biallelic mutations of the CEBPA gene (CEBPAbi) are generally associated with favorable prognosis in patients with acute myeloid leukemia (AML). Monoallelic mutations of the CEBPA gene in carboxy-terminal DNA-binding region (CEBPAsmbZIP) and amino-terminal transactivation domains (CEBPAsmTAD) indicate distinct clinical characteristics and therapeutic outcomes. However, further investigation is required to fully understand these differences. In this retrospective study, we enrolled 77 AML patients with CEBPA mutations, including 53 with CEBPAbi, 12 with CEBPAsmbZIP and 12 with CEBPAsmTAD. The clinical characteristics of the three CEBPAmut groups presented significant differences in age, FAB classification, hemoglobin level and platelet count at diagnosis. The CEBPAsmTAD group exhibited shorter 2-year overall survival (OS) and relapse-free survival (RFS) compared to the CEBPAbi group and CEBPAsmbZIP group in AML patients. The most common co-mutations observed in CEBPAmut AML patients were TET2 and GATA2, which had no effect on prognosis. 2-year RFS of 27 CEBPAmut AML patients who underwent allo-HSCT was better than those who did not. MRD3 positive was identified as an influencing factor for 2-year OS and RFS. Allo-HSCT was found to improve the prognosis of CEPBAmut AML patients with positive MRD3 and adverse co-mutations.

Concomitant targeting of FLT3 and SPHK1 exerts synergistic cytotoxicity in FLT3-ITD+ acute myeloid leukemia by inhibiting ß-catenin activity via the PP2A-GSK3ß axis.

BACKGROUND: Approximately 25-30% of patients with acute myeloid leukemia (AML) have FMS-like receptor tyrosine kinase-3 (FLT3) mutations that contribute to disease progression and poor prognosis. Prolonged exposure to FLT3 tyrosine kinase inhibitors (TKIs) often results in limited clinical responses due to diverse compensatory survival signals. Therefore, there is an urgent need to elucidate the mechanisms underlying FLT3 TKI resistance. Dysregulated sphingolipid metabolism frequently contributes to cancer progression and a poor therapeutic response. However, its relationship with TKI sensitivity in FLT3-mutated AML remains unknown. Thus, we aimed to assess mechanisms of FLT3 TKI resistance in AML. METHODS: We performed lipidomics profiling, RNA-seq, qRT-PCR, and enzyme-linked immunosorbent assays to determine potential drivers of sorafenib resistance. FLT3 signaling was inhibited by sorafenib or quizartinib, and SPHK1 was inhibited by using an antagonist or via knockdown. Cell growth and apoptosis were assessed in FLT3-mutated and wild-type AML cell lines via Cell counting kit-8, PI staining, and Annexin-V/7AAD assays. Western blotting and immunofluorescence assays were employed to explore the underlying molecular mechanisms through rescue experiments using SPHK1 overexpression and exogenous S1P, as well as inhibitors of S1P2, ß-catenin, PP2A, and GSK3ß. Xenograft murine model, patient samples, and publicly available data were analyzed to corroborate our in vitro results. RESULTS: We demonstrate that long-term sorafenib treatment upregulates SPHK1/sphingosine-1-phosphate (S1P) signaling, which in turn positively modulates ß-catenin signaling to counteract TKI-mediated suppression of FLT3-mutated AML cells via the S1P2 receptor. Genetic or pharmacological inhibition of SPHK1 potently enhanced the TKI-mediated inhibition of proliferation and apoptosis induction in FLT3-mutated AML cells in vitro. SPHK1 knockdown enhanced sorafenib efficacy and improved survival of AML-xenografted mice. Mechanistically, targeting the SPHK1/S1P/S1P2 signaling synergizes with FLT3 TKIs to inhibit ß-catenin activity by activating the protein phosphatase 2 A (PP2A)-glycogen synthase kinase 3ß (GSK3ß) pathway. CONCLUSIONS: These findings establish the sphingolipid metabolic enzyme SPHK1 as a regulator of TKI sensitivity and suggest that combining SPHK1 inhibition with TKIs could be an effective approach for treating FLT3-mutated AML.

Electroacupuncture Alleviates Pain by Suppressing P2Y12R-Dependent Microglial Activation in Monoarthritic Rats.

Electroacupuncture (EA) effectively improves arthritis-induced hyperalgesia and allodynia by repressing spinal microglial activation, which plays a crucial role in pain hypersensitivity following tissue inflammation. However, the mechanism by which EA suppresses spinal microglial activation in monoarthritis (MA) remains unclear. In the present study, a rat model of MA was established through unilateral ankle intra-articular injection of complete Freund's adjuvant (CFA). The relationship among P2Y12 receptor (P2Y12R) expression, spinal microglial activation, and EA analgesia was investigated using quantitative real-time PCR (qRT‒PCR), western blotting, immunofluorescence (IF), and behavioral testing. The results found that EA treatment at the ipsilateral "Huantiao" (GB30) and "Yanglingquan" (GB34) acupoints markedly attenuated pain and spinal microglia M1 polarization in MA rats. In particular, P2Y12R expression was significantly increased at the mRNA and protein levels in the spinal dorsal horn in MA rats, whereas EA treatment effectively repressed the MA-induced upregulation of P2Y12R. IF analysis further revealed that most P2Y12R was expressed in microglia in the spinal dorsal horn. Pharmacological inhibition of P2Y12R by its antagonist (AR-C69931MX) decreased MA-induced spinal microglial activation and subsequent proinflammatory cytokine production. Consequently, AR-C69931MX significantly intensified the anti-pain hypersensitive function of EA in MA rats. Taken together, these results demonstrate that EA alleviates MA-induced pain by suppressing P2Y12R-dependent microglial activation.

Hypothalamic Gene Expression in a Rat Model of Chronic Unpredictable Mild Stress Treated with Electroacupuncture.

Depression is characterized by the loss of pleasure and a depressed mood, and it is a common mental disorder in the twenty-first century. Multiple gene imbalances, which are considered pathological factors in depression, were detected in the brain. Electroacupuncture is an effective therapeutic approach for depression that has minimal side effects. As a crucial structure in the hypothalamus-pituitary-adrenal, the hypothalamus plays a key role in depression. Our study focused on the transcriptome level in the hypothalamus of depressive rats. After chronic unpredictable mild stress, the rats exhibited depressive-like behaviors, such as decreased sucrose consumption in the SPT, increased time in the central area of the OFT and increased immobility in the FST. Moreover, electroacupuncture alleviated depressive behaviors. Because of the importance of the hypothalamus in depression, we next detected gene expression in the hypothalamus. A total of 510 genes (125 upregulated genes and 385 downregulated genes) were detected in the hypothalamus of depressive rats. 15 of the 125 upregulated genes and 63 of the 385 downregulated genes could be altered by electroacupuncture, which suggests the antidepressant effect of electroacupuncture. Our study also provided the evidence that regulation of transcriptome in the hypothalamus might be a potential mechanism of electroacupuncture treatment.

Recent advances in palladium-catalyzed sulfonylation via SO2 insertion.

The importance of sulfonyl-group-containing compounds, such as sulfonamides, sulfones, sulfinate esters, and sulfonyl fluorides, in pharmaceuticals, bioactive molecules, and natural products cannot be overstated. The new development of palladium-catalyzed sulfonylation via SO2 insertion represents a crucial advancement in organic synthesis, enabling the direct α,α-difunctionalization of SO2 and providing efficient access to an array of structure-diverse sulfonyl-containing compounds. Although there have been numerous reviews about SO2 insertion, many of them only cover specific aspects of palladium-catalyzed reactions, leading to an oversight of some important works. Besides, these reviews often lack detailed discussions and systematic conclusion on reaction mechanisms, and fail to comprehensively summarize the significant research achievements in palladium-catalyzed reactions over the past few years. Herein, we aim to systematically consolidate the recent advances in palladium-catalyzed sulfonylation via SO2 insertion, elucidate the underlying reaction mechanism, and highlight some unsolved challenges in this segment. This review seeks to serve as a valuable resource for researchers, assisting in the continued development of palladium-catalyzed sulfonylation methodologies.

Application of GaS nanotubes as efficient catalysts in photocatalytic hydrolysis: a first principles study.

Photocatalytic hydrogen production is a promising and sustainable technology that converts solar energy into hydrogen energy with the assistance of semiconductor photocatalysts. Herein, we investigated the geometric structure and electronic and photocatalytic properties of single-walled GaS nanotubes under the framework of density functional theory with HSE06 as an exchange-correlation function. This paper presents the first study on the geometric structure, electron, and photocatalytic properties of single-walled GaS nanotubes. The results show that the strain energy and formation energy of GaS nanotubes decrease, while the structure is more stable, with increasing radius. Our study shows that after rolling from the slab, the nanotubes undergo a transition from an indirect band gap to a direct band gap and have appropriate band gaps for absorbing visible light. Moreover, it is speculated that the large disparity between the effective mass of electrons and holes can reduce charge carrier recombination. Among them, the nanotube with a diameter larger than (35, 0) showed promising band edge positions for photocatalytic hydrolysis redox potential with pH values between 0 and 7. Based on these properties, we believe that GaS nanotubes will be promising in photocatalytic hydrolysis.

Thymoquinone inhibits lung cancer stem cell properties via triggering YAP degradation.

Due to the characteristics of high recurrence and metastasis, it is still difficult to cure lung cancer. Cancer stem cells (CSCs) are a group of tumor cells with self-renewal ability and differentiation potential, which are responsible for lung cancer recurrence. Therefore, targeting CSCs may provide a new strategy for lung cancer treatment. Thymoquinone (TQ), the main active ingredient isolated from black seed oil, has shown significant anti-cancer effects in various cancers. However, the effect of TQ on lung cancer stem cells (LCSCs) has never been clarified. In the present study, we successfully separated and enriched lung cancer tumorsphere cells. Our data showed that TQ significantly inhibited the stem-like properties of LCSCs. In addition, we found TQ promoted Yes-associated protein (YAP) phosphorylation and ubiquitination, and the inhibitory effects of TQ on LCSCs could be enhanced by silencing YAP. Taken together, these results suggest that TQ, functions by targeting YAP, may be a potential therapeutic agent against lung cancer.

Influence on therapeutic outcome of platelet count at diagnosis in patients with de novo non-APL acute myeloid leukemia.

BACKGROUND: Platelet (PLT) count at diagnosis plays an important role in cancer development and progression in solid tumors. However, it remains controversial whether PLT count at diagnosis influences therapeutic outcome in patients with non-acute promyelocytic leukemia (APL) acute myeloid leukemia (AML). METHODS: This study analyzed the relationship between PLT count at diagnosis and genetic mutations in a cohort of 330 newly diagnosed non-APL AML patients. The impact of PLT count on complete remission, minimal residual disease status and relapse-free survival (RFS) were evaluated after chemotherapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT). RESULTS: Our studies showed that patients with DNMT3A mutations have a higher PLT count at diagnosis, while patients with CEBPA biallelic mutations or t(8;21)(q22; q22) translocation had lower PLT count at diagnosis. Furthermore, non-APL AML patients with high platelet count (> 65 × 109/L) at diagnosis had worse response to induction chemotherapy and RFS than those with low PLT count. In addition, allo-HSCT could not absolutely attenuated the negative impact of high PLT count on the survival of non-APL AML patients. CONCLUSION: PLT count at diagnosis has a predictive value for therapeutic outcome for non-APL AML patients.

Overlapping roles for PLK1 and Aurora A during meiotic centrosome biogenesis in mouse spermatocytes.

The establishment of bipolar spindles during meiotic divisions ensures faithful chromosome segregation to prevent gamete aneuploidy. We analyzed centriole duplication, as well as centrosome maturation and separation during meiosis I and II using mouse spermatocytes. The first round of centriole duplication occurs during early prophase I, and then, centrosomes mature and begin to separate by the end of prophase I to prime formation of bipolar metaphase I spindles. The second round of centriole duplication occurs at late anaphase I, and subsequently, centrosome separation coordinates bipolar segregation of sister chromatids during meiosis II. Using a germ cell-specific conditional knockout strategy, we show that Polo-like kinase 1 and Aurora A kinase are required for centrosome maturation and separation prior to metaphase I, leading to the formation of bipolar metaphase I spindles. Furthermore, we show that PLK1 is required to block the second round of centriole duplication and maturation until anaphase I. Our findings emphasize the importance of maintaining strict spatiotemporal control of cell cycle kinases during meiosis to ensure proficient centrosome biogenesis and, thus, accurate chromosome segregation during spermatogenesis.

Renal Safety of Sacubitril/Valsartan: A Meta-Analysis of Randomized Controlled Trials.

ABSTRACT: As a first-line therapy, sacubitril/valsartan (S/V) plays a significant role in the treatment of heart failure. However, its effect on renal function is still uncertain. We searched PubMed, EMBASE, the Cochrane Library, and Clinical Trials for randomized controlled trials to evaluate the effect of S/V on renal function in patients. The results are reported as the mean difference, relative ratio, and 95% confidence intervals. A total of 13 randomized controlled trials were included (19,367 patients). Among them, 11 studies focused on patients with heart failure, 1 on patients with acute myocardial infarction, and 1 on patients with chronic kidney disease. We found that fewer worsening renal function events, elevated creatine level events, and severe hyperkalemia events (blood potassium >6.0 mmol/L) occurred in the S/V group than those in the renin-angiotensin-aldosterone system inhibitor (RASi) group. The estimated glomerular filtration rate decreased in both the S/V group and the RASi group, but the change was more obvious in the RASi group. There was no significant difference in hyperkalemia events (blood potassium >5.5 mmol/L) between the 2 groups. Subgroup analysis showed that with the extension of follow-up time (>6 months), worsening renal function events occurred less frequently in the S/V group than in the RASi group. Existing evidence has shown that S/V is superior to RASi in general renal safety. Perhaps with the prolongation of treatment time, the advantages of S/V are more obvious.

Safety of prone emergence from general endotracheal anesthesia in patients undergoing ERCP: a randomized controlled trial.

BACKGROUND: Conventional supine emergence and prone extubation from general endotracheal anesthesia (GEA) are associated with extubation-related adverse events (ERAEs). Given the minimally invasive nature of endoscopic retrograde cholangiopancreatography (ERCP) as well as the improved ventilation/perfusion matching and easier airway opening in the prone position, we aimed to assess the safety of prone emergence and extubation in patients undergoing ERCP under GEA. METHODS: Totally, 242 eligible patients were recruited and randomized into the supine extubation group (n = 121; supine group) and the prone extubation group (n = 121; prone group). The primary endpoint was the incidence of ERAEs during emergence, including hemodynamic fluctuations, coughing, stridor, and hypoxemia requiring airway maneuvers. The secondary endpoints included the incidence of monitoring disconnections, extubation time, recovery time, room exit time, and post-procedure sore throat. RESULTS: The incidence of ERAEs was significantly lower in the prone group compared with the supine group (8.3% vs 34.7%, OR = 0.17, 95% CI 0.18-0.56; P < 0.001). Moreover, the prone group demonstrated no monitoring disconnections, shorter extubation time and room exit time, faster recovery, and, lower frequency and milder sore throat after the procedure. CONCLUSIONS: For patients undergoing ERCP under GEA, compared with supine, prone emergence, and extubation had remarkably lower rates of EAREs and better recovery, and can maintain continuous monitoring and improve efficiency.

High-fat stimulation induces atrial neural remodeling by reducing NO production via the CRIF1/eNOS/P21 axi.

BACKGROUND: Autonomic remodeling of the atria plays a pivotal role in the development of atrial fibrillation (AF) and exerts a substantial influence on the progression of this condition. Hyperlipidemia is a predisposing factor for AF, but its effect on atrial nerve remodeling is unclear. The primary goal of this study was to explore the possible mechanisms through which the consumption of a high-fat diet (HFD) induces remodeling of atrial nerves, and to identify novel targets for clinical intervention. METHODS: Cell models were created in vitro by subjecting cells to palmitic acid (PA), while rat models were established by feeding them a high-fat diet. To investigate the interplay between cardiomyocytes and nerve cells in a co-culture system, we utilized Transwell cell culture plates featuring a pore size of 0.4 µm. The CCK-8 assay was employed to determine cell viability, fluorescent probe DCFH-DA and flow cytometry were utilized for measuring ROS levels, JC-1 was used to assess the mitochondrial membrane potential, the Griess method was employed to measure the nitric oxide (NO) level in the supernatant, a fluorescence-based method was used to measure ATP levels, and MitoTracker was utilized for assessing mitochondrial morphology. The expression of pertinent proteins was evaluated using western blotting (WB) and immunohistochemistry techniques. SNAP was used to treat nerve cells in order to replicate a high-NO atmosphere, and the level of nitroso was assessed using the iodoTMT reagent labeling method. RESULTS: The study found that cardiomyocytes' mitochondrial morphology and function were impaired under high-fat stimulation, affecting nitric oxide (NO) production through the CRIF1/SIRT1/eNOS axis. In a coculture model, overexpression of eNOS in cardiomyocytes increased NO expression. Moreover, the increased Keap1 nitrosylation within neuronal cells facilitated the entry of Nrf2 into the nucleus, resulting in an augmentation of P21 transcription and a suppression of proliferation. Atrial neural remodeling occurred in the HFD rat model and was ameliorated by increasing myocardial tissue eNOS protein expression with trimetazidine (TMZ). CONCLUSIONS: Neural remodeling is triggered by high-fat stimulation, which decreases the production of NO through the CRIF1/eNOS/P21 axis. Additionally, TMZ prevents neural remodeling and reduces the occurrence of AF by enhancing eNOS expression.

Hydrogen improves exercise endurance in rats by promoting mitochondrial biogenesis.

BACKGROUND: Previous studies have shown that hydrogen water has antioxidant and anti-inflammatory effects on exercise-induced fatigue; however, its molecular mechanism remains unclear. METHODS: Adult male Sprague-Dawley rats were randomly divided into a pure water drinking group (NC) and a hydrogen water drinking group (HW) (n = 7), and 2-week treadmill training was used to establish a sports model. Gut bacterial community profiling was performed using 16S rRNA gene sequencing analysis. The expression levels of mitochondrial energy metabolism-related genes and the levels of sugar metabolites and enzymes were measured. RESULTS: The exercise tolerance of rats in the HW group significantly improved, and the distribution and diversity of intestinal microbes were altered. Hydrogen significantly upregulated genes related to mitochondrial biogenesis, possibly via the Pparγ/Pgc-1α/Tfam pathway. In addition, hydrogen effectively mediated the reprogramming of skeletal muscle glucose metabolism. CONCLUSION: Our findings establish a critical role for hydrogen in improving endurance exercise performance by promoting mitochondrial biogenesis via the Pparγ/Pgc-1α/Tfam pathway.

The discovery and utilization of favorable genes in Oryza longistaminata.

Asian cultivated rice has been domesticated from ancestors of the wild rice species Oryza rufipogon. During this process, important changes have occurred in many agronomic traits, such as plant height, grain shattering, and panicle shape, and the yield has also greatly increased. However, many favored traits (e.g., stress resistance) have been lost. The genome of O. longistaminata is of the same AA type as O. sativa, harboring many genes conferring resistance to biotic and abiotic stresses, and it is considered as a potential gene pool for genetic improvement of O. sativa. In this review, we summarize the basic research on O. longistaminata, including its resistance to biotic and abiotic stresses, its rhizome traits, and other traits that are of potential application value, such as bacterial blight resistance, drought resistance, heat tolerance, self-incompatibility, nitrogen efficiency, and high yield. Furthermore, we present the current applied research progress on perennial rice breeding based on the rhizome trait of O. longistaminata. Lastly, the possibility of de novo domestication of O. longistaminata is discussed. We expect this article to provide information to enhance the basic research of O. longistaminata and accelerate the genetic improvement of cultivated rice.

A yes-associated protein 1- Notch1 receptor positive feedback loop promotes breast cancer lung metastasis by attenuating the bone morphogenetic protein 4-SMAD family member 1/5 signaling.

The Notch1 (Notch1 receptor) and yes-associated protein 1 (YAP1) signaling can regulate breast cancer metastasis. This study aimed at investigating whether and how these two signal pathways crosstalk to promote breast cancer lung metastasis. Here, we show that YAP1 expression was positively correlated with Notch1 in breast cancer according to bioinformatics and experimental validation. Mechanistically, YAP1 with TEA domain transcription factors (TEADs) enhanced Jagged1(JAG1)-Notch1 signaling. Meanwhile, Notch1 promoted YAP1 stability in breast cancer cells by inhibiting the ß-TrCP-mediated degradation, thereby, forming a YAP1- JAG1/Notch1 positive feedback loop in breast cancer. Furthermore, YAP1 enhanced the mammosphere formation and stemness of MDA-MB-231 cells by attenuating the inhibition of the BMP4-SMAD1/5 signaling. In vivo, the YAP1- JAG1/Notch1 positive feedback loop promoted the lung colonization of MDA-MB-231 cells. Our data for the first time indicate that the YAP1-Notch1 positive feedback loop promotes lung metastasis of breast cancer by modulating self-renewal and inhibiting the BMP4-SMAD1/5 signaling.