Switchable Single- to Multiwavelength Conventional Soliton and Bound-State Soliton Generated from a NbTe2 Saturable Absorber-Based Passive Mode-Locked Erbium-Doped Fiber Laser.

As a member of transition metal dichalcogenides (TMDs), NbTe2 has a work function of 5.32 eV and a band gap of 0 eV at the Fermi level, which enables it to possess broadband absorption characteristics and has huge potential in optoelectronic devices. In this work, a combination of liquid phase exfoliation (LPE) and optical deposition methods (ODMs) were used to fabricate a NbTe2 saturable absorber (SA). Based on the NbTe2 SA, a ring passive mode-locked erbium-doped fiber laser (PML-EDFL) was constructed by adding NbTe2 SA into the laser cavity. A switchable single- to multiwavelength (dual/triple/quadruple) conventional soliton (CS) and a bound-state soliton (BS) were observed for the first time. The results reveal that NbTe2 SA has excellent saturable absorption characteristics (modulation depth of 2.6%, saturation intensity of 177.4 MW/cm2, and unsaturated loss of 63.8%) and can suppress mode competition and stabilize multiwavelength oscillation. This study expands the applications of NbTe2 nanosheets in ultrafast optoelectronics. The proposed switchable PML-EDFL has extensive applications in high-capacity all-optical communication, high-sensitivity optical fiber sensing, high-precision spectral measurements, and high-energy-efficiency photon neural networks.

Understanding mercury accumulation in mosses of two subalpine forests in China.

The role of forest ecosystems in the global mercury (Hg) biogeochemical cycle is widely recognized; however, using litterfall as a surrogate to assess the Hg sink function of forests encounters limitations. We investigated the accumulation characteristics and influencing factors of Hg in mosses from two remote subalpine forests in southwestern China. The results indicated that there was high Hg accumulation in subalpine forest mosses, with average concentrations of 82 ± 49 ng g-1 for total mercury (THg) and 1.3 ± 0.8 ng g-1 for methylmercury (MeHg). We demonstrated that the accumulation capacity of Hg in mosses was significantly dependent on species and substrates (micro-habitats), the mosses on tree trunks exhibited significantly elevated Hg accumulation levels (THg 132 ± 56 ng g-1, MeHg 1.6 ± 0.2 ng g-1) compared to mosses in other substrates. The surface morphologies and biochemical components of leaf (phyllidia), such as cation exchange capacity (CEC), pectin, uronic acid, and metallothionein, play a crucial role in the accumulation of Hg by mosses. These findings provide valuable insights into Hg accumulation in forest mosses. Suggesting that the contribution of mosses Hg accumulation should be considered when assessing atmospheric Hg sinks of forests.

Nicotine restores olfactory function by activation of prok2R/Akt/FoxO3a axis in Parkinson's disease.

BACKGROUND: Olfactory dysfunction occurs frequently in Parkinson's disease (PD). In this study, we aimed to explore the potential biomarkers and underlying molecular pathways of nicotine for the treatment of olfactory dysfunction in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD mice. METHODS: MPTP was introduced into C57BL/6 male mice to generate a PD model. Regarding in vivo experiments, we performed behavioral tests to estimate the protective effects of nicotine in MPTP-induced PD mice. RNA sequencing and traditional molecular methods were used to identify molecules, pathways, and biological processes in the olfactory bulb of PD mouse models. Then, in vitro experiments were conducted to evaluate whether nicotine can activate the prok2R/Akt/FoxO3a signaling pathway in both HEK293T cell lines and primary olfactory neurons treated with 1-methyl-4-phenylpyridinium (MPP+). Next, prok2R overexpression (prok2R+) and knockdown (prok2R-) were introduced with lentivirus, and the Akt/FoxO3a signaling pathway was further explored. Finally, the damaging effects of MPP+ were evaluated in prok2R overexpression (prok2R+) HEK293T cell lines. RESULTS: Nicotine intervention significantly alleviated olfactory and motor dysfunctions in mice with PD. The prok2R/Akt/FoxO3a signaling pathway was activated after nicotine treatment. Consequently, apoptosis of olfactory sensory neurons was significantly reduced. Furthermore, prok2R+ and prok2R- HEK293T cell lines exhibited upregulation and downregulation of the Akt/FoxO3a signaling pathway, respectively. Additionally, prok2R+ HEK293T cells were resistant to MPP+-induced apoptosis. CONCLUSIONS: This study showed the effectiveness and underlying mechanisms of nicotine in improving hyposmia in PD mice. These improvements were correlated with reduced apoptosis of olfactory sensory neurons via activated prok2R/Akt/FoxO3a axis. These results explained the potential protective functions of nicotine in PD patients.

Gut microbiota derived from fecal microbiota transplantation enhances body weight of Mimas squabs.

Objective: Compared to Mimas pigeons, Shiqi pigeons exhibit greater tolerance to coarse feeding because of their abundant gut microbiota. Here, to investigate the potential of utilizing intestinal flora derived from Shiqi pigeons, the intestinal flora and body indices of Mimas squabs were evaluated after fecal microbiota transplantation (FMT) from donors. Methods: A total of 90 one-day-old squabs were randomly divided into the control group (CON), the low-concentration group (LC) and the high-concentration group (HC): gavaged with 200 µL of bacterial solution at concentrations of 0, 0.1 and 0.2 g/15 mL, respectively. Results: The results suggested that FMT improved the body weight of Mimas squabs in the HC and LC groups (p < 0.01), and 0.1 g/15 mL was the optimal dose during FMT. After 16S rRNA sequencing was performed, compared to those in the CON group, the abundance levels of microflora, especially Lactobacillus, Muribaculaceae and Megasphaera (p < 0.05), in the FMT-treated groups were markedly greater. Random forest analysis indicated that the main functions of key microbes involve pathways associated with metabolism, further illustrating their important role in the host body. Conclusion: FMT has been determined to be a viable method for augmenting the weight and intestinal microbiota of squabs, representing a unique avenue for enhancing the economic feasibility of squab breeding.

Phosphorus release from newly inundated soils and variation in benthic algal nutrient limitation induced by rising water levels of Qinghai Lake, China.

The mobilization of internal phosphorus (P) plays a crucial role in transitioning nutrient limitations within lake ecosystems. While previous research has extensively examined P release in littoral zones influenced by fluctuating water levels, there is a paucity of studies addressing the implications of sustained water level rise in this context, particularly as it pertains to nutrient limitations in benthic algae. To address this gap, we conducted an integrated study in Qinghai Lake. In the field sampling and microcosm experiment, we found that P concentrations are elevated in areas subjected to short-term inundation compared to those enduring prolonged inundation, primarily due to the dissolution of sedimentary P fractions. The results of nutrient diffusing substrata (NDS) bioassays indicated that benthic algae in Qinghai Lake displayed either P limitation or NP co-limitation. The transition from P limitation to NP co-limitation suggested that internal P release may serve to ameliorate nutrient limitations in benthic algae. This phenomenon could potentially contribute to the proliferation of Cladophora in the littoral zones of Qinghai Lake, thereby posing long-term implications for the lake's aquatic ecosystem, particularly under conditions of sustained water level rise.

Electroacupuncture reduces oxidative stress response and improves secondary injury of intracerebral hemorrhage in rats by activating the peroxisome proliferator-activated receptor-γ/nuclear factor erythroid2-related factor 2/γ-glutamylcysteine synthetase pathway.

Intracerebral hemorrhage (ICH) is a severe stroke subtype. Secondary injury is a key factor leading to neurological deficits after ICH. Electroacupuncture (EA) can improve the neurological function after ICH, however, its internal mechanism is still unclear. The aim of this study is to investigate whether EA could ameliorate secondary injury after ICH through antioxidative stress and its potential regulatory mechanism. A rat model of ICH was established by injecting autologous blood into striatum. After the intervention of EA and EA combined with peroxisome proliferator-activated receptor-γ (PPARγ) blocker, Zea-longa scores, modified neurological severity scores and open field tests were used to evaluate the neurological function of the rats. Flow cytometry detected tissue reactive oxygen species (ROS) levels. Tissue tumor necrosis factor-α (TNF-α) levels were analyzed by enzyme-linked immunosorbent assays. The protein expressions of PPAR γ, nuclear factor erythroid2-related factor 2 (Nrf2) and γ-glutamylcysteine synthetase (γ-GCS) were detected by Western blot. Immunohistochemistry was used to observe the activation of microglia. The demyelination degree of axon myelin was observed by transmission electron microscope. Compared with the model group, EA intervention improved neurological function, decreased ROS and TNF-α levels, increased the protein expression of PPARγ, Nrf2 and γ-GCS, and reduced the activation of microglia, it also alleviated axonal myelin sheath damage. In addition, the neuroprotective effect of EA was partially attenuated by PPARγ blocker. EA ameliorated the neurological function of secondary injury after ICH in rats, possibly by activating the PPARγ/Nrf2/γ-GCS signaling pathway, reducing microglia activation, and inhibiting oxidative stress, thus alleviating the extent of axonal demyelination plays a role.

Cell cycle associated protein 1 associates with immune infiltration and ferroptosis in gastrointestinal cancer.

Background: Cell Cycle-Associated Protein 1 (CAPRIN1) play an important role in cell proliferation, oxidative stress, and inflammatory response. Nonetheless, its role in tumor immunity and ferroptosis is largely unknown in gastrointestinal cancer patients. Methods: Through comprehensive bioinformatics, we investigate CAPRIN1 expression patterns and its role in diagnosis, functional signaling pathways, tumor immune infiltration and ferroptosis of different gastrointestinal cancer subtypes. Besides, immunohistochemistry (IHC) and immune blot were used to validate our esophagus cancer clinical data. The ferroptotic features of CAPRIN1 in vitro were assessed through knockdown assays in esophagus cancer cells. Results: CAPRIN1 expression was significantly upregulated, correlated with poor prognosis, and served as an independent risk factor for most gastrointestinal cancer. Moreover, CAPRIN1 overexpression positively correlated with gene markers of most infiltrating immune cells, and immune checkpoints. CAPRIN1 knockdown significantly decreased the protein level of major histocompatibility complex class I molecules. We also identified a link between CAPRIN1 and ferroptosis-related genes in gastrointestinal cancer. Knockdown of CAPRIN1 significantly increased the production of lipid reactive oxygen species and malondialdehyde. Inhibition of CAPRIN1 expression promoted ferroptotic cell death induced by RAS-selective lethal 3 and erastin in human esophagus cancer cells. Conclusion: Collectively, our results demonstrate that CAPRIN1 is aberrantly expressed in gastrointestinal cancer, is associated with poor prognosis, and could potentially influence immune infiltration and ferroptosis.

Genome-Wide Identification and Expression Analysis of the PUB Gene Family in Zoysia japonica under Salt Stress.

The U-box protein family of ubiquitin ligases is important in the biological processes of plant growth, development, and biotic and abiotic stress responses. Plants in the genus Zoysia are recognized as excellent warm-season turfgrass species with drought, wear and salt tolerance. In this study, we conducted the genome-wide identification of plant U-box (PUB) genes in Zoysia japonica based on U-box domain searching. In total, 71 ZjPUB genes were identified, and a protein tree was constructed of AtPUBs, OsPUBs, and ZjPUBs, clustered into five groups. The gene structures, characteristics, cis-elements and protein interaction prediction network were analyzed. There were mainly ABRE, ERE, MYB and MYC cis-elements distributed in the promoter regions of ZjPUBs. ZjPUBs were predicted to interact with PDR1 and EXO70B1, related to the abscisic acid signaling pathway. To better understand the roles of ZjPUBs under salt stress, the expression levels of 18 ZjPUBs under salt stress were detected using transcriptome data and qRT-PCR analysis, revealing that 16 ZjPUBs were upregulated in the roots under salt treatment. This indicates that ZjPUBs might participate in the Z. japonica salt stress response. This research provides insight into the Z. japonica PUB gene family and may support the genetic improvement in the molecular breeding of salt-tolerant zoysiagrass varieties.

mTOR signaling promotes rapid m6A mRNA methylation to regulate NK-cell activation and effector functions.

Natural killer (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 the numerous 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. Deficiency of methyltransferase-like 3 (METTL3) or METTL14 moderately influenced NK-cell homeostasis, while double knockout of METTL3/14 significantly impacted NK-cell homeostasis, maturation, and antitumor immunity. This suggests a cooperative role of METTL3 and METTL14 in regulating NK-cell development and effector functions. Using methylated RNA immunoprecipitation sequencing (MeRIP-seq), we demonstrated that genes involved in NK-cell effector functions, such as Prf1 and Gzmb, were directly modified by m6A methylation. Furthermore, inhibiting mTOR complex 1 (mTORC1) activation prevented m6A methylation levels from increasing when NK cells were activated, and this could be restored by S-adenosylmethionine (SAM) supplementation. Collectively, we have unraveled crucial roles for rapid m6A mRNA methylation downstream of the mTORC1-SAM signal axis in regulating NK-cell activation and effector functions.

Surface coordination induced a quasi p-n junction for efficient visible light driven degradation of tetracycline over hydroxyapatite.

The removal of antibiotics from aquatic solutions remains a global environmental challenge. In this work, the photocatalytic removal of a typical antibiotic-tetracycline (TC) using hydroxyapatite (HAp) as a catalyst was investigated. It was impressive that TC could be efficiently degraded by HAp under visible light irradiation, even though both HAp and TC exhibited poor harvesting in visible light region. The experimental and theoretical explorations were undertaken to thoroughly investigate the underlying mechanism of visible light degradation of TC over HAp. The results indicated that the formed TC-HAp complexes via surface coordination played an important role as photosensitizers for the visible light response. Together with the formation of a quasi p-n junction via band alignment, the photogenerated electrons in the highest unoccupied molecular orbital (HOMO) of TC-HAp were excited to the lowest unoccupied molecular orbital (LUMO) and subsequently migrated to the conduction band of HAp to achieve the efficient charge separation. Superoxide radicals and holes were found to be the major active species for TC degradation. The toxicity evaluation showed that TC could be transferred to the lower toxic intermediates, and deep oxidation with prolonged reaction time was necessary to eliminate the toxicity of TC. This work demonstrates the surface coordination with subsequent quasi p-n junction mechanism of TC degradation over HAp under visible light, which will stimulate us to explore new efficient photocatalytic systems for the degradation of various contaminants.

GBP2 inhibits pathological angiogenesis in the retina via the AKT/mTOR/VEGFA axis.

Pathological retinal angiogenesis is not only the hallmark of retinopathies, but also a major cause of blindness. Guanylate binding protein 2 (GBP2) has been reported to be associated with retinal diseases such as diabetic retinopathy and hypoxic retinopathy. However, GBP2-mediated pathological retinal angiogenesis remains largely unknown. The present study aimed to investigate the role of GBP2 in pathological retinal angiogenesis and its underlying molecular mechanism. In this study, we established oxygen-induced retinopathy (OIR) mice model for in vivo study and hypoxia-induced angiogenesis in ARPE-19 cells for in vitro study. We demonstrated that GBP2 expression was markedly downregulated in the retina of mice with OIR and ARPE-19 cells treated with hypoxia, which was associated with pathological retinal angiogenesis. The regulatory mechanism of GBP2 in ARPE-19 cells was studied by GBP2 silencing and overexpression. The regulatory mechanism of GBP2 in the retina was investigated by overexpressing GBP2 in the retina of OIR mice. Mechanistically, GBP2 downregulated the expression and secretion of vascular endothelial growth factor (VEGFA) in ARPE-19 cells and retina of OIR mice. Interestingly, overexpression of GBP2 significantly inhibited neovascularization in OIR mice, conditioned medium of GBP2 overexpressing ARPE-19 cells inhibited angiogenesis in human umbilical vein endothelial cells (HUVECs). Furthermore, we confirmed that GBP2 downregulated VEGFA expression and angiogenesis by inhibiting the AKT/mTOR signaling pathway. Taken together, we concluded that GBP2 inhibited pathological retinal angiogenesis via the AKT/mTOR/VEGFA axis, thereby suggesting that GBP2 may be a therapeutic target for pathological retinal angiogenesis.

Engineering lauric acid-based nanodrug delivery systems for restoring chemosensitivity and improving biocompatibility of 5-FU and OxPt against Fn-associated colorectal tumor.

Colorectal cancer (CRC) occurs in the colorectum and ranks second in the global incidence of all cancers, accounting for one of the highest mortalities. Although the combination chemotherapy regimen of 5-fluorouracil (5-FU) and platinum(IV) oxaliplatin prodrug (OxPt) is an effective strategy for CRC treatment in clinical practice, chemotherapy resistance caused by tumor-resided Fusobacterium nucleatum (Fn) could result in treatment failure. To enhance the efficacy and improve the biocompatibility of combination chemotherapy, we developed an antibacterial-based nanodrug delivery system for Fn-associated CRC treatment. A tumor microenvironment-activated nanomedicine 5-FU-LA@PPL was constructed by the self-assembly of chemotherapeutic drug derivatives 5-FU-LA and polymeric drug carrier PPL. PPL is prepared by conjugating lauric acid (LA) and OxPt to hyperbranched polyglycidyl ether. In principle, LA is used to selectively combat Fn, inhibit autophagy in CRC cells, restore chemosensitivity of 5-FU as well as OxPt, and consequently enhance the combination chemotherapy effects for Fn-associated drug-resistant colorectal tumor. Both in vitro and in vivo studies exhibited that the tailored nanomedicine possessed efficient antibacterial and anti-tumor activities with improved biocompatibility and reduced non-specific toxicity. Hence, this novel anti-tumor strategy has great potential in the combination chemotherapy of CRC, which suggests a clinically relevant valuable option for bacteria-associated drug-resistant cancers.

Intracoronary microcatheter indwelling for continuous pumping of low-dose thrombolytic drugs: A new approach to reperfusion in acute myocardial infarction.

Reperfusion therapy of acute myocardial infarction (AMI) refers to physical or chemical recanalization and restoration of blood flow to an occluded coronary artery, and current techniques for reperfusion therapy include intravenous thrombolysis, percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). The number of patients receiving emergency CABG in the real world is decreasing due to the disadvantages of CABG and the improvement in PCI procedures. Thrombolytic therapy has some disadvantages such as low recanalization rate, high risk of reocclusion and bleeding, and short time window. On the other hand, intracoronary interventional therapy may meet the requirements of "early, complete and persistent" patency of coronary arteries at different time points. However, in the emergency PCI, although thrombus aspiration via a catheter or balloon dilation is performed, residual thrombus with heavy or low TIMI (thrombolysis in myocardial infarction) myocardial perfusion grading is still observed in some patients, suggesting disordered microcirculation. Currently, the treatment of microcirculatory disturbance in emergency PCI mainly employed injection of tirofiban, adenosine, thrombolytic agent or other drugs into the local area via a microcatheter in a short time, all of which can significantly reduce the thrombus load and improve TIMI perfusion. Herein, we report that a microcatheter was indwelled in the coronary artery for continuous pumping of low-dose thrombolytic drugs as reperfusion therapy in 12 patients with acute and subacute MI.

Synthetic MRI and amide proton transfer-weighted MRI for differentiating between benign and malignant sinonasal lesions.

OBJECTIVES: To explore the value of the synthetic MRI (SyMRI), combined with amide proton transfer-weighted (APTw) MRI for quantitative and morphologic assessment of sinonasal lesions, which could provide relative scale for the quantitative assessment of tissue properties. METHODS: A total of 80 patients (31 malignant and 49 benign) with sinonasal lesions, who underwent the SyMRI and APTw examination, were retrospectively analyzed. Quantitative parameters (T1, T2, proton density (PD)) and APT % were obtained through outlining the region of interest (ROI) and comparing the two groups utilizing independent Student t test or a Wilcoxon test. Receiver operating characteristic curve (ROC), Delong test, and logistic regression analysis were performed to assess the diagnostic efficiency of one-parameter and multiparametric models. RESULTS: SyMRI-derived mean T1, T2, and PD were significantly higher and APT % was relatively lower in benign compared to malignant sinonasal lesions (p < 0.05). The ROC analysis showed that the AUCs of the SyMRI-derived quantitative (T1, T2, PD) values and APT % ranged from 0.677 to 0.781 for differential diagnosis between benign and malignant sinonasal lesions. The T2 values showed the best diagnostic performance among all single parameters for differentiating these two masses. The AUCs of combined SyMRI-derived multiple parameters with APT % (AUC = 0.866) were the highest than that of any single parameter, which was significantly improved (p < 0.05). CONCLUSION: The combination of SyMRI and APTw imaging has the potential to reflect intrinsic tissue characteristics useful for differentiating benign from malignant sinonasal lesions. CLINICAL RELEVANCE STATEMENT: Combining synthetic MRI with amide proton transfer-weighted imaging could function as a quantitative and contrast-free approach, significantly enhancing the differentiation of benign and malignant sinonasal lesions and overcoming the limitations associated with the superficial nature of endoscopic nasal sampling. KEY POINTS: • Synthetic MRI and amide proton transfer-weighted MRI could differentiate benign from malignant sinonasal lesions based on quantitative parameters. • The diagnostic efficiency could be significantly improved through synthetic MRI + amide proton transfer-weighted imaging. • The combination of synthetic MRI and amide proton transfer-weighted MRI is a noninvasive method to evaluate sinonasal lesions.

Penicilloneines A and B, Quinolone-Citrinin Hybrids from a Starfish-Derived Penicillium sp.

Penicilloneines A (1) and B (2) are the first reported quinolone-citrinin hybrids. They were isolated from the starfish-derived fungus Penicillium sp. GGF16-1-2, and their structures were elucidated using spectroscopic, chemical, computational, and single-crystal X-ray diffraction methods. Penicilloneines A (1) and B (2) share a common 4-hydroxy-1-methyl-2(1H)-quinolone unit; however, they differ in terms of citrinin moieties, and these two units are linked via a methylene bridge. Penicilloneines A (1) and B (2) exhibited antifungal activities against Colletotrichum gloeosporioides, with lethal concentration 50 values of 0.02 and 1.51 µg/mL, respectively. A mechanistic study revealed that 1 could inhibit cell growth and promote cell vacuolization and consequent disruption of the fungal cell walls via upregulating nutrient-related hydrolase genes, including putative hydrolase, acetylcholinesterase, glycosyl hydrolase, leucine aminopeptidase, lipase, and beta-galactosidase, and downregulating their synthase genes 3-carboxymuconate cyclase, pyruvate decarboxylase, phosphoketolase, and oxalate decarboxylase.

RTC_TongueNet: An improved tongue image segmentation model based on DeepLabV3.

Objective: Tongue segmentation as a basis for automated tongue recognition studies in Chinese medicine, which has defects such as network degradation and inability to obtain global features, which seriously affects the segmentation effect. This article proposes an improved model RTC_TongueNet based on DeepLabV3, which combines the improved residual structure and transformer and integrates the ECA (Efficient Channel Attention Module) attention mechanism of multiscale atrous convolution to improve the effect of tongue image segmentation. Methods: In this paper, we improve the backbone network based on DeepLabV3 by incorporating the transformer structure and an improved residual structure. The residual module is divided into two structures and uses different residual structures under different conditions to speed up the frequency of shallow information mapping to deep network, which can more effectively extract the underlying features of tongue image; introduces ECA attention mechanism after concat operation in ASPP (Atrous Spatial Pyramid Pooling) structure to strengthen information interaction and fusion, effectively extract local and global features, and enable the model to focus more on difficult-to-separate areas such as tongue edge, to obtain better segmentation effect. Results: The RTC_TongueNet network model was compared with FCN (Fully Convolutional Networks), UNet, LRASPP (Lite Reduced ASPP), and DeepLabV3 models on two datasets. On the two datasets, the MIOU (Mean Intersection over Union) and MPA (Mean Pixel Accuracy) values of the classic model DeepLabV3 were higher than those of FCN, UNet, and LRASPP models, and the performance was better. Compared with the DeepLabV3 model, the RTC_TongueNet network model increased MIOU value by 0.9% and MPA value by 0.3% on the first dataset; MIOU increased by 1.0% and MPA increased by 1.1% on the second dataset. RTC_TongueNet model performed best on both datasets. Conclusion: In this study, based on DeepLabV3, we apply the improved residual structure and transformer as a backbone to fully extract image features locally and globally. The ECA attention module is combined to enhance channel attention, strengthen useful information, and weaken the interference of useless information. RTC_TongueNet model can effectively segment tongue images. This study has practical application value and reference value for tongue image segmentation.

Mitochondrial respiratory chain component NDUFA4: a promising therapeutic target for gastrointestinal cancer.

Gastrointestinal cancer, one of the most common cancers, continues to be a major cause of mortality and morbidity globally. Accumulating evidence has shown that alterations in mitochondrial energy metabolism are involved in developing various clinical diseases. NADH dehydrogenase 1 alpha subcomplex 4 (NDUFA4), encoded by the NDUFA4 gene located on human chromosome 7p21.3, is a component of mitochondrial respiratory chain complex IV and integral to mitochondrial energy metabolism. Recent researchers have disclosed that NDUFA4 is implicated in the pathogenesis of various diseases, including gastrointestinal cancer. Aberrant expression of NDUFA4 leads to the alteration in mitochondrial energy metabolism, thereby regulating the growth and metastasis of cancer cells, indicating that it might be a new promising target for cancer intervention. This article comprehensively reviews the structure, regulatory mechanism, and biological function of NDUFA4. Of note, the expression and roles of NDUFA4 in gastrointestinal cancer including colorectal cancer, liver cancer, gastric cancer, and so on were discussed. Finally, the existing problems of NDUFA4-based intervention on gastrointestinal cancer are discussed to provide help to strengthen the understanding of the carcinogenesis of gastrointestinal cancer, as well as the development of new strategies for clinical intervention.

[Genetic analysis of a child with Hypotrichosis simplex].

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a child with Hypotrichosis 14. METHODS: A child who had presented at the Henan Provincial People's Hospital on May 4, 2020 due to hair thinning was selected as the study subject. Clinical data of the child was collected. Peripheral venous blood samples were collected from the child and her parents. Genomic DNA was extracted and subjected to whole exome sequencing. Candidate variants were validated by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 5-year-old female, had presented with thin, soft lanugo-like hair which was easy to fall off. The child was found to harbor compound heterozygous missense variants of the LSS gene, namely c.1609G>A (p.V537M) in exon 17 and c.802T>G (p.F268V) in exon 8, which were respectively inherited from her father and mother. Both variant sites were highly conserved, though based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as variants of unknown significance (PM2_Supporting+PP3+PP4). CONCLUSION: The c.1609G>A (p.V537M) and c.802T>G (p.F268V) compound heterozygous variants of the LSS gene probably underlay the clinical phenotype in this patient.

Phillyrin improves myocardial remodeling in salt-sensitive hypertensive mice by reducing endothelin1 signaling.

OBJECTIVES: Prolonged exposure to chronic hypertension places the heart under excessive strain, resulting in myocardial remodeling. Phillyrin, derived from the natural plant Forsythia suspensa, has been found to possess cardioprotective properties. The objective of this study is to investigate the role and mechanism of phillyrin in hypertension-induced myocardial remodeling in mice. METHODS: We constructed a mouse model of salt-sensitive hypertension. The mice were treated with varying doses of phillyrin, and their blood pressure, cardiac function, cardiac hypertrophy, fibrosis, inflammation, and other conditions were assessed. KEY FINDINGS: Our research findings demonstrated that phillyrin has the potential to lower blood pressure, enhance cardiac function, and mitigate cardiac hypertrophy, fibrosis, and inflammatory responses in deoxycorticosterone acetate-salt hypertension mice. In hypertensive mice, there was an elevated expression of endothelin1 (ET-1) in heart tissue, which can be reduced by phillyrin. Additionally, phillyrin effectively reduced the hypertrophy of H9c2 cells induced by ET-1 stimulation. CONCLUSIONS: Our research highlights the therapeutic capabilities of phillyrin in the treatment of myocardial remodeling through the reduction of ET-1 signaling. These results contribute to the advancement of novel applications for phillyrin and establish a solid conceptual basis for future investigations in this area.

Supplementing Glucose Intake Reverses the Inflammation Induced by a High-Fat Diet by Increasing the Expression of Siglec-E Ligands on Erythrocytes.

Siglec-9/E is a cell surface receptor expressed on immune cells and can be activated by sialoglycan ligands to play an immunosuppressive role. Our previous study showed that increasing the expression of Siglec-9 (the human paralog of mouse Siglec-E) ligands maintains functionally quiescent immune cells in the bloodstream, but the biological effects of Siglec-9 ligand alteration on atherogenesis were not further explored. In the present study, we demonstrated that the atherosclerosis risk factor ox-LDL or a high-fat diet could decrease the expression of Siglec-9/E ligands on erythrocytes. Increased expression of Siglec-E ligands on erythrocytes caused by dietary supplementation with glucose (20% glucose) had anti-inflammatory effects, and the mechanism was associated with glucose intake. In high-fat diet-fed apoE-/- mice, glucose supplementation decreased the area of atherosclerotic lesions and peripheral inflammation. These data suggested that increased systemic inflammation is attenuated by increasing the expression of Siglec-9/E ligands on erythrocytes. Therefore, Siglec-9/E ligands might be valuable targets for atherosclerosis therapy.