CDKL3 is a promising biomarker for diagnosis and prognosis prediction in patients with hepatocellular carcinoma.

Cyclin-dependent kinase-like 3 (CDKL3) has been identified as an oncogene in certain types of tumors. Nonetheless, its function in hepatocellular carcinoma (HCC) is poorly understood. In this study, we conducted a comprehensive analysis of CDKL3 based on data from the HCC cohort of The Cancer Genome Atlas (TCGA). Our analysis included gene expression, diagnosis, prognosis, functional enrichment, tumor microenvironment and metabolic characteristics, tumor burden, mRNA expression-based stemness, alternative splicing, and prediction of therapy response. Additionally, we performed a cell counting kit-8 assay, TdT-mediated dUTP nick-end Labeling staining, migration assay, wound healing assay, colony formation assay, and nude mouse experiments to confirm the functional relevance of CDKL3 in HCC. Our findings showed that CDKL3 was significantly upregulated in HCC patients compared to controls. Various bioinformatic analyses suggested that CDKL3 could serve as a potential marker for HCC diagnosis and prognosis. Furthermore, CDKL3 was found to be involved in various mechanisms linked to the development of HCC, including copy number variation, tumor burden, genomic heterogeneity, cancer stemness, and alternative splicing of CDKL3. Notably, CDKL3 was also closely correlated with tumor immune cell infiltration and the expression of immune checkpoint markers. Additionally, CDKL3 was shown to independently function as a risk predictor for overall survival in HCC patients by multivariate Cox regression analysis. Furthermore, the knockdown of CDKL3 significantly inhibited cell proliferation in vitro and in vivo, indicating its role as an oncogene in HCC. Taken together, our findings suggest that CDKL3 shows promise as a biomarker for the detection and treatment outcome prediction of HCC patients.

Cooperative amplification of Prussian blue as a signal indicator and functionalized metal-organic framework-based electrochemical biosensor for an ultrasensitive HE4 assay.

Human epididymis protein 4 (HE4), a diagnostic biomarker of ovarian cancer, is crucial for monitoring the early stage of the disease. Hence, it is highly important to develop simple, inexpensive, and user-friendly biosensors for sensitive and quantitative HE4 assays. Herein, a new sandwich-type electrochemical immunosensor based on Prussian blue (PB) as a signal indicator and functionalized metal-organic framework nanocompositesas efficient signal amplifiers was fabricated for quantitative analysis of HE4. In principle, ketjen black (KB) and AuNPs modified on TiMOF (TiMOF-KB@AuNPs) could accelerate electron transfer on the electrode surface and act as a matrix for the immobilization of antibodies via cross-linking to improve the determination sensitivity. The PB that covalently binds to labeled antibodies endows the biosensors with intense electrochemical signals. Furthermore, the concentration of HE4 could be indirectly detected by monitoring the electroactivity of PB. Benefiting from the high signal amplification ability of the PB and MOF nanocomposites, this strategy displayed a wide linear range (0.1-80 ng mL-1) and a lower detection limit (0.02 ng mL-1). Hence, this study demonstrated great promise for application in clinical ovarian cancer diagnosis and treatment, and provided a new platform for detecting other cancer biomarkers.

Imaging features of pediatric meningiomas: emphasis on unusual locations.

PURPOSE: This article aims to analyze pediatric meningioma's imaging characteristics, especially those in unusual locations. METHODS: Pediatric patients with pathologically confirmed meningiomas at our hospital from January 2010 to January 2024 were enrolled. Meningiomas located in the cerebral convexity, parasagittal falcine region, anterior skull base, middle skull base, sphenoid ridge, cerebellopontine angle (CPA), olfactory groove, or juxtasella were considered in usual locations. Meningiomas found in other areas were considered in unusual locations. Clinical information, pathology results, and imaging features of pediatric meningiomas in usual and usual locations were analyzed and compared. RESULTS: A total of 18 patients (19 meningiomas) were enrolled, including 14 males and 4 females, with an average age of 14 years (ranging from 6 to 18 years). A total of 12 (63.2%) meningiomas were in the unusual location, including four (33.3%) were intraparenchymal, four (33.3%) were intraventricular, two (16.7%) were intraosseous, one (8.3%) case was in the paranasal sinus, and one (8.3%) was intraspinal. The meningiomas in unusual locations usually lacked the meningeal tail sign, and the misdiagnosis rate on preoperative imaging was significantly higher than that of meningiomas in usual locations. CONCLUSION: Pediatric meningiomas are prone to occur in unusual locations. When they occur in usual locations, they often lack typical radiographic features of meningiomas, leading to potential misdiagnosis before surgery. Recognition of the imaging characteristics of meningiomas in unusual locations in children may facilitate accurate preoperative imaging diagnosis.

Bottom-Up Defect Modification Through Oily-Allicin Modified Buried Interface Achieving Highly Efficient and Stable Perovskite Solar Cells.

The buried interface properties of the perovskite solar cells (PSCs) play a crucial role in the power conversion efficiency (PCE) and operational stability. The metal-oxide/perovskite heterogeneous interfaces are highly defective and cause serious ion migration. However, the buried and unexposed bottom interface and simultaneous stabilization of grain boundaries receive less attention and effective solutions. To tackle this problem, a solid-liquid strategy is employed by introducing oily-additive allicin at the buried interface to passivate the shallow (VI and Vo) and deep traps (VPb and PbI). Interestingly, oily status allicin fills the pinholes at the heterointerface and wraps the perovskite grains, suppressing the ion migration during the photoaging process. As a result, an outstanding PCE of 25.07% is achieved with a remarkable fill factor (FF) of 84.03%. The modified devices can maintain 94.51% of the original PCE after light soaking under 1-sun illumination for 1000 h. This work demonstrates a buried interface modification method that employs an eco-friendly additive, which helps promote the development of PSCs with high performance and stability.

TMAO Impairs Mouse Aortic Vasodilation by Inhibiting TRPV4 Channels in Endothelial Cells.

Trimethylamine oxide (TMAO) is an intestinal flora metabolite associated with risk of cardiovascular diseases. Transient receptor potential vanilloid 4 (TRPV4) is a Ca2+-permeable ion channel that is essential for vasodilation and endothelial function. Currently, there are few studies on the effect of TMAO on TRPV4 channels. In the present study, Ca2+ imaging of vascular tissue showed that TMAO inhibited TRPV4-mediated Ca2+ influx into aortic endothelial cells in a dose-dependent manner. Furthermore, a whole-cell patch clamp assay showed that TMAO blocked TRPV4-mediated cation currents. Notably, results of aortic vascular tension measurement showed that TMAO impaired endothelium-dependent vasodilation in mouse aortic vessels through the TRPV4-NO pathway. Our results indicated that TMAO inhibited Ca2+ entry in endothelial cells and impaired vasodilation through the TRPV4-NO pathway in mice. These results provide scientific evidence for novel pathogenic mechanisms underlying the role of TMAO in cardiovascular disease.

Physicochemical, structural and metabolic products of yogurt as affected by Coriolus versicolor fermented sweet potato pulp water.

Sweet potato pulp water (SPPW) is a kind of sweet potato starch processing by-product with rich nutrition but low utilization. The impacts of different proportions of Coriolus versicolor (C. versicolor, CV) fermented sweet potato pulp water (CV-SPPW) on the physicochemical, structural and metabolic properties of yogurt were investigated. Compared with 0% group, the hardness index, elasticity index and cohesion of the 10% sample group increased by 1.9-fold, 55.7% and 1.39-fold, respectively. When CV-SPPW was added at an amount of 10%, the microstructure and sensory scores of yogurts were considered as the optimal. Metabolic pathway analysis indicated that the changes of yogurts were mainly involved in sugar metabolism and amino acid metabolism, and that the carbohydrate metabolites produced mainly included cellobiose, maltitol, d-trehalose and d-maltose. The CV-SPPW improved the structural characteristics of yogurts to varying degrees and the fermented yogurts exhibited better viscosity properties.

Sodium Crotonate Alleviates Diabetic Kidney Disease Partially Via the Histone Crotonylation Pathway.

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes, inflammation and fibrosis play an important role in its progression. Histone lysine crotonylation (Kcr) was first identified as a new type of post-translational modification in 2011. In recent years, prominent progress has been made in the study of sodium crotonate (NaCr) and histone Kcr in kidney diseases. However, the effects of NaCr and NaCr-induced Kcr on DKD remain unclear. In this study, db/db mice and high glucose-induced human tubular epithelial cells (HK-2) were used respectively, and exogenous NaCr and crotonoyl-coenzyme A (Cr-CoA) as intervention reagents, histone Kcr and DKD-related indicators were detected. The results confirmed that NaCr had an antidiabetic effect and decreased blood glucose and serum lipid levels and alleviated renal function and DKD-related inflammatory and fibrotic damage. NaCr also induced histone Kcr and histone H3K18 crotonylation (H3K18cr). However, NaCr and Cr-CoA-induced histone Kcr and protective effects were reversed by inhibiting the activity of Acyl-CoA synthetase short-chain family member 2 (ACSS2) or histone acyltransferase P300 in vitro. In summary, our data reveal that NaCr may mitigate DKD via an antidiabetic effect as well as through ACSS2 and P300-induced histone Kcr, suggesting that Kcr may be the potential molecular mechanism and prevention target of DKD.

Untargeted metabolomics revealed the mechanism of aucubin on glucocorticoid-induced osteoporosis in mice through modulating arachidonic acid metabolism.

Glucocorticoid-induced osteoporosis (GIOP) represents the most prevalent form of secondary osteoporosis. Aucubin (AU), a principal active component found in traditional herbal medicines such as Eucommia ulmoides, has been demonstrated to enhance osteoblast differentiation. Nonetheless, the precise therapeutic effects of AU on GIOP and the complex underlying regulatory mechanisms warrant further investigation. We first established a GIOP model in female mice and then assessed the therapeutic effects of AU using micro-CT analysis, biomechanical testing, measurements of serum calcium (Ca) and phosphorus (P) levels, and histological analyses using Hematoxylin and Eosin (HE) and Masson staining. Subsequently, non-targeted metabolomics was employed in order to study the effects of AU on serum metabolites in GIOP mice. The levels of the factors related to these metabolites were quantified using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blot analyses. Finally, the effects of AU on osteoblastic and osteoclastic differentiation were examined. We found that AU significantly ameliorated bone microarchitecture and strength in GIOP mice. It mitigated pathological damages such as impairment of trabecular bone structure and reduction in collagen fibers, while concurrently elevating serum levels of Ca and P. Non-targeted metabolomics revealed that Arachidonic acid (AA) metabolism serves as a common pathway between the control and GIOP groups, as well as between the high-dose AU (AUH) and GIOP groups. AU notably upregulates prostaglandin-endoperoxide synthase 2 (PTGS2) and microsomal prostaglandin-E synthase 1 (PTGES) expression and downregulates prostaglandin-H2 D-isomerase (PTGDS) expression. Furthermore, AU treatment increased the expression of runt-related transcription factor 2 (Runx2) and transcription factor Sp7 (Osterix), enhanced serum alkaline phosphatase (ALP) activity, and reduced osteoclast expression. These results indicate that AU is a potential drug for treating GIOP, and its mechanism is related to regulating AA metabolism and promoting osteoblast differentiation. However, the key targets of AU in treating GIOP still need further exploration.

Unveiling non-classical glycosylation patterns in Bombyx mori nucleopolyhedrovirus GP64: Insights into viral entry and fusion.

The glycoprotein GP64 of alphabaculovirus is crucial for viral entry and fusion. Here, we investigated the N-glycosylation patterns of Bombyx mori nucleopolyhedrovirus (BmNPV) GP64 and its signal peptide (SP) cleaved form, SPΔnGP64, along with their impacts on viral infectivity and fusogenicity. Through deglycosylation assays, we confirmed N-glycosylation of BmNPV GP64 on multiple sites. Mutational analysis targeting predicted N-glycosylation sites revealed diverse effects on viral infectivity and cell fusion. Particularly noteworthy were mutations at sites 175, which resulted in complete loss of infectivity and fusion capacity. Furthermore, LC-MS/MS analysis uncovered unexpected non-classical N-glycosylation sites, including N252, N302, N367, and N471, with only N302 and N471 identified in SPΔnGP64. Subsequent investigation highlighted the critical roles of these residues in BmNPV amplification and fusion, underscoring the essentiality of N367 glycosylation for GP64 fusogenicity. Our findings provide valuable insights into the non-classical glycosylation landscape of BmNPV GP64 and its functional significance in viral biology.

Immunosuppressive leucosesterterpane and penta-nor-leucosesterterpane sesterterpenoids from Leucosceptrum canum.

Five undescribed leucosesterterpane sesterterpenoids, leucosceptrines A-E, two undescribed penta-nor-leucosesterterpane (C20) sesterterpenoids, nor-leucosceptrines A and B, and three known analogues, were obtained from the aerial parts of Leucosceptrum canum of Chinese origin. Leucosceptrines A-C are the first examples of leucosesterterpane-type sesterterpenoids with unclosed dihydropyran rings and reverse configurations at chiral centers C-4 and/or C-12. Nor-leucosceptrines A and B possesses an unusual penta-nor-leucosesterterpane skeleton. Their structures were unambiguously elucidated through comprehensive spectroscopic analyses and single-crystal X-ray diffraction. A plausible biogenetic pathway for these sesterterpenoids was proposed. The immunosuppressive effects of these isolates on the secretion of the cytokine IFN-γ by T cells stimulated with anti-CD3/CD28 monoclonal antibodies were observed with different potencies.

Neuronal representation of visual working memory content in the primate primary visual cortex.

The human ability to perceive vivid memories as if they "float" before our eyes, even in the absence of actual visual stimuli, captivates the imagination. To determine the neural substrates underlying visual memories, we investigated the neuronal representation of working memory content in the primary visual cortex of monkeys. Our study revealed that neurons exhibit unique responses to different memory contents, using firing patterns distinct from those observed during the perception of external visual stimuli. Moreover, this neuronal representation evolves with alterations in the recalled content and extends beyond the retinotopic areas typically reserved for processing external visual input. These discoveries shed light on the visual encoding of memories and indicate avenues for understanding the remarkable power of the mind's eye.

Metal-Organic-Framework Derived Co-Mo Multimetal Oxide Semiconductors: Selective Trace-Level Hydrogen Sulfide Detection.

The development of a highly selective and trace-level gas sensing platform for detecting hydrogen sulfide (H2S) remains a formidable challenge. To solve this problem, Co-Mo multimetal oxide semiconductors are rationally tailored by employing metal organic frameworks (MOFs) as self-sacrificial templates. The MOF-derived Co3O4/ß-CoMoO4 based gas sensors displays high sensitivity (Rg/Ra = 22) to 10 ppm of H2S and ultralow limit of detection (10 ppb H2S). The formation of p-p heterojunction and multivalence states of Mo play a crucial role in electron transfer and oxygen adsorption. A sensor array constructed from four Co3O4/ß-CoMoO4 materials with different Co/Mo ratios demonstrates a superior selective discrimination of H2S from other VOCs and malodorous gases by principal component analysis (PCA). Besides, a H2S gas sensing and alarming platform was designed for monitoring the environment contaminated with H2S. This finding provides a feasible approach for the discovery of highly efficient gas sensors to monitor environmental H2S concentration.

Nonuniform and pathway-specific laminar processing of spatial frequencies in the primary visual cortex of primates.

The neocortex comprises six cortical layers that play a crucial role in information processing; however, it remains unclear whether laminar processing is consistent across all regions within a single cortex. In this study, we demonstrate diverse laminar response patterns in the primary visual cortex (V1) of three male macaque monkeys when exposed to visual stimuli at different spatial frequencies (SFs). These response patterns can be categorized into two groups. One group exhibit suppressed responses in the output layers for all SFs, while the other type shows amplified responses specifically at high SFs. Further analysis suggests that both magnocellular (M) and parvocellular (P) pathways contribute to the suppressive effect through feedforward mechanisms, whereas amplification is specific to local recurrent mechanisms within the parvocellular pathway. These findings highlight the non-uniform distribution of neural mechanisms involved in laminar processing and emphasize how pathway-specific amplification selectively enhances representations of high-SF information in primate V1.

Hyphal Als proteins act as CR3 ligands to promote immune responses against Candida albicans.

Patients with decreased levels of CD18 (ß2 integrins) suffer from life-threatening bacterial and fungal infections. CD11b, the α subunit of integrin CR3 (CD11b/CD18, αMß2), is essential for mice to fight against systemic Candida albicans infections. Live elongating C. albicans activates CR3 in immune cells. However, the hyphal ligands that activate CR3 are not well defined. Here, we discovered that the C. albicans Als family proteins are recognized by the I domain of CD11b in macrophages. This recognition synergizes with the ß-glucan-bound lectin-like domain to activate CR3, thereby promoting Syk signaling and inflammasome activation. Dectin-2 activation serves as the "outside-in signaling" for CR3 activation at the entry site of incompletely sealed phagosomes, where a thick cuff of F-actin forms to strengthen the local interaction. In vitro, CD18 partially contributes to IL-1ß release from dendritic cells induced by purified hyphal Als3. In vivo, Als3 is vital for C. albicans clearance in mouse kidneys. These findings uncover a novel family of ligands for the CR3 I domain that promotes fungal clearance.

Characterization and health risks of short- and medium-chain chlorinated paraffins in the gas and size-fractionated particulate phases in ambient air.

Short-chain and medium-chain chlorinated paraffins (SCCPs and MCCPs) have garnered significant attention because they have persistence and potential toxicity, and can undergo long-distance transport. Chlorinated paraffins (CPs) inhaled in the size-fractionated particulate phase and gas phase can carry different risks to human health due to their ability to accumulate in different regions of the respiratory tract and exhibit varying deposition efficiencies. In our study, large-volume ambient air samples in both the size-fractionated particulate phase (Dp < 1.0 µm, 1.0-2.5 µm, 2.5-10 µm, and Dp ≥ 10 µm) and gas phase were collected simultaneously in Beijing using an active sampler. The overall levels of SCCPs and MCCPs were relatively high, the ranges being 57-881 and 30-385 ng/m3, respectively. SCCPs tended to be partitioned in the gas phase (on average 75% of the ΣSCCP concentration), while MCCPs tended to be partitioned in the particulate phase (on average 62% of the ΣMCCP concentration). Significant correlations were discovered between the logarithm-transformed gas-particle partition coefficients (KP) and predicted subcooled vapor pressures (PL0) (p < 0.01 for SCCPs and MCCPs) and between the logarithm-transformed KP values and octanol-air partition coefficients (KOA) (p < 0.01 for SCCPs and MCCPs). Thus, the slopes indicated that organic matter absorption was the dominant process involved in gas-particle partitioning. We used the ICRP model to calculate deposition concentrations for particulate-associated CPs in head airways region (15.6-71.4 ng/m³), tracheobronchial region (0.8-4.8 ng/m³), and alveolar region (5.1-21.9 ng/m³), then combined these concentrations with the CP concentrations in the gas phase to calculate estimated daily intakes (EDIs) for inhalation. The EDIs for SCCPs and MCCPs through inhalation of ambient air for the all-ages group were 67.5-184.2 ng/kg/day and 19.7-53.7 ng/kg/day, respectively. The results indicated that SCCPs and MCCPs in ambient air do not currently pose strong risks to human health in the study area.

Inhibition of miR-142-3p promotes intestinal epithelial proliferation and barrier function after ischemia/reperfusion injury by targeting FoxM1.

Damage of intestinal barrier function (BF) after ischemia/reperfusion (I/R) injury can induce serious complications and high mortality. MicroRNAs (miRNAs) are involved in intestinal mucosal BF and epithelial proliferation after I/R injury have been reported. We aimed to investigate the role and regulatory mechanism of miR-142-3p (miR-142) in intestinal epithelial proliferation and BF after I/R injury. We detected the proliferation, barrier function and miR-142 expression in clinical ischemic intestinal tissues. Furthermore, we induced an in vivo intestinal I/R injury mouse model and in vitro IEC-6 cells hypoxia/reoxygenation (H/R) injury model. After increasing and decreasing expression of miR-142, we detected the proliferation and barrier function of intestinal epithelial cells after I/R or H/R injury. We found that miR-142 expression was significantly increased in clinical ischemic intestinal mucosa and mouse intestinal mucosa exposed to I/R injury, and there was an inverse relationship between miR-142 and proliferation/BF. Inhibition of miR-142 significant promoted intestinal epithelial proliferation and BF after I/R injury. Furthermore, inhibition of miR-142 improved overall survival rate of mice after I/R injury. MiR-142 directly targeted FoxM1 which was identified by bioinformatics analysis and luciferase activity assay in IEC-6 cells. Inhibition of miR-142 promotes intestinal epithelial proliferation and BF after I/R injury in a FoxM1-mediated manner.

Genomic evidence for evolutionary history and local adaptation of two endemic apricots: Prunus hongpingensis and P. zhengheensis.

Apricot, belonging to the Armeniaca section of Rosaceae, is one of the economically important crop fruits that has been extensively cultivated. The natural wild apricots offer valuable genetic resources for crop improvement. However, some of them are endemic, with small populations, and are even at risk of extinction. In this study we unveil chromosome-level genome assemblies for two southern China endemic apricots, Prunus hongpingensis (PHP) and P. zhengheensis (PZH). We also characterize their evolutionary history and the genomic basis of their local adaptation using whole-genome resequencing data. Our findings reveal that PHP and PZH are closely related to Prunus armeniaca and form a distinct lineage. Both species experienced a decline in effective population size following the Last Glacial Maximum (LGM), which likely contributed to their current small population sizes. Despite the observed decrease in genetic diversity and heterozygosity, we do not observe an increased accumulation of deleterious mutations in these two endemic apricots. This is likely due to the combined effects of a low inbreeding coefficient and strong purifying selection. Furthermore, we identify a set of genes that have undergone positive selection and are associated with local environmental adaptation in PHP and PZH, respectively. These candidate genes can serve as valuable genetic resources for targeted breeding and improvement of cultivated apricots. Overall, our study not only enriches our comprehension of the evolutionary history of apricot species but also offers crucial insights for the conservation and future breeding of other endemic species amidst rapid climate changes.

Pathological variations and immune response in Channa argus infected with pathogenic Nocardia seriolae strain.

Nocardia seriolae pathogen causes chronic granulomatous disease, reportedly affecting over 40 species of marine and freshwater cultured fish. Hence, research is required to address and eliminate this significant threat to the aquaculture industry. In this respect, a reliable and reproducible infection model needs to be established to better understand the biology of this pathogen and its interactions with the host during infection, as well as to develop new vaccines or other effective treatment methods. In this study, we examined the pathogenicity of the pathogen and the immune response of snakehead (Channa argus) juvenile to N. seriolae using a range of methods and analyses, including pathogen isolation and identification, histopathology, Kaplan-Meier survival curve analysis, and determination of the median lethal dose (LD50) and cytokine expression. We have preliminarily established a N. seriolae - C. argus model. According to our morphological and phylogenetic analysis data, the isolated strain was identified as N. seriolae and named NSE01. Eighteen days post-infection of healthy juvenile C. argus with N. seriolae NSE01, the mortality rate in all four experimental groups (intraperitoneally injected with 1 × 105 CFU/mL - 1 × 108 CFU/mL of bacterial suspension) (n = 120) was 100 %. The LD50 of N. seriolae NSE01 for juvenile C. argus was determined to be 1.13 × 106 CFU/fish. Infected juvenile C. argus had significant pathological changes, including visceral tissue swelling, hemorrhage, and the presence of numerous nodules of varying sizes in multiple tissues. Further histopathological examination revealed typical systemic granuloma formation. Additionally, following infection with N. seriolae NSE01, the gene expression of important cytokines, such as Toll-like receptor genes TLR2, TLR13, interleukin-1 receptor genes IL1R1, IL1R2, and interferon regulatory factor IRF2 were significantly upregulated in different tissues, indicating their potential involvement in the host immune response and regulation against N. seriolae. In conclusion, juvenile C. argus can serve as a suitable model for N. seriolae infection. The establishment of this animal model will facilitate the study of the pathogenesis of nocardiosis and the development of vaccines.