Leaf-like MSX/TiN heterojunction photocathodes mimicking plant cell - An effective strategy to enhance photoelectrocatalytic carbon dioxide reduction and systematic mechanism investigation.

Semiconductors, such as metal oxides and metal sulfides (MSX), are widely investigated as effectively catalytic materials to convert carbon dioxide (CO2) and water into chemicals under simulated solar light. These valuable investigations might address both the energy crisis and climate change in our modern society. Herein, a novel strategy to construct leaf-like heterojunctions of VS-ZnIn2S4/TiN-x is reported. The new semiconductor heterojunctions were then applied to photoelectrocatalytic CO2 reduction, achieving excellent performance (formate formation rate of 1173.2 µM h-1 cm-2) attributed to the plant cell-like morphology and enhanced electron mobility from the heterojunction interfaces to the active sites on the surface. Our findings suggest that titanium nitride (TiN) with good conductivity can improve the photoelectrocatalytic ability of MSX through heterojunction construction. The photocathode VS-ZnIn2S4/TiN-3 exhibits 81.0 % selectivity toward C2 products by optimizing the material structure and reaction conditions. According to the systematic investigation of operando Fourier transform infrared (FTIR) spectra, common intermediates such as *COO-, *COOH, *CO, *CHO, *COCHO, and *COCH3 reported in the literature were carefully verified. Among these, the carbene specie serve as the key intermediate responsible for generating other intermediates and resulting in all products.

Pressure loading regulates the stemness of liver cancer stem cells via YAP/BMF signaling axis.

Cancer stem cells (CSCs) are considered the major cause of the occurrence, progression, chemoresistance/radioresistance, recurrence, and metastasis of cancer. Increased interstitial fluid pressure (IFP) is a key feature of solid tumors. Our previous study showed that the distribution of liver cancer stem cells (LCSCs) correlated with the mechanical heterogeneity within liver cancer tissues. However, the regulation of liver cancer's mechanical microenvironment on the LCSC stemness is not fully understood. Here, we employed a cellular pressure-loading device to investigate the effects of normal IFP (5 mmHg), as well as increased IFP (40 and 200 mmHg) on the stemness of LCSCs. Compared to the control LCSCs (exposure to 5 mmHg pressure loading), the LCSCs exposed to 40 mmHg pressure loading exhibited significantly upregulated expression of CSC markers (CD44, EpCAM, Nanog), enhanced sphere and colony formation capacities, and tumorigenic potential, whereas continuously increased pressure to 200 mmHg suppressed the LCSC characteristics. Mechanistically, pressure loading regulated Yes-associated protein (YAP) activity and Bcl-2 modifying factor (BMF) expression. YAP transcriptionally regulated BMF expression to affect the stemness of LCSCs. Knockdown of YAP and overexpression of BMF attenuated pressure-mediated stemness and tumorgenicity, while YAP-deficient and BMF-deletion recused pressure-dependent stemness on LCSCs, suggesting the involvement of YAP/BMF signaling axis in this process. Together, our findings provide a potential target for overcoming the stemness of CSCs and elucidate the significance of increased IFP in cancer progression.

Optical Coherence Tomography Angiography Analysis of Peripapillary Choroidal Microvascular Density in normal-tension Glaucoma and Primary open-angle Glaucoma.

PRCIS: Glaucoma patients had a reduction in the inner annulus peripapillary choroidal microvascular density (PCMD) that became worse as the glaucoma severity progressed, which might provide new evidence supporting the vascular theory. PURPOSE: To compare PCMD among normal-tension glaucoma (NTG), primary open-angle glaucoma (POAG), and healthy controls using optical coherence tomography (OCT) angiography (OCTA). METHODS: The study included 40 POAG, 25 NTG, and 33 healthy controls. All subjects underwent OCT and OCTA testing. Inner annulus and outer annulus PCMD, as well as peripapillary vessel density (VD), was calculated. One-way analysis of variance was used to compare the vascular parameters of the three groups. Pearson correlation analysis or Spearman correlation test was used to evaluate the correlation between PCMD and glaucomatous severity factors. The spatial positional relationship between PCMD and corresponding peripapillary retinal nerve fiber layer (RNFL) thickness and visual field (VF) mean deviation (MD) was also assessed. RESULTS: The average and four quadrants of the inner annulus PCMD and peripapillary VD in the two glaucomatous groups were significantly lower than in normal eyes (P<0.05). Strong correlations were found between inner annulus PCMD and VF MD, peripapillary VD, and RNFL in POAG patients. Similarly, the inner annulus PCMD in NTG patients was strongly correlated with peripapillary VD and RNFL (all r>0.5). Strong positional correlations were found between inner superior quadrantal PCMD and RNFL thickness in both POAG and NTG patients (r=0.566, r=0.731, respectively). Likewise, inner inferior quadrantal PCMD exhibited a strong correlation with RNFL thickness in POAG patients (r=0.608). Strong positional correlations were also found between inner superior PCMD and VF MD in both POAG and NTG patients (r=0.589, r=0.622, respectively). Inner inferior PCMD exhibited a moderate correlation with VF MD in both POAG and NTG patients (r=0.487, r=0.440, respectively). CONCLUSION: The study found that the inner annulus PCMD decreased to varying degrees in NTG and POAG patients. The inner annulus PCMD was closely related to the structural and visual function parameters of glaucoma in both NTG and POAG. Furthermore, inner PCMD demonstrated a spatial correlation with corresponding RNFL thickness and VF MD.

Discovering functional interactions among schizophrenia-risk genes by combining behavioral genetics with cell biology.

Despite much progress in identifying risk genes for polygenic brain disorders, their core pathogenic mechanisms remain poorly understood. In particular, functions of many proteins encoded by schizophrenia risk genes appear diverse and unrelated, complicating the efforts to establish the causal relationship between genes and behavior. Using various mouse lines, recent studies indicate that alterations of parvalbumin-positive (PV+) GABAergic interneurons can lead to schizophrenia-like behavior. PV+ interneurons display fast spiking and contribute to excitation-inhibition balance and network oscillations via feedback and feedforward inhibition. Here, we first summarize different lines of genetically modified mice that display motor, cognitive, emotional, and social impairments used to model schizophrenia and related mental disorders. We highlight ten genes, encoding either a nuclear, cytosolic, or membrane protein. Next, we discuss their functional relationship in regulating fast spiking and other aspects of PV+ interneurons and in the context of other domains of schizophrenia. Future investigations combining behavioral genetics and cell biology should elucidate functional relationships among risk genes to identify the core pathogenic mechanisms underlying polygenic brain disorders.

Highly thermostable RhB@Zr-Eddc for the selective sensing of nitrofurazone and efficient white light emitting diode.

Highly thermostable RhB@Zr-Eddc composites with the Rhodamine B (RhB) enclosed into the nanocages of Zr-Eddc was synthesized by one-pot method under hydrothermal conditions, whose structure, morphology and stability were characterized through the X-ray powder diffractometry (XRD), scanning electron microscopy (SEM) and thermogravimetric analysis (TGA). RhB@Zr-Eddc showed the highly thermal stability up to 550°C and emitted the bright red-light emission at 605 nm, which could highly selective detect the nitrofurazone (NFZ) among eleven other antibiotics in aqueous solution. Furthermore, via combining the RhB@Zr-Eddc with commercial green phosphor (Y3Al5O12:Ce3+, Ga3+), the mixture was encapsulated onto a 455 nm blue LED chip, creating an ex-cellent white light emitting diode (WLED) device with the correlated colour temperature (CCT) of 4710 K, luminous efficiency (LE) of 43.17 lm/w and Color Rendering Index (CRI) of 89.2.

A Neutral Polysaccharide from Medicago Sativa L.: Structural Properties and Hypoglycemic Activity In Vitro and In Vivo.

Medicago sativa polysaccharides (MSPs) are beneficial compounds extracted from Medicago sativa L. that exhibit multiple medicinal activities. However, little is known about their hypoglycemic effects. In this study, MSP-II-a, a neutral polysaccharide with an Mw of 4.3×104 Da, was isolated and purified from M. sativa L. Monosaccharide composition analysis determined that MSP-II-a was composed of arabinose, glucose, galactose, mannose, rhamnose, and xylose in a molar ratio of 2.1 : 4.0 : 1.1:0.4 : 1.4 : 1.1. Structural characterization of MSP-II was performed using a combination of methylation analysis, Fourier transform infrared spectroscopy, and scanning electron microscopy. The results showed that MSP-II-a was mainly comprised of 1,4-p-Glc, 1,3,4-Rha, and 1,3-p-Gal glycosidic linkages, revealing a mesh-like texture with irregular blade shapes. In vitro assays demonstrated that MSP-II-a, at concentrations of 200 and 400 µg/mL, promoted glucose uptake in insulin-resistant 3T3-L1 adipocytes. In vivo studies have shown that MSP-II-a significantly alleviates insulin resistance by reducing fasting blood glucose levels and increasing hepatic glycogen synthesis in HFD/STZ-induced diabetic mice. These findings revealed that MSP-II-a is a promising source of bioactive polysaccharides with potential hypoglycemic activity.

Chrysanthemum lavandulifolium homolog CYCLIN A2;1 modulates cell division in ray florets.

The morphology of ray florets in chrysanthemums is tightly associated with cell division and expansion, both of which require proper progression of the cell cycle. Here, we identified a Chrysanthemum lavandulifolium homolog, CYCLIN A2;1 (CYCA2;1), the expression of which in ray florets is negatively correlated with petal width. We found that CYC2a, a TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR (TCP) transcription factor in the CYCLOIDEA2 (CYC2) family, interacts with and stabilizes CYC2b, and the latter can bind to the promoter of CYCA2;1 to activate its transcription. Overexpression of CYCA2;1 in C. lavandulifolium reduced the size of capitula and ray florets. Cytological analysis revealed that CYCA2;1 overexpression inhibited both cell division and expansion via repression of the mitotic cell cycle in ray florets, the latitudinal development of which was more relatively negatively influenced, thereby leading to increased ratios of petal length to width at later developmental stages. Yeast two-hybrid library screening revealed multiple proteins that interacted with CYCA2;1 including ACTIN-RELATED PROTEIN7 (ARP7), and silencing ARP7 inhibited the development of ray florets. Co-immunoprecipitation assays confirmed that CYCA2;1 could induce the degradation of ARP7 to inhibit the development of ray florets. Taken together, our results indicate the presence of a regulatory network in ray floret development in chrysanthemum consisting of CYC2b-CYCA2;1-ARP7 that acts via governing mitosis. The identification of this network has the potential to facilitate breeding efforts targeted at producing novel ornamental traits in the flowers.

Case report: PCA-2-associated encephalitis with different clinical phenotypes: a two-case series and literature review.

Purkinje cell cytoplasmic antibody type 2 (PCA-2), identified in 2000, targets the widely distributed microtubule-associated protein 1B in the central and peripheral nervous systems, leading to diverse clinical phenotypes of neurological disorders. We report two cases of PCA-2-associated encephalitis, each presenting with distinct onset forms and clinical manifestations, thereby illustrating the phenotypic variability of PCA-2-related diseases. The first patient was diagnosed with PCA-2-associated autoimmune cerebellitis and undifferentiated small cell carcinoma with metastasis in mediastinal lymph nodes of unknown primary origin. The second patient was diagnosed with PCA-2-associated limbic encephalitis. Our findings underscore the superior sensitivity of positron emission tomography-computed tomography over brain magnetic resonance imaging in the early detection of PCA-2-associated encephalitis. Given the high risk of relapse and suboptimal response to traditional immunotherapy in PCA-2-related neurological disorders, this study highlights the need for a deeper understanding of their pathogenesis to develop more effective treatments to control symptoms and improve patient prognosis.

Matrix stiffening facilitates stemness of liver cancer stem cells by YAP activation and BMF inhibition.

Matrix stiffening is one of the major risk factors for hepatocellular carcinoma (HCC) and drives tumor progression. The extracellular matrix (ECM) stiffness of HCC displays mechanical heterogeneity, with stiffness increasing from the core to the invasive frontier. The distribution of liver cancer stem cells (CSCs) is related to this mechanical property. However, it is not sufficiently understood how heterogeneous matrix stiffness regulates the stemness of CSCs. In this study, we developed an adjustable gelatin/alginate hydrogel to investigate the effect of various matrix stiffnesses on CSC stemness under three-dimensional culture conditions. Gelatin/alginate hydrogel with the stiffness of soft (5 kPa), medium (16 kPa), and stiff (81 kPa) were prepared by altering the concentration of calcium ions. It was found that a stiffer matrix promoted stemness-associated gene expression, reduced drug sensitivity, enhanced sphere-forming and clonogenic ability, and tumorigenic potential. Mechanistically, matrix stiffening facilitates CSC stemness by increasing Yes-associated protein (YAP) activity and inhibiting Bcl-2 modifying factor (BMF) expression. Knockdown of YAP or overexpression of BMF significantly attenuated matrix stiffening-induced stemness, suggesting the involvement of YAP and BMF in this process. Together, our results unravel the regulatory mechanism of heterogeneous matrix stiffness on CSC stemness and also provide a novel therapeutic strategy for eradicating CSCs and improving the efficiency of HCC treatment.

The diagnostic ability of peripapillary vessel density in primary open-angle glaucoma suspects.

OBJECTIVE: To assess the diagnostic ability of peripapillary vessel density (pVD) in primary open-angle glaucoma suspect (GS) patients. METHODS: Sixteen primary open-angle GS patients (22 eyes) and 20 normal controls (22 eyes) were included. In the GS group, OCTA measurements of pVD (superior, inferior, nasal, temporal, and global), OCT measurements of retinal nerve fiber layer (RNFL) thickness, disc area, rim area and ganglion cell complex (GCC) thickness were examined. In the control group, pVD measurements were performed. The vessel density between the two groups was compared. The correlation between OCTA and OCT parameters was evaluated. The receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of OCTA measurements. RESULTS: The global (P < 0.001), nasal (P = 0.003), and inferior (P = 0.002) quadrant pVD in GS group was considerably lower than the control group. The global pVD was positively correlated with the inferior RNFL thickness (r = 0.492, P = 0.023) and rim area (r = 0.483, P = 0.027). The inferior pVD was positively correlated with the inferior RNFL thickness (r = 0.648, P = 0.001), the nasal RNFL thickness (r = 0.441, P = 0.045), the rim area (r = 0.439, P = 0.046) and the GCC thickness (r = 0.472, P = 0.048). The global pVD had the best diagnostic value (AUC=0.825, sensitivity 86.36 %, specificity 72.73 %, cutoff value 45 %), followed by the inferior (AUC=0.749) and nasal (AUC=0.748) quadrant pVD. CONCLUSION: In primary open-angle GS patients, the global and inferior quadrant pVD was lower than that of normal people, and it was positively correlated with the inferior RNFL thickness and rim area. The diagnostic value of pVD for discriminating GS from normal people was excellent with high sensitivity and specificity.

Identification of key genes for triacylglycerol biosynthesis and storage in herbaceous peony (Paeonia lactifolra Pall.) seeds based on full-length transcriptome.

BACKGROUND: The herbaceous peony (Paeonia lactiflora Pall.) is extensively cultivated in China due to its root being used as a traditional Chinese medicine known as 'Radix Paeoniae Alba'. In recent years, it has been discovered that its seeds incorporate abundant unsaturated fatty acids, thereby presenting a potential new oilseed plant. Surprisingly, little is known about the full-length transcriptome sequencing of Paeonia lactiflora, limiting research into its gene function and molecular mechanisms. RESULTS: A total of 484,931 Reads of Inserts (ROI) sequences and 1,455,771 full-Length non-chimeric reads (FLNC) sequences were obtained for CDS prediction, TF analysis, SSR analysis and lncRNA identification. In addition, gene function annotation and gene structure analysis were performed. A total of 4905 transcripts were related to lipid metabolism biosynthesis pathway, belonging to 28 enzymes. We use these data to identify 10 oleosin (OLE) and 5 diacylglycerol acyltransferase (DGAT) gene members after de-redundancy. The analysis of physicochemical properties and secondary structure showed them similarity in gene family respectively. The phylogenetic analysis showed that the distribution of OLE and DGAT family members was roughly the same as that of Arabidopsis. Quantitative real-time polymerase chain reaction (qRT-PCR) analyses revealed expression changes in different seed development stages, and showed a trend of increasing and then decreasing. CONCLUSION: In summary, these results provide new insights into the molecular mechanism of triacylglycerol (TAG) biosynthesis and storage during the seedling stage in Paeonia lactiflora. It provides theoretical references for selecting and breeding oil varieties and understanding the functions of oil storage as well as lipid synthesis related genes in Paeonia lactiflora.

ELMO1 regulates macrophage directed migration and attenuates inflammation via NF-κB signaling pathway in primary biliary cholangitis.

BACKGROUND & AIMS: Primary biliary cholangitis (PBC), a typical autoimmune liver disease, is characterized by an increased infiltration of immune cells. However, the specific molecular mechanisms regulating immune cell migration in PBC are unknown. Engulfment and cell motility 1 (ELMO1) plays an important function in cellular dynamics. In view of this, the aim of this study was to explore the expression of ELMO1 in PBC, its effects on the proliferation, migration, and secretion of inflammatory factors by the mainly regulated immune cells and the specific molecular mechanisms behind it. METHODS: To determine the expression of ELMO1 in PBC and its major regulatory immune cells in PBC. The migratory and proliferative capacities of ELMO1-deficient macrophages were measured, and their pro-inflammatory cytokine secretion was also detected and explored mechanistically. RESULTS: ELMO1 expression was up-regulated in the PBC patients and positively correlated with alkaline phosphatase (ALP). ELMO1 mainly regulated macrophages in the liver of PBC patients. Knockdown of ELMO1 did not affect macrophage proliferation, however,knockdown of ELMO1 significantly inhibited macrophage migration,downstream RAC1 activity was diminished, and reduced F-actin synthesis. Knockdown of ELMO1 reduced macrophage inflammatory factor secretion and NF-κB signaling pathway activity was decreased. CONCLUSIONS: ELMO1 regulates macrophage directed migration and attenuates inflammation via NF-κB signaling pathway in primary biliary cholangitis.

The association between physical activity intensity and frailty risk among older adults across different age groups and genders: Evidence from four waves of the China Health and Retirement Longitudinal Survey.

"Exercise is the best medicine" is well known, but the optimal dose of physical activity (PA) for males and females across different age groups is still unknown. This study, using data from the four waves of CHARLS, aimed to determine the optimal PA dose that reduces frailty risks among older adults across various age groups and both sexes. We created a frailty index score using 63 health-related variables and used 0.21 as the frailty cut point. Binary logistic regression was used to compare the effect of vigorous, moderate, and light intensity PA under IPAQ criteria on frailty risk. The study found that regardless of whether males or females, the optimal effect of vigorous-intensity PA in reducing the risk of frailty is consistently observed throughout the entire old age career. Moreover, the age groups at which moderate-intensity PA reduces the risk of frailty were from age 70 for males and from age 80 for females. And light-intensity PA had no effect on reducing the risk of frailty. Moderate and vigorous intensity of PA in older adults should be promoted, but guidelines and recommendations must account for optimal associations with PA dose across genders and age groups.

Large regions of homozygosity in prenatal diagnosis.

Chromosomal microarrays (CMA) incorporate single nucleotide polymorphisms to enable the detection of regions of homozygosity (ROH). Here, we retrospectively analyzed 6288 prenatal cases who performed CMA to explored the clinical implications of large ROH in prenatal diagnosis. We analyzed cases with ROH larger than 10 megabases and reviewed the ultrasound findings; karyotype results and pregnancy follow-up data. Cases with possible imprinting disorders were assessed by methylation-specific multiplex ligation-dependent probe amplification. In total, we identified 50 cases with large ROH and chromosomes 1 and 2 were the most affected. About 59.18% of the ROH cases had ultrasound abnormalities, with the most common findings being ultrasound soft-marker abnormalities. There were seven fetuses had ROH which covered almost the entire chromosome and four had terminal ROH that involved almost the entire long arm of the chromosomes, which indicated uniparental disomy (UPD), of which 70% showed abnormal ultrasound findings. Ten cases with multiple ROH on different chromosomes indicated the third to fifth degree of consanguinity. In this study, we highlighted the clinical relevance of large ROH related to UPD. The analysis of ROH allowed us to gain further understanding of complex cytogenetic and disease mechanisms in prenatal diagnosis.

The etiology and differential diagnosis of "autoimmune hepatitis-like liver disease" in children: a single-center retrospective study.

Background: Children with autoimmune hepatitis (AIH) often present with symptoms similar to those of other liver diseases. This study consists of a comparison between the clinical and histological characteristics of AIH and those of other four AIH-like liver diseases [i.e., drug-induced liver injury (DILI), gene deficiency, infectious liver disease and other etiology of liver disease], as well as an evaluation of the AIH scoring system's diagnostic performance. Methods: All children with AIH-like liver disease at our center from January 2013 to December 2022 were included. The clinical and histological characteristics of the AIH group were retrospectively analyzed and compared with those of the other four groups. Results: A total of 208 children were included and divided into AIH group (18 patients), DILI group (38 patients), gene deficiency group (44 patients), infectious liver disease group (74 patients), and other etiology group (34 patients). The antinuclear antibodies (ANA) ≥ 1:320 rate was significantly higher in the AIH compared to the other four groups after multiple testing correction (p < 0.0125), while patients with positive antibodies to liver-kidney microsomal-1 (anti-LKM1, n = 3) and smooth muscle antibodies (SMA, n = 2) were only observed in the AIH group. The positive rates of antibodies to liver cytosol type1 (anti-LC1) and Ro52 were higher than those in the other four groups. The serum immunoglobulin G (IgG) and globulin levels, as well as the proportions of portal lymphoplasmacytic infiltration, lobular hepatitis with more than moderate interface hepatitis, and lobular hepatitis with lymphoplasmacytic infiltration, were significantly higher in the AIH group than in the other four groups after multiple testing correction (p < 0.0125). The cirrhosis rate in the AIH group was higher than that in the DILI and infectious liver disease groups (p < 0.0125). Both the simplified (AUC > 0.73) and the revised systems (AUC > 0.93) for AIH have good diagnostic performance, with the latter being superior (p < 0.05). Conclusion: Positive autoantibodies (ANA ≥ 1:320 or anti-LKM1 positive, or accompanied by SMA, anti-LC1 or Ro-52 positive) and elevated serum IgG or globulin levels contribute to early recognition of AIH. The presence of lobular hepatitis with more than moderate interface hepatitis and lymphoplasmacytic infiltration contribute to the diagnosis of AIH.

Exploring the underlying mechanisms of enteritis impact on golden pompano (Trachinotus ovatus) through multi-omics analysis.

Enteritis posed a significant health challenge to golden pompano (Trachinotus ovatus) populations. In this research, a comprehensive multi-omics strategy was implemented to elucidate the pathogenesis of enteritis by comparing both healthy and affected golden pompano. Histologically, enteritis was characterized by villi adhesion and increased clustering after inflammation. Analysis of the intestinal microbiota revealed a significant increase (P < 0.05) in the abundance of specific bacterial strains, including Photobacterium and Salinivibrio, in diseased fish compared to the healthy group. Metabolomic analysis identified 5479 altered metabolites, with significant impacts on terpenoid and polyketide metabolism, as well as lipid metabolism (P < 0.05). Additionally, the concentrations of several compounds such as calcitetrol, vitamin D2, arachidonic acid, and linoleic acid were significantly reduced in the intestines of diseased fish post-enteritis (P < 0.05), with the detection of harmful substances such as Efonidipine. In transcriptomic profiling, enteritis induced 68 upregulated and 73 downregulated genes, predominantly affecting steroid hormone receptor activity (P < 0.05). KEGG pathway enrichment analysis highlighted upregulation of SQLE and CYP51 in steroidogenesis, while the HSV-1 associated MHC1 gene exhibited significant downregulation. Integration of multi-omics results suggested a potential pathogenic mechanism: enteritis may have resulted from concurrent infection of harmful bacteria, specifically Photobacterium and Salinivibrio, along with HSV-1. Efonidipine production within the intestinal tract may have blocked certain calcium ion channels, leading to downregulation of MHC1 gene expression and reduced extracellular immune recognition. Upregulation of SQLE and CYP51 genes stimulated steroid hormone synthesis within cells, which, upon binding to G protein-coupled receptors, influenced calcium ion transport, inhibited immune activation reactions, and further reduced intracellular synthesis of anti-inflammatory substances like arachidonic acid. Ultimately, this cascade led to inflammation progression, weakened intestinal peristalsis, and villi adhesion. This study utilized multi-level omics detection to investigate the pathological symptoms of enteritis and proposed a plausible pathogenic mechanism, providing innovative insights into enteritis verification and treatment in offshore cage culture of golden pompano.

Genomic landscape and tumor mutational features of resected preinvasive to invasive lung adenocarcinoma.

Introduction: Adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) are considered pre-invasive forms of lung adenocarcinoma (LUAD) with a 5-year recurrence-free survival of 100%. We investigated genomic profiles in early tumorigenesis and distinguished mutational features of preinvasive to invasive adenocarcinoma (IAC) for early diagnosis. Methods: Molecular information was obtained from a 689-gene panel in the 90 early-stage LUAD Chinese patients using next-generation sequencing. Gene signatures were identified between pathology subtypes, including AIS/MIA (n=31) and IAC (n=59) in this cohort. Mutational and clinicopathological information was also obtained from the Cancer Genome Atlas (TCGA) as a comparison cohort. Results: A higher mutation frequency of TP53, RBM10, MUC1, CSMD, MED1, LRP1B, GLI1, MAP3K, and RYR2 was observed in the IAC than in the AIS/MIA group. The AIS/MIA group showed higher mutation frequencies of ERBB2, BRAF, GRIN2A, and RB1. Comparable mutation rates for mutually exclusive genes (EGFR and KRAS) across cohorts highlight the critical transition to invasive LUAD. Compared with the TCGA cohort, EGFR, KRAS, TP53, and RBM10 were frequently mutated in both cohorts. Despite limited gene mutation overlap between cohorts, we observed variant mutation types in invasive LUAD. Additionally, the tumor mutation burden (TMB) values were significantly lower in the AIS/MIA group than in the IAC group in both the Chinese cohort (P=0.0053) and TCGA cohort (P<0.01). Conclusion: These findings highlight the importance of distinguishing preinvasive from invasive LUAD in the early stages of LUAD and both pathology and molecular features in clinical practice, revealing genomic tumor heterogeneity and population differences.

The causal relationship between physical activity, sedentary behavior and brain cortical structure: a Mendelian randomization study.

Physical activity and sedentary behavior, both distinct lifestyle behaviors associated with brain health, have an unclear potential relationship with brain cortical structure. This study aimed to determine the causal link between physical activity, sedentary behavior, and brain cortical structure (cortical surface area and thickness) through Mendelian randomization analysis. The inverse-variance weighted method was primarily utilized, accompanied by sensitivity analyses, to confirm the results' robustness and accuracy. Analysis revealed nominally significant findings, indicating a potential positive influence of physical activity on cortical thickness in the bankssts (ß = 0.002 mm, P = 0.043) and the fusiform (ß = 0.002 mm, P = 0.018), and a potential negative association of sedentary behavior with cortical surface area in the caudal middle frontal (ß = -34.181 mm2, P = 0.038) and the pars opercularis (ß = -33.069 mm2, P = 0.002), alongside a nominally positive correlation with the cortical surface area of the inferior parietal (ß = 58.332 mm2, P = 0.035). Additionally, a nominally significant negative correlation was observed between sedentary behavior and cortical thickness in the paracentral (ß = -0.014 mm, P = 0.042). These findings offer insights into how lifestyle behaviors may influence brain cortical structures, advancing our understanding of their interaction with brain health.

Ros-responsive nano-platform for lipid-specific fluorescence imaging of atherosclerosis.

Fluorescent probes that specifically targeting Lipid droplets (LDs) have shown potential in biological imaging. Albeit, their in vivo applications are limited due to the hydrophobicity, low signal-to-noise ratio (SNR) and LDs-specificity. Thus, we designed a novel probe namely MeOND, and a reactive oxygen species (ROS)-responsive nano-platform to improve in vivo LDs-specific imaging. MeOND exhibits a remarkable twisted intramolecular charge transfer (TICT) effect with a strongly enhanced near-infrared emission in low-polarity lipid environment. Also, MeOND demonstrates satisfactory biocompatibility and superior intracellular LDs imaging capabilities. MeOND encapsulated nano-platform (MeOND@PMM) presented favorable water solubility and biocompatibility. MeOND@PMM remains stable in physiological conditions but quickly degrades in the environment of elevated ROS level. The released MeOND could then light up the intracellular LDs in atherosclerotic plaques. The design of the probe and nano-platform is expected to provide a better tool for the scientific research of LDs and LDs-related diseases.