Comparative analysis of the performance of hepatobiliary agents in depicting MRI features of microvascular infiltration in hepatocellular carcinoma.

OBJECTIVE: To compare the ability to depict MRI features of hepatobiliary agents in microvascular infiltration (MVI) of hepatocellular carcinoma (HCC) during different stages of dynamic enhancement MRI. MATERIALS AND METHODS: A retrospective study included 111 HCC lesions scanned with either Gd-EOB-DTPA or Gd-BOPTA. All cases underwent multiphase dynamic contrast-enhanced scanning before surgery, including arterial phase (AP), portal venous phase (PVP), transitional phase (TP), delayed phase (DP), and hepatobiliary phase (HBP). Two abdominal radiologists independently evaluated MRI features of MVI in HCC, such as peritumoral hyperenhancement, incomplete capsule, non-smooth tumor margins, and peritumoral hypointensity. Finally, the results were reviewed by the third senior abdominal radiologist. Chi-square (χ2) Inspection for comparison between groups. P < 0.05 is considered statistically significant. Receiver operating characteristic (ROC) curve was used to evaluate correlation with pathology, and the area under the curve (AUC) and 95% confidence interval (95% CI) were calculated. RESULTS: Among the four MVI evaluation signs, Gd-BOPTA showed significant differences in displaying two signs in the HBP (P < 0.05:0.000, 0.000), while Gd-EOB-DTPA exhibited significant differences in displaying all four signs (P < 0.05:0.005, 0.006, 0.000, 0.002). The results of the evaluations of the two contrast agents in the DP phase with incomplete capsulation showed the highest correlation with pathology (AUC: 0.843, 0.761). By combining the four MRI features, Gd-BOPTA and Gd-EOB-DTPA have correlated significantly with pathology, and Gd-BOPTA is better (AUC: 0.9312vs0.8712). CONCLUSION: The four features of hepatobiliary agent dynamic enhancement MRI demonstrate a good correlation with histopathological findings in the evaluation of MVI in HCC, and have certain clinical significance.

Socioeconomic Status, Length of Stay, and Postoperative Complications in Oral Cavity Squamous Cell Carcinoma.

Background: Despite universal healthcare in Canada, low socioeconomic status (SES) has been associated with worse survival in oral cavity squamous cell carcinoma (OCSCC) patients. However, the relationship between SES and outcomes during the acute postoperative period is poorly defined. Hamilton, Ontario, presents a unique population with widely varying SES within the same geography. The objective of this study was to examine the relationship between SES, length of hospital stay (LOHS), and postoperative complications in OCSCC. Methods: Newly diagnosed OCSCC patients receiving primary surgical treatment from 2010 to 2014 were identified within a prospectively collected database. Inclusion criteria included age >18 years old, pathological diagnosis of oral cavity cancer, and primary surgical treatment with curative intent. Patients were excluded if they were undergoing palliative treatment or had previous head and neck surgery/radiotherapy. Postal codes were used to identify neighborhood-level socioeconomic variables via 2011 Canada Census data. Income quartiles were defined from groups of neighboring municipalities based on Canada Census definitions. Demographic, social, pathological, staging, and treatment data were collected through chart review. Results: One hundred and seventy-four patients were included in the final analysis. OCSCC patients with lower SES were more likely to be younger (P = .041), male (P = .040), have significant tobacco and alcohol use (P = .001), higher Charlson Comorbidity Index (CCI; P = .014), lower levels of education (P = .001), and have lower employment levels (P = .001). Lower SES patients had higher clinical tumor (P = .006) and clinical nodal (P = .004) staging and were more likely to receive adjuvant therapy (P = .001) and G-tubes (P = .001). Multivariable regression analysis showed that low SES was a statistically significant predictor of postoperative complications [ß 2.50 (95% confidence interval (CI) 0.200, 3.17); P = .014] and LOHS [ß 2.03 (95% CI 1.06, 2.99); P = .0001]. Tobacco and alcohol use, clinical tumor, and nodal stage, CCI, and planned adjuvant therapy were also statistically significant predictors of postoperative complications and LOHS (P < .05). Conclusion: Patients with lower SES have more advanced OCSCC disease with increased comorbidities that owes itself to more acute postoperative complications and LOHS within this study population. Patients with low SES should be identified as patients that require more support during their cancer treatment.

Liquid Phase Exfoliation of Few-Layer Non-Van der Waals Chromium Sulfide.

Exfoliation of 2D non-Van der Waals (non-vdW) semiconductor nanoplates (NPs) from inorganic analogs presents many challenges ahead for further exploring of their advanced applications on account of the strong bonding energies. In this study, the exfoliation of ultrathin 2D non-vdW chromium sulfide (2D Cr2S3) by means of a combined facile liquid-phase exfoliation (LPE) method is successfully demonstrated. The morphology and structure of the 2D Cr2S3 material are systematically examined. Magnetic studies show an obvious temperature-dependent uncompensated antiferromagnetic behavior of 2D Cr2S3. The material is further loaded on TiO2 nanorod arrays to form an S-scheme heterojunction. Experimental measurements and density functional theory (DFT) calculations confirm that the formed TiO2@Cr2S3 S-scheme heterojunction facilitates the separation and transmission of photo-induced electron/hole pairs, resulting in a significantly enhanced photocatalytic activity in the visible region.

Imidazolyl Lipids Enhanced LNP Endosomal Escape for Ferroptosis RNAi Treatment of Cancer.

Treatments for cancer that incorporate small interfering RNA (siRNA) to target iron-dependent ferroptosis are thought to be highly promising. However, creating a reliable and clinically feasible siRNA delivery system continues to be a major obstacle in the field of cancer treatment. Here, three imidazole-based ionizable lipid nanoparticles (LNPs) with pH-sensitive effects are rationally designed and synthesized for siRNA delivery. LNPs formulated with the top-performing lipid (O12-D3-I3) encapsulating FVII siRNA (FVII@O-LNP) elicited greater gene silencing than those with the benchmark Onpattro lipid DLin-MC3-DMA (MC3) due to its stronger endosomal escape. Moreover, Fc-siRNA@O-LNPs encapsulated with ferrocene (Fc) and SLC7A11/Nrf2-targeted siRNA is formulated. The outcomes demonstrate optimal safety profiles and a significant anti-tumor effect by inducing long-lasting and efficient ferroptosis through a synergistic action in vivo. In summary, this work shows that imidazolyl lipid-prepared LNPs are efficient delivery vehicles for cancer therapy and ferroptosis-targeting siRNA administration, both of which have extensive clinical application potential.

Exogenous silicon induces aluminum tolerance in white clover (Trifolium repens) by reducing aluminum uptake and enhancing organic acid secretion.

Excessive aluminum (Al) in acidic soils is a primary factor that hinders plant growth. The objective of the present study was to investigate the effect and physiological mechanism of exogenous silicon (Si) in alleviating aluminum toxicity. Under hydroponic conditions, 4 mM Al significantly impeded the growth of white clover; however, pretreatments with 1 mM Si mitigated this inhibition, as evidenced by notable changes in growth indicators and physiological parameters. Exogenous silicon notably increased both shoot and root length of white clover and significantly decreased electrolyte leakage (EL) and malondialdehyde (MDA) content compared to aluminum treatments. This positive effect was particularly evident in the roots. Further analysis involving hematoxylin staining, scanning electron microscopy (SEM), and examination of organic acids (OAs) demonstrated that silicon relieved the accumulation of bioactive aluminum and ameliorated damage to root tissues in aluminum-stressed plants. Additionally, energy-dispersive X-ray (EDX) analysis revealed that additional silicon was primarily distributed in the root epidermal and cortical layers, effectively reducing the transport of aluminum and maintaining the balance of exchangeable cations absorption. These findings suggest that gradual silicon deposition in root tissues effectively prevents the absorption of biologically active aluminum, thereby reducing the risk of mineral nutrient deficiencies induced by aluminum stress, promoting organic acids exudation, and compartmentalizing aluminum in the outer layer of root tissues. This mechanism helps white clover alleviate the damage caused by aluminum toxicity.

Local dynamics and failure of inhomogeneous polymer networks.

Inhomogeneous crosslinked polymers are powerful platforms for materials design, because they can be synthesized from materials that provide complimentary properties to the resulting gel. For example, a membrane with both glassy and rubbery domains will be mechanically robust while enabling transport. The dynamics, and mechanical and failure properties of rubbery/glassy conetworks are only beginning to be studied, and there is likely to be strong heterogeneities in the dynamics and mechanical response. In this study, we use coarse-grained molecular dynamics simulations to generate microphase separated rubbery/glassy polymer networks with a bicontinuous morphology via in silico crosslinking. We study the effect of phase boundary on the local mobility gradient, and our simulation results reveal an asymmetric shift in the local mobility gradient across the interface that extends deeper into the phase with a lower Tg when the system temperature is between the glass transition temperatures of the two phases. Moreover, by employing a model that allows bond breaking, we examine the microscopic mechanism for failure in these networks as a function of the molecular weight of polymer strands between crosslinks and the number fraction of the glassy domain. Under uniaxial extension, we find that the stress is initially larger in the glassy domain. As the deformation proceeds, the segmental dynamics of the two phases homogenize, and subsequently bond breaking begins.

Constructing fine-grained spatiotemporal neonatal functional atlases with spectral functional network learning.

The early stages of human development are increasingly acknowledged as pivotal in laying the groundwork for subsequent behavioral and cognitive development. Spatiotemporal (4D) brain functional atlases are important in elucidating the development of human brain functions. However, the scarcity of such atlases for early life stages stems from two primary challenges: (1) the significant noise in functional magnetic resonance imaging (fMRI) that complicates the generation of high-quality atlases for each age group, and (2) the rapid and complex changes in the early human brain that hinder the maintenance of temporal consistency in 4D atlases. This study tackles these challenges by integrating low-rank tensor learning with spectral embedding, thereby proposing a novel, data-driven 4D functional atlas generation framework based on spectral functional network learning (SFNL). This method utilizes low-rank tensor learning to capture common functional connectivity (FC) patterns across different ages, thus optimizing FCs for each age group to improve the temporal consistency of functional networks. Incorporating spectral embedding aids in mitigating potential noise in FC networks derived from fMRI data by reconstructing networks in the spectral space. Utilizing SFNL-generated functional networks enables the creation of consistent and highly qualified spatiotemporal functional atlases. The framework was applied to the developing Human Connectome Project (dHCP) dataset, generating the first neonatal 4D functional atlases with fine-grained temporal and spatial resolutions. Experimental evaluations focusing on functional homogeneity, reliability, and temporal consistency demonstrated the superiority of our framework compared to existing methods for constructing 4D atlases. Additionally, network analysis experiments, including individual identification, functional systems development, and local efficiency assessments, further corroborate the efficacy and robustness of the generated atlases. The 4D atlases and related codes will be made publicly accessible (https://github.com/zhaoyunxi/neonate-atlases).

Effects of bacterial extracellular vesicles derived from oral and gastrointestinal pathogens on systemic diseases.

Oral microbiota and gastrointestinal microbiota, the two largest microbiomes in the human body, are closely correlated and frequently interact through the oral-gut axis. Recent research has focused on the roles of these microbiomes in human health and diseases. Under normal conditions, probiotics and commensal bacteria can positively impact health. However, altered physiological states may induce dysbiosis, increasing the risk of pathogen colonization. Studies suggest that oral and gastrointestinal pathogens contribute not only to localized diseases at their respective colonized sites but also to the progression of systemic diseases. However, the mechanisms by which bacteria at these local sites are involved in systemic diseases remain elusive. In response to this gap, the focus has shifted to bacterial extracellular vesicles (BEVs), which act as mediators of communication between the microbiota and the host. Numerous studies have reported the targeted delivery of bacterial pathogenic substances from the oral cavity and the gastrointestinal tract to distant organs via BEVs. These pathogenic components subsequently elicit specific cellular responses in target organs, thereby mediating the progression of systemic diseases. This review aims to elucidate the extensive microbial communication via the oral-gut axis, summarize the types and biogenesis mechanisms of BEVs, and highlight the translocation pathways of oral and gastrointestinal BEVs in vivo, as well as the impacts of pathogens-derived BEVs on systemic diseases.

Hernandezine acts as a CDK4 suppressor inhibiting tumor growth by the CDK4/PKM2/NRF2 axis in colon cancer.

BACKGROUND: The cyclin-dependent kinase 4 (CDK4) interacts with its canonical and non-canonical substrates modulating the cell cycle in tumor cells. However, the potential substrates and the beyond-cell-cycle-regulated functions of CDK4 in colon cancer (CC) are still unknown. Hernandezine (HER) is previously verified to induce G0/G1 phase arrest and autophagic cell death in human cancer cells, which implies that HER might target G0/G1 phase-related proteins, including CDK4. PURPOSE: The present study tried to investigate the glycolytic metabolism and oxidative stress functions of CDK4 in colon cancer. Furthermore, the inhibitory effects and potential binding sites of HER on CDK4, as well as its anti-tumor activity were investigated in CC cells. METHODS: The mass spectrometry assay was performed to identify potential endogenous substrates of CDK4 and the correlation between glycolytic metabolic rate and CDK4 level in COAD patient tissues. Meanwhile, after inhibiting the activity or the expression of CDK4, the binding capacity of CDK4 to PKM2 and NRF2 and the latter two protein distributions in cytoplasm and nucleus were detected in CC cells. In vitro, the regulatory effects of the CDK4-PKM2-NRF2 axis on glycolysis and oxidative stress were performed by ECAR, OCR, and ROS assay. The inhibitory effect of HER on CDK4 activity was explored in CC cells and the potential binding sites were predicted and testified in vitro. Furthermore, tumor growth inhibition of HER by suppressing the CDK4-PKM2-NRF2 axis was also investigated in vitro and in vivo. RESULTS: PKM2 and NRF2 were identified as endogenous substrates of CDK4 and, high-expressed CDK4 was associated with low-level glycolysis in COAD. In vitro, inactivated CDK4 facilitated CDK4-PKM2-NRF2 complex formation which resulted in 1) inhibited PKM2 activity and retarded the glycolytic rate; 2) cytoplasm-detained NRF2 failed to transcript anti-oxidative gene expressions and induced oxidant stress. Additionally, as a CDK4 inhibitor, HER developed triple anti-tumor effects including induced G0/G1 phase arrest, suppressed glycolysis, and disrupted the anti-oxidative capacity of CC cells. CONCLUSION: The results first time revealed that CDK4 modulated glycolytic and anti-oxidative capacity of CC cells via bound to its endogenous substrates, PKM2 and NRF2. Additionally, 140Asp145Asn amino acid sites of CDK4 were potential targets of HER. HER exerts anti-tumor activity by inhibited the activity of CDK4, promoted the CDK4-PKM2-NRF2 complex formation in the CC cells.

Visual effect of air pollution on the need for arousal and variety-seeking behavior.

Research on air pollution, one of the most common environmental factors, has primarily focused on its effects on physical, mental, and cognitive health. However, air pollution-induced achromatic color of an environment, which is a prominent feature of air pollution, has received little attention. This study explored the visual effects of air pollution on the variety-seeking purchase behavior of consumers through two scenario-based experiments and primed manipulation (Study 1 and Study 2) and one natural experiment using data from a local fruit chain store (Study 3). Study 1 tested the main effect of air pollution on the variety-seeking behavior and found that primed air pollution increased variety-seeking when consumers purchased beverages. Study 2 broadened the category and tested the mechanism, and the results indicated that primed air pollution increased the variety of purchased chocolates and demonstrated the mediating effect of the need for arousal. Study 3 tested the boundary condition and extended the external validity with actual purchases. The results revealed that severe air pollution increased the purchased SKUs by 22.9% and visibility reduced the moderation effect. This research extended the literature on the visual effect of air pollution by providing evidence of the effects of air pollution on variety-seeking behavior through the need for arousal. And, product managers could leverage the results by offering a greater variety of goods on days with air pollution to increase sales.

Yolk-shelled silver nanowire@amorphous metal-organic framework for controlled drug delivery and light-promoting infected wound healing.

Bacteria-infected wounds healing has been greatly hindered by antibiotic resistance and persistent inflammation. It is crucial to develop multifunctional nanocomposites that possess effective antibacterial properties and can simultaneously accelerate the wound healing process to overcome the above challenges. Herein, we prepared a yolk-shell structured Ag nanowires (NWs)@amorphous hollow ZIF-67 by etching ZIF-67 onto the Ag NWs for infected wound healing for the first time. The etched hollow structure of amorphous ZIF-67 in the nanocomposite makes it a promising platform for loading healing-promoting drugs. We extensively studied the antibacterial and healing-promoting properties of the curcumin (CCM)-loaded nanocomposite (Ag NWs@C-HZ67). Ag NWs, being noble metal materials with plasmonic effects, can absorb a broad range of natural light and convert it to thermal energy. This photothermal conversion further improves the release of antibacterial components and wound healing drugs when exposed to light. During the healing process of an infected wound, Ag and Co ions were released from Ag NWs@C-HZ67 upon direct contact with the wound exudate and under the influence of light irradiation. Simultaneously, the loaded CCM leaked out to repair the infected wound. The minimum inhibitory concentrations of the Ag NWs@C-HZ67 groups against Escherichia coli and Staphylococcus aureus bacteria decreased to 3 and 3 µg ml-1 when exposed to white light. Furthermore, an in vivo assessment of infected wound healing demonstrated that combining Ag NWs@C-HZ67 with light significantly accelerated the wound healing process, achieving 70% healing by the 6th day and almost complete healing by the 8th day. This advanced nanocomposite, consisting of components that possess antibacterial and growth-promoting properties, offers a safe, effective and clinically-translatable solution for accelerating the healing process of infected wounds.

Optimal scanning parameters of lumbar bone density measured by fast kilovoltage-switching dual-energy computed tomography (DECT).

Background: The technological innovation of fast kilovoltage (KV)-switching dual-energy computed tomography (DECT) has enabled the accurate measurement of vertebral bone density; however, it does not account for the effects of abdominal fat and ribs on the vertebral body. In our study, a European spine phantom (ESP) was used to establish an abdominal phantom for normal weight and obese people, and to explore the best scanning parameters for DECT to measure the bone mineral density (BMD) of the human lumbar spine. Methods: Revolution CT was used to conduct energy spectrum scanning for each body mode. A total of 20 sets of energy spectrum scans was conducted and each set of conditions was scanned 10 times. The data conformed to a normal distribution, and the differences between the measured and actual values of ESP L1-3 vertebrae were compared using a one-sample t-test, and quantitative data were described by x ¯ ± s . A P value <0.05 was considered statistically significant. Relative error (RE) and root mean square error (RMSE) of BMD measurements were calculated for different scanning conditions in normal and obese populations. Results: When simulating the upper abdominal condition (L1-2 level, fat area 140 cm2, with rib influence) in a normal weight population, there was no statistical difference (P>0.05) in BMD measurements for each vertebra at 0.8 s/rotation (rot) with different tube currents, the smallest RE at 0.8 s/rot, 190 mA condition, and the smallest RMSE for L1 and 2 vertebral BMD measurements at 190 mA; when simulating the abdominal condition at the L4 level in a normal weight population (fat area of 240 cm2, no rib influence), there were no statistical differences between the measurements at 0.8 s/rot, 190 and 275 mA conditions (P>0.05), and the RE and RMSE in the 190 mA condition was smaller than that in the 275 mA condition. Simulating the upper abdominal condition in the obese population (L1-2 level, fat area 340 cm2, with rib influence), there were no statistical difference between the measurements in the 0.8 s/rot, 315 and 355 mA conditions (P>0.05), the RE and RMSE in the 315 mA condition was less than those in the 355 mA; simulated obese abdominal condition at the L4 level in the population (fat area 450 cm2, no rib influence) resulted in 0.8 s/rot, no statistical difference in measurements between 315 mA (P>0.05), RE in 315 mA conditions were L1: 3.75%, L2: -1.06%, L3: 0.42%, and the RMSE under 315 mA condition were L1: 2.13, L2: 1.21, L3: 1.66. Conclusions: When using Revolution CT to measure lumbar spine bone density, 0.8 s/rot at 190 mA may be the best scanning parameter for a normal weight population, and 0.8 s/rot at 315 mA may be the best scanning parameter for an obese population.

Eco-health risks and main sources of persistent pollutants bound by bus stops dust in Qingyang city, an important energy base on the west side of the Ziwuling primitive Forest.

In this study, we examined the persistent pollutant contents [harmful elements (HEs), cadmium (Cd, 0.1 mg/kg) âˆ¼ barium (Ba, 881.1 mg/kg)] and polycyclic aromatic hydrocarbons [PAHs; Acenaphthylene (Acy), Acenaphthene (Ace), Fluorene (Flu), Benzo(k)fluoranthene (BkF), Benzo(a)pyrene (BaP) (0 mg/kg) âˆ¼ BaP (10.2 mg/kg)] in bus stop dust (BSD) from Qingyang, Northwest China. The Nemerow composite pollution index of the eight types of PAHs and ∑16PAHs indicated severe pollution. The carcinogenic risk of the persistent pollutant in BSD to adults was 1.6 times greater than the acceptable upper limit for the human body, while the noncarcinogenic risk was small to five daily bus passenger groups. Clustering and principal component analysis showed that 12 kinds of HEs were mainly derived from coal and fuel combustion and 16 kinds of PAHs were mainly derived from biomass combustion, organic matter decomposition, and chemical applications.

The role of ST3GAL4 in glioma malignancy, macrophage infiltration, and prognostic outcomes.

Background: Glioma, a prevalent malignancy of the brain and spinal cord, poses a considerable threat to human health. The association between aberrant sialic acid modification and glioma progression has been suggested, but the precise mechanism is still elusive. ST3GAL4, a sialoglycosyltransferase, is implicated in increased metastatic potential and poor prognosis in various cancers; however, its specific role in glioma requires further elucidation. Methods: We evaluated ST3GAL4 expression levels and their clinical relevance using the TCGA database, and we assessed immune infiltration via the Tumor Immune Evaluation Resource (TIMER) database. In vitro experiments were performed to determine the effects of ST3GAL4 knockdown on glioma cell malignancy, with additional co-culture assays to assess its impact on macrophage phenotype. Results: ST3GAL4 expression was markedly elevated in glioma tissues compared to normal brain tissues, with a strong correlation to glioma patient clinical characteristics. Survival analyses and receiver operating characteristic (ROC) curves suggested that ST3GAL4 is a feasible diagnostic and prognostic biomarker for glioma. Knockdown studies revealed that ST3GAL4 inhibition reduces glioma cell line proliferation, migration, and invasion, while causing G1 phase cell cycle arrest. ST3GAL4 appears to mediate glioma progression through extracellular matrix reorganization and EMT signaling pathway activation, further contributing to M2 macrophage polarization and infiltration within the tumor microenvironment. Conclusion: Our research highlights the critical role of ST3GAL4 in glioma development, positioning it as a promising candidate for diagnostic and therapeutic interventions.

Bacterial community analysis of the skin microbiota of cultured Chinese giant salamander infected with Ranavirus.

Skin microorganisms are an important component of host innate immunity and serve as the first line of defense against pathogenic infections. The relative abundance of bacterial species, microbial community assembly, and secretion of specific bacterial metabolites are closely associated with host health. In this study, we investigated the association between the skin microbiome and Ranavirus, and compared the bacterial community assemblage, alpha and beta diversity, and functional predictions of the skin bacterial assemblage in cultured healthy Chinese giant salamanders (Andrias davidianus) and individuals infected with Chinese giant salamander iridovirus (GSIV or ADRV). To achieve this, we employed 16S rRNA amplicon sequencing. The results identified Proteobacteria, Firmicutes, Bacteroidota, and Actinobacteriota as the dominant phyla in the diseased and healthy groups. Alpha diversity analysis indicated that the skin bacterial community in the diseased group exhibited no significant differences in bacterial species diversity and lower species richness compared to the healthy group. Beta diversity suggested that the two group bacterial community was quite different. Kyoto encyclopedia of genes and genomes (KEGG) pathway analyze and clusters of orthologous groups of proteins (COG) function predictions revealed that changes and variations occurred in the metabolic pathways and function distribution of skin bacterial communities in two groups.

Cribiform and intraductal carcinoma in hereditary prostate cancer: clinical and pathological analysis of 20 cases.

Cribiform and intraductal carcinoma are patterns of aggressive prostate carcinoma. This study investigated the clinical and pathological features of hereditary prostate cancer. Twenty cases of hereditary prostate cancer from 11 family lines treated at the First Affiliated Hospital of Zhejiang University School of Medicine between 2016-2022 were included to summarize the clinical and pathological features by analyzing clinical information including follow up the survival of the patients and pathological features. Of the 20 hereditary prostate cancer cases, 19 were radical prostate specimens and 1 was a biopsy specimen. The mean age at diagnosis of the patients was 67.55 years and the mean PSA was 15.44 ng/ml, of which 10 cases had PSA ≥ 10 ng/ml and 5 cases had PSA ≥ 20 ng/ml. Of the 19 radical prostate specimens, Gleason cribriform pattern (Gleason grade 4) of PCa is observed in 15 cases (78.95%), and intraductal carcinoma, usually a rare form, is seen in 9 cases (47.3%). Two cases demonstrated pelvic lymph node metastasis, and 7 cases (35%) belonged to high-risk or very high-risk PCa. One case (5.26%) showed partial deletion of expression of RB1, and 13 cases (68.42%) showed deletion of expression of PTEN. Follow-up was 4-90 months, 2 cases had biochemical recurrence and 1 case died from prostate cancer. The mean age at diagnosis of this group of patients with hereditary prostate cancer was 67.55 years, the mean preoperative PSA was 15.44 ng/ml, and their histomorphology was characterized by a high percentage of intraductal carcinoma and cribriform pattern of the prostate.

Mitochondrial Dysfunction: A Roadmap for Understanding and Tackling Cardiovascular Aging.

Cardiovascular aging is a progressive remodeling process constituting a variety of cellular and molecular alterations that are closely linked to mitochondrial dysfunction. Therefore, gaining a deeper understanding of the changes in mitochondrial function during cardiovascular aging is crucial for preventing cardiovascular diseases. Cardiac aging is accompanied by fibrosis, cardiomyocyte hypertrophy, metabolic changes, and infiltration of immune cells, collectively contributing to the overall remodeling of the heart. Similarly, during vascular aging, there is a profound remodeling of blood vessel structure. These remodeling present damage to endothelial cells, increased vascular stiffness, impaired formation of new blood vessels (angiogenesis), the development of arteriosclerosis, and chronic vascular inflammation. This review underscores the role of mitochondrial dysfunction in cardiac aging, exploring its impact on fibrosis and myocardial alterations, metabolic remodeling, immune response remodeling, as well as in vascular aging in the heart. Additionally, we emphasize the significance of mitochondria-targeted therapies in preventing cardiovascular diseases in the elderly.

Crosstalk among proximal tubular cells, macrophages, and fibroblasts in acute kidney injury: single-cell profiling from the perspective of ferroptosis.

The link between ferroptosis, a form of cell death mediated by iron and acute kidney injury (AKI) is recently gaining widespread attention. However, the mechanism of the crosstalk between cells in the pathogenesis and progression of acute kidney injury remains unexplored. In our research, we performed a non-negative matrix decomposition (NMF) algorithm on acute kidney injury single-cell RNA sequencing data based specifically focusing in ferroptosis-associated genes. Through a combination with pseudo-time analysis, cell-cell interaction analysis and SCENIC analysis, we discovered that proximal tubular cells, macrophages, and fibroblasts all showed associations with ferroptosis in different pathways and at various time. This involvement influenced cellular functions, enhancing cellular communication and activating multiple transcription factors. In addition, analyzing bulk expression profiles and marker genes of newly defined ferroptosis subtypes of cells, we have identified crucial cell subtypes, including Egr1 + PTC-C1, Jun + PTC-C3, Cxcl2 + Mac-C1 and Egr1 + Fib-C1. All these subtypes which were found in AKI mice kidneys and played significantly distinct roles from those of normal mice. Moreover, we verified the differential expression of Egr1, Jun, and Cxcl2 in the IRI mouse model and acute kidney injury human samples. Finally, our research presented a novel analysis of the crosstalk of proximal tubular cells, macrophages and fibroblasts in acute kidney injury targeting ferroptosis, therefore, contributing to better understanding the acute kidney injury pathogenesis, self-repairment and acute kidney injury-chronic kidney disease (AKI-CKD) progression.

Forensic features and phylogenetic structure survey of four populations from southwest China via the autosomal insertion/deletion markers.

Insertion/Deletion (InDel) polymorphisms, characterized by their smaller amplicons, reduced mutation rates, and compatibility with the prevalent capillary electrophoresis (CE) platforms in forensic laboratories, significantly contribute to the advancement and application of genetic analysis. Guizhou province in China serves as an important region for investigating the genetic structure, ethnic group origins, and human evolution. However, DNA data and the sampling of present-day populations are lacking, especially about the InDel markers. Here, we reported data on 47 autosomal InDels from 592 individuals from four populations in Guizhou (Han, Dong, Yi, and Chuanqing). Genotyping was performed with the AGCU InDel 50 kit to evaluate their utility for forensic purposes and to explore the population genetic structure. Our findings showed no significant deviations from Hardy-Weinberg and linkage equilibriums. The combined power of discrimination (CPD) and the combined power of exclusion (CPE) for each population demonstrated that the kit could be applied to forensic individual identification and was an effective supplement for parentage testing. Genetic structure analyses, including principal component analysis, multidimensional scaling, genetic distance calculation, STRUCTURE, and phylogenetic analysis, highlighted that the genetic proximity of the studied populations correlates with linguistic, geographical, and cultural factors. The observed genetic variances within four research populations were less pronounced than those discerned between populations across different regions. Notably, the Guizhou Han, Dong, and Chuanqing populations showed closer genetic affiliations with linguistically similar groups than the Guizhou Yi. These results underscore the potential of InDel markers in forensic science and provide insights into the genetic landscape and human evolution in multi-ethnic regions like Guizhou. Key points: InDel markers show promise for forensic individual identification and parentage testing via the AGCU InDel 50 kit.Genetic analysis of Guizhou populations reveals correlations with linguistic, geographical, and cultural factors.Guizhou Han, Dong, and Chuanqing populations showed closer genetic affiliations with linguistically similar groups than the Guizhou Yi.

Polydopamine-modified black phosphorus nanosheet drug delivery system for the treatment of ischemic stroke.

Black phosphorus (BP), as a representative metal-free semiconductor, has been extensively explored. It has a higher drug loading capacity in comparison to conventional materials and also possesses excellent biocompatibility and biodegradability. Furthermore, BP nanosheets can enhance the permeability of the blood-brain barrier (BBB) upon near-infrared (NIR) irradiation, owing to their photothermal effect. However, the inherent instability of BP poses a significant limitation, highlighting the importance of surface modification to enhance its stability. Ischemic stroke (IS) is caused by the occlusion of blood vessels, and its treatment is challenging due to the hindrance caused by the BBB. Therefore, there is an urgent need to identify improved methods for bypassing the BBB for more efficient IS treatment. This research devised a novel drug delivery approach based on pterostilbene (Pte) supported by BP nanosheets, modified with polydopamine (PDA) to form BP-Pte@PDA. This system shows robust stability and traverses the BBB using effective photothermal mechanisms. This enables the release of Pte upon pH and NIR stimuli, offering potential therapeutic advantages for treating IS. In a middle cerebral artery occlusion mouse model, the BP-Pte@PDA delivery system significantly reduced infarct size, and brain water content, improved neurological deficits, reduced the TLR4 inflammatory factor expression, and inhibited cell apoptosis. In summary, the drug delivery system fabricated in this study thus demonstrated good stability, therapeutic efficacy, and biocompatibility, rendering it suitable for clinical application.