A microenvironment responsive polyetheretherketone implant with antibacterial and osteoimmunomodulatory properties facilitates osseointegration.

Failure of intraosseous prostheses is primarily attributed to implant loosening and infections. Current primary therapeutic modalities, such as antibiotics and local debridement, not only face challenges in thoroughly eliminating obstinate adhered bacteria but also encounter difficulties in ameliorating undue inflammatory reactions and regenerating impaired peri-implant bone tissues. Polyetheretherketone (PEEK) has excellent mechanical and physicochemical characteristics and has been used extensively as a medical biomaterial. However, the limited bactericidal and osseointegrative activities of bioinert PEEK restrict its clinical application. Herein, a microenvironment responsive coating with immobilised immunomodulatory magnesium ions (Mg2+) and disinfectant cerium oxide nanoparticles (CNPs) is designed via ion coordination mediated by polydopamine (PDA) and electrospinning based on collagen structure-bionic silk fibroin (SF). By utilising the pH responsiveness of SF, CNPs exhibit potent antibacterial effects in an acidic environment (pH 5.0) caused by local bacterial infection. Due to the chelation interaction with PDA and the constraint of SF, Mg2+ is slowly released, ameliorating the local immune microenvironment and boosting osteogenesis by upregulating M2 phenotype macrophages. Bioinformatics analysis indicates that the inflammation is suppressed via the NF-κB signaling pathway. Overall, this SF-based coating maximizes the synergistic effect of CNPs and Mg2+, offering enhanced antibacterial and osteoimmunomodulatory bioactivity for successful implantation.

Differential correlations of changes in in vivo neuroimaging markers of hippocampal volume and arteriolosclerosis with declining financial and health literacy in old age.

Financial and health literacy is essential for older adults to navigate complex decision processes in late life. However, the neurobiological basis of age-related decline in financial and health literacy is poorly understood. This study aimed to characterize progression of neurodegenerative and vascular conditions over time, and to assess how these changes coincide with declining financial and health literacy in old age. Data came from 319 community-living older adults who were free of dementia at baseline, and underwent annual literacy assessments, as well as biennial 3-Tesla neuroimaging scans. Financial and health literacy was assessed using a battery of 32 items. Two in vivo neuroimaging markers of neurodegenerative and cerebrovascular conditions were used, i.e., hippocampal volume and the ARTS marker of arteriolosclerosis. A multivariate linear mixed effects model estimated the simultaneous changes in financial and health literacy, hippocampal volume, and the ARTS score. Over a mean of 7 years of follow-up, these older adults experienced a significant decline in financial and health literacy, a significant reduction in hippocampal volume, and a significant progression in ARTS score. Individuals with faster hippocampal atrophy had faster decline in literacy. Similarly, those with faster progression in ARTS also had faster decline in literacy. The correlation between the rates of hippocampal atrophy and declining literacy, however, was stronger than the correlation between the progression of ARTS with declining literacy. These findings suggest that neurodegeneration and, to a lesser extent, cerebrovascular conditions are correlated with declining financial and health literacy in old age.

Safe and potent anti-CD19 CAR T-cells with shRNA-IL-6 gene silencing element in patients with refractory or relapsed B-cell acute lymphoblastic leukemia.

Severe cytokine release syndrome (sCRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) have limited the widespread use of chimeric antigen receptor T (CAR T)-cell therapy. We designed a novel anti-CD19 CAR (ssCART-19) with a small hairpin RNA (shRNA) element to silence the interleukin-6 (IL-6) gene, hypothesizing it could reduce sCRS and ICANS by alleviating monocyte activation and proinflammatory cytokine release. In a post hoc analysis of two clinical trials, we compared ssCART-19 with common CAR T-cells (cCART-19) in relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). Among 87 patients, 47 received ssCART-19 and 40 received cCART-19. Grade ≥3 CRS occurred in 14.89% (7/47) of the ssCART-19 group versus 37.5% (15/40) in the cCART-19 group (p = 0.036). ICANS occurred in 4.26% (2/47) of the ssCART-19 group (all grade 1) compared to 15% (2/40) of the cCART-19 group. Patients in the ssCART-19 group showed comparable rates of treatment response (calculated with rates of complete remission and incomplete hematological recovery) were 91.49% (43/47) for ssCART-19 and 85% (34/40) for cCART-19 (p = 0.999). With a median follow-up of 21.9 months, cumulative nonrelapse mortality was 10.4% for ssCART-19 and 13.6% for cCART-19 (p = 0.33). Median overall survival was 37.17 months for ssCART-19 and 32.93 months for cCART-19 (p = 0.40). Median progression-free survival was 24.17 months for ssCART-19 and 9.33 months for cCART-19 (p = 0.23). These data support the safety and efficacy of ssCART-19 for r/r B-ALL, suggesting its potential as a promising therapy.

Modification Strategies and Prospects for Enhancing the Stability of Black Phosphorus.

Black phosphorus is a two-dimensional layer material with promising applications due to its many excellent physicochemical properties, including high carrier mobility, ambipolar field effect and unusual in-plane anisotropy. Currently, BP has been widely used in biomedical engineering, photocatalysis, semiconductor devices, and energy storage electrode materials. However, the unique structure of BP makes it highly chemically active, leading to its easy oxidation and degradation in air, which limits its practical applications. Recently, researchers have proposed a number of initiatives that can address the environmental instability of BP, and the application of these physical and chemical passivation techniques can effectively enhance the environmental stability of BP, including four modification methods: covalent functionalization, non-covalent functionalization, surface coordination, physical encapsulation and edge passivation. This review highlights the mechanisms of the above modification techniques in addressing the severe instability of BP in different application scenarios, as well as the advantages and disadvantages of each method. This review can provide guidance for more researchers in studying the marvellous properties of BP and accelerate the practical application of BP in different fields.

Application of a single-cell-RNA-based biological-inspired graph neural network in diagnosis of primary liver tumors.

Single-cell technology depicts integrated tumor profiles including both tumor cells and tumor microenvironments, which theoretically enables more robust diagnosis than traditional diagnostic standards based on only pathology. However, the inherent challenges of single-cell RNA sequencing (scRNA-seq) data, such as high dimensionality, low signal-to-noise ratio (SNR), sparse and non-Euclidean nature, pose significant obstacles for traditional diagnostic approaches. The diagnostic value of single-cell technology has been largely unexplored despite the potential advantages. Here, we present a graph neural network-based framework tailored for molecular diagnosis of primary liver tumors using scRNA-seq data. Our approach capitalizes on the biological plausibility inherent in the intercellular communication networks within tumor samples. By integrating pathway activation features within cell clusters and modeling unidirectional inter-cellular communication, we achieve robust discrimination between malignant tumors (including hepatocellular carcinoma, HCC, and intrahepatic cholangiocarcinoma, iCCA) and benign tumors (focal nodular hyperplasia, FNH) by scRNA data of all tissue cells and immunocytes only. The efficacy to distinguish iCCA from HCC was further validated on public datasets. Through extending the application of high-throughput scRNA-seq data into diagnosis approaches focusing on integrated tumor microenvironment profiles rather than a few tumor markers, this framework also sheds light on minimal-invasive diagnostic methods based on migrating/circulating immunocytes.

Collaborative Effect of Matrix Metalloproteinases on Type I Collagen Degradation and Muscle Softening in Sea Bass (Lateolabrax japonicus) during Cold Storage.

Matrix metalloproteinases (MMPs) play critical roles in the degradation of collagens, while their mechanism remains unclear. In the present study, the involvement of matrix metalloproteinases (MMPs) in collagen degradation of sea bass muscle during cold storage was explored. Immunohistochemical staining results showed significant degradation of type I collagen in the connective tissue of muscle endomysium during cold storage, thus affecting the muscle structural integrity and quality. Western blot analysis revealed an increment in the α1 chain and a decrease in the ß and γ chains of type I collagen. Immunofluorescence staining showed that MMP-2, MMP-9, and MMP-13 were distributed in the endomysium surrounding the muscle fibers. Additionally, the catalytic domains of MMP-2, MMP-9, and MMP-13 with biological activities were successfully expressed. The degradation trend of type I collagen by MMPs under 4 °C was similar to that of muscle collagen during cold storage, suggesting that the degradation of type I collagen was attributed to the cooperative action of the MMPs. In conclusion, our study elucidated that the MMPs-engaged degradation of type I collagen is quite possibly the leading cause of sea bass muscle softening during cold storage.

Distinction of papillary and adamantinomatous craniopharyngioma: Clinical features, surgical nuances and hypothalamic outcomes.

OBJECTIVE: Understanding the differences of suprasellar papillary and adamantinomatous craniopharyngiomas (PCPs/ACPs) is pivotal for target therapy, surgical strategy or postoperative management. Here, the clinical features, surgical nuances and postoperative hypothalamic outcomes of PCPs were systematically recapitulated. METHODS: 24 PCPs and 52 ACPs underwent initial surgery were retrospectively reviewed. Clinical data, quantified third ventricle (3rd V) occupation and optic chiasm distortion were compared, as well as intra-operative findings, operating notes and prognosis. Moreover, analysis of tumor/3rd V relationship and hypothalamic outcomes were also performed. RESULTS: Tumors were more likely to occupies the 3rd V cavity in PCPs. Chiasm distortion of "compressed forward" was the most common pattern (45.8 %) in PCPs, whereas "stretched forward" pattern accounted the highest (42.5 %) in ACPs. Besides, round-shaped with less calcification, duct-like recess, solid consistency, rare subdiaphragmatic invasion, visible lower stalk and improved postoperative visual outcome were more frequently observed in PCPs. The basal membranes of the tumor epithelium and the reactive gliosis were separated by a layer of collagen fibers in most PCPs, which differs from ACPs in the morphological examination of tumor/3rd V floor interface. In daytime sleepiness and memory difficulty, the PCPs showed significantly better outcomes than the ACPs groups, and PCPs suffered less postoperative weight gain (p < 0.05) than ACPs among adult-onset cases. CONCLUSION: PCPs are different from ACPs regards the clinical features, operative techniques and outcomes. If necessary, PCPs are suggested more amenable to total removal since its less invasiveness to the 3rd V floor and better hypothalamic outcomes.

Cellular senescence: A new perspective on the suppression of periodontitis (Review).

Cellular senescence, characterized by cell cycle arrest, can result in tissue dysfunction when senescent cells persist and accumulate. Periodontitis, a chronic inflammatory condition caused by the interaction between bacteria and the immune system of the host, primarily manifests as damage to periodontal tissues. Aging and inflammation are interlinked processes that exacerbate each other. The progression of localized chronic periodontal inflammation is often accelerated in conjunction with tissue and organ aging. The presence of senescent cells and release of inflammatory cytokines, immune modulators, growth factors and proteases that are associated with the senescence­associated secretory phenotype contribute to the deterioration of periodontal tissues. The present review aimed to elucidate the mechanisms of cellular senescence and its potential impact on periodontitis, offering novel insights for modulating the inflammatory microenvironment of periodontal tissues.

Unveiling the impact of nitrogen deficiency on alkaloid synthesis in konjac corms (Amorphophallus muelleri Blume).

BACKGROUND: Konjac corms are known for their alkaloid content, which possesses pharmacological properties. In the primary cultivation areas of konjac, nitrogen deficiency is a common problem that significantly influences alkaloid synthesis. The impact of nitrogen deficiency on the alkaloids in konjac corms remains unclear, further complicated by the transition from mother to daughter corms during their growth cycle. RESULTS: This study examined 21 alkaloids, including eight indole alkaloids, five isoquinoline alkaloids, and eight other types of alkaloids, along with the associated gene expressions throughout the development of Amorphophallus muelleri Blume under varying nitrogen levels. Nitrogen deficiency significantly reduced corm diameter and fresh weight and delayed the transformation process. Under low nitrogen conditions, the content of indole alkaloids and the expression of genes involved in their biosynthesis, such as tryptophan synthase (TRP) and tryptophan decarboxylase (TDC), exhibited a substantial increase in daughter corms, with fold changes of 61.99 and 19.31, respectively. Conversely, in the mother corm, TDC expression was markedly reduced, showing only 0.04 times the expression level observed under 10 N treatment. The patterns of isoquinoline alkaloid accumulation in corms subjected to nitrogen deficiency were notably distinct from those observed for indole alkaloids. The accumulation of isoquinoline alkaloids was significantly higher in mother corms, with expression levels of aspartate aminotransferase (GOT), chorismate mutase (CM), tyrosine aminotransferase (TAT), and pyruvate decarboxylase (PD) being 4.30, 2.89, 921.18, and 191.40 times greater, respectively. Conversely, in daughter corms, the expression levels of GOT and CM in the 0 N treatment were markedly lower (0.01 and 0.83, respectively) compared to the 10 N treatment. CONCLUSIONS: The study suggests that under nitrogen deficiency, daughter corms preferentially convert chorismate into tryptophan to synthesize indole alkaloids, while mother corms convert it into tyrosine, boosting the production of isoquinoline alkaloids. This research provides valuable insights into the mechanisms of alkaloid biosynthesis in A. muelleri and can aid in developing nitrogen fertilization strategies and in the extraction and utilization of alkaloids.

Event-Assisted Blurriness Representation Learning for Blurry Image Unfolding.

The goal of blurry image deblurring and unfolding task is to recover a single sharp frame or a sequence from a blurry one. Recently, its performance is greatly improved with introduction of a bio-inspired visual sensor, event camera. Most existing event-assisted deblurring methods focus on the design of powerful network architectures and effective training strategy, while ignoring the role of blur modeling in removing various blur in dynamic scenes. In this work, we propose to implicitly model blur in an image by computing blurriness representation with an event-assisted blurriness encoder. The learning of blurriness representation is formulated as a ranking problem based on specially synthesized pairs. Blurriness-aware image unfolding is achieved by integrating blur relevant information contained in the representation into a base unfolding network. The integration is mainly realized by the proposed blurriness-guided modulation and multi-scale aggregation modules. Experiments on GOPRO and HQF datasets show favorable performance of the proposed method against state-of-the-art approaches. More results on real-world data validate its effectiveness in recovering a sequence of latent sharp frames from a blurry image.

TR4 and BCL11A Repress γ-globin Transcription via Independent Mechanisms.

Nuclear receptor TR4 was previously shown to bind to the -117 position of the -globin gene promoters in vitro, which overlaps the more recently described BCL11A binding site. The role of TR4 in human -globin gene repression has not been extensively characterized in vivo, while any relationship between TR4 and BCL11A regulation through the -globin promoters is unclear at present. We show here that TR4 and BCL11A competitively bind in vitro to distinct, overlapping sequences, including positions overlapping -117 of the -globin promoter. We found that TR4 represses -globin transcription and HbF accumulation in vivo in a BCL11A-independent manner. Finally, examination of the chromatin occupancy of TR4 within the -globin locus, when compared to BCL11A, shows that both bind avidly to the locus control region and other sites, but that only BCL11A binds to the -globin promoters at statistically significant frequency. These data resolve an important discrepancy in the literature, and thus clarify possible approaches to the treatment of sickle cell disease and -thalassaemia.

A single-dose circular RNA vaccine prevents Zika virus infection without enhancing dengue severity in mice.

Antibody-dependent enhancement (ADE) is a potential concern for the development of Zika virus (ZIKV) vaccines. Cross-reactive but poorly neutralizing antibodies, usually targeting viral pre-membrane or envelope (E) proteins, can potentially enhance dengue virus (DENV) infection. Although E domain III (EDIII) contains ZIKV-specific epitopes, its immunogenicity is poor. Here, we show that dimeric EDIII, fused to human IgG1 Fc fragment (EDIII-Fc) and encoded by circular RNA (circRNA), induces better germinal center reactions and higher neutralizing antibodies compared to circRNAs encoding monomeric or trimeric EDIII. Two doses of circRNAs encoding EDIII-Fc and ZIKV nonstructural protein NS1, another protective antigen, prevent lethal ZIKV infection in neonates born to immunized C57BL/6 mice and in interferon-α/ß receptor knockout adult C57BL/6 mice. Importantly, a single-dose optimized circRNA vaccine with improved antigen expression confers potent and durable protection without inducing obvious DENV ADE in mice, laying the groundwork for developing flavivirus vaccines based on circRNAs encoding EDIII-Fc and NS1.

Visual and fluorescent detection of Moraxella catarrhalis by multiple cross displacement amplification-based assay.

Moraxella catarrhalis (M. catarrhalis), once considered as a harmless commensal bacterium, is now recognized as a significant pathogen associated with human mucosal infection. Hence, development of rapid, accurate, and user-friendly detection method is crucial for effective control and management of M. catarrhalis infections. Here, we introduce the M. catarrhalis MCDA-FRT assay, a novel diagnostic approach based on multiple cross displacement amplification (MCDA) for the visual and fluorescent (FRT) detection of M. catarrhalis. This innovative method amplifies the target sequence through MCDA reaction and provides results through the visual observation of a fluorescent signal when exposed to blue light. The generation of the fluorescent signal is facilitated by the cleavage of the restriction endonuclease Nb.BsrDⅠ. The M. catarrhalis MCDA-FRT assay can efficiently detect M. catarrhalis at a temperature of 65 °C in 40 min. It exhibits a remarkable sensitivity of 35 fg of M. catarrhalis genomic DNA, with a specificity of 100%. Furthermore, the assay accurately identified all M. catarrhalis-infected clinical samples tested. In conclusion, the M. catarrhalis MCDA-FRT assay showcases outstanding performance in terms of simplicity, sensitivity, and specificity, which can be used as a promising diagnostic tool for the swift and reliable detection of M. catarrhalis in both field and basic medical settings.

Genome-wide identification and expression analysis of SlKFB gene family (Solanum lycopersicum) and the molecular mechanism of SlKFB16 and SlKFB34 under drought.

Environmental stress significantly affects plant growth and productivity. The effects of drought stress on plants are reflected primarily in enzyme activity, membrane systems, and cell-water loss. Here, the Kelch repeat F-box (KFB) protein family in tomato was systematically identified and analysed. Using bioinformatics, we identified 37 SlKFB family members in the tomato genome and analysed their protein structure, phylogenetic relationships, chromosome distribution, and expression under drought or biotic-stress conditions. Transcriptome data revealed that SlKFB members exhibit differential responses to drought stress, with significant differences in SlKFB16 and SlKFB34 expression. Functional analysis revealed that SlKFB16 functions in the cytoplasm and SlKFB34 in the nucleus and cytoplasm. Under drought stress, SlKFB16 and SlKFB34-silencing significantly reduced reactive oxygen species scavenging and resistance to drought stress. These findings provide a reference for further studies of the mechanisms of SlKFB16 and SlKFB34 in drought stress in tomato as well as a foundation for enhancing their resistance to drought stress.

Associations between structural neuroimaging markers of Alzheimer's risk and scam susceptibility.

Older adults with greater scam susceptibility are at greater risk for mild cognitive impairment and incident Alzheimer's dementia, regardless of baseline cognition. This, combined with documented associations between scam susceptibility and beta amyloid at death suggests that scam susceptibility may be an earlier indicator of pathological aging than cognition. Little, however, is known about whether in vivo neuroimaging markers of early-stage risk for Alzheimer's dementia are also related to scam susceptibility; such knowledge will inform upon the associations of neurodegenerative processes with scam susceptibility and may help identify vulnerable individuals. Participants were 472 community-based adults without dementia (age ~ 81y; 75% women) from the Rush Memory and Aging Project. Baseline 3T MRI T1-weighted structural and T2-weighted FLAIR data were used to assess the cortical thickness 'signature' of Alzheimer's disease (AD-CT) and white matter hyperintensity (WMH) burden, respectively. Scam susceptibility was measured using a questionnaire that assessed behaviors associated with vulnerability to fraud and scams. Demographically-adjusted linear effects regression models determined the relationship of each neuroimaging measure, first separately and then combined, with scam susceptibility. Reduced AD-CT was associated with higher levels of scam susceptibility (estimate=-0.10, standard error = 0.03, p = 0.002). WMH burden was not associated with scam susceptibility either alone or when combined in the same model as AD-CT (p-values ≥ 0.14). Results for AD-CT persisted after the inclusion of WMH burden. AD-CT was associated with scam susceptibility in older adults without dementia possibly signaling an in vivo profile of this behavior.

The evaluation of next-generation probiotics on broiler growth performance, gut morphology, gut microbiome, nutrient digestibility, in addition to enzyme production of Bacillus spp. in vitro.

Considerable research has been conducted into the efficacy of individual probiotics in broiler production, however information on the most effective combinations of synergistic Bacillus probiotic is lacking. This study investigated the impact of different Bacillus strain combinations in broiler chickens, as well as in vitro enzyme production. In experiment one, a total of 576 Ross 308 broilers at 1 d old were grown for 21 d across 6 treatments of maize-soybean diets (n = 12 pens per treatment) to compare three different strain combinations (formulation 1 [F1]: 3 strains Bacillus amyloliquefaciens; F2: Bacillus coagulans and 2 strains B. amyloliquefaciens; F3: B. coagulans, Bacillus licheniformis and 2 strains B. amyloliquefaciens; F5: Bacillus subtilis, B. licheniformis and 2 strains B. amyloliquefaciens), positive control (PC), and a negative control antibiotic treatment group (NC). In Exp. 2, a total of 360 one-day-old ROSS308 broilers were used to test five treatments (n = 9) including PC, NC, F1 and F5 (selected from Exp. 1), and F4 (Bacillus pumilis and 2 strains B. amyloliquefaciens) in a maize-soybean diet. B. amyloliquefaciens F1 demonstrated a significant improvement in feed conversion ratio (FCR) compared to F2 at d 14 (1.49 vs 2.10; P = 0.038) and the body weight (BW) at d 21 (847.0 g vs 787.4 g) compared to other combinations (P = 0.027). The FCR at d 21 tended to be lower in birds fed F1 (1.46 vs 1.66) compared to the control (P = 0.068). Probiotic treatments had significantly improved nutrient digestibility compared to the PC and NC. Also, probiotic treatments supported the growth of Streptococcus, a common commensal genus and reduced the abundance of genera that correlated with low weight gain such as Akkermansia. Experiment two revealed that F4 improved FCR (P < 0.001) and BW at 28 d (P = 0.014). In vitro testing showed a high production of protease and amylase by Bacillus. Thus, the addition of Bacillus probiotics, particularly containing B. amyloliquefaciens strains and Bacillus pumilus, into the diet of broiler chickens improves production performance, nutrient digestibility, and allows the proliferation of beneficial gut microbiota.

Enhanced Nitric Oxide Delivery Through Self-Assembling Nanoparticles for Eradicating Gram-Negative Bacteria.

In the current battle against antibiotic resistance, the resilience of Gram-negative bacteria against traditional antibiotics is due not only to their protective outer membranes but also to mechanisms like efflux pumps and enzymatic degradation of drugs, underscores the urgent need for innovative antimicrobial tactics. Herein, this study presents an innovative method involving the synthesis of three furoxan derivatives engineered to self-assemble into nitric oxide (NO) donor nanoparticles (FuNPs). These FuNPs, notably supplied together with polymyxin B (PMB), achieve markedly enhanced bactericidal efficacy against a wide spectrum of bacterial phenotypes at considerably lower NO concentrations (0.1-2.8 µg mL-1), which is at least ten times lower than the reported data for NO donors (≥200 µg mL-1). The bactericidal mechanism is elucidated using confocal, scanning, and transmission electron microscopy techniques. Neutron reflectometry confirms that FuNPs initiate membrane disruption by specifically engaging with the polysaccharides on bacterial surfaces, causing structural perturbations. Subsequently, PMB binds to lipid A on the outer membrane, enhancing permeability and resulting in a synergistic bactericidal action with FuNPs. This pioneering strategy underscores the utility of self-assembly in NO delivery as a groundbreaking paradigm to circumvent traditional antibiotic resistance barriers, marking a significant leap forward in the development of next-generation antimicrobial agents.

Ecological risk threshold for chromium in Chinese soils and its prediction models.

The derivation of chromium (Cr) ecological risk thresholds in soils remains limited, despite their importance as measurement standards and indicators for enacting soil protection policies. In this study, toxicity of Cr in soil to different species was tested based on Log-Logistic dose-effect relationship. On this basis, combined with Cr toxicity measurement data in literature, the ecological risk threshold HC5 for protecting 95% species safety in soils with different properties was obtained by fitting species sensitivity distribution curve (SSD). This research collected various Cr toxicological data from Chinese cropland soils, based on 31 different endpoints covering soil fauna, functional indicators of microorganisms, terrestrial plants, etc., sourced from both our laboratory and existing literature. We applied the SSD method to estimate the hazardous concentration of Cr for HC5 and ultimately established a predictive model according to HC5 and different soil properties. As a result, the EC10 (an effective concentration of Cr resulting in 10% suppression of terminal biological activity) based on 7 different soils and 4 endpoints ranged from 16.8 to 148.0 mg kg-1, and the hormesis of Cr induction reached up to 109%. Overall, the toxicity (EC10) to microorganisms was much lower, while it was higher for graminoids. All the toxicity data were corrected through an aging factor with up to 540 days of equilibration before fitting the SSD curves. After that, a prediction model considering HC5 values and soil properties was established as LogHC5 = 3.003LogpH +0.651LogOC +0.013LogCEC - 0.476. The model was well-verified in field experiments, as the actual and predicted values fell within a 2-fold error range. This approach offers a rigorous scientific foundation for determining the Cr ecological risk threshold and could be important for the conservation of ecological species in soils.

Proteogenomic Identification and Analysis of KIF5B as a Prognostic Signature for Hepatocellular Carcinoma.

BACKGROUND: Metabolic disorders are significant risk factors for liver cancer, particularly Hepatocellular Carcinoma (HCC). However, the molecular genetic basis of metabolic reprogramming in the liver remains largely uncertain. OBJECTIVE: This study aimed to investigate some novel prognostic biomarkers in HCC by using proteogenomic and transcriptomic analysis and explore the potential role of specific prognostic genes in HCC. METHODS: Here, we have presented a proteogenomic analysis of 10 pairs of HCC. Protein co-expression and pathway analysis were performed to investigate the biological characteristics of HCC. Protein and mRNA expression profiles of multi-cohorts were integrated to detect novel prognostic protein markers of HCC. The carcinogenic roles of candidate prognostic markers were further evaluated by MTS assay, colony formation, monolayer wound healing assay, and xenograft models. RESULTS: A total of 2086 proteins with significantly different expressions were detected in HCC. Pathways related to oncogenic signaling and insulin-related metabolism have been found to be dysregulated and differentially regulated in HCC. We have identified the novel prognostic biomarkers, KIF5B, involved in liver metabolic reprogramming. The biomarkers were identified using multivariable COX regression analysis from two independent proteomic datasets (Fudan Cohort and our recruited cohort) and the TCGA mRNA database. Both the protein and mRNA up-regulation of KIF5B have been found to be associated with a poor clinical outcome in HCC. Insulin activated the protein expression of KIF5B in HCC. Knocking out KIF5B expression by sgRNA decreased the protein expression of FASN and SCD1 and the intracellular triglyceride concentration. Silencing KIF5B suppressed HCC cell proliferation and colony formation in vitro, as well as HCC growth in xenograft models. CONCLUSION: Our findings have suggested KIF5B protein to function as a novel prognostic biomarker in HCC. KIF5B expression has been found to activate the AKT/mTOR pathway and reprogram triglyceride metabolism, leading to HCC development. Targeting KIF5B may be an effective strategy in the clinical treatment of HCC.

Analysis of contributing factors and nursing interventions for postoperative agitation following general anesthesia in thoracotomy patients.

To analyze the factors influencing agitation during emergence from general anesthesia in patients undergoing thoracotomy and to explore corresponding nursing interventions to optimize the postoperative recovery process. This study included 200 patients who underwent thoracotomy with general anesthesia at our hospital between January 12, 2022, and June 1, 2023. After surgery, all patients were closely monitored in the Intensive Care Unit (ICU). Based on their agitation status during emergence from anesthesia, patients were divided into 2 groups: an observation group (87 cases with agitation) and a control group (113 cases without agitation). We performed univariate analysis and multivariate logistic regression to identify risk factors for agitation. Based on these findings, we proposed targeted nursing strategies to address the causes of agitation, prevent complications, and meet patient care needs. Univariate analysis showed significant differences between the observation and control groups regarding age, propofol dosage, duration of surgery, infusion volume, and preoperative cognitive dysfunction (P < .05). Multivariate logistic regression identified 3 key risk factors: age over 60 years, surgery duration over 2 hours, and preoperative cognitive dysfunction. Based on these findings, we developed targeted nursing strategies to reduce the incidence of agitation and promote smooth recovery. Agitation during emergence from general anesthesia in patients undergoing thoracotomy is closely related to factors such as age and surgery duration. Developing personalized nursing plans based on these factors can enhance postoperative monitoring and care, thereby reducing agitation and improving recovery quality.