Liver stiffness in hepatocellular carcinoma and chronic hepatitis patients: Hepatitis B virus infection and transaminases should be considered.

BACKGROUND: Liver condition is a crucial prognostic factor for patients with hepatocellular carcinoma (HCC), but a convenient and comprehensive method to assess liver condition is lacking. Liver stiffness (LS) measured by two-dimensional shear wave elastography may help in assessing liver fibrosis and liver condition. Chronic hepatitis B (CHB) is an important risk factor for HCC progression, but LS was found to be less reliable in assessing liver fibrosis following hepatitis viral eradication. We hypothesize that the status of hepatitis virus infection would affect the accuracy of LS in assessing the liver condition. AIM: To test the feasibility and impact factors of using LS to assess liver condition in patients with HCC and CHB. METHODS: A total of 284 patients were retrospectively recruited and classified into two groups on the basis of serum CHB virus hepatitis B virus (HBV)-DNA levels [HBV-DNA ≥ 100.00 IU/mL as Pos group (n = 200) and < 100.00 IU/mL as Neg group (n = 84)]. Correlation analyses and receiver operating characteristic analyses were conducted to evaluate the relationship between LS and liver condition. RESULTS: A significant correlation was found between LS and most of the parameters considered to have the ability to evaluate liver condition (P < 0.05). When alanine aminotransferase (ALT) concentrations were normal (≤ 40 U/L), LS was correlated with liver condition indices (P < 0.05), but the optimal cutoff of LS to identify a Child-Pugh score of 5 was higher in the Neg group (9.30 kPa) than the Pos group (7.40 kPa). When ALT levels were elevated (> 40 U/L), the correlations between LS and liver condition indices were not significant (P > 0.05). CONCLUSION: LS was significantly correlated with most liver condition indices in patients with CHB and HCC. However, these correlations varied according to differences in HBV-DNA and transaminase concentrations.

Ultrasomics in liver cancer: Developing a radiomics model for differentiating intrahepatic cholangiocarcinoma from hepatocellular carcinoma using contrast-enhanced ultrasound.

BACKGROUND: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) represent the predominant histological types of primary liver cancer, comprising over 99% of cases. Given their differing biological behaviors, prognoses, and treatment strategies, accurately differentiating between HCC and ICC is crucial for effective clinical management. Radiomics, an emerging image processing technology, can automatically extract various quantitative image features that may elude the human eye. Reports on the application of ultrasound (US)-based radiomics methods in distinguishing HCC from ICC are limited. AIM: To develop and validate an ultrasomics model to accurately differentiate between HCC and ICC. METHODS: In our retrospective study, we included a total of 280 patients who were diagnosed with ICC (n = 140) and HCC (n = 140) between 1999 and 2019. These patients were divided into training (n = 224) and testing (n = 56) groups for analysis. US images and relevant clinical characteristics were collected. We utilized the XGBoost method to extract and select radiomics features and further employed a random forest algorithm to establish ultrasomics models. We compared the diagnostic performances of these ultrasomics models with that of radiologists. RESULTS: Four distinct ultrasomics models were constructed, with the number of selected features varying between models: 13 features for the US model; 15 for the contrast-enhanced ultrasound (CEUS) model; 13 for the combined US + CEUS model; and 21 for the US + CEUS + clinical data model. The US + CEUS + clinical data model yielded the highest area under the receiver operating characteristic curve (AUC) among all models, achieving an AUC of 0.973 in the validation cohort and 0.971 in the test cohort. This performance exceeded even the most experienced radiologist (AUC = 0.964). The AUC for the US + CEUS model (training cohort AUC = 0.964, test cohort AUC = 0.955) was significantly higher than that of the US model alone (training cohort AUC = 0.822, test cohort AUC = 0.816). This finding underscored the significant benefit of incorporating CEUS information in accurately distinguishing ICC from HCC. CONCLUSION: We developed a radiomics diagnostic model based on CEUS images capable of quickly distinguishing HCC from ICC, which outperformed experienced radiologists.

Exploring the Role of Ubiquitin-Proteasome System in the Pathogenesis of Parkinson's Disease.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder among the elderly population. The pathogenesis of PD encompasses genetic alterations, environmental factors, and age-related neurodegenerative processes. Numerous studies have demonstrated that aberrant functioning of the ubiquitin-proteasome system (UPS) plays a crucial role in the initiation and progression of PD. Notably, E3 ubiquitin ligases serve as pivotal components determining substrate specificity within UPS and are intimately associated with the regulation of various proteins implicated in PD pathology. This review comprehensively summarizes the mechanisms by which E3 ubiquitin ligases and deubiquitinating enzymes modulate PD-associated proteins and signaling pathways, while exploring the intricate relationship between UPS dysfunctions and PD etiology. Furthermore, this article discusses recent research advancements regarding inhibitors targeting PD-related E3 ubiquitin ligases.

Molecular Characterization of High and Low Virulent Escherichia coli Clinical Strains Isolated from Patients with Urinary Tract Infections with or without Bacteremia in Southern Taiwan.

Objective: The most common extraintestinal pathogen and infection site is uropathogenic Escherichia coli (UPEC), which causes urinary tract infections (UTIs). UPEC is also a common pathogen in bloodstream infections; in severe cases, it can lead to death. Although host and bacterial virulence factors have been demonstrated to be associated with UTI pathogenesis, the role of the related contributing factors in UTI and urinary source bacteremia is not yet fully understood. This study aimed to compare and analyze the factors contributing to urinary bacteremia in patients with UTI. Methods: A total of 171 E. coli strains collected from patients with UTI and urinary source bacteremia at Chiayi Christian Hospital were used. Phylogenetic groups and virulence factors were determined using PCR. Drug resistance patterns were determined using the disk diffusion assay. Results: Previous studies have demonstrated that fimbriae and papGII may be associated with first-step infections and severe UTIs, respectively. As expected, highly virulent E. coli strains (belonging to the phylogenetic B2 and D groups) were dominant in the bacteremic UTI (90%) and UTI (86.27%) groups. However, our results showed that the UTI group had a significantly higher prevalence of sfa/focDE (belonging to the S and FIC fimbriae) than the bacteremic UTI group (29.4% vs 12.5%; p=0.008). In the bacteremic group, we found that sfa/focDE was only detected in highly virulent strains. The bacteremic UTI group had a significantly higher prevalence of papGII (belonging to P fimbriae) than the UTI group (55.8% vs 37.3%; p=0.026). In addition, the P fimbriae gene cluster, including papC, papEF, and papGII, was predominant in highly virulent strains. Notably, our results show that multidrug-resistant (MDR) strains were significantly less virulent than non MDR strains. Conclusion: Taken together, our results provide insights into the contributing factors in patients with UTI and urinary bacteremia.

Biosynthesis Progress of High-Energy-Density Liquid Fuels Derived from Terpenes.

High-energy-density liquid fuels (HED fuels) are essential for volume-limited aerospace vehicles and could serve as energetic additives for conventional fuels. Terpene-derived HED biofuel is an important research field for green fuel synthesis. The direct extraction of terpenes from natural plants is environmentally unfriendly and costly. Designing efficient synthetic pathways in microorganisms to achieve high yields of terpenes shows great potential for the application of terpene-derived fuels. This review provides an overview of the current research progress of terpene-derived HED fuels, surveying terpene fuel properties and the current status of biosynthesis. Additionally, we systematically summarize the engineering strategies for biosynthesizing terpenes, including mining and engineering terpene synthases, optimizing metabolic pathways and cell-level optimization, such as the subcellular localization of terpene synthesis and adaptive evolution. This article will be helpful in providing insight into better developing terpene-derived HED fuels.

BCLAF1 binds SPOP to stabilize PD-L1 and promotes the development and immune escape of hepatocellular carcinoma.

Interaction between programmed death-1 (PD-1) ligand 1 (PD-L1) on tumor cells and PD-1 on T cells allows tumor cells to evade T cell-mediated immune surveillance. Strategies targeting PD-1/PD-L1 have shown clinical benefits in a variety of cancers. However, limited response rates in hepatocellular carcinoma (HCC) have prompted us to investigate the molecular regulation of PD-L1. Here, we identify B cell lymphoma-2-associated transcription factor 1 (BCLAF1) as a key PD-L1 regulator in HCC. Specifically, BCLAF1 interacts with SPOP, an E3 ligase that mediates the ubiquitination and degradation of PD-L1, thereby competitively inhibiting SPOP-PD-L1 interaction and subsequent ubiquitination and degradation of PD-L1. Furthermore, we determined an SPOP-binding consensus (SBC) motif mediating the BCLAF1-SPOP interaction on BCLAF1 protein and mutation of BCLAF1-SBC motif disrupts the regulation of the SPOP-PD-L1 axis. In addition, BCLAF1 expression was positively correlated with PD-L1 expression and negatively correlated with biomarkers of T cell activation, including CD3 and CD8, as well as with the level of immune cell infiltration in HCC tissues. Besides, BCLAF1 depletion leads to a significant reduction of PD-L1 expression in vitro, and this reduction of PD-L1 promoted T cell-mediated cytotoxicity. Notably, overexpression of BCLAF1 sensitized tumor cells to checkpoint therapy in an in vitro HCC cells-Jurkat cells co-culture model, whereas BCLAF1-SBC mutant decreased tumor cell sensitivity to checkpoint therapy, suggesting that BCLAF1 and its SBC motif serve as a novel therapeutic target for enhancing anti-tumor immunity in HCC.

Discovery of new dibenzodiazepine derivatives as antibacterials against intracellular bacteria.

The emergence and spread of multidrug-resistant bacteria underscore the critical need for novel antibacterial interventions. In our screening of 12 synthesized thienobenzodiazepines, pyridobenzodiazepines, and dibenzodiazepines, we successfully identified a small molecule compound SW33. Notably, SW33 demonstrated potent inhibitory activity against intracellular multidrug-resistant and fluoroquinolone-resistant strains of S. typhimurium in both macrophages and epithelial cells. Furthermore, SW33 was also effective against intramacrophagic Salmonella typhi, Yersinia enterocolitica, and Listeria monocytogenes. These significant findings suggest that SW33 possesses broad-spectrum activity against intracellular bacteria.

The electronic structure of the active center of Co3Se4 electrocatalyst was adjusted by Te doping for efficient oxygen evolution.

In order to enhance the energy efficiency of water electrolysis, it is imperative to devise electrocatalysts for oxygen evolution reaction that are both non-precious metal-based and highly efficient. Efficient catalyst design is generally based on electronic structural engineering. Considering the electronegativity disparity between selenium (Se) and tellurium (Te), the tunable bandgaps, and the conductive metallic nature of Te. We designed a material wherein Te atoms are uniformly doped onto the surface of Cobalt tetra selenide (Co3Se4) nanorods, leading to the synthesis of a defect-rich material. Experimental results demonstrate that Te doping in Co3Se4 increases active sites and optimizes the electronic structure of Co cations, enhancing the design of multi-defect structures. This promotes the generation of the Co(oxy) hydroxide (CoOOH) active phase, enhancing catalytic activity by maximizing the binding strength between Co sites and oxygenated intermediates. Te-Co3Se4 nanorods exhibit good catalytic activity for oxygen evolution reactions, with an overpotential of 269 mV at a driving current density of 50 mA cm-2 and excellent stability in alkaline media (over 100 h). This discovery indicates the feasibility of strategically combining various imperfect structures, thereby unlocking the latent potential of diverse catalysts in electrocatalytic reactions.

MePP2C24, a cassava (Manihot esculenta) gene encoding protein phosphatase 2C, negatively regulates drought stress and abscisic acid responses in transgenic Arabidopsis thaliana.

Abscisic acid (ABA) signaling plays a crucial role in plant development and response to abiotic/biotic stress. However, the function and regulation of protein phosphatase 2C (PP2C), a key component of abscisic acid signaling, under abiotic stress are still unknown in cassava, a drought-tolerant crop. In this study, a cassava PP2C gene (MePP2C24) was cloned and characterized. The MePP2C24 transcripts increased in response to mannitol, NaCl, and ABA. Overexpression of MePP2C24 in Arabidopsis resulted in increased sensitivity to drought stress and decreased sensitivity to exogenous ABA. This was demonstrated by transgenic lines having higher levels of malondialdehyde (MDA), ion leakage (IL), and reactive oxygen species (ROS), lower activities of catalase (CAT) and peroxidase (POD), and lower proline content than wild type (WT) under drought stress. Moreover, MePP2C24 overexpression caused decrease in expression of drought-responsive genes related to ABA signaling pathway. In addition, MePP2C24 was localized in the cell nucleus and showed self-activation. Furthermore, many MePYLs (MePYL1, MePYL4, MePYL7-9, and MePYL11-13) could interact with MePP2C24 in the presence of ABA, and MePYL1 interacted with MePP2C24 in both the presence and absence of ABA. Additionally, MebZIP11 interacted with the promoter of MePP2C24 and exerted a suppressive effect. Taken together, our results suggest that MePP2C24 acts as a negative regulator of drought tolerance and ABA response.

Application of metagenomic next-generation sequencing in prevention and control of infection in solid organ transplantation / 器官移植

Organ transplantation has become an effective treatment for multiple end-stage diseases. However, the recipients of organ transplantation need to take immunosuppressive drugs for a long time after operation, which leads to low immune function and relatively high incidence of bacterial, viral and fungal infections. Traditional microbial detection methods, such as pathogen culture, immunological detection and polymerase chain reaction, have been widely applied in infection detection, whereas these methods may cause problems, such as long detection time and presumed pathogens. Metagenomic next-generation sequencing has been widely adopted in infection prevention and control in organ transplantation in recent years due to high detection rate and comprehensive detection of pathogen spectrum. In this article, the application of metagenomic next-generation sequencing in the prevention and control of infection in solid organ transplantation was reviewed, aiming to provide reference for the diagnosis and treatment of transplantation-related infection.

Complementary Role of CEUS and CT/MR LI-RADS for Diagnosis of Recurrent HCC.

PURPOSE: We retrospectively compared the diagnostic performance of contrast-enhanced ultrasonography (CEUS) and contrast-enhanced computer tomography-magnetic resonance imaging (CT/MRI) for recurrent hepatocellular carcinoma (HCC) after curative treatment. MATERIALS AND METHODS: After curative treatment with 421 ultrasound (US) detected lesions, 303 HCC patients underwent both CEUS and CT/MRI. Each lesion was assigned a Liver Imaging Reporting and Data System (LI-RADS) category according to CEUS and CT/MRI LI-RADS. Receiver-operating characteristic (ROC) curves were computed to determine the optimal diagnosis algorithms for CEUS, CT and MRI. The diagnostic accuracy, sensitivity, specificity, and area under the curve (AUC) were compared between CEUS and CT/MRI. RESULTS: Among the 421 lesions, 218 were diagnosed as recurrent HCC, whereas 203 lesions were diagnosed as benign. In recurrent HCC, CEUS detected more arterial hyperenhancement (APHE) and washout than CT and more APHE than MRI. CEUS yielded better diagnostic performance than CT (AUC: 0.981 vs. 0.958) (p = 0.024) comparable diagnostic performance to MRI (AUC: 0.952 vs. 0.933) (p > 0.05) when using their optimal diagnostic criteria. CEUS missed 12 recurrent HCCs, CT missed one, and MRI missed none. The detection rate of recurrent HCC on CEUS (94.8%, 218/230) was lower than that on CT/MRI (99.6%, 259/260) (p = 0.001). Lesions located on the US blind spots and visualization score C would hinder the ability of CEUS to detect recurrent HCC. CONCLUSION: CEUS demonstrated excellent diagnostic performance but an inferior detection rate for recurrent HCC. CEUS and CT/MRI played a complementary role in the detection and characterization of recurrent HCC.

Advance in Mechanical Load for Muscle and Tendon Stiffness (review) / 中国康复理论与实践

The stiffness can respond to the function of muscle and tendon. Resistance training leads to the change of muscle-tendon stiffness, and various with the patterns and strength of contraction. This paper reviewed the impacts of mechanical load on stiffness of muscle and tendon, to explore the adaptation of muscle and tendon to mechanical load.

Anti-inflammatory role of microRNA let-7c in LPS treated alveolar macrophages by targeting STAT3

OBJECTIVE@#To explore the expression of microRNA (miRNA) let-7c and its function in chronic obstructive pulmonary disease (COPD) and alveolar macrophage cells.@*METHODS@#Real time PCR was performed to detect the expression of miRNA let-7c in the lung tissue of COPD patients and COPD model in mice. MiRNA let-7c was overexpressed in alveolar macrophages isolated from mice and its effect was measured by the production of pro-inflammation cytokines and the protein level of signal transducer and activator of transcription 3 (STAT3) as well as phosphorylation level of STAT3 after LPS stimulation. Luciferase assay was used to detect the binding of miRNA let-7c and 3'UTR of STAT3.@*RESULTS@#MiRNA let-7c expression was significantly lower in patients with COPD compared with control group, and the similar result was found in COPD mice and LPS stimulated alveolar macrophages. Overexpression of miRNA let-7c in alveolar macrophages inhibited LPS-induced increasing of tumor necrosis factor alpha, interleukin-6 and interleukin-1β. Luciferase assay showed STAT3 was a targeting of miRNA let-7c in alveolar macrophages.@*CONCLUSIONS@#MiRNA let-7c low expression in COPD can regulate inflammatory responses by targeting STAT3 in alveolar macrophage, which may provide a new target for COPD treatment strategies.

Anti-inflammatory role of microRNA let-7c in LPS treated alveolar macrophages by targeting STAT3

Objective: To explore the expression of microRNA (miRNA) let-7c and its function in chronic obstructive pulmonary disease (COPD) and alveolar macrophage cells. Methods: Real time PCR was performed to detect the expression of miRNA let-7c in the lung tissue of COPD patients and COPD model in mice. MiRNA let-7c was overexpressed in alveolar macrophages isolated from mice and its effect was measured by the production of pro-inflammation cytokines and the protein level of signal transducer and activator of transcription 3 (STAT3) as well as phosphorylation level of STAT3 after LPS stimulation. Luciferase assay was used to detect the binding of miRNA let-7c and 3'UTR of STAT3. Results: MiRNA let-7c expression was significantly lower in patients with COPD compared with control group, and the similar result was found in COPD mice and LPS stimulated alveolar macrophages. Overexpression of miRNA let-7c in alveolar macrophages inhibited LPS-induced increasing of tumor necrosis factor alpha, interleukin-6 and interleukin-1β. Luciferase assay showed STAT3 was a targeting of miRNA let-7c in alveolar macrophages. Conclusions: MiRNA let-7c low expression in COPD can regulate inflammatory responses by targeting STAT3 in alveolar macrophage, which may provide a new target for COPD treatment strategies.

Potential role of miRNAs in age-related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

?A great number of miRNAs have been shown to play critical roles in pathological angiogenesis, the oxidative stress response, immune response and inflammation, all of which have been shown to have important roles in the pathogenesis and progression of age- related macular degeneration ( AMD) . Here we reviewed the pathological processes involved in AMD and the roles of miRNAs in these processes, and discussed potential miRNAs-based therapeutics for AMD.

Qualitative study on psychological state of male nursing students / 现代临床护理

Objective To analyze the psychological state of male nursing students in clinical practice.Method The method of qualitative research was used to interview 20 male nursing students to analyze data and come out with a theme.Results The psychological state of the male nursing students included the following three aspects:intense psychological pressure,unstable mood, low self-esteem and anxiety and depression.Conclusions Establishing nursing communication course using situational simulation and role play and inviting psychological consultants to have face-to-face communication with them for the improvement of mental conditions are good for them to complete their courses and find a nursing position in the future market?

Effects of valsartan on aortic angiotensin converting enzyme 2 expression after aortic balloon injury in rats / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the process and mechanism of neointimal formation, the level of angiotensin II and angiotensin (1-7), the expression of angiotensin converting enzyme 2(ACE2), angiotensin II type 1 receptor (AT(1)R), extracellular signal regulated kinase (ERK) and the effects of valsartan on them after aortic balloon injury in rats.</p><p><b>METHODS</b>Aortic endothelial denudation of rats was induced by 2F balloon catheter. Thirty-six rats were randomly allocated into three groups: Group 1 (n = 12): controls; Group 2 (n = 12): aortic balloon injury; Group 3 (n = 12): valsartan (20 mg×kg(-1)×d(-1)) given from 1 day before injury to 14 and 28 days after aortic injury. The expression of ACE2 and AT1, the level of P-ERK, AngII, Ang(1-7) and intimal thickening were investigated by RT-PCR technique, immunohistochemistry, Western blot, radioimmunological method, enzyme linked immunosorbent assay (ELISA) and HE stain, respectively.</p><p><b>RESULTS</b>(1) The proliferation of vascular smooth muscle cells (VSMC) and the intimal thickening were evidenced at day 14 and 28 after aortic balloon injury. (2) The mRNA and protein expressions of ACE2 decreased significantly, but AT(1)R mRNA and protein expression increased significantly at day 14 and 28 after balloon injury. (3) The level of AngII and p-ERK increased and Ang(1-7) reduced after balloon injury. (4) Valsartan not only attenuated the proliferation of VSMC and the intimal thickening but also upregulated the expression of ACE2 and the level of Ang(1-7) and downregulated the expression of AT(1)R and the level of AngII, p-ERK in this model.</p><p><b>CONCLUSION</b>Intimal thickening after balloon injury is linked with reduced expression of ACE2.Valsartan can inhibit the intimal thickening possibly by upregulating ACE2 and Ang(1-7) and downregulating AT(1) in this model.</p>