Cathepsin L induces cellular senescence by upregulating CUX1 and p16INK4a.

Cathepsin L (CTSL) has been implicated in aging and age-related diseases, such as cardiovascular diseases, specifically atherosclerosis. However, the underlying mechanism(s) is not well documented. Recently, we demonstrated a role of CUT-like homeobox 1 (CUX1) in regulating the p16INK4a-dependent cellular senescence in human endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) via its binding to an atherosclerosis-associated functional SNP (fSNP) rs1537371 on the CDKN2A/B locus. In this study, to determine if CTSL, which was reported to proteolytically activate CUX1, regulates cellular senescence via CUX1, we measured the expression of CTSL, together with CUX1 and p16INK4a, in human ECs and VSMCs undergoing senescence. We discovered that CUX1 is not a substrate that is cleaved by CTSL. Instead, CTSL is an upstream regulator that activates CUX1 transcription indirectly in a process that requires the proteolytic activity of CTSL. Our findings suggest that there is a transcription factor in between CTSL and CUX1, and cleavage of this factor by CTSL can activate CUX1 transcription, inducing endothelial senescence. Thus, our findings provide new insights into the signal transduction pathway that leads to atherosclerosis-associated cellular senescence.

Refinement of efficient encodings of movement in the dorsolateral striatum throughout learning.

The striatum is required for normal action selection, movement, and sensorimotor learning. Although action-specific striatal ensembles have been well documented, it is not well understood how these ensembles are formed and how their dynamics may evolve throughout motor learning. Here we used longitudinal 2-photon Ca 2+ imaging of dorsal striatal neurons in head-fixed mice as they learned to self-generate locomotion. We observed a significant activation of both direct- and indirect-pathway spiny projection neurons (dSPNs and iSPNs, respectively) during early locomotion bouts and sessions that gradually decreased over time. For dSPNs, onset- and offset-ensembles were gradually refined from active motion-nonspecific cells. iSPN ensembles emerged from neurons initially active during opponent actions before becoming onset- or offset-specific. Our results show that as striatal ensembles are progressively refined, the number of active nonspecific striatal neurons decrease and the overall efficiency of the striatum information encoding for learned actions increases.

Beyond monetary value: how reward type drives cheating in a gender-judgment task.

Background: Investigating the effects of monetary incentives on dishonest behavior provides valuable insights into human integrity and ethical decision-making processes. This study is conducted through the lens of self-concept maintenance theory. Aim: The aim of this study is to examine the influence of different types of rewards (score-based vs. monetary) and their magnitude on dishonest behavior within a gender judgment task. Method: Using a quantitative experimental design, this study involved 116 participants who were randomly assigned to conditions that differed in reward type (score or money) and magnitude (10 yuan vs. 50 yuan). Dishonest behavior was assessed using a gender judgment task with mechanisms to simulate conditions conducive to planned cheating. Results: Results revealed significant differences in dishonesty rates between score and money conditions, with a higher proportion of dishonest participants observed in the score condition compared to the money condition. The timing of initial cheating was earlier in the score condition compared to the money condition. No significant differences were found in the proportion of dishonest participants, the cheating rate, or the timing of initial cheating across reward levels within either condition. The rate of cheating increased over time, suggesting a temporal dynamic in unethical decision making. Conclusion: The study demonstrates that the nature of rewards significantly influences the likelihood of dishonest behavior, with intangible score-based rewards facilitating rationalizations for dishonesty more readily than tangible financial incentives. These findings enrich the understanding of moral psychology by highlighting the complex interplay between reward types, ethical rationalization, and the dynamics of dishonest behavior.

Progress of Infection and Replication Systems of Hepatitis B Virus.

Despite the long-standing availability of effective prophylaxis, chronic hepatitis B virus (HBV) infection remains a formidable public health threat. Antiviral treatments can limit viral propagation, but prolonged therapy is necessary to control HBV replication. Robust in vitro models of HBV infection are indispensable prerequisites for elucidating viral pathogenesis, delineating virus-host interplay and developing novel therapeutic, preventative countermeasures. Buoyed by advances in molecular techniques and tissue culture systems, investigators have engineered numerous in vitro models of the HBV life cycle. However, all current platforms harbor limitations in the recapitulation of natural infection. In this article, we comprehensively review the HBV life cycle, provide an overview of existing in vitro HBV infection and replication systems, and succinctly present the benefits and caveats in each model with the primary objective of constructing refined experimental models that closely mimic native viral infection and offering robust support for the ambitious "elimination of hepatitis by 2030" initiative.

Adolescent suicidal ideation: dissecting the role of sex in depression and NSSI predictors.

BACKGROUND: Suicidal ideation (SI) is increasingly prevalent among adolescents, often arising from depression and linked with non-suicidal self-injury (NSSI). Previous studies have noted significant sex differences in the manifestation and predictors of SI, depression, and NSSI. AIM: This study aims to analyze and compare the relationships between SI, depression, and NSSI among male and female adolescents, examining whether these associations differ based on sex. METHODS: A total of 368 adolescents (M = 15.43, SD = 1.22, about 56.2% female participants), both from clinical and school settings, were assessed for SI, depression, NSSI, and other related variables. Network analysis was utilized to explore the interconnections among these variables, focusing on identifying sex-specific patterns. Logistic regression was used to confirm the findings from the network analysis. RESULTS: The network analysis revealed significant sex differences in the relationships between SI, depression, and NSSI. In the female network, the edge weights between SI and NSSI (0.93) and between SI and depression (0.31) were much higher compared to the male network (0.29 and 0, respectively). Centrality indices (strength, betweenness, closeness, and expected influence) for SI, NSSI, and depression were also higher in the female network. Logistic regression confirmed these findings, with depression being a potential predictor of SI only in females (OR = 1.349, p = 0.001) and NSSI having a stronger influence on SI in females (OR = 13.673, p < 0.001) than in males (OR = 2.752, p = 0.037). CONCLUSION: The findings underscore the necessity of considering sex differences when predicting suicidal ideation from depression and NSSI in adolescents. Intervention and prevention strategies should be tailored to address these distinct patterns in male and female adolescents.

NGS panel enhance precise diagnosis of myeloid neoplasms under WHO-HAEM5 and International Consensus Classification: An observational study.

This study aimed to assess hematological diseases next-generation sequencing (NGS) panel enhances the diagnosis and classification of myeloid neoplasms (MN) using the 5th edition of the WHO Classification of Hematolymphoid Tumors (WHO-HAEM5) and the International Consensus Classification (ICC) of Myeloid Tumors. A cohort of 112 patients diagnosed with MN according to the revised fourth edition of the WHO classification (WHO-HAEM4R) underwent testing with a 141-gene NGS panel for hematological diseases. Ancillary studies were also conducted, including bone marrow cytomorphology and routine cytogenetics. The cases were then reclassified according to WHO-HAEM5 and ICC to assess the practical impact of these 2 classifications. The mutation detection rates were 93% for acute myeloid leukemia (AML), 89% for myelodysplastic syndrome (MDS), 94% for myeloproliferative neoplasm (MPN), and 100% for myelodysplasia/myeloproliferative neoplasm (MDS/MPN) (WHO-HAEM4R). NGS provided subclassified information for 26 and 29 patients with WHO-HAEM5 and ICC, respectively. In MPN, NGS confirmed diagnoses in 16 cases by detecting JAK2, MPL, or CALR mutations, whereas 13 "triple-negative" MPN cases revealed at least 1 mutation. NGS panel testing for hematological diseases improves the diagnosis and classification of MN. When diagnosed with ICC, NGS produces more classification subtype information than WHO-HAEM5.

Development of Rapid Bioactivity-Expressed Zr-50Ti Alloys by Surface Treatment with Modified Simulated Body Fluid.

Zr-50Ti alloys are promising biomaterials due to their excellent mechanical properties and low magnetic susceptibility. However, Zr-50Ti alloys do not inherently bond well with bone. This study aims to enhance the bioactivity and bonding strength of Zr-50Ti alloys for orthopedic implant materials. Initially, the surface of Zr-50Ti alloys was treated with a sulfuric acid solution to create a microporous structure, increasing surface roughness and area. Subsequently, low crystalline calcium phosphate (L-CaP) precipitation was controlled by adding Mg2+ and/or CO32- ions in modified simulated body fluid (m-SBF). The treated Zr-50Ti alloys were then subjected to cold isostatic pressing to force m-SBF into the micropores, followed by incubation to allow L-CaP formation. The apatite-forming process was tested in simulated body fluid (SBF). The results demonstrated that the incorporation of Mg2+ and/or CO32- ions enabled the L-CaP to cover the entire surface of Zr-50Ti alloys within only one day. After short-term soaking in SBF, the L-CaP layer, modulated by Mg2+ and/or CO32- ions, formed a uniform hydroxyapatite (HA) coating on the surface of the Zr-50Ti alloys, showing potential for optimized bone integration. After soaking in SBF for 14 days, the bonding strength between the apatite layer and alloy has the potential to meet the orthopedic application requirement of 22 MPa. This study demonstrates an effective method to enhance the bioactivity and bonding strength of Zr-50Ti alloys for orthopedic applications.

An Investigative Study on the Oral Health Condition of Individuals Undergoing 3D-Printed Customized Dental Implantation.

BACKGROUND: The advent of three-dimensional (3D) printing technology has revolutionized the field of dentistry, enabling the precise fabrication of dental implants. By utilizing 3D printing, dentists can devise implant plans prior to surgery and accurately translate them into clinical procedures, thereby eliminating the need for multiple surgical procedures, reducing surgical discomfort, and enhancing surgical efficiency. Furthermore, the utilization of digital 3D-printed implant guides facilitates immediate restoration by precisely translating preoperative implant design plans, enabling the preparation of temporary restorations preoperatively. METHODS: This comprehensive study aimed to assess the postoperative oral health status of patients receiving personalized 3D-printed implants and investigate the advantages and disadvantages between the 3D-printed implant and conventional protocol. Additionally, variance analysis was employed to delve into the correlation between periodontal status and overall oral health. Comparisons of continuous paired parameters were made by t-test. RESULTS: The results of our study indicate a commendable one-year survival rate of over 94% for 3D-printed implants. This finding was corroborated by periodontal examinations and follow-up surveys using the Oral Health Impact Profile-14 (OHIP-14) questionnaire, revealing excellent postoperative oral health status among patients. Notably, OHIP-14 scores were significantly higher in patients with suboptimal periodontal health, suggesting a strong link between periodontal health and overall oral well-being. Moreover, we found that the operating time (14.41 ± 4.64 min) was less statistically significant than for the control group (31.76 ± 6.83 min). CONCLUSION: In conclusion, personalized 3D-printed implant surgery has emerged as a reliable clinical option, offering a viable alternative to traditional implant methods. However, it is imperative to gather further evidence-based medical support through extended follow-up studies to validate its long-term efficacy and safety.

Advances of ultrasound in tumor immunotherapy.

Immunotherapy has become a revolutionary method for treating tumors, offering new hope to cancer patients worldwide. Immunotherapy strategies such as checkpoint inhibitors, chimeric antigen receptor T-cell (CAR-T) therapy, and cancer vaccines have shown significant potential in clinical trials. Despite the promising results, there are still limitations that impede the overall effectiveness of immunotherapy; the response to immunotherapy is uneven, the response rate of patients is still low, and systemic immune toxicity accompanied with tumor cell immune evasion is common. Ultrasound technology has evolved rapidly in recent years and has become a significant player in tumor immunotherapy. The introductions of high intensity focused ultrasound and ultrasound-stimulated microbubbles have opened doors for new therapeutic strategies in the fight against tumor. This paper explores the revolutionary advancements of ultrasound combined with immunotherapy in this particular field.

Robot-assisted surgery for dental implant placement: A narrative review.

OBJECTIVE: To determine the current status and accuracy of robotic computer-assisted implant surgery (CAIS) applications by examining the associated clinical and experimental outcomes. DATA AND SOURCES: PubMed, Medline, and Cochrane Library databases were searched for relevant studies published between January 2000 and November 2023, and focusing on robotic CAIS in dental implant surgery. All search results were then manually reviewed to identify only the pertinent articles. Only in vitro and clinical studies were included in this narrative review, with implant placement accuracy considered the main outcome. RESULT: Based on our inclusion and exclusion criteria, we included 21 studies (with 1085 implant sites); of them, 8 were clinical studies, 12 were in vitro studies, and 1 included both an in vitro study and a case series. The ranges of the mean implant shoulder, apical, and angular deviations were respectively 0.43-1.04 mm, 0.53-1.06 mm, and 0.77°-3.77° in the clinical studies and 0.23-1.04 mm, 0.24-2.13 mm, and 0.43°-3.78° in the in vitro studies, respectively. CONCLUSION: The accuracy of robotic CAIS in dental implant procedures appears to be within the clinically acceptable ranges. However, further relevant clinical trials validating the existing evidence are needed. CLINICAL SIGNIFICANCE: Robotic CAIS can achieve clinically acceptable implant placement accuracy. This innovative technology may improve the precision and success rates of dental implant procedures, with benefit for surgeons and patients.

Unitig-centered pan-genome machine learning approach for predicting antibiotic resistance and discovering novel resistance genes in bacterial strains.

In current genomic research, the widely used methods for predicting antimicrobial resistance (AMR) often rely on prior knowledge of known AMR genes or reference genomes. However, these methods have limitations, potentially resulting in imprecise predictions owing to incomplete coverage of AMR mechanisms and genetic variations. To overcome these limitations, we propose a pan-genome-based machine learning approach to advance our understanding of AMR gene repertoires and uncover possible feature sets for precise AMR classification. By building compacted de Brujin graphs (cDBGs) from thousands of genomes and collecting the presence/absence patterns of unique sequences (unitigs) for Pseudomonas aeruginosa, we determined that using machine learning models on unitig-centered pan-genomes showed significant promise for accurately predicting the antibiotic resistance or susceptibility of microbial strains. Applying a feature-selection-based machine learning algorithm led to satisfactory predictive performance for the training dataset (with an area under the receiver operating characteristic curve (AUC) of > 0.929) and an independent validation dataset (AUC, approximately 0.77). Furthermore, the selected unitigs revealed previously unidentified resistance genes, allowing for the expansion of the resistance gene repertoire to those that have not previously been described in the literature on antibiotic resistance. These results demonstrate that our proposed unitig-based pan-genome feature set was effective in constructing machine learning predictors that could accurately identify AMR pathogens. Gene sets extracted using this approach may offer valuable insights into expanding known AMR genes and forming new hypotheses to uncover the underlying mechanisms of bacterial AMR.

An In Vitro Evaluation of the Effect of Bifidobacterium longum L556 on Microbiota Composition and Metabolic Properties in Patients with Coronary Heart Disease (CHD).

Bifidobacterium longum (B. longum) is a beneficial anaerobic bacteria that may improve cardiovascular disease (CVD). We studied B. longum L556, isolated from healthy human feces, in coronary heart disease (CHD) patients through anaerobic fermentation in vitro. Results showed that B. longum L556 increased Lactobacillus, Faecalibacterium, Prevotella, and Alistipes, while reducing Firmicutes to Bacteroidetes, Eggerthella, Veillonella, Holdemanella, and Erysipelotrichaceae_UCG-003 in the gut microbiota of CHD patients. B. longum L556 also enhanced anti-inflammatory effects by modulating gut microbiota and metabolites like SCFAs. Additionally, it regulated lipid and amino acid metabolism in fermentation metabolites from the CHD group. These findings suggest that B. longum L556 has potential for improving CHD by modulating the intestinal microbiota, promoting SCFA production, and regulating lipid metabolism and inflammation.

Latent profile analysis of Eysenck's personality dimensions and psychological constructs in university students.

Background: The exploration of personality traits in relation to psychological constructs has become increasingly relevant in understanding the mental health of university students (the emerging adulthood). Studies have focused on how dimensions intersect with various psychological parameters. Aim: The study aims to identify distinct personality profiles among university students based on Eysenck's personality dimensions and investigate how these profiles differ across psychological constructs. Method: A quantitative methodology was utilized, involving 708 university students from Wenzhou and Nanjing in China as participants. The research employed the Eysenck Personality Questionnaire along with other psychological measures. Latent Profile Analysis was applied to categorize the participants into distinct personality profiles. Results: Four distinct personality profiles emerged: 'The Reserved Analyst,' 'The Social Diplomat,' 'The Unconventional Pragmatist,' and 'The Impulsive Truth-Teller.' Significant differences were found among these profiles on various psychological constructs. 'The Social Diplomat' exhibited the most adaptive psychological profile, with higher cognitive reappraisal (F = 45.818, p < 0.001, η2 = 0.163), meaning in life (F = 17.764, p < 0.001, η2 = 0.070), and positive coping (F = 40.765, p < 0.001, η2 = 0.148) compared to other profiles. Conversely, 'The Reserved Analyst' showed higher intolerance of uncertainty (F = 13.854, p < 0.001, η2 = 0.056) and state anxiety (F = 26.279, p < 0.001, η2 = 0.101). Conclusion: This study enriches the understanding of personality traits in relation to psychological constructs within the context of university student populations. By identifying distinct personality profiles, it lays the groundwork for developing tailored mental health strategies that cater to the specific needs of different student groups.

Acacetin alleviates autoimmune myocarditis by regulating CD4+ T cell mitochondrial respiration.

BACKGROUND: Myocarditis refers to an autoimmune inflammatory response of the myocardium with characterization of self-reactive CD4+ T cell activation, which lacks effective treatment and has a poor prognosis. Acacetin is a natural flavonoid product that has been reported to have anti-inflammatory effects. However, acacetin has not been investigated in myocarditis. METHODS: Oral acacetin treatment was administered in an experimental autoimmune myocarditis model established with myosin heavy chain-alpha peptide. Echocardiography, pathological staining, and RT-qPCR were used to detect cardiac function, myocardial injury, and inflammation levels. Flow cytometry was utilized to detect the effect of acacetin on CD4+ T cell function. RNA-seq, molecular docking, and microscale thermophoresis (MST) were employed to investigate potential mechanisms. Seahorse analysis, mitoSOX, JC-1, and mitotracker were utilized to detect the effect of acacetin on mitochondrial function. RESULTS: Acacetin attenuated cardiac injury and fibrosis as well as heart dysfunction, and reduced cardiac inflammatory cytokines and ratio of effector CD4+ T and Th17 cells. Acacetin inhibited CD4+ T cell activation, proliferation, and Th17 cell differentiation. Mechanistically, the effects of acacetin were related to reducing mitochondrial complex II activity thereby inhibiting mitochondrial respiration and mitochondrial reactive oxygen species in CD4+ T cells. CONCLUSION: Acacetin may be a valuable therapeutic drug in treating CD4+ T cell-mediated myocarditis.

Trends in the global, regional, and national burden of testicular cancer from 1990 to 2019: an observational study with 30-year global data.

BACKGROUND: Testicular cancer (TC) is currently the most common malignancy in young and middle-aged men. A comprehensive assessment of TC burden is in lack. METHOD: Global incidence, deaths, and disability-adjusted life-years (DALYs) of TC from 1990 to 2019 were obtained. Estimated annual percentage change (EAPC) was calculated to quantify trends in TC changes during the period. Relationships between disease burden and age, sociodemographic index (SDI) levels, human development index (HDI) were further analyzed. RESULTS: Globally, incident cases of TC more than doubled from 1990 to 2019, together with an increasing of global age-standardized incidence rates (ASIR) of TC from 1.9 to 2.8. The age-standardized deaths rates (ASDR) remained stable from 0.31 to 0.28. The similar results were reflected in the disability-adjusted life-years (DALYs). In 2019, the highest ASIR were found in Southern Latin America, Central Europe and Western Europe. Analogously, the highest ASDR were found in Southern Latin America followed by Central Latin America and Central Europe. The burden of incidence increased with SDI, appropriately reached a peak at about 0.78, and then declined. Similarly, the burden of deaths increased with SDI, met a maximum at about 0.7. CONCLUSIONS: From 1990 to 2019, the ASIR of TC has increased significantly, while the ASDR has been relatively stable and slightly decreased. The disease burden of TC is shifting to regions and countries with moderate to high levels of development. TC remains a rapidly growing global health problem, and new changes in TC burden should be considered when formulating new TC control policies.

Bacterial membrane vesicles: orchestrators of interkingdom interactions in microbial communities for environmental adaptation and pathogenic dynamics.

Bacterial membrane vesicles (MVs) have attracted increasing attention due to their significant roles in bacterial physiology and pathogenic processes. In this review, we provide an overview of the importance and current research status of MVs in regulating bacterial physiology and pathogenic processes, as well as their crucial roles in environmental adaptation and pathogenic infections. We describe the formation mechanism, composition, structure, and functions of MVs, and discuss the various roles of MVs in bacterial environmental adaptation and pathogenic infections. Additionally, we analyze the limitations and challenges of MV-related research and prospect the potential applications of MVs in environmental adaptation, pathogenic mechanisms, and novel therapeutic strategies. This review emphasizes the significance of understanding and studying MVs for the development of new insights into bacterial environmental adaptation and pathogenic processes. Overall, this review contributes to our understanding of the intricate interplay between bacteria and their environment and provides valuable insights for the development of novel therapeutic strategies targeting bacterial pathogenicity.

Mental toughness in adolescents: bridging family relationships and depression across personality traits.

BACKGROUND: Adolescence is a pivotal stage vulnerable to mental health issues like anxiety and depression. While family relationships, mental toughness, and personality traits are known to impact adolescent mental health, their interactive and moderating roles are not fully understood. AIM: This study aims to investigate the mediating role of mental toughness in the relationship between family relationships and depression among high school students, and to examine the varying impacts of personality traits on this mediation. METHOD: A cross-sectional study was conducted on a sample of 734 adolescents. Participants completed measures assessing family relationships, mental toughness, personality traits, and mental health outcomes (depression). Latent Profile Analysis, Multiple Regression Analysis, and Structural Equation Modeling, to investigate these relationships. RESULTS: The study found that mental toughness significantly mediates the relationship between family relationships and depression. Notably, this mediating effect varied between personality type; it was more pronounced in the moderate-reserved type compared to the proactive-engaged type. LPA identified two distinct personality types of students based on their personality traits, with differential patterns of family relationships, mental toughness, and depression. Multiple regression analysis indicated that character and adaptability, components of mental toughness, were significant negative predictors of depression. CONCLUSION: The study contributes to understanding the dynamics of adolescent mental health, particularly in the context of Chinese high school students. It underscores the importance of considering family dynamics, personality traits, and mental toughness in developing effective mental health interventions for adolescents.

Ferrocene-Based Antioxidant Self-Healing Hydrogel via the Biginelli Reaction for Wound Healing.

The development of antioxidant wound dressings to remove excessive free radicals around wounds is essential for wound healing. In this study, we developed an efficient strategy to prepare antioxidant self-healing hydrogels as wound dressings by combining multicomponent reactions (MCRs) and postpolymerization modification. A polymer containing ferrocene and phenylboronic acid groups was developed via the Biginelli reaction, followed by efficient modification. This polymer is antioxidant due to its ferrocene moieties and can rapidly cross-link poly(vinyl alcohol) to realize an antioxidant self-healing hydrogel through dynamic borate ester linkages. This hydrogel has low cytotoxicity and is biocompatible. In in vivo experiments, this hydrogel is superior to existing clinical dressings in promoting wound healing. This study demonstrates the value of the Biginelli reaction in exploring biomaterials, potentially offering insights into the design of other multifunctional polymers and related materials using different MCRs.

Characteristics of cold-adapted carbonic anhydrase and efficient carbon dioxide capture based on cell surface display technology.

Carbonic anhydrase (CA) is currently under investigation because of its potential to capture CO2. A novel N-domain of ice nucleoproteins (INPN)-mediated surface display technique was developed to produce CA with low-temperature capture CO2 based on the mining and characterization of Colwellia sp. CA (CsCA) with cold-adapted enzyme structural features and catalytic properties. CsCA and INPN were effectively integrated into the outer membrane of the cell as fusion proteins. Throughout the display process, the integrity of the membrane of engineered bacteria BL21/INPN-CsCA was maintained. Notably, the study affirmed positive applicability, wherein 94 % activity persisted after 5 d at 15 °C, and 73 % of the activity was regained after 5 cycles of CO2 capture. BL21/INPN-CsCA displayed a high CO2 capture capacity of 52 mg of CaCO3/mg of whole-cell biocatalysts during CO2 mineralization at 25 °C. Therefore, the CsCA functional cell surface display technology could contribute significantly to environmentally friendly CO2 capture.