Research Hotspots and Development Trends on Apolipoprotein B in the Field of Atherosclerosis: A Bibliometric Analysis.

BACKGROUND: Cardiovascular diseases caused by atherosclerosis (AS) are the leading causes of disability and death worldwide. Apolipoprotein B (ApoB), the core protein of low-density lipoproteins, is a major contributor to cardiovascular disease-related morbidity and mortality, with apolipoprotein B (ApoB) playing a critical role in its pathogenesis. However, no bibliometric studies on the involvement of ApoB in AS have been published. This study aimed to conduct a comprehensive bibliometric analysis to explore the current and future trends regarding the role of ApoB in AS. METHODS: Utilizing the Web of Science Core Collection, a thorough search was conducted for ApoB in AS-related papers related to research on ApoB in the field of AS during 1991-2023. The analysis focused on annual publication trends, leading countries/regions and institutions, influential authors, journal and key journals. CiteSpace and VOSviewer were employed to visualize reference co-citations, and keyword co-occurrences, offering insights into the research landscape and emerging trends. RESULTS: This bibliometric analysis employed network diagrams for cluster analysis of a total of 2105 articles and reviews, evidencing a discernible upward trend in annual publication volume. This corpus of research emanates from 76 countries/regions and 2343 organizations, illustrating the widespread international engagement in ApoB-related AS studies. Notably, the United States and the University of California emerge as the most prolific contributors, which underscores their pivotal roles in advancing this research domain. The thematic investigation has increasingly focused on elucidating the mechanistic involvement of ApoB in atherosclerosis, its potential as a diagnostic biomarker, and its implications for therapeutic strategies. CONCLUSION: This bibliometric analysis provides the first comprehensive perspective on the evolving promise of ApoB in AS-related research, emphasizing the importance of this molecule in opening up new diagnostic and therapeutic avenues. This study emphasizes the need for continued research and interdisciplinary efforts to strengthen the fight against AS. Furthermore, it emphasizes the critical role of international collaboration and interdisciplinary exploration in leveraging new insights to achieve clinical breakthroughs, thereby addressing the complexities of AS by focusing on ApoB.

Alterations of pathogen transmission patterns and attenuated immune stimulation might be the cause of increased adult respiratory infections cases in 2023, results from a multi-center study in mainland China.

Background: Several respiratory infections outbreaks have been observed in mainland China after reduction of non-pharmaceutical interventions. Other countries have seen increases in respiratory infections outside typical seasons post-COVID-19, warranting investigation into underlying causes. Methods: We established monitoring networks for suspected respiratory infection in 14 tertiary hospitals nationwide. PCR for SARS-CoV-2, influenza A and B were performed on 3708 respiratory specimens and deep sequencing were conducted to identify co-infections or newly emerging microbes in 2023. Viral evolutionary analysis was completed. We retrospectively detected serum antibody level for various respiratory pathogens from 4324 adults without respiratory infections over 7 years to observe its dynamic curves. Findings: SARS-CoV-2 and influenza A were the main pathogens during outbreaks in 2023, bacterial-virus and bacterial-bacterial co-infections were most detected, but community co-infections didn't significantly increase pneumonia incidence. Different SARS-CoV-2 and influenza variants were present in different outbreaks, and no novel pathogens were found. The epidemiological patterns of influenza A, COVID-19 and etc. were altered, exhibiting characteristics of being "staggered" compared to most global regions, and potentially led to "overlapping prevalence". Binding antibody testing showed regular fluctuation, without significant decrease against common respiratory pathogens in adults. Influenza A antibody stimulation was attenuated during the 2023 outbreak. Conclusions: "Misaligned" alteration in seasonal respiratory disease patterns possibly caused combined epidemics, leading to cases spike in China, 2023. In adults, antibody levels didn't show significant decline, but reduced immune response to influenza during 2020-2023 emphasizes the need for consistent vaccination during pandemics.

A novel SALL1 C757T mutation in a Chinese family causes a rare disease --Townes-Brocks syndrome.

BACKGROUND: Townes-Brocks syndrome (TBS) is a rare genetic disorder characterized by imperforate anus, dysplastic ears, thumb malformations, and other abnormalities. Previous studies have revealed that mutations in the SALL1 gene can disrupt normal development, resulting in the characteristic features of Townes-Brocks syndrome. Spalt-like transcription factors (SALLs) are highly conserved proteins that play important roles in various cellular processes, including embryonic development, cell differentiation, and cell survival. Over 400 different variants or mutations have been reported in the SALL1 gene in individuals with TBS. Most of these variants lead to the formation of premature termination codons (PTCs), also known as nonsense mutations. The majority of these PTCs occur in a specific region of the SALL1 gene called the "hotspot region", which is particularly susceptible to mutation. METHODS: In this study, we conducted whole-exome sequencing on a three-generation Chinese family with anorectal malformations. RESULTS: We identified a novel heterozygous mutation (chr16:51175376:c.757 C > T p.Gln253*) in the SALL1 gene. Molecular analysis revealed a heterozygous C to T transition at nucleotide position 757 in exon 2 of the SALL1 (NM_002968) gene. This mutation is predicted to result in the substitution of the Gln253 codon with a premature stop codon (p.Gln253*). The glutamine-rich domain forms a long alpha helix, enabling the mutant protein to interact with the wild-type SALL1 protein. This interaction may result in steric hindrance effects on the wild-type SALL1 protein. CONCLUSIONS: Our findings have expanded the mutation database of the SALL1 gene, which is significant for genetic counseling and clinical surveillance in the affected family. Furthermore, our study enhances the understanding of Townes-Brocks syndrome and has the potential to improve its diagnosis and treatment.

Sensitivity-Enhancing Strategies of Graphene Field-Effect Transistor Biosensors for Biomarker Detection.

The ultrasensitive recognition of biomarkers plays a crucial role in the precise diagnosis of diseases. Graphene-based field-effect transistors (GFET) are considered the most promising devices among the next generation of biosensors. GFET biosensors possess distinct advantages, including label-free, ease of integration and operation, and the ability to directly detect biomarkers in liquid environments. This review summarized recent advances in GFET biosensors for biomarker detection, with a focus on interface functionalization. Various sensitivity-enhancing strategies have been overviewed for GFET biosensors, from the perspective of optimizing graphene synthesis and transfer methods, refinement of surface functionalization strategies for the channel layer and gate electrode, design of biorecognition elements and reduction of nonspecific adsorption. Further, this review extensively explores GFET biosensors functionalized with antibodies, aptamers, and enzymes. It delves into sensitivity-enhancing strategies employed in the detection of biomarkers for various diseases (such as cancer, cardiovascular diseases, neurodegenerative disorders, infectious viruses, etc.) along with their application in integrated microfluidic systems. Finally, the issues and challenges in strategies for the modulation of biosensing interfaces are faced by GFET biosensors in detecting biomarkers.

The Critical Role of the Shroom Family Proteins in Morphogenesis, Organogenesis and Disease.

The Shroom (Shrm) family of actin-binding proteins has a unique and highly conserved Apx/Shrm Domain 2 (ASD2) motif. Shroom protein directs the subcellular localization of Rho-associated kinase (ROCK), which remodels the actomyosin cytoskeleton and changes cellular morphology via its ability to phosphorylate and activate non-muscle myosin II. Therefore, the Shrm-ROCK complex is critical for the cellular shape and the development of many tissues, including the neural tube, eye, intestines, heart, and vasculature system. Importantly, the structure and expression of Shrm proteins are also associated with neural tube defects, chronic kidney disease, metastasis of carcinoma, and X-link mental retardation. Therefore, a better understanding of Shrm-mediated signaling transduction pathways is essential for the development of new therapeutic strategies to minimize damage resulting in abnormal Shrm proteins. This paper provides a comprehensive overview of the various Shrm proteins and their roles in morphogenesis and disease.

A Novel Homozygous RHOH Variant Associated with T Cell Dysfunction and Recurrent Opportunistic Infections.

RHOH, an atypical small GTPase predominantly expressed in hematopoietic cells, plays a vital role in immune function. A deficiency in RHOH has been linked to epidermodysplasia verruciformis, lung disease, Burkitt lymphoma and T cell defects. Here, we report a novel germline homozygous RHOH c.245G > A (p.Cys82Tyr) variant in a 21-year-old male suffering from recurrent, invasive, opportunistic infections affecting the lungs, eyes, and brain. His sister also succumbed to a lung infection during early adulthood. The patient exhibited a persistent decrease in CD4+ T, B, and NK cell counts, and hypoimmunoglobulinemia. The patient's T cell showed impaired activation upon in vitro TCR stimulation. In Jurkat T cells transduced with RHOHC82Y, a similar reduction in activation marker CD69 up-regulation was observed. Furthermore, the C82Y variant showed reduced RHOH protein expression and impaired interaction with the TCR signaling molecule ZAP70. Together, these data suggest that the newly identified autosomal-recessive RHOH variant is associated with T cell dysfunction and recurrent opportunistic infections, functioning as a hypomorph by disrupting ZAP70-mediated TCR signaling.

Predictive model for totally implanted venous access ports­related long­term complications in patients with lung cancer.

Totally implanted venous access ports (TIVAPs), which are typically used in oncological chemotherapy and parenteral nutritional support, are convenient and safe, and thus offer patients a higher quality of life. However, insertion or removal of the device requires a minor surgical operation. Long-term complications (>30 days post insertion), such as catheter migration, catheter-related thrombosis and infection, are major reasons for TIVAP removal and are associated with a number of factors such as body mass index and hemoglobin count. Since management of complications is typically time-consuming and costly, a predictive model of such events may be of great value. Therefore, in the present study, a predictive model for long-term complications following TIVAP implantation in patients with lung cancer was developed. After excluding patients with a large amount of missing data, 902 patients admitted to The First Affiliated Hospital with Nanjing Medical University (Nanjing, China) were ultimately included in the present study. Of the included patients, 28 had complications, indicating an incidence rate of 3.1%. Patients were randomly divided into training and test cohorts (7:3), and three machine learning-based anomaly detection algorithms, namely, the Isolation Forest, one-class Support Vector Machines (one-class SVM) and Local Outlier Factor, were used to construct a model. The performance of the model was initially evaluated by the Matthew's correlation coefficient (MCC), area under curve (AUC) and accuracy. The one-class SVM model demonstrated the highest performance in classifying the risk of complications associated with the use of the intracavitary electrocardiogram method for TIVAP implantation in patients with lung cancer (MCC, 0.078; AUC, 0.62; accuracy, 66.0%). In conclusion, the predictive model developed in the present study may be used to improve the early detection of TIVAP-related complications in patients with lung cancer, which could lead to the conservation of medical resources and the promotion of medical advances.

Longitudinal Analysis of Humoral and Cellular Immune Response up to 6 Months after SARS-CoV-2 BA.5/BF.7/XBB Breakthrough Infection and BA.5/BF.7-XBB Reinfection.

The rapid mutation of SARS-CoV-2 has led to multiple rounds of large-scale breakthrough infection and reinfection worldwide. However, the dynamic changes of humoral and cellular immunity responses to several subvariants after infection remain unclear. In our study, a 6-month longitudinal immune response evaluation was conducted on 118 sera and 50 PBMC samples from 49 healthy individuals who experienced BA.5/BF.7/XBB breakthrough infection or BA.5/BF.7-XBB reinfection. By studying antibody response, memory B cell, and IFN-γ secreting CD4+/CD8+ T cell response to several SARS-CoV-2 variants, we observed that each component of immune response exhibited distinct kinetics. Either BA.5/BF.7/XBB breakthrough infection or BA.5/BF.7-XBB reinfection induces relatively high level of binding and neutralizing antibody titers against Omicron subvariants at an early time point, which rapidly decreases over time. Most of the individuals at 6 months post-breakthrough infection completely lost their neutralizing activities against BQ.1.1, CH.1.1, BA.2.86, JN.1 and XBB subvariants. Individuals with BA.5/BF.7-XBB reinfection exhibit immune imprinting shifting and recall pre-existing BA.5/BF.7 neutralization antibodies. In the BA.5 breakthrough infection group, the frequency of BA.5 and XBB.1.16-RBD specific memory B cells, resting memory B cells, and intermediate memory B cells gradually increased over time. On the other hand, the frequency of IFN-γ secreting CD4+/CD8+ T cells induced by WT/BA.5/XBB.1.16 spike trimer remains stable over time. Overall, our research indicates that individuals with breakthrough infection have rapidly declining antibody levels but have a relatively stable cellular immunity that can provide some degree of protection from future exposure to new antigens.

Proteomic and Cellular Characterization of Omicron Breakthrough Infections and a Third Homologous or Heterologous Boosting Vaccination in a Longitudinal Cohort.

The understanding of dynamic plasma proteome features in hybrid immunity and breakthrough infection is limited. A deeper understanding of the immune differences between heterologous and homologous immunization could assist in the future establishment of vaccination strategies. In this study, 40 participants who received a third dose of either a homologous BBIBP-CorV or a heterologous ZF2001 protein subunit vaccine following two doses of inactivated coronavirus disease 2019 vaccines and 12 patients with BA2.2 breakthrough infections were enrolled. Serum samples were collected at days 0, 28, and 180 following the boosting vaccination and breakthrough and then analyzed using neutralizing antibody tests and mass spectrometer-based proteomics. Mass cytometry of peripheral blood mononuclear cell samples was also performed in this cohort. The chemokine signaling pathway and humoral response markers (IgG2 and IgG3) associated with infection were found to be upregulated in breakthrough infections compared to vaccination-induced immunity. Elevated expression of IGKV, IGHV, IL-17 signaling, and the phagocytosis pathway, along with lower expression of FGL2, were correlated with higher antibody levels in the boosting vaccination groups. The MAPK signaling pathway and Fc gamma R-mediated phagocytosis were more enriched in the heterologous immunization groups than in the homologous immunization groups. Breakthrough infections can trigger more intensive inflammatory chemokine responses than vaccination. T-cell and innate immune activation have been shown to be closely related to enhanced antibody levels after vaccination and therefore might be potential targets for vaccine adjuvant design.

Clinical Characteristics, Treatment, and Prognosis of Osteoarticular Brucellosis: A Retrospective Real-World Study in Shenyang, China, 2014-2019.

This study aimed to assess the clinical characteristics, treatment, and prognosis of osteoarticular brucellosis. We conducted a retrospective study enrolling brucellosis patients from the Sixth People's Hospital of Shenyang between September 2014 and June 2019. A total of 1917 participants were admitted during this period. After applying propensity score matching, we retrospectively analyzed 429 patients with osteoarthritis and 429 patients without osteoarthritis. The primary outcome was treatment completion. The secondary outcome was symptom disappearance and seroconversion. Brucellosis patients with osteoarthritis had longer treatment course (160 [134.3-185.7] vs. 120 [102.3-137.7] d, p = 0.008) than those without osteoarthritis. The most common involved site was lumbar vertebrae (290 [67.6%]) in brucellosis patients with osteoarthritis. Longer symptom duration (90 [83.0-97.0] vs. 42 [40.2-43.8], p < 0.001) along with no significant difference in seroconversion (180 [178.8-181.2] vs. 180 [135.1-224.9], p = 0.212) was observed in osteoarthritis patients with treatment course >90 d. Peripheral joint involvement (adjusted hazard ratio [95% confidence interval] 1.485 [1.103-1.999]; p = 0.009) had a shorter symptom duration compared with shaft joint involvement. No significant differences were observed in treatment therapy between doxycycline plus rifampin (DR) or plus cephalosporins (DRC) in treatment course (p = 0.190), symptom persistence (p = 0.294), and seroconversion (p = 0.086). Lumbar vertebra was the most commonly involved site. Even if all symptoms disappeared, Serum agglutination test potentially remained positive in some patients. Compared with peripheral arthritis, shaft arthritis was the high-risk factor for longer symptom duration. The therapeutic effects were similar between DR and DRC. In summary, our study provided important insights into the clinical characteristics, treatment, and outcomes of osteoarticular brucellosis. Clinical Trial Registration number: NCT04020536.

Docosahexaenoic Acid Supplementation for Neonatal Hyperbilirubinemia: A Double-Blind, Randomized Clinical Trial.

Docosahexaenoic acid (DHA) is an essential component for brain development during fetal and early postnatal life. Hyperbilirubinemia is characterized by abnormally high levels of bilirubin in the bloodstream, frequently leading to jaundice in newborns. In severe instances, this condition can progress to neurological damage or kernicterus, a form of brain damage. Initial cell-based experiments conducted by our research team revealed that DHA significantly enhances the survival rate of nerve cells treated with bilirubin and diminishes the oxidative stress indicated by reduced peroxide activity caused by unconjugated bilirubin (UCB). Further investigations through animal studies demonstrated that DHA effectively mitigates bilirubin-induced brain injury in neonatal rats. However, the potential of DHA to decrease the incidence of bilirubin-induced brain damage in clinical settings has not been previously explored or reported. Infants with neonatal hyperbilirubinemia (n = 30 per group) participated in a double-blind, randomized, placebo-controlled parallel study. They received either 100 mg/d DHA or placebo syrup immediately when they were diagnosed. The study found that the bilirubin level at 48 hours of treatment, serum neuron-specific enolase (NSE) levels, mean phototherapy duration, and abnormal rate of cranial magnetic resonance imaging (MRI) were lower in the DHA group than those in the control group (P < .05). These results suggested that DHA is effective as an adjuvant treatment for hyperbilirubinemia in children. It can reduce the incidence of neonatal hyperbilirubinemia brain injury and plays a certain protective role. Clinical study on protective effect of DHA on neonatal bilirubin injury is registered at Chinese Clinical Trial Registry as ChiCTR2300070250.

Enhancing insulin sensitivity in type 2 diabetes mellitus using apelin-loaded small extracellular vesicles from Wharton's jelly-derived mesenchymal stem cells: a novel therapeutic approach.

BACKGROUND: Type 2 diabetes mellitus (T2DM), characterized by ß-cell dysfunction and insulin resistance (IR), presents considerable treatment challenges. Apelin is an adipocyte-derived factor that shows promise in improving IR; however, it is limited by poor targeting and a short half-life. In the present study, engineered small extracellular vesicles (sEVs) derived from Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) loaded with apelin were used to address the limitations of the therapeutic application of apelin. METHODS: WJ-MSCs were transduced to obtain engineered sEVs loaded with overexpressed apelin (apelin-MSC-sEVs) and the control sEVs (MSC-sEVs). T2DM mice were injected with apelin-MSC-sEVs and MSC-sEVs, and blood glucose monitoring, glucose and insulin tolerance tests, confocal microscopy, and immunocytochemical analysis were performed. IR models of 3T3-L1 adipocytes were employed to detect GLUT4 expression in each group using western blotting; the affected pathways were determined by measuring the changes in Akt and AMPK signaling and phosphorylation. RESULTS: Upon successful engineering, WJ-MSCs demonstrated significant overexpression of apelin. The genetic modification did not adversely impact the characteristics of sEVs, ranging from surface protein markers, morphology, to particle size, but generated apelin-overexpressed sEVs. Apelin-MSC-sEVs treatment resulted in notable enhancement of Akt and AMPK pathway activities within 3T3-L1 adipocytes and adipose tissues of T2DM mice. Furthermore, the apelin-loaded sEVs significantly reduced plasma glucose levels, increased pancreatic ß-cell proliferation, improved insulin and glucose tolerance, and modulated pro-inflammatory cytokine profiles, compared to mice treated with the control sEVs. CONCLUSION: Our study developed novel genetically engineered apelin-loaded sEVs derived from WJ-MSCs, and demonstrated their potent role in augmenting insulin sensitivity and regulating inflammatory responses, highlighting their therapeutic promise in T2DM management. The findings open new avenues for the development of clinically viable treatments for T2DM in humans using the apelin-loaded sEVs.

Prognostic value of poly-microorganisms detected by droplet digital PCR and pathogen load kinetics in sepsis patients: a multi-center prospective cohort study.

This study aimed to investigate the prognostic value of a novel droplet digital polymerase chain reaction (DDPCR) assay in sepsis patients. In this prospective cohort study, univariable and multivariable Cox regressions were used to assess risk factors for 28-day mortality. We also monitored pathogen load together with clinical indicators in a subgroup of the cohort. A total of 107 sepsis patients with positive baseline DDPCR results were included. Detection of poly-microorganisms [adjusted hazard ratio (HR) = 3.19; 95% confidence interval (CI) = 1.34-7.62; P = 0.009], high Charlson Comorbidity Index (CCI) score (adjusted HR = 1.14; 95% CI = 1.01-1.29; P = 0.041), and Sequential Organ Failure Assessment (SOFA) score (adjusted HR = 1.18; 95% CI = 1.05-1.32; P = 0.005) at baseline were independent risk factors for 28-day mortality while initial pathogen load was not associated (adjusted HR = 1.17; 95% CI = 0.82-1.66; P = 0.385). Among 63 patients with serial DDPCR results, an increase in pathogen load at days 6-8 compared to baseline was a risk factor for 28-day mortality (P = 0.008). Also, pathogen load kinetics were significantly different between day-28 survivors and nonsurvivors (P = 0.022), with a decline overtime only in survivors and an increase from days 3 and 4 to days 6-8 in nonsurvivors. Using DDPCR technique, we found that poly-microorganisms detected and increased pathogen load a week after sepsis diagnosis were associated with poor prognosis.IMPORTANCEThis prospective study was initiated to explore the prognostic implications of a novel multiplex PCR assay in sepsis. Notably, our study was the largest cohort of sepsis with droplet digital polymerase chain reaction pathogen monitoring to date, allowing for a comprehensive evaluation of the prognostic significance of both pathogen species and load. We found that detection of poly-microorganisms was an independent risk factors for 28-day mortality. Also, pathogen load increase 1 week after sepsis diagnosis was a risk factor for 28-day mortality, and differential pathogen load kinetics were identified between day-28 survivors and nonsurvivors. Overall, this study demonstrated that pathogen species and load were highly correlated with sepsis prognosis. Patients exhibiting conditions mentioned above face a more adverse prognosis, suggesting the potential need for an escalation of antimicrobial therapy.Registered at ClinicalTrials.gov (NCT05190861).

Influence of Dyadic Coping Model on Anxiety and Depression Level and Treatment Compliance in Glaucoma Patients.

Objective: To investigate the influence of the dyadic coping model on anxiety and depression levels and treatment compliance in glaucoma patients. Methods: According to the random number table method, 80 glaucoma patients were assigned into an observation group and a control group, with 40 cases in each group are recruited from January 2021 to February 2022. Both groups received routine preoperative glaucoma care; in addition, the observation group received a 10-week dyadic coping model intervention. The dyadic coping model is a therapeutic approach that involves the collaborative efforts of both patients and their close partners or caregivers to cope with stressors and challenges related to the perioperative period. The baseline data questionnaires were collected before the intervention, and the outcome was evaluated 10 weeks later using the Anxiety and Depression Self-Rating Scale and the Treatment Compliance Scale. Results: After intervention, the treatment compliance of glaucoma in the observation group was significantly better than that in the control group, and the anxiety and depression level in the observation group was significantly lower than that in the control group (P < .05). Conclusion: The dyadic coping model intervention for glaucoma patients can successfully increase treatment compliance and lower anxiety and depression levels.

A higher non-HDL-C/HDL-C ratio was associated with an increased risk of progression of nonculprit coronary lesion in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

BACKGROUND: The ratio of nonhigh-density lipoprotein cholesterol (non-HDL-C) to high-density lipoprotein cholesterol (HDL-C) has been shown associated with various metabolic diseases and atherosclerosis in primary prevention. However, there is limited evidence on the relationship between the non-HDL-C/HDL-C ratio and progression of nonculprit coronary lesion (NCCL) after percutaneous coronary intervention (PCI). HYPOTHESIS: Our study aimed to investigate the potential association between the non-HDL-C/HDL-C ratio and NCCL progression in patients with acute coronary syndrome (ACS) undergoing PCI. METHODS: We conducted a retrospective analysis of ACS patients who underwent coronary angiography twice at a single center from 2016 to 2022. Lipid measurements, demographic, clinical, and other laboratory data were collected from electronic medical records. NCCLs were evaluated using quantitative coronary angiography. The primary outcome was the progression of NCCL. Patients were categorized based on NCCL progression and tertiles of the non-HDL-C/HDL-C ratio. Associations were analyzed using univariate and multivariate logistic regression analysis. RESULTS: The study included 329 ACS patients who underwent PCI, with a median follow-up angiography of 1.09 years. We found NCCL progression in 95 (28.9%) patients with acceptable low-density lipoprotein cholesterol control (median: 1.81 mmol/L). Patients in the top tertile of the non-HDL-C/HDL-C ratio had a higher risk of NCCL progression. After adjusting for potential confounding factors, the non-HDL-C/HDL-C ratio remained a significant predictor for NCCL progression (adjusted odds ratio: 1.45; 95% confidence interval: 1.14-1.86; p < 0.05). CONCLUSIONS: The non-HDL-C/HDL-C ratio predicts NCCL progression in ACS patients following PCI, providing a valuable tool for risk assessment and enhancing secondary prevention of atherosclerotic cardiovascular disease.

Mycobacterium tuberculosis hijacks host macrophages-derived interleukin 16 to block phagolysosome maturation for enhancing intracellular growth.

The discovery of promising cytokines and clarification of their immunological mechanisms in controlling the intracellular fate of Mycobacterium tuberculosis (Mtb) are necessary to identify effective diagnostic biomarkers and therapeutic targets. To escape immune clearance, Mtb can manipulate and inhibit the normal host process of phagosome maturation. Phagosome maturation arrest by Mtb involves multiple effectors and much remains unknown about this important aspect of Mtb pathogenesis. In this study, we found that interleukin 16 (IL-16) is elevated in the serum samples of Tuberculosis (TB) patients and can serve as a specific target for treatment TB. There was a significant difference in IL-16 levels among active TB, latent TB infection (LTBI), and non-TB patients. This study first revealed that macrophages are the major source of IL-16 production in response to Mtb infection, and elucidated that IL-16 can promote Mtb intracellular survival by inhibiting phagosome maturation and suppressing the expression of Rev-erbα which can inhibit IL-10 secretion. The experiments using zebrafish larvae infected with M. marinum and mice challenged with H37Rv demonstrated that reducing IL-16 levels resulted in less severe pathology and improved survival, respectively. In conclusion, this study provided direct evidence that Mtb hijacks the host macrophages-derived interleukin 16 to enhance intracellular growth. It is suggesting the immunosuppressive role of IL-16 during Mtb infection, supporting IL-16 as a promising therapeutic target.

Potent and broadly neutralizing antibodies against sarbecoviruses induced by sequential COVID-19 vaccination.

The current SARS-CoV-2 variants strikingly evade all authorized monoclonal antibodies and threaten the efficacy of serum-neutralizing activity elicited by vaccination or prior infection, urging the need to develop antivirals against SARS-CoV-2 and related sarbecoviruses. Here, we identified both potent and broadly neutralizing antibodies from a five-dose vaccinated donor who exhibited cross-reactive serum-neutralizing activity against diverse coronaviruses. Through single B-cell sorting and sequencing followed by a tailor-made computational pipeline, we successfully selected 86 antibodies with potential cross-neutralizing ability from 684 antibody sequences. Among them, PW5-570 potently neutralized all SARS-CoV-2 variants that arose prior to Omicron BA.5, and the other three could broadly neutralize all current SARS-CoV-2 variants of concern, SARS-CoV and their related sarbecoviruses (Pangolin-GD, RaTG13, WIV-1, and SHC014). Cryo-EM analysis demonstrates that these antibodies have diverse neutralization mechanisms, such as disassembling spike trimers, or binding to RBM or SD1 to affect ACE2 binding. In addition, prophylactic administration of these antibodies significantly protects nasal turbinate and lung infections against BA.1, XBB.1, and SARS-CoV viral challenge in golden Syrian hamsters, respectively. Importantly, post-exposure treatment with PW5-5 and PW5-535 also markedly protects against XBB.1 challenge in these models. This study reveals the potential utility of computational process to assist screening cross-reactive antibodies, as well as the potency of vaccine-induced broadly neutralizing antibodies against current SARS-CoV-2 variants and related sarbecoviruses, offering promising avenues for the development of broad therapeutic antibody drugs.