Identification of sex-specific biomarkers related to programmed cell death and analysis of immune cells in ankylosing spondylitis.

Ankylosing spondylitis (AS) stands as a persistent inflammatory ailment predominantly impacting the axial skeleton, with the immune system and inflammation intricately entwined in its pathogenesis. This study endeavors to elucidate gender-specific patterns in immune cell infiltration and diverse forms of cell demise within the AS milieu. The aim is to refine the diagnosis and treatment of gender-specific AS patients, thereby advancing patient outcomes. In the pursuit of our investigation, two datasets (GSE25101 and GSE73754) pertinent to ankylosing spondylitis (AS) were meticulously collected and normalized from the GEO database. Employing the CIBERSORT algorithm, we conducted a comprehensive analysis of immune cell infiltration across distinct demographic groups and genders. Subsequently, we discerned differentially expressed genes (DEGs) associated with various cell death modalities in AS patients and their healthy counterparts. Our focus extended specifically to ferroptosis-related DEGs (FRDEGs), cuproptosis-related DEGs (CRDEGs), anoikis-related DEGs (ARDEGs), autophagy-related DEGs (AURDEGs), and pyroptosis-related DEGs (PRDEGs). Further scrutiny involved discerning disparities in these DEGs between AS patients and healthy controls, as well as disparities between male and female patients. Leveraging machine learning (ML) methodologies, we formulated disease prediction models employing cell death-related DEGs (CDRDEGs) and identified biomarkers intertwined with cell death in AS. Relative to healthy controls, a myriad of differentially expressed genes (DEGs) linked to cell death surfaced in AS patients. Among AS patients, 82 FRDEGs, 29 CRDEGs, 54 AURDEGs, 21 ARDEGs, and 74 PRDEGs were identified. In male AS patients, these numbers were 78, 33, 55, 24, and 94, respectively. Female AS patients exhibited 66, 41, 40, 17, and 82 DEGs in the corresponding categories. Additionally, 36 FRDEGs, 14 CRDEGs, 19 AURDEGs, 10 ARDEGs, and 36 PRDEGs exhibited differential expression between male and female AS patients. Employing machine learning techniques, LASSO, RF, and SVM-RFE were employed to discern key DEGs related to cell death (CDRDDEGs). The six pivotal CDRDDEGs in AS patients, healthy controls, were identified as CLIC4, BIRC2, MATK, PKN2, SLC25A5, and EDEM1. For male AS patients, the three crucial CDRDDEGs were EDEM1, MAP3K11, and TRIM21, whereas for female AS patients, COX7B, PEX2, and RHEB took precedence. Furthermore, the trio of DDX3X, CAPNS1, and TMSB4Y emerged as the key CDRDDEGs distinguishing between male and female AS patients. In the realm of immune correlation, the immune infiltration abundance in female patients mirrored that of healthy controls. Notably, key genes exhibited a positive correlation with T-cell CD4 memory activation when comparing male and female patient samples. This study engenders a more profound comprehension of the molecular underpinnings governing immune cell infiltration and cell death in ankylosing spondylitis (AS). Furthermore, the discernment of gender-specific disparities among AS patients underscores the clinical significance of these findings. By identifying DEGs associated with diverse cell death modalities, this study proffers invaluable insights into potential clinical targets for AS patients, taking cognizance of gender-specific nuances. The identification of gender-specific biological targets lays the groundwork for the development of tailored diagnostic and therapeutic strategies, heralding a pivotal step toward personalized care for AS patients.

Global biomarker trends in triple-negative breast cancer research: a bibliometric analysis.

BACKGROUND: Triple-negative breast cancer (TNBC) is defined as breast cancer that is negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2) in cancer tissue. The lack of specific biomarkers makes the diagnosis and prognosis of TNBC challenging. METHOD: A comprehensive literature review and bibliometric analysis was performed using CiteSpace, VOSviewer and Scimago Graphica. RESULTS: TNBC biomarker research has been growing rapidly in recent years, reflecting the enormous academic interest in TNBC biomarker research. A total of 127 journals published relevant studies and 1749 authors were involved in the field, with developed countries such as the United States, France, and the United Kingdom contributing greatly to the field. Collaborative network analysis found that the research in this field has not yet formed good communication and interaction, and the partnership should be strengthened in the future in order to promote the in-depth development of TNBC biomarker research. Comprehensive analysis of keywords and co-cited literature, etc. found that TNBC biomarker research mainly focuses on immune checkpoint markers, microenvironment-related markers, circulating tumour DNA, metabolic markers, genomics markers and so on. These research hotspots will help to better understand the molecular characteristics and biological processes of TNBC, and provide more accurate biomarkers for its diagnosis, treatment and prognosis. CONCLUSIONS: The bibliometric analysis highlighted global trends and key directions in TNBC biomarker research. Future developments in TNBC biomarker research are likely to be in the direction of multi-omics integration, meticulous study of the microenvironment, targeted therapeutic biomarkers, application of liquid biopsy, application of machine learning and artificial intelligence, and individualised therapeutic strategies. Young scholars should learn and collaborate across disciplines, pay attention to new technologies and methods, improve their data analysis skills, and continue to follow up on the latest research trends in order to meet the challenges and opportunities in the field of TNBC biomarkers.

Assessing the associations of 1,400 blood metabolites with major depressive disorder: a Mendelian randomization study.

Background and objectives: Major Depressive Disorder (MDD) is one of the most prevalent and debilitating health conditions worldwide. Previous studies have reported a link between metabolic dysregulation and MDD. However, evidence for a causal relationship between blood metabolites and MDD is lacking. Methods: Using a two-sample bidirectional Mendelian randomization analysis (MR), we assessed the causal relationship between 1,400 serum metabolites and Major Depressive Disorder (MDD). The Inverse Variance Weighted method (IVW) was employed to estimate the causal association between exposures and outcomes. Additionally, MR-Egger regression, weighted median, simple mode, and weighted mode methods were used as supplementary approaches for a comprehensive appraisal of the causality between blood metabolites and MDD. Pleiotropy and heterogeneity tests were also conducted. Lastly, the relevant metabolites were subjected to metabolite function analysis, and a reverse MR was implemented to explore the potential influence of MDD on these metabolites. Results: After rigorous screening, we identified 34 known metabolites, 13 unknown metabolites, and 18 metabolite ratios associated with Major Depressive Disorder (MDD). Among all metabolites, 33 were found to have positive associations, and 32 had negative associations. The top five metabolites that increased the risk of MDD were the Arachidonate (20:4n6) to linoleate (18:2n6) ratio, LysoPE(18:0/0:0), N-acetyl-beta-alanine levels, Arachidonate (20:4n6) to oleate to vaccenate (18:1) ratio, Glutaminylglutamine, and Threonine to pyruvate ratio. Conversely, the top five metabolites that decreased the risk of MDD were N6-Acetyl-L-lysine, Oleoyl-linoleoyl-glycerol (18:1 to 18:2) [2] to linoleoyl-arachidonoyl-glycerol (18:2 to 20:4) [2] ratio, Methionine to phosphate ratio, Pregnanediol 3-O-glucuronide, and 6-Oxopiperidine-2-carboxylic acid. Metabolite function enrichment was primarily concentrated in pathways such as Bile Acid Biosynthesis (FDR=0.177), Glutathione Metabolism (FDR=0.177), Threonine, and 2-Oxobutanoate Degradation (FDR=0.177). In addition, enrichment was noted in pathways like Valine, Leucine, and Isoleucine Biosynthesis (p=0.04), as well as Ascorbate and Aldarate Metabolism (p=0.04). Discussion: Within a pool of 1,400 blood metabolites, we identified 34 known metabolites and 13 unknown metabolites, as well as 18 metabolite ratios associated with Major Depressive Disorder (MDD). Additionally, three functionally enriched groups and two metabolic pathways were selected. The integration of genomics and metabolomics has provided significant insights for the screening and prevention of MDD.

Du-moxibustion ameliorates depression-like behavior and neuroinflammation in chronic unpredictable mild stress-induced mice.

BACKGROUND: Neuroinflammation is involved in the advancement of depression. Du-moxibustion can treat depression. Here, we explored whether Du-moxibustion could alleviate neuroglia-associated neuro-inflammatory process in chronic unpredictable mild stress (CUMS) mice. METHODS: C57BL/6J mice were distributed into five groups. Except for the CON group, other four groups underwent CUMS for four consecutive weeks, and Du-moxibustion was given simultaneously after modeling. Behavioral tests were then carried out. Additionally, Western blot was conducted to measure the relative expression levels of high-mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor-kappa B (NF-κB). Immunofluorescence was employed to evaluate the positive cells of ionized calcium binding adapter molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP). Furthermore, interleukin-1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) were analyzed using an ELISA assay. RESULTS: We found that CUMS induced depression-like behaviors, such as reduced sucrose preference ratio, decreased locomotor and exploratory activity, decreased the time in open arms and prolonged immobility. Furthermore, versus the CON group, the expression of HMGB1, TLR4, MyD88, NF-κB, positive cells of Iba-1, IL-1ß and TNF-α were increased but positive cells of GFAP were decreased in CUMS group. However, the detrimental effects were ameliorated by treatment with CUMS+FLU and CUMS+DM. LIMITATIONS: A shortage of this study is that only CUMS model of depression were used, while other depression model were not included. CONCLUSIONS: Du-moxibustion alleviates depression-like behaviors in CUMS mice mainly by reducing neuroinflammation, which offers novel insights into the potential treatment of depression.

An Electrode-Crosstalk-Suppressing Smart Polymer Electrolyte for High Safety Lithium-Ion Batteries.

Electrode crosstalk between anode and cathode at elevated temperatures is identified as a real culprit triggering the thermal runaway of lithium-ion batteries. Herein, to address this challenge, a novel smart polymer electrolyte is prepared through in situ polymerization of methyl methacrylate and acrylic anhydride monomers within a succinonitrile-based dual-anion deep eutectic solvent. Owing to the abundant active unsaturated double bonds on the as-obtained polymer matrix end, this smart polymer electrolyte can spontaneously form a dense crosslinked polymer network under elevated temperatures, effectively slowing down the crosstalk diffusion kinetics of lithium ions and active gases. Impressively, LiCoO2/graphite pouch cells employing this smart polymer electrolyte demonstrate no thermal runaway even at the temperature up to 250 °C via accelerating rate calorimeter testing. Meanwhile, because of its abundance of functional motifs, this smart polymer electrolyte can facilitate the formation of stable and thermally robust electrode/electrolyte interface on both electrodes, ensuring the long cycle life and high safety of LIBs. In specific, this smart polymer electrolyte endows 1.1 Ah LiCoO2/graphite pouch cell with a capacity retention of 96% after 398 cycles at 0.2 C.

Chasing weakly-bound biological water in aqueous environment near the peptide backbone by ultrafast 2D infrared spectroscopy.

There has been a long-standing debate as to how many hydrogen bonds a peptide backbone amide can form in aqueous solution. Hydrogen-bonding structural dynamics of N-ethylpropionamide (a ß-peptide model) in water was examined using infrared (IR) spectroscopy. Two amide-I sub bands arise mainly from amide C=O group that forms strong H-bonds with solvent water molecules (SHB state), and minorly from that involving one weak H-bond with water (WHB state). This picture is supported by molecular dynamics simulations and ab-initio calculations. Further, thermodynamics and kinetics of the SHB and WHB species were examined mainly by chemical-exchange two-dimensional IR spectroscopy, yielding an activation energy for the SHB-to-WHB exchange of 13.25 ± 0.52 kJ mol‒1, which occurs in half picosecond at room temperature. Our results provided experimental evidence of an unstable water molecule near peptide backbone, allowing us to gain more insights into the dynamics of the protein backbone hydration.

Global biomarker trends in Parkinson's disease research: A bibliometric analysis.

As the second most common neurodegenerative disease globally, Parkinson's disease (PD) affects millions of people worldwide. In recent years, the scientific publications related to PD biomarker research have exploded, reflecting the growing interest in unraveling the complex pathophysiology of PD. In this study, we aim to use various bibliometric tools to identify key scientific concepts, detect emerging trends, and analyze the global trends and development of PD biomarker research.The research encompasses various stages of biomarker development, including exploration, identification, and multi-modal research. MOVEMENT DISORDERS emerged as the leading journal in terms of publications and citations. Key authors such as Mollenhauer and Salem were identified, while the University of Pennsylvania and USA stood out in collaboration and research output. NEUROSCIENCES emerged as the most important research direction. Key biomarker categories include α-synuclein-related markers, neurotransmitter-related markers, inflammation and immune system-related markers, oxidative stress and mitochondrial function-related markers, and brain imaging-related markers. Furthermore, future trends in PD biomarker research focus on exosomes and plasma biomarkers, miRNA, cerebrospinal fluid biomarkers, machine learning applications, and animal models of PD. These trends contribute to early diagnosis, disease progression monitoring, and understanding the pathological mechanisms of PD.

Site specifically probing the unfolding process of human telomere i-motif DNA using vibrationally enhanced alkynyl stretch.

The microscopic unfolding process of a cytosine-rich DNA forming i-motif by hemi-protonated base pairs is related to gene regulation. However, the detailed thermal unfolding mechanism and the protonation/deprotonation status of site-specific cytosine in DNA in a physiological environment are still obscure. To address this issue, a vibration-enhanced CC probe tagged on 5'E terminal cytosine of human telomere i-motif DNA was examined using linear and nonlinear infrared (IR) spectroscopies and quantum-chemistry calculations. The CC probe extended into the major groove of the i-motif was found using nonlinear IR results only to introduce a minor steric effect on both steady-state structure and local structure dynamics; however, its IR absorption profile effectively reports the cleavage of the hemi-protonated base pair of C1-C13 upon the unfolding with C1 remaining protonated. The temperature mid-point (Tm) of the local transition reported using the CC tag was slightly lower than the Tm of global transition, and the enthalpy of the former exceeds 60% of the global transition. It is shown that the base-pair unraveling is noncooperative, with outer base pairs breaking first and being likely the rate limiting step. Our results offered an in-depth understanding of the macroscopic unfolding characteristics of the i-motif DNA and provided a nonlinear IR approach to monitoring the local structural transition and dynamics of DNA and its complexes.

Electrolyte Engineering Toward High Performance High Nickel (Ni ≥ 80%) Lithium-Ion Batteries.

High nickel (Ni ≥ 80%) lithium-ion batteries (LIBs) with high specific energy are one of the most important technical routes to resolve the growing endurance anxieties. However, because of their extremely aggressive chemistries, high-Ni (Ni ≥ 80%) LIBs suffer from poor cycle life and safety performance, which hinder their large-scale commercial applications. Among varied strategies, electrolyte engineering is very powerful to simultaneously enhance the cycle life and safety of high-Ni (Ni ≥ 80%) LIBs. In this review, the pivotal challenges faced by high-Ni oxide cathodes and conventional LiPF6 -carbonate-based electrolytes are comprehensively summarized. Then, the functional additives design guidelines for LiPF6 -carbonate -based electrolytes and the design principles of high voltage resistance/high safety novel electrolytes are systematically elaborated to resolve these pivotal challenges. Moreover, the proposed thermal runaway mechanisms of high-Ni (Ni ≥ 80%) LIBs are also reviewed to provide useful perspectives for the design of high-safety electrolytes. Finally, the potential research directions of electrolyte engineering toward high-performance high-Ni (Ni ≥ 80%) LIBs are provided. This review will have an important impact on electrolyte innovation as well as the commercial evolution of high-Ni (Ni ≥ 80%) LIBs, and also will be significant to breakthrough the energy density ceiling of LIBs.

Safety and Pharmacokinetic Assessment of the FIC CLDN18.2/4-1BB Bispecific Antibody in Rhesus Monkeys.

Gastric cancer is one of the most common cancers worldwide, particularly in China, with over half a million new cases and over 400 thousand deaths in 2022. Zolbetuximab, a first-in-class investigational monoclonal antibody (mAb) targeting tumor-associated antigen CLDN18.2 which is highly expressed on gastric cancer cells, was recently reported to meet the primary endpoint in Phase III trial as first-line treatment in CLDN18.2 positive and HER2-negative gastric cancers. In the present study, we developed a humanized bispecific antibody (bsAb) CLDN18.2/4-1BB named PM1032. PM1032 activates immune cells via CLDN18.2 mediated crosslinking of 4-1BB, a potent stimulator of T/NK cells. It induced strong immunological memory in multiple tumor-bearing animal models, indicating significant potential as an effective treatment for CLDN18.2 positive cancers such as gastric cancer. Since liver and gastrointestinal (GI) related toxicities were reported in 4-1BB and CLDN18.2 targeting programs during the clinical development, respectively, extensive pharmacokinetics (PK) and safety profile characterization of PM1032 was performed in rhesus monkeys. PM1032 had a half-life comparable to a conventional IgG1 mAb, and serum drug concentration increased in a dose-dependent pattern. Furthermore, PM1032 was generally well tolerated, with no significant abnormalities observed in toxicity studies, including the liver and stomach. In summary, PM1032 demonstrated good PK and an exceptional safety profile in rhesus monkeys supporting further investigation in clinical studies.

Du-Moxibustion in a Mouse Model of Ankylosing Spondylitis.

Ankylosing spondylitis (AS) is a progressively worsening and disabling form of arthritis that primarily affects the axial skeleton. This disease mainly involves the spine and the sacroiliac joint. Fusion of the spine and the sacroiliac joint may occur in the later stage of the disease, resulting in spinal stiffness and kyphosis, as well as difficulty in walking, which seriously affects the quality of work and daily living activities and imposes a heavy burden on the patient, the family, and society. Increasing attention has been paid to non-pharmacotherapy as an alternative therapy for AS. Moxibustion is an ancient therapeutic technique used in Traditional Chinese Medicine (TCM). Du-moxibustion therapy, a unique and innovative external treatment developed on the basis of ordinary moxibustion, has a definite therapeutic effect on AS. Du-moxibustion skillfully combines the compatible techniques of TCM to integrate meridians, acupoints, Chinese herbal medicine, and moxibustion. This paper describes the operation procedures and precautions to be taken during Du-moxibustion in experimental mice in detail to provide an experimental basis for the study of the mechanism of Du-moxibustion in the treatment of AS.

Frontiers in chronic fatigue syndrome research: An analysis of the top 100 most influential articles in the field.

Chronic fatigue syndrome (CFS) is a complex constellation of symptoms that significantly reduces the quality of life among affected individuals and increases public health expenditures. We conducted a search on the Web of Science Core Collection database and selected the top 100 cited articles in the field of CFS. Several literature analysis tools, including CiteSpace 6.1.R6, VOSviewer 1.6.19, and Scimago Graphica 1.0.30, were utilized to integrate the most influential research papers and academic journals in order to obtain a comprehensive understanding of the CFS field. The top 100 highly-cited publications were published in 67 reputable journals, with contributions from 250 institutions across 26 countries/regions involved in CFS research. This demonstrates the extensive attention and coverage of CFS research by high-quality academic journals and institutions, highlighting the interdisciplinary and multidisciplinary nature of CFS studies. The journal with the highest publication volume and total citations was Lancet. The top 5 co-occurring keywords were chronic fatigue syndrome, cognitive behavior therapy, epidemiology, definition, and disorders, indicating the ongoing attention researchers have devoted to the diagnostic criteria and clinical studies of CFS. Cluster analysis results suggested that primary care, infectious retrovirus, gene expression, and metabolomics may become the focal points and trends in future CFS research. The prospective research directions in this field include the search for biological markers, with a particular focus on immunology; the advancement of diagnostic techniques; the screening of risk genes associated with CFS; and the conduct of epidemiological investigations.

Pancreatic Ductal Adenocarcinoma: The Characteristics of Contrast-Enhanced Ultrasound Are Correlated with the Hypoxic Microenvironment.

A hypoxic microenvironment is associated with an increased risk of metastasis, treatment resistance and poor prognosis of pancreatic ductal adenocarcinoma (PDAC). This study aimed to identify contrast-enhanced ultrasound (CEUS) characteristics that could predict the hypoxic microenvironment of PDAC. A total of 102 patients with surgically resected PDAC who underwent CEUS were included. CEUS qualitative and quantitative characteristics were analyzed. The expression of hypoxia-inducible factor-1α (HIF-1) and glucose transporter-1 (GLUT1) were demonstrated by immunohistochemistry. The associations between CEUS characteristics and the HIF-1α and GLUT1 expression of PDACs were evaluated. We found that HIF-1α-high PDACs and GLUT1-high PDACs had a larger tumor size and were more prone to lymph node metastasis. There was a significant positive linear correlation between the expression of HIF-1α and GLUT1. CEUS qualitative characteristics including completeness of enhancement and peak enhancement degree (PED) were related to the expression of HIF-1α and GLUT1. A logistic regression analysis showed that tumor size, lymph node metastasis, incomplete enhancement and iso-enhancement of PED were independent predictors for HIF-1α-high PDACs and GLUT1-high PDACs. As for quantitative characteristics, HIF-1α-high PDACs and GLUT1-high PDACs showed higher peak enhancement (PE) and wash-in rate (WIR). CEUS can effectively reflect the hypoxia microenvironment of PDAC, which may become a noninvasive imaging biomarker for prognosis prediction and individualized treatment.

Predicting glypican-3 expression in hepatocellular carcinoma: A comprehensive analysis using combined contrast-enhanced ultrasound and clinical factors.

OBJECTIVE: Glypican-3 (GPC3) has emerged as a significant marker for the diagnosis and prognosis of hepatocellular carcinoma (HCC) and has garnered considerable attention as an immunotherapeutic target. In this study, we propose a combination of preoperative contrast-enhanced ultrasound (CEUS) imaging features and clinical factors to predict the positive expression of GPC3 in HCC patients. METHODS: We retrospectively included 30 cases of GPC3-negative HCC and 115 cases of GPC3-positive HCC patients who underwent conventional ultrasound and CEUS evaluation. We assessed and compared the clinical characteristics, conventional ultrasound features, and CEUS features between the two groups of HCC patients. Based on the clinical and ultrasound features between the two groups, we developed a binary logistic regression model for predicting GPC3-positive HCC. RESULTS: A total of 145 HCC patients were included in this study. Binary logistic regression analysis showed that AFP > 20 ng/mL (OR = 4.047; 95% CI: 1.467-11.16; p = 0.007), arterial phase hyperenhancement (APHE) (OR = 12.557; 95% CI: 3.608-43.706; p < 0.001), and asynchronous perfusion (OR = 4.209; 95% CI: 1.206-14.691; p = 0.024) were predictive factors for GPC3-positive HCC. Receiver operating characteristic (ROC) analysis was conducted to predict GPC3-positive expression. The model combining the three independent predictive factors showed good predictive performance (AUC 0.817, 95% CI: 0.731-0.902, sensitivity: 91.3%, specificity: 60.0%). This combined model demonstrated excellent discriminatory ability to predict GPC3-positive HCC. CONCLUSION: Preoperative integration of CEUS features and clinical factors can non-invasively and effectively identify GPC3-positive HCC patients, providing valuable assistance in making personalized treatment decisions.

The Control Method of Autonomous Flight Avoidance Barriers of UAVs in Confined Environments.

This paper proposes an improved 3D-Vector Field Histogram (3D-VFH) algorithm for autonomous flight and local obstacle avoidance of multi-rotor unmanned aerial vehicles (UAVs) in a confined environment. Firstly, the method employs a target point coordinate system based on polar coordinates to convert the point cloud data, considering that long-range point cloud information has no effect on local obstacle avoidance by UAVs. This enables UAVs to effectively utilize obstacle information for obstacle avoidance and improves the real-time performance of the algorithm. Secondly, a sliding window algorithm is used to estimate the optimal flight path of the UAV and implement obstacle avoidance control, thereby maintaining the attitude stability of the UAV during obstacle avoidance flight. Finally, experimental analysis is conducted, and the results show that the UAV has good attitude stability during obstacle avoidance flight, can autonomously follow the expected trajectory, and can avoid dynamic obstacles, achieving precise obstacle avoidance.

Ultrasound-Mediated PLGA-PEI Nanobubbles Carrying STAT6 SiRNA Enhances NSCLC Treatment via Repolarizing Tumor-associated Macrophages from M2 to M1 Phenotypes.

BACKGROUND: Tumor-associated macrophages (TAMs) are crucial for non-small cell lung cancer (NSCLC) development. OBJECTIVE: In this study, polylactic acid-co-glycolic acid (PLGA)-polyethylenimine (PEI) nanobubbles (NBs) carrying STAT6 siRNA were prepared and combined with ultrasound-mediated nanobubbles destruction (UMND) to silence the STAT6 gene, ultimately repolarizing TAMs from the M2 to the M1 phenotype, treating NSCLC in vitro. METHODS: PLGA-PEI NBs-siRNA were prepared and characterised, and their respective ultrasound imaging, biological stabilities and cytotoxicities were detected. Transfection efficiency was evaluated by fluorescence microscopy and flow cytometry. Repolarization of THP-1-derived M2-like macrophages was determined by qPCR and flow cytometry. NSCLC cells (A549) were co-cultured with transfected M2-like macrophages or their associated conditioned medium (CM). Western blotting was used to detect STAT6 gene silencing in M2-like macrophages and markers of epithelial and mesenchymal in A549 cells. The proliferation of A549 cells was detected using CCK-8 and cell colony formation assays. Transwell assays were used to detect the migration and invasion of A549 cells. RESULTS: PLGA-PEI NBs-siRNA had an average size of 223.13±0.92nm and a zeta potential of about -5.59±0.97 mV. PLGA-PEI NBs showed excellent ultrasonic imaging capability in addition to biological stability to protect siRNA from degradation. UMND enhanced PLGA-PEI NBs-STAT6 siRNA transfection in M2-like macrophages, which made M2-like macrophages repolarize to M1-like macrophages and prevented proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in A549 cells. CONCLUSION: UMND enhanced PLGA-PEI NBs-STAT6 siRNA to repolarize TAMs from the M2 to the M1 phenotype, thus treating NSCLC. These findings provide a promising therapeutic approach for enhancing NSCLC immunotherapy.

Linking Career Exploration, Self-Reflection, Career Calling, Career Adaptability and Subjective Well-Being: A Self-Regulation Theory Perspective.

Introduction: In the post-pandemic era, the cultivation of vocational adaptability among college students holds equal significance to fostering subjective well-being in the face of an increasingly daunting professional landscape. This intricate process can be influenced by exploratory expeditions into potential career paths, sincere introspection, and a profound sense of vocation. Methods: Drawing upon Bandura's self-regulation theory, this research project employed structural equation modeling (SEM) to scrutinize the interconnectedness between career exploration, self-reflection, vocational calling, vocational adaptability, and subjective well-being within a sample of 1077 Chinese undergraduates. Results: The findings demonstrated that career exploration and self-reflection positively predicted career adaptability and subjective well-being. In addition, career calling had a significant mediating effect in this model. Conclusion: The findings of this study shed light on the significance of career exploration and self-reflection in fostering both adolescent career adaptability and subjective well-being. And are expected to provide a reference for the career construction and development of college students and career education in colleges and universities.

Ultrasonography in the evaluation of various factors of developmental dysplasia of the hip in infants: Results from a retrospective study in a large hospital of northwest China.

BACKGROUND: The occurrence and development of developmental dysplasia of the hip (DDH) are related to a variety of factors, which have been reported in the literature, but the literature does not mention factors related to the severity of DDH. The purpose of this study is to analyze the related factors of the occurrence and severity of DDH in combination with the Graf ultrasonic diagnostic classification. METHODS: This study was a monocentric retrospective study describing the factors associated with DDH in a large hospital of northwest China. A total of 3046 infants (6092 hips) within 6 months after birth using the Graf method were admitted to our department between 2014 and 2018. We analyzed data of DDH. After reviewing medical charts and diagnostic examination results, we assessed whether factors such as ethnicity, gender, gestational age, birth weight, diagnosis age, maternal age, mode of delivery, fetal presentation, amniotic fluid volume and birth order, had any effect on development of hip. RESULT: ① Analysis showed that DDH mostly occurs in female and left hip joint, related to intrauterine fetal presentation, amniotic fluid volume, gestational age, mode of delivery, prenatal weight, and diagnosis age after birth, and the occurrence of DDH is also related to maternal age (All P＜0.05). Ethnicity and first born showed have no obvious correlation with DDH incidence (p = 0.718, 0.147, respectively). ② The strongest correlation was found with amniotic fluid, followed by birth weight. ③ The severity of DDH was correlated with ethnicity, births, prenatal weight, gestational age, diagnosis age and maternal age (All P＜0.05, respectively). ④ There were significant differences in treatment methods, duration and prognosis among different types of DDH. CONCLUSIONS: The occurrence and development of DDH are related to a variety of factors. Ultrasound examination can provide an early assessment of the hip development status of infants and may play an important role in establishing an early clinical diagnosis treatment and monitoring and prognosis.

Genetic association between ankylosing spondylitis and major depressive disorders: Shared pathways, protein networks and the key gene.

The prevalence of ankylosing spondylitis (AS) and major depressive disorders (MDD) becomes increasingly pronounced, exerting a significant impact on the life quality of contemporary people. Although there is mounting evidence of a link between AS and major depression disorders, the specific interactions between the two have not been thoroughly investigated. To this end, this study aimed to check whether the gene expression profiles of patients with AS and major depression disorders overlapped, and whether there were any functional links between the identified genes via protein-protein interactions. Herein, the relationship between the 4 datasets (GSE73754, GSE98793, GSE25101, and GSE54564) chosen from the Gene Expression Omnibus for evaluation and validation was investigated using gene characterization and functional enrichment. Then, following Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes that explore the biological processes of common genes and demonstrate the interrelationships between common genes, hub genes were obtained using the STRING database and the application cytoHubba plugin of Cytoscape software. The correlation between the gene and 22 types of immuno-infiltrating cells was explored, and the key gene as well as the diagnostic efficiency of the key gene was obtained through verification. A total of 204 shared genes were discovered, the majority of which were functionally enriched in Ribosome, Coronavirus disease COVID19, Starch and sucrose metabolism, and Galactose metabolism. Then, efforts were made to go through STRING. Immuno-infiltration studies revealed that Neutrophils, T cells CD8, T cells CD4 naive, T cells CD4 memory resting, T cells CD4 memory activated, and T cells regulatory were associated with the pathogenesis of AS and MDD. Additionally, the receiver operating characteristic curve revealed that the key gene MRPL13 played diagnostic roles in AS and MDD after intersecting 10 hub genes with 37 differential expression genes from the 2 validation datasets. The obtained results suggest an overlapping genetic structure between AS and major depression disorders. MRPL13 may provide key insights into the relationship between AS and MDD.

Positive valence ≠ positive effect: impact of positive meta-stereotypes on the cognitive performance.

The aim of this study was to examine how positive meta-stereotypes impacted cognitive performance among disadvantaged groups and the mediating effect of negative emotions. In Experiments 1 and 2, Chinese migrant children and rural college students were randomly allocated to the positive meta-stereotype, negative meta-stereotype, or a non-meta-stereotype activation group to examine positive meta-stereotypes' effect on creativity and working memory performance. Both experiments revealed that positive meta-stereotypes had a choking under-pressure effect on cognitive performance, and negative emotions may act as significant mediators between meta-stereotypes and cognitive performance. The choking under pressure effect may occur under positive meta-stereotypes, necessitating more clarification on meta-stereotypes' negative effects.